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ASN DIALYSIS CURRICULUM ASN DIALYSIS ADVISORY GROUP

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Page 1: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

ASN DIALYSIS CURRICULUM

ASN DIALYSIS ADVISORY GROUP

This image cannot currently be displayed

The Challenge of Sudden Cardiac Death in Hemodialysis Patients

Patrick Pun MD MHS

Division of Nephrology

Department of Medicine

Duke University

2

This image cannot currently be displayed

Learning Objectives

Describe the epidemic of sudden cardiac death (SCD) among CKD (and particularly ESKD) patients

Describe unique risk factors which may explain the high risk of SCD in hemodialysis patients

Describe what we know about SCD prevention and management in hemodialysis patients

This image cannot currently be displayed

Sudden Death is the Leading Cause of Death in Dialysis Patients

AMICHF

ArrhythmiaSCA

Other cardiac

CVA

Infection

WithdrawalMalignancy

All other

USRDS ADR 2011

261

SCD

Prevalent Dialysis Patients 2007-2009

This image cannot currently be displayed

The risk of SCD in ESKD-HD is 20x greater than the general population

18942

73

125

241

0

5

10

15

20

25

30

Gen Pop CVD CKD3-4 CKD 5 ND ESRD-HD

Eve

nts

100

0 p

t-ye

ars

Pun et al Kidney Int 2009 Sep76(6)652-8

N=19440

11 increase risk per 10 mlmin GFR decline

Duke catheterization database

Presenter
Presentation Notes
The relative risk of SCD is remarkably higher in HD pts compared to other populations In the gen pop the risk of SCA is about 2 events per 1000 pt years In patients with CV risk factors the rate doubles and using the Duke Catherization database we found that the rate incrementally increases with kidney disease and concurrent CAD patients with CKD stage 3 and 4 here and pt with advanced CKD 5 but not on dialysis here Notice however the marked increase in SCA events among patients receiving RRT HD nearly doubles

This image cannot currently be displayed

Risk of Sudden Cardiac Death after Dialysis InitiationPD vs HD

What is also clear is that the risk of SCD increases in relationship to the number of years on dialysis Again data from the USRDS showing the increasing cumulative probability of SCD with each passing month on HD

USRDS ADR 2011 6

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 2: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

The Challenge of Sudden Cardiac Death in Hemodialysis Patients

Patrick Pun MD MHS

Division of Nephrology

Department of Medicine

Duke University

2

This image cannot currently be displayed

Learning Objectives

Describe the epidemic of sudden cardiac death (SCD) among CKD (and particularly ESKD) patients

Describe unique risk factors which may explain the high risk of SCD in hemodialysis patients

Describe what we know about SCD prevention and management in hemodialysis patients

This image cannot currently be displayed

Sudden Death is the Leading Cause of Death in Dialysis Patients

AMICHF

ArrhythmiaSCA

Other cardiac

CVA

Infection

WithdrawalMalignancy

All other

USRDS ADR 2011

261

SCD

Prevalent Dialysis Patients 2007-2009

This image cannot currently be displayed

The risk of SCD in ESKD-HD is 20x greater than the general population

18942

73

125

241

0

5

10

15

20

25

30

Gen Pop CVD CKD3-4 CKD 5 ND ESRD-HD

Eve

nts

100

0 p

t-ye

ars

Pun et al Kidney Int 2009 Sep76(6)652-8

N=19440

11 increase risk per 10 mlmin GFR decline

Duke catheterization database

Presenter
Presentation Notes
The relative risk of SCD is remarkably higher in HD pts compared to other populations In the gen pop the risk of SCA is about 2 events per 1000 pt years In patients with CV risk factors the rate doubles and using the Duke Catherization database we found that the rate incrementally increases with kidney disease and concurrent CAD patients with CKD stage 3 and 4 here and pt with advanced CKD 5 but not on dialysis here Notice however the marked increase in SCA events among patients receiving RRT HD nearly doubles

This image cannot currently be displayed

Risk of Sudden Cardiac Death after Dialysis InitiationPD vs HD

What is also clear is that the risk of SCD increases in relationship to the number of years on dialysis Again data from the USRDS showing the increasing cumulative probability of SCD with each passing month on HD

USRDS ADR 2011 6

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 3: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Learning Objectives

Describe the epidemic of sudden cardiac death (SCD) among CKD (and particularly ESKD) patients

Describe unique risk factors which may explain the high risk of SCD in hemodialysis patients

Describe what we know about SCD prevention and management in hemodialysis patients

This image cannot currently be displayed

Sudden Death is the Leading Cause of Death in Dialysis Patients

AMICHF

ArrhythmiaSCA

Other cardiac

CVA

Infection

WithdrawalMalignancy

All other

USRDS ADR 2011

261

SCD

Prevalent Dialysis Patients 2007-2009

This image cannot currently be displayed

The risk of SCD in ESKD-HD is 20x greater than the general population

18942

73

125

241

0

5

10

15

20

25

30

Gen Pop CVD CKD3-4 CKD 5 ND ESRD-HD

Eve

nts

100

0 p

t-ye

ars

Pun et al Kidney Int 2009 Sep76(6)652-8

N=19440

11 increase risk per 10 mlmin GFR decline

Duke catheterization database

Presenter
Presentation Notes
The relative risk of SCD is remarkably higher in HD pts compared to other populations In the gen pop the risk of SCA is about 2 events per 1000 pt years In patients with CV risk factors the rate doubles and using the Duke Catherization database we found that the rate incrementally increases with kidney disease and concurrent CAD patients with CKD stage 3 and 4 here and pt with advanced CKD 5 but not on dialysis here Notice however the marked increase in SCA events among patients receiving RRT HD nearly doubles

This image cannot currently be displayed

Risk of Sudden Cardiac Death after Dialysis InitiationPD vs HD

What is also clear is that the risk of SCD increases in relationship to the number of years on dialysis Again data from the USRDS showing the increasing cumulative probability of SCD with each passing month on HD

USRDS ADR 2011 6

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 4: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Sudden Death is the Leading Cause of Death in Dialysis Patients

AMICHF

ArrhythmiaSCA

Other cardiac

CVA

Infection

WithdrawalMalignancy

All other

USRDS ADR 2011

261

SCD

Prevalent Dialysis Patients 2007-2009

This image cannot currently be displayed

The risk of SCD in ESKD-HD is 20x greater than the general population

18942

73

125

241

0

5

10

15

20

25

30

Gen Pop CVD CKD3-4 CKD 5 ND ESRD-HD

Eve

nts

100

0 p

t-ye

ars

Pun et al Kidney Int 2009 Sep76(6)652-8

N=19440

11 increase risk per 10 mlmin GFR decline

Duke catheterization database

Presenter
Presentation Notes
The relative risk of SCD is remarkably higher in HD pts compared to other populations In the gen pop the risk of SCA is about 2 events per 1000 pt years In patients with CV risk factors the rate doubles and using the Duke Catherization database we found that the rate incrementally increases with kidney disease and concurrent CAD patients with CKD stage 3 and 4 here and pt with advanced CKD 5 but not on dialysis here Notice however the marked increase in SCA events among patients receiving RRT HD nearly doubles

This image cannot currently be displayed

Risk of Sudden Cardiac Death after Dialysis InitiationPD vs HD

What is also clear is that the risk of SCD increases in relationship to the number of years on dialysis Again data from the USRDS showing the increasing cumulative probability of SCD with each passing month on HD

USRDS ADR 2011 6

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 5: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

The risk of SCD in ESKD-HD is 20x greater than the general population

18942

73

125

241

0

5

10

15

20

25

30

Gen Pop CVD CKD3-4 CKD 5 ND ESRD-HD

Eve

nts

100

0 p

t-ye

ars

Pun et al Kidney Int 2009 Sep76(6)652-8

N=19440

11 increase risk per 10 mlmin GFR decline

Duke catheterization database

Presenter
Presentation Notes
The relative risk of SCD is remarkably higher in HD pts compared to other populations In the gen pop the risk of SCA is about 2 events per 1000 pt years In patients with CV risk factors the rate doubles and using the Duke Catherization database we found that the rate incrementally increases with kidney disease and concurrent CAD patients with CKD stage 3 and 4 here and pt with advanced CKD 5 but not on dialysis here Notice however the marked increase in SCA events among patients receiving RRT HD nearly doubles

This image cannot currently be displayed

Risk of Sudden Cardiac Death after Dialysis InitiationPD vs HD

What is also clear is that the risk of SCD increases in relationship to the number of years on dialysis Again data from the USRDS showing the increasing cumulative probability of SCD with each passing month on HD

USRDS ADR 2011 6

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 6: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Risk of Sudden Cardiac Death after Dialysis InitiationPD vs HD

What is also clear is that the risk of SCD increases in relationship to the number of years on dialysis Again data from the USRDS showing the increasing cumulative probability of SCD with each passing month on HD

USRDS ADR 2011 6

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 7: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Why is the SCD rate so high Possible explanations

Misclassification

Same disease as general population just worse

Novel risk factors New Disease

Presenter
Presentation Notes
We can posit several possible explanations why the SCD rate is so high in HD First is it possible that we are and grossly overestimating the SCD rate and counting events are not true SCD Can the increased SCD rate be understood in the context of what we know about the same disease in the GP just much worse Or really is a Is more of a novel disease with novel risk factors13

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 8: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

SCD Traditional Definitions

bullWitnessed cardiac arrest - Within an hour of symptom onset

bullUnwitnessed death- Unexpected- Patient known to be well in the last 24 hours- No other clear non-cardiac cause of death

bullOut of hospital occurrence of unanticipated non-traumatic cardiac death

bullUsually due to ventricular tachyarrhythmia

bullDoes this apply to dialysis patients

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 9: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Probably not just due to misclassification Some assurances

Registrydeath certificate data prone to misclassification

363 HD patients with witnessed outpt SCD

bull Sensitivity of registry definition 70-83

bull Specificity of registry definition 90

SCD rate is consistent across data sources

bull In clinical trials [HEMO trial 4D trial]

bull In prospective HD cohorts [CHOICE cohort]

Increased rate of SCD unlikely due to just misclassfication

Pun et al Clin J Am Soc Nephrol 2012 Jan7(1)116-22Herzog et al Kidney Int 2011 Sep80(6)572-86

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 10: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA

Cardiomyopathy(Decreased EF)

Arrhythmic Triggers(Ischemia)

SCAMalignant Arrhythmias

Conventional CHD-related Risk Factors

HDpatients

CKD

Patients

Presenter
Presentation Notes
It is generally understood that SCD requires two main ingredients Structural heart disease and acute arrhythmic trigger In the GP cardiomyopathy with decreased LVEF is by far the most power powerful predictor of SCD risk and acute ischemia is most often the acute arrhtyhmic trigger Conventional CHD-related factors produce both ischemic cardiomyopathy and triggers for SCD Whether or not this is the same process we are seeing in chronic kidney disease patients is in question 13

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 11: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction

Bleyer Kidney Int 2006 Jun69(12)2268-73Yamada Clin J Am Soc Nephrol 2010 Oct5(10)1793-8Mangrum et al Heart Rhythm 2005 2(5)S41 Park et al J Am Soc Nephrol 2012 Oct23(10)1725-34

01020304050607080

WFU (n=88) UVA(n=31)

Perc

ent o

f SC

D

EF

lt35

EF

gt35

EF

gt35

EF

lt35

bull Only 7 Systolic Dysfunction in CRiC

bull 5 in incident HD cohort

bull Increased SCA risk cannot be explained by SD IHD disease alone

Presenter
Presentation Notes
What do we see when we look at underlying cardiac dz in CKD pts with SCD In both a case series of SCD victims from WFU and from UVA the the prevalene of low EF was quite small with 70 of patients without any evidence of systolic dysfunction Also in the CRiC study (observational cohort of pts with moderate CKD) the reported prevalence of systolic dysfuntion is only 7 and a large study of incident dialysis patients also showed that systolic dysfunction is also low at 5 This complicates the paradigm of low EF being the strongest predictor of SCD risk Therefore it seems apparaent that the increased SCA risk in CKD pts canrsquot be fully explained by systolic dysfunction and conventional IHD alone 131313

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 12: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common

Left Ventricular Hypertrophybull56 of HD pts without CADbullEtiologic associations with

bull Chronic ECFV excess vascular accessbull Pressure loading hypertensionbull Anemiabull Mineral-bone-disease hyperphosphatemiabull Aluminum

bullLVMIgt125 gm2 = 30 increased risk of death at 5 yrs

bullLVH= Increased rate of arrhythmias

bull Increased myocardial fibrosis with diffuse subendocardialenhancement

Meier et al Nephron 2001 Mar87(3)199-214Silverberg et al KI 1989Ayus et al JASN 2005Mark PB et al Kidney International (2006) 69 1839ndash1845

Presenter
Presentation Notes
First LVH is highly prevalent in ESRD patients An increase in LV mass is seen in up to 56 HD pts who do not have CHD There are etiologic associations with chronic (ECFV) excess and increased demand of AVF pressure loading and HTN Anemia secondary hyperparathyroidism (SHPT) Aluminum toxicity In fact LVH has emerged as a powerful predictor of cardiac mortality Having a LVMIgt125 is associated with a 30 increased 5 yr mortality (50 vs 20 Silverberg)ndash Whehter or not this is due to sudden death is uncertain but in the general population LVH has been associated with an increased rate of arrhythmias likely due to decreased myocardial reserve and ischemia tolerance and increased myocardial fibrosis 13

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 13: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week

Foley et al NEJM 2011 365 1099

Mortality and CV events on Days of the Dialysis Week

32000 US HD patients

Rat

e pe

r 10

0 pt

yea

rs

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 14: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Hemodialysis as an acute trigger for SCD

Potentially due to rapid shifts in

bull Potassium

bull Calcium

bull Fluid

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 15: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Role of Serum Potassium in SCA

Study of 500 witnessed peridialytic SCA vs 1600 matched controls

Risk linked to extremes of serum potassium (K)

Lowest risk at K ~ 50

Pun et al Kidney Int 2011 Jan79(2)218-27

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 16: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Role of Dialysate Potassium in SCA

Use of low potassium diaysate (lt2 meqL) was associated with a two-fold increase in risk of SCA

Mean Predialysis serum K was in the normal range (49 meqL)

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The way potassium is removed on dialysis is via diffusion down a concentration gradient ie exposure of the serum to a low potassium dialysate bath This figure shows the relationship of low K dialysate and SCA As shown in Panel B The solid bar shows the of SCA patients exposed to low potassium dialysate (defined as lt2 meqL) during the last dialysis treatment hashed bar depicts control patients Nearly 20 of SCA pts were exposed to low potassium baths at the time of the event as compared to 11 controls As shown in Panel A the increased use of low potassium dialsate could not be justified by higher pre-dialysis serum potassium among case patients as the mean predialysis k was 49 (as shown here) and there was no difference between the groups 13----- Meeting Notes (9111 2347) -----13Remind people what low dialysate potassium does

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 17: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]

Difference in risk between low and high K dialysate decreases as serum K increases

No indication of benefit for low K dialysate at any level of serum K

Pun et al Kidney Int 2011 Jan79(2)218-27

Presenter
Presentation Notes
The observation of increased risk with low K dialysate and with elevated pt K begs the question whether or not low K may actually be beneficial for these pts The curves to the right examine the CA probability by predialysis serum K for patients who were prescribed low K baths (red) vs non-low K baths As shown here the difference in risk between low and high K dialysate is greatest at low serum K and decreases as serum K increases However from this analysis we did not see any indication of benefit for low K dialysate even among patients with high serum potassium

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 18: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Ca 2+ mmolL gradient

Calcium Low Calcium Dialysate Associates With Increased risk of SCD

Pun et Al Clin J Am Soc Nephrol 2013 May8(5)797-803

Pro

babi

lity

of S

udde

n D

eath

Matched Case Control Study of 2100 patients

bull 50 Increase in SCA risk with dialysate calcium lt25 meqL

bull Risk rises incrementally with increasing serum dialysate gradient

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 19: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo

HD Exposure

Odds Ratio

1L Fluid Removal on HD

51

15L Fluid Removal on HD

116

2L Fluid Removal on HD

262

Burton JO et al Clin J Am Soc Nephrol (2009) 4 914-920

bull Hemodialysis procedure can reduce myocardial

blood flow even in absence of significant CAD

bull A myocardial ldquostunrdquo may be detected from

echocardiogram regional wall motion abnormalities

(RWMAs)

bull RWMAs present in 50-64 of patients and

associated with poor outcomes

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 20: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Cardiomyopathy

Arrhythmic Triggers

SCAMalignant

ArrhythmiasConventional CHD-related Risk Factors

Unique CKD- related Risk factors

LVH

AnemiaCaPhosPTH

Uremia

Inflammation Malnutrition

Autonomic Instability

Volume shifts

Electrolyte shifts

Dialysis Reactions

Unique CKD-related Risk factors

ESKD-HDpatients

CKD

Patients

SCA in CKD A complex interplay of traditional and CKD-related risk factors

Presenter
Presentation Notes
There are also other unique CKD-specific CA triggers which may contribute to susceptibility to arrest

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 21: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Management of SCD

Prevent Sudden Cardiac Arrest

bullMedical therapies to treat underlying cardiac disease

bullReduce exposure to triggers

Improve survival following SCA

bullDefibrillation

Presenter
Presentation Notes
So there are Two fundamental approaches to manage SCA risk First is treating and preventing underlying cardiac disease reduce exposure to triggers which wersquove already talked about germane to HD pts Second is to improve survival after a SCA occurs and defibrillators have been pivotal in this regard What do we know about the efficacy of these treatments in HD patients

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 22: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Medical Therapies for SCD Prevention Beta Blockers

bull Beta Blockers shown to be helpful for prevention in pts with minimal or no CKD

bull Poor Implementation Only 24 of dialysis patients with CAD or prior MI are on beta blockers

bull Only one randomized trial of beta-blockers in ESRD

bull 114 pts with DCM randomized to Carvedilol or placebo

bull Significant survival advantage non significant reduction (24) in SCD

Cice JACC 2003 411438-44

Presenter
Presentation Notes
What about medical therapies for cardiomyopathy BBL have been shown to be helpful in preventing SCD in post MI pts with minimal or no CKD We also know that there is poor implementation of BBL-- only 24 of dialysis patients with documented CAD or prior MI are on BBL There is only one RCT I know of using BBL which enrolled 114 pts with DCM to carvedillol or placebo and as you can see here resulted in significant improvement in survival and and 24 reduction in SCD although non-significant 1313 So what do we know about emd114 pts 23 class III mean EF 2613SCD risk decreased by 24 but not statistically significant

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 23: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Medical Therapies for SCD Prevention PhosphorusSHPT

Observational study of 12833 HD patients

bull6 increase in SCD per 1 mgdl increase in Phos

bull7 increase in SCD per 10 mgdl increase is CaxPhos product

bull20 increase with phos gt65

bull6 increase with PTHgt495

PTH

Ganesh et Al JASN 2001

Hyperphosphatemia can provoke vascular calcification endothelial dysfunction and atherosclerosis

Presenter
Presentation Notes
Tie in for CKD BMD

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 24: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Benefit in ESRD not clearly known for

bull Statins

bull 4D AURORA studies negative

bull SHARP Reduction in coronary revascularization cardiac events seen only in 23 pts with predialysis CKD not in 13 pts with ESRD

bull ACEIARB

bull Antiplatelet agents

bull Vitamin D

Other Medical Therapies for SCD Prevention

Presenter
Presentation Notes
Statin- SHARP STUDY showed nonsignificant

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 25: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Implantable Cardioverter Defibrillators in HD patients

Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17

Herzog et al Kidney Int 2005 Aug68(2)818-25

No ESRD patients included in any randomized trialsbull Secondary prevention ICD (ICD after cardiac arrest)

bull Two retrospective studies show benefit ICD after cardiac arrest compared to patients with cardiac arrest and no ICDbull HR 086 (95 CI 081-091) bull Subject to indication bias

bull Primary prevention (prophylactic ICD)bull No data on mortality benefit in ESRD compared to controlsbull Increased mortality risk of complications in ESRD

compared to non-ESRD ICD recipients

Agarwal et al Heart Rhythm 2009 Nov6(11)1565-71

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 26: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Diminishing Benefit of Primary ICD with CKD

Pun et al Am J Kidney Dis 2014 Feb 8epub ahead of print

Meta-analysis of 3 randomized controlled trialsbull 2867 patients

bull 363 with eGFRlt60 no HD patients

bull Diminishing survival benefit of ICD vs no ICD with lower eGFR

Presenter
Presentation Notes
Another landmark study in favor of primary prevention ICDs- the MADIT 2 study-- They found an overall 30 reduction in mortality benefit of ICDs vs conventional therapy in pts with ICM and decreased EF Again no dialysis patients but look at the benefit of ICD among different subgroups with decreased eGFR Although underpowered with only 80 pts in this subgroup there was no significant benefit either for all-cause mortality or SCD in patients with GFR lt35 It seems clear that benefit of ICDs in pts with advanced renal dz is not the same as those without renal dz

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 27: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Why might primary ICDs not be beneficial

bull Increased defibrillation thresholds in CKD and ESRD pts compared to normal

bull ESRD patients not having ldquoshockablerdquo events 38 of ICD recipients on dialysis still die of arrhythmia

bull Competing risks may outweigh benefits

bull Death 45 annuallybull Bacteremia 52bull Device infection 42 (vs 07)bull Generator replacement 39 (vs lt2)bull Vascular Access Complications

Wase J Interv Card Electrophysiol 2004 Dec11(3)199-204Charytan et al Am J Kidney Dis 2011 Sep58(3)409-17Drew et al Am J Kidney Dis 2011 Sep58(3)494-496

Presenter
Presentation Notes
Why might ICDs not be effective in HD pts First 13Second competing risks may outweigh benefits The annual incidence of hellip13Specific to HD pts vascular access compromise is of particular concern given the importance of stable permanent dialysis access and the association of dialysis catheters with poor outcomes A recent case series of 43 HD pts with ICDrsquos showed that 62 developed central venous stenosis ipsilateral to the device and 48 of these patients were permanently catheter dependent as a result 131313 General population Device infection about 07 annually Explantation for malfunction lt2 annually1313Of these 43 patients 34 (79) underwent imaging of the central veins 21 of the 34 patients (62) had demonstrable central vein stenoses 17 of which were ipsilateral to the cardiac device The mean number of accesses including access present at the time of device insertion was 39 1113092 27 for patients with versus 28 1113092 23 for those without central stenoses Of patients without devices 297 of 547 (54) underwent imaging of central veins and 94 of the 297 (32) had an identified central stenosis (P 1113094 0001 compared with those with imaging) Ten of 21 (48) patients with a cardiac device and central vein stenosis were deemed catheter dependent after device insertion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 28: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

Treat Cardiomyopathy

bullAssess at baseline and q3yrs (2005 KDOQI guideline)

bullUse beta-blocker for dilated cardiomyopathy EF lt35

bullControl SHPT and phosphorus

bullUnclear if other proven therapeutic interventions will also be beneficial in dialysis patients

Reduce and monitor triggers

bullAvoid low potassium and low calcium dialysate

bullReview and adjust prescription dialysis regularly in response to laboratory data

bullReduce IDWGavoid large volume shifts

bullMore frequentlonger dialysis sessions

Presenter
Presentation Notes
Pulling it together How can we rise to meet the challenge of SCA in HD pts given what we know today First I think it is reasonable that we should make an effort to treat cardiomyopathy The KDOQI guidelines suggest that ECHOcardiogram should be performed at baseline and every 3 yrs following There is evidence to support BBL for pts with with dilated CM and EFlt35 but it is unclear if other proven therapeutic interventions will also be beneficial in HD pt Second we should make an effort to reduce and monitor for triggers for SCA If possible we should avoid very low potassium and low calcium dialysate be cognizant of potential interactions with QT prolonging medications Should Review and adjust HD prescriptions regularly in response to labs Direct efforts towards reducing IDWGlarge volume shifts and consider frequent longer dialysis sessions

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 29: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

Rising to the Challenge of SCD in Hemodialysis Patients

ICDsbullNo evidence to support prophylactic primary ICDs in dialysis patients

bull Counsel patients regarding likelihood of decreased benefits and increased risks compared to general population

bullConsider ICDs for secondary prevention

bullCoordinated care bt nephrologists and EP

Presenter
Presentation Notes
Regarding ICDs I think there is evidence to support the use of secondary prevention ICDs very unclear benefit with primary ICDs and there is a definite need for greater coordinationa and communication between nephrologists and EP given the potential complications of ICDs 13

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
Page 30: ASN DIALYSIS ADVISORY GROUP · Death in Hemodialysis Patients. Patrick Pun, ... • Chronic ECFV excess/ vascular access ... The way potassium is removed on dialysis is via diffusion

This image cannot currently be displayed

We need

bullLarge cohort studies assessing risk factors with carefully adjudicated endpoints

bull Clinical variables

bull Dialysis variables

bull CardiacEP variables

bull Biomarkers

bullRCT

bull Beta blockers

bull Potassium management

bull ICDs (ICD2 trial wearable ICD subQ ICD)

Rising to the Challenge of SCD in Hemodialysis Patients

Presenter
Presentation Notes
As far where we go from here from a research standpoint I think we really need to start from the beginningndash we need large cohort studies which assess risk factors with carefuly adjudicated endpointsndash we need to better understand the relationship between traditional clinical variables cardiacelectrophysiologic variables and traditional and novel biomarkers with SCA risk and whether or not any of these can serve as effective risk stratification tools From a therapy standpoint we also need to start from the beginningndash BBL trials of intensive potassiumcalcium management and of course ICDs including some of the newer less invasive defibrillation devices such as wearable ICDs and other leadless iCDs to avoid problems with vascular access) 13----- Meeting Notes (9111 1732) -----13RCT of potassium and calcium management
  • Slide Number 1
  • Slide Number 2
  • Learning Objectives
  • Sudden Death is the Leading Cause of Death in Dialysis Patients
  • The risk of SCD in ESKD-HD is 20x greater than the general population
  • Risk of Sudden Cardiac Death after Dialysis Initiation PD vs HD
  • Why is the SCD rate so high Possible explanations
  • SCD Traditional Definitions
  • Probably not just due to misclassification Some assurances
  • SCD Pathophysiology Cardiomyopathy + Acute Trigger=SCA
  • Underlying cardiac disease in CKD SCD is rarely traditional ischemic cardiomyopathy with systolic dysfunction
  • Differences in Structural Heart Disease LVH and Diffuse Myocardial Scarring are more Common
  • SCD Acute Triggers SCD and Arrhythmias occur most frequently on the first hemodialysis day of the week
  • Hemodialysis as an acute trigger for SCD
  • Role of Serum Potassium in SCA
  • Role of Dialysate Potassium in SCA
  • Potassium Homeostasis and Risk of SCA Low [K ] bath for High Pt [K]
  • Slide Number 18
  • Amount and Rate of Fluid Removal During HD Associates With Myocardial ldquoStunningrdquo
  • Slide Number 20
  • Management of SCD
  • Medical Therapies for SCD Prevention Beta Blockers
  • Medical Therapies for SCD Prevention PhosphorusSHPT
  • Other Medical Therapies for SCD Prevention
  • Implantable Cardioverter Defibrillators in HD patients
  • Diminishing Benefit of Primary ICD with CKD
  • Why might primary ICDs not be beneficial
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients
  • Rising to the Challenge of SCD in Hemodialysis Patients

Various Dialysis Machines Comparison Hemodialysis Units

Why Dialysis Medications Matter?Stromayer).pdf · Why Dialysis Medications Matter? ... for Hemodialysis Patients ... Adherence to dialysis medications is assessed by

Cancers, Chemotherapies and Hemodialysis...Cancers, Chemotherapies and Hemodialysis: A retrospective study Lydia BENHOCINE A.BENZIANE M.BENABADJI Departementof Nephrology Dialysis

Manitoba Renal Program Home Dialysis Handbook · 2015-05-22 · Manitoba Renal Program Home Dialysis Handbook Information about Peritoneal Dialysis and Home Hemodialysis ... (kidney

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ASN Dialysis Curriculum

Home Hemodialysis: Infrastructure, Water, and Machines … · Home Hemodialysis: Infrastructure, Water, and Machines in the ... • Home Dialysis Central, ... disinfection method

Mar Cor Purification Dialysis Water Product Catalog€¦ · Dialysis Water Products. Dialysis Water Products. Mar Cor Purification is the largest supplier of hemodialysis water systems

Bacteremia in Hemodialysis and Peritoneal Dialysis Patients

From Peritoneal Dialysis to Hemodialysis How could we ... · From Peritoneal Dialysis to Hemodialysis How could we improve the transition ? Th Lobbedez CHU de Caen Self Dialysis Meeting

Dialysis (Hemodialysis and Peritoneal)

ATTACHMENT - REQUIRED STATE AGENCY FINDINGS · hemodialysis. Home training for peritoneal dialysis and home hemodialysis are provided by Elizabeth City Dialysis Center. According

ASN DIALYSIS · PDF fileASN Dialysis Curriculum Drug Dosing in Dialysis Patients . Jula K. Inrig, MD, MHS ... Calcium channel blocker: amlodipineis not dialyzable

Hemodialysis Abstracts from the Annual Dialysis Conference

ASN DIALYSIS ADVISORY GROUP · • Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes

Hemodialysis and peritoneal dialysis

HOME HEMODIALYSIS Have You Ever Considered Home Dialysis?

Hemodialysis Author Interviews from the 2012 ASN Renal Week

Nikkiso Hemodialysis Equipmentssaudiarabia-jccme.jp/japantech/pdf/8_nikkiso.pdf · Dialysis System Diagram RO water Dialysis Fluid Reverse Osmosis Equipment Dialysis Fluid Delivery

UNDERSTANDING HEMODIALYSIS - Healthcare | … HEMODIALYSIS. 2 FRESENIUS MEDICA CARE CONTENTS Hemodialysis – from the early days to today ... first, osmosis and dialysis became popular

Water for Dialysis - mcpur.comwater_for_dialysis).pdf · Water for Dialysis Your Hemodialysis Need People undergoing hemodialysis require a high level of patient care. Part of that

Body Mass Index - Hemodialysis, Inc. - dialysis hemodialysis books

Dialysis Dosing: Kinetics Versus Physiology KDIGO · Hemodialysis Hemodiafiltration technologies Intensive Hemodialysis Ability for solute clearance, frequency and therapy duration

DIALYSIS TECHNICIAN · DIALYSIS People with end stage renal disease can be treated with hemodialysis or peritoneal dialysis. DEFINITION Dialysis is a technique in which substance

Hemodialysis Access: Dialysis Catheters€¦ · hemodialysis catheter is for urgent hemodialysis while the . patient is waiting for an AVF to be created or to mature. Hemodialysis

ASN DIALYSIS ADVISORY GROUP · hemodialysis patients ... • Initial studies demonstrated clinical improvement with increase in Hgblevels to 9-10 g/dl range

Body Water - Body Weight - Hemodialysis, Inc. - dialysis

ASN DIALYSIS CURRICULUM Dialysis Curriculum Continuous Quality Improvement in Dialysis Units . Uptal D. Patel, MD • Affiliations • Duke Clinical Research Institute

Hemodialysis ompared to Inside this Issue Peritoneal Dialysis...Hemodialysis Peritoneal dialysis What is usually involvedhours a day. Before hemodialysis treatments can begin, your

American Dialysis College (ADC) - Hemodialysis, Inc Dialysis College Page 6 of 38 American Dialysis College Catalog School Year 2016 – 2018 In addition, goals of the American Dialysis

ASN DIALYSIS ADVISORY GROUP · •Increased ultrafiltration, longer dialysis •More than 3 hemodialysis treatments per week, •Additional exchanges for peritoneal dialysis KDQOI,

Home HEMODIALYSIS PATIENT MANUAL - Home Dialysis …

Hemodialysis.com | Hemodialysis | Dialysis | Kidney Disease