arash karnama, do, facc oklahoma heart institute€¦ · · 2017-08-02arash karnama, do, facc...

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The Latest and Greatest in Cardiology

Arash Karnama, DO, FACC

Oklahoma Heart Institute

Topics

CT-FFR CHF -Cardiomems

Valvular Heart Disease – TAVR

update, Mitral Clip

Electrophysiology – Leadless PPM,

Watchman, Cryoablation

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CT-FFR

FFR from CTA

C.A. Taylor, T.A. Fonte, J.K. Min, et al. (2013) Computational Fluid Dynamics Applied to Cardiac Computed Tomography for Noninvasive Quantification of Fractional Flow Reserve: Scientific Basis. Journal of the American College of Cardiology. Vol. 61, Issue 22, pp. 2233-2241.

Courtesy Paul Temple from HeartFlow.

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Build anatomic heart model from CTA

Assign myocardial territory to individual arteries

Requires good quality CTA image data


FFR from CTA

Allometric scaling laws can be applied to estimate physiologic parameters, e.g. coronary flow, under baseline conditions given organ mass

Qcrestµ Mmyo

β

1: Model REST coronary blood flow given left ventricular myocardial mass and assignment of myocardium to each coronary artery


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FFR from CTA

1. Healthy and diseased vessels adapt to amount of flow they carry

2. Power law relationships of form Q dk apply to different vascular beds – including coronary arteries

3. Since mean pressure (P) is essentially constant down the length of the coronary arteries at rest

AND P=QR

AND Q dk

THUS R d-k

2: Model microcirculatory vascular bed flow resistance at REST, inversely proportional to size of feeding vessel.


FFR from CTA

1. When the heart lacks O2, breakdown of ATP results in release of adenosine → vasodilation

2. Exogenous administration of adenosine elicits maximum hyperemic response by forcing complete smooth muscle cell relaxation

3. Standard of care for induction of hyperemia in non-invasive tests and the cath lab Intravenous administration of adenosine elicits

remarkably consistent vasodilatory response in normal subjects at sufficient doses

3: Model predictable change in microcirculatory resistance in response to ADENOSINE


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FFR from CTA

• Now we have:

• Resting coronary blood flow

• Resting coronary vascular resistance

• Adenosine-induced coronary vascular resistance

• And adenosine-induced coronary blood flow can be determined!

And… Watson is needed

Mass Conservation (1 equation):

Momentum Balance (3 equations):

0

yx zvv v

x y z

22 2

2 2 2

22 2

2 2 2

2

yx x x x x zx y z

y y y y yx zx y z

z z z zx y z

vv v v v v vpv v v

t x y z x x y z

v v v v vv vpv v v

t x y z y x y z

vv v v v pv v v

t x y z z

2 2

2 2 2

yx zv v

x y z

where is the fluid density, and is the fluid viscosity (both assumed known).

We solve these for ( , , , ), ( , , , ), ( , , , ), ( , , , )

for every point in the 3D model and over whatever time

x y zv x y z t v x y z t v x y z t p x y z t

interval we are interested in.

MOMENTUM conservation: These equations come from the application of Newton’s 2nd law, F=ma to a fluid

MASS conservation: This law states that blood is an incompressible fluid

4: Solve equations of mass and momentum conservation to calculate coronary flow with ADENOSINE


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Make a supercomputer do it


Standard: 12-15 hours, High priority: 4-6 hours

Testing FFR-CT• DISCOVER-FLOW

• 103 patients underwent CTA, cath with FFR, blinded FFR-CT

• Cath-FFR<0.8 = reference

• Specificity improved: 40% to 82% (reduced false positives!)

• Sensitivity similar: 88% vs 91%

Koo, et al. JACC 2011.

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Testing FFR-CT• DE FACTO

• 252 patients underwent CTA, cath with FFR, blinded FFR-CT


• Specificity improvement not as good: 40% to 52%


Min, et al. JAMA 2012.

Testing FFR-CT• NXT

• 254 patients underwent CTA , cath with FFR, blinded FFR-CT


• Specificity improved: 60% to 86%


Norgaard, et al. JACC 2014.

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Not for stents or grafts

Confirmation

• 2 meta-analyses since FDA approval both found

• FFR-CT improved specificity and overall accuracy for ischemic disease compared to CTA only

• Adding FFR-CT did not change sensitivity

• FFR-CT effectively cuts the rate of incorrectly assuming disease on CTA causes ischemia

(Baumann S, et al. Acad Radiol 2016)

(Tan XW, et al. Int J Cardiol 2017)

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FFR-CT impact on decision making

• RIPCORD

• 200 patients with CTA + FFR-CT

• 3 blinded interventionalists made consensus initial plan of management based on CTA alone

• Then FFR-CT results are provided, and the interventionalists decide whether to modify plan

• In 72 patients (36%), FFR-CT changed management approach

Curzen, et al. JACC Cardiovasc Img 2016.

FFR-CT impact on decision making• RIPCORD

• 36% of management plans changed after FFR-CT

• FFR-CT eliminated need for more information after CTA

• FFR-CT positive (<0.8)

• 23% of 51-70% stenoses

• 54% of 71-90% stenoses

• 70% of >90% stenoses

Curzen, et al. JACC Cardiovasc Img 2016.

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FFR-CT impact on cath

• PLATFORM

• 584 patients intermediate probability for stenotic CAD• 204 planned for noninvasive testing

• 380 planned for cath

• Both groups randomized to original plan or CT with FFR-CT

• Outcomes• Rate of coronary catheterization

• Cardiac events at 90 days

Douglas, et al. EHJ 2015.

FFR-CT impact on cath• PLATFORM

• In the group originally headed for cath, use of FFR-CT

• Cancelled 60% of caths, none of these patients had a cardiac event at 90 days

• Resulted in 60% less cathshowing nonobstructive disease (73% vs 12%)

• No difference in overall rate of revascularization

Douglas, et al. EHJ 2015.

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OHI Case

~60% stenosis

60% mid LAD stenosis, 70-80% D2 stenosis

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Who gets FFR-CT?

• FFR-CT became available at OHI on May 1• @ HMC, BMC, and HHS

• Only center in Oklahoma to have the service

• Referring clinicians order coronary CTA as usual

• CTA reader discretion to proceed with FFR-CT

• If we use RIPCORD study data:• Borderline 50% or nearly 50% stenoses

• 50-69% stenoses

• Select 70-99% stenoses

• FFR-CT cannot save a nondiagnostic CTA!

Limitations

• Patients with nondiagnostic scans do not suddenly become diagnostic because of FFR-CT

• FFR-CT cannot be interpreted in isolation

• FFR-CT was tested against gold standard vasodilation cath FFR, not instantaneous wave-free ratio (iFR)

• Still waiting for data to help determine utility in the acute symptomatic setting

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Conclusion• With the addition of FFR-CT, coronary CTA now provides

• High sensitivity for detecting anatomic stenoses

• High sensitivity for differentiating amongst no disease, nonstenotic disease, stenotic disease, and severe high-risk disease

• Good specificity for identifying hemodynamically important disease when measured by cath-FFR

• A big leap forward for noninvasive CAD testing!

Congestive Heart Failure

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DESPITE MEDICAL ADVANCES Heart Failure hospitalization is a worsening epidemic

Significant Reduction in Coronary Deaths1

050

100150200250300350400

1980 1985 1990 1995 2000 2005 2010

Significant Increase in HF Hospitalizations2

-

5,000,000

10,000,000

15,000,000

20,000,000

1980-84 1985-89 1990-94 1995-99 2000-2004

1. Graph adapted from NIH, Accessed 2016.2. Graph adapted from Fang J, et al. JACC, 2008.

THE PROBLEM:Unless focused, dramatic measures are taken, the clinical and financial

burden to society is only going to escalate.

Deaths/100,000 PopulationNumber of HF Hospitalizations With HF as

Primary or Secondary Diagnosis, by 5-Year Time Period

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The CLINICAL burden :heart failure is A GROWING GLOBAL CONCERN FOR PATIENTS, PROVIDERS AND

HEALTH CARE SYSTEMSUNITED STATES

1. AHA 2016 Statistics at a Glance, 2016.2. Krumholz HM, et al. Circ Cardiovas Qual Outcomes 2009.3. Heidenreich PA et al. Circ Heart Failure 2013.

HIGH INCIDENCE, HIGH PREVALENCE AND POOR PROGNOSIS

despite advances in the treatment of heart failure over the past few decades.

Projected to increase to > 8M people ≥ 18 years of age with HF by 20301

915,000people ≥ 45 years of age are newly diagnosed each year with HF.1

For AHA/ACC stage C/D patients diagnosed with HF:

| PREVALENCE

|INCIDENCE

|MORTALITY

50% readmitted within 6

months.2

2.2%prevalence1

5.7M HF patients1

50% will die within 5

years.3

15

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The ECONOMIC burden:heart failure is a significant and growing contributor to overall HEALTH system costs

Total medical costs for HF are projected

to

increase to $70B by 2030, a 2x increase

from 2013.*

1. CDC NCHS National Hospital Discharge Survey, 2000-10.2. Blekcer et al. JACC, 2013.3. Yancy et al. JACC, 2006.

4. Yancy CW, et al. Circulation, 2013. 5. Krumholz HM, et al. Circ Cardiovas Qual Outcomes 2009.6. Wexler DJ, et al. Am Heart J, 2001.

50% of the costs are

attributed to hospitalization.

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> 3,000,000hospitalizations include HF as a contributor.2

~5 daysaverage length

of hospital stay3

> 1,100,000hospitalizations for

HF1

~25%all-cause readmission within 30 days; ~50% within 6 months.5,6

HOSPITALIZATIONS & READMISSIONS COSTS

Despite advances in medical therapies to treat heart failure, the hospitalization rate has not changed significantly from 2000. As a result, heart failure continues to be a

MAJOR DRIVER OF OVERALL HEALTH CARE COSTS.

UNITED STATES

*Study projections assumes HF prevalence remains constant and continuation of current hospitalization practices

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Current HF Management: Why aren’t current parameters working?

Graph adapted from Adamson PB, et al. Curr Heart Fail Reports, 2009.

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Current HF Management: How can we get ahead of symptoms associated with acute decompensation?

Graph adapted from Adamson PB, et al. Curr Heart Fail Reports, 2009.

Cardiomems™ hf system

A Personalized, Proactive Approach to Manage HF

by Monitoring PA Pressure

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Delivers insight into the early onset of worsening HF to more proactively manage HF patients and improve outcomes

cardiomems™ HF System:Provides clarity in the management of heart failure

Pulmonary Artery Pressure Sensor

Patient Electronics System

Merlin.net™ PCN

Target location for PA pressure sensor

Abraham WT, Lancet, 2011

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CHAMPION TRIAL design: RANDOMIZED (Part 1) AND OPEN ACCESS (part 2)

CardioMEMS™ PA Sensor Implanted n = 550

Treatment Groupn = 270

Control Groupn = 280

Transition to Former Treatment Group

n = 177

Transition to Former Control Group

n = 170

1. Abraham W, et al. Lancet, 2011.2. Abraham W, et al. Lancet, 2016.

PART 1: RANDOMIZED ACCESS1

Study Exitn = 110

Study Exitn = 93

PART 2: OPEN ACCESS2

Previously hospitalized patients (past 12 months) with NYHA class III HF for at least 3 months, regardless of LVEF

All took daily readings.

RANDOMIZATION

CardioMEMS™ Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association (NYHA) Class III Heart Failure Patients (CHAMPION) Trail

TRIAL HYPOTHESIS: In addition to basing treatment on signs and symptoms, adjusting medications based on PA pressures will reduce HF-related hospitalizations.

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CHAMPION TRIAL design: part 1: Prospective, multi-center, randomized, controlled,

single-blind clinical trial

CardioMEMS™ PA Sensor Implanted n = 550


Traditional HF management guided by PA pressure

information


Traditional HF management

PURPOSEEvaluate the safety and efficacy of the CardioMEMS™ HF System in reducing HF related hospitalizations in NYHA class III heart failure patients.

Primary Endpoint: Rate of HF hospitalization

Secondary Endpoints:

Change in PA pressure at 6 months

No. of pts admitted to hospital for HF

Days alive outside of hospital QOL (MLHFQ)

Study exits < 6 mos.: 26 (9.3%) Total20 (7.1%) Death6 (2.2%) Other

Study exits < 6 mos.:26 (9.6%) Total

15 (5.6%) Death11 (4.0%) OtherTreatment group

managed to target PA pressures:

Systolic 15 – 35 mmHgDiastolic 8 – 20 mmHgMean 10 – 25 mmHg

Abraham W, et al. Lancet, 2011.

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CHAMPION TRIAL RESULTS: PART 1 and PART 2: 31 MONTHS Average FOLLOW-UP

CardioMEMS™ PA Sensor Implanted

n = 550



Transition to Former Treatment Group

n = 177

Transition to Former Control Group

n = 170

Study Exitn = 110

Study Exitn = 93

Completed Open Accessn = 119

Completed Open Accessn = 127

Study Exitn = 43

Study Exitn = 58

PART 1: RANDOMIZED ACCESS1

18 months

PART 2: OPEN ACCESS2

13 months

1. Abraham W, et al. Lancet, 2011.2. Abraham W, et al. Lancet, 2016.

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CHAMPION Trial results:PRIMARY ENDPOINT

Abraham W, et al. Lancet, 2016.

Patients managed with PA pressure data had

SIGNIFICANT RELATIVE RISK

REDUCTIONas compared to the control group.

PART 1: RANDOMIZED ACCESS PART 2: OPEN ACCESS

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0 90 180 270 360 450 540 630 720 810 900 990 1080

Cum

ulat

ive

Haz

ard

Rat

e

Days From Implant

33% Relative Risk Reduction in HF Hospitalizations in Treatment Group vs.

Control Group

Treatment

Control

# at Risk

Control 280 267 254 241 210 175 131 101 62 27 12 5 0

Treatment 270 262 246 235 197 164 125 105 75 38 8 3 0

p=0.017

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CHAMPION Trial results:Primary Safety Endpoints and Secondary Endpoints

Treatment(n = 270)

Control(n = 280)

P-value

Primary Safety Endpoints

Device-related or system-related complications3 (1%) 3 (1%)

Total 8 (1%)* < 0.0001

Pressure-sensor failures 0 0 < 0.0001

SecondaryEndpoints

Change from baseline in PA mean pressure (mean AUC [mm Hg x days])

-156 33 0.008

Number and proportion of patients hospitalized for HF (%) 55 (20%) 80 (29%) 0.03

Days alive and out of hospital for HF (mean ± SD) 174.4 ± 31.1 172.1 ± 37.8 0.02

Quality of life (Minnesota Living with Heart Failure Questionnaire, mean ± SD)

45 ± 26 51±25 0.02

* Total of 8 DSRCs including 2 events in Consented not implanted patients (n = 25)

Abraham WT, et al. Lancet, 2011.

ALL ENDPOINTS MET.Both primary safety endpoints and all secondary endpoints were met at 6 months.


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PA

Mea

n P

rea

sure

AU

C (

mm

Hg

-Da

ys)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 0.0077

Treatment (-155.7 mmHg-Days)Control (33.1 mmHg-Days)

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CHAMPION Trial results:PA PRESSURE MEAN CHANGE FROM BASELINE

Abraham WT, et al. Lancet, 2011.


Monitoring PA pressure with the CardioMEMS™ HF System allows management of the pressure spikes that lead directly to

exacerbation, as well as the long-term trends.

By targeting PA pressure ranges and titrating medications, the overall mean PA pressure is reduced over time.

Treatment (-155.7 mmHg-Days)Control (33.1 mmHg-Days)P

A M

ean

Pre

asu

re A

UC

(m

mH

g-D

ays)

P = 0.0077

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Champion trial SUB-analysis:medical therapy interventions

Analyze medical therapy data from the CHAMPION trial to determine which interventions were linked to decreases in HF hospitalizations during PA pressure guided management. PURPOSE

Medication changes based on PA pressure information were more effective in reducing HF hospitalizations than using signs

& symptoms alone.

Costanzo, et al. JACC Heart Failure 2016.

2468

1547

293 293 23996

1061

585

104 144 16068

0

500

1000

1500

2000

2500

Med

icat

ion

Ch

ange

s

Frequency of Medication Changes by Drug Class

PA Pressure Guided HF Management (Treatment Group)Standard of Care HF Management Only (Control Group)

Significantly more changes in medication doses in the Treatment Group than in the Control Group.

Diuretics were the most frequently adjusted medication and the changes were significantly higher in the Treatment Group.

RESULTS

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CardioMems™ HF system indicated for NYHA Class III – WHY?

We’ve studied several heart failure populations:

• 34% reduction in hospitalizations in NYHA Class III from COMPASS-HF (p < 0.001, retrospective subgroup analysis)1

• 37% reduction in hospitalizations in NYHA Class III from CHAMPION (p < 0.001, prospective full duration follow-up)2

• NYHA Class II patients were too well to impact heart failure outcomes (REDUCEhf)3

• NYHA Class IV (ACC/AHA stage D) were too sick to impact heart failure outcomes (COMPASS-HF)1

1. Bourge RC, et al. J Am Coll Cardiol, 2008.2. Abraham WT, et al. Lancet, 2011.3. Adamson PB, et al. J Cardiac Fail, 2010.

The CardioMEMS™ HF System is indicated for wirelessly measuring and

monitoring pulmonary artery (PA) pressure and heart rate in New York Heart

Association (NYHA) Class III heart failure patients who have been hospitalized for

heart failure in the previous year.

Data demonstrates that previously hospitalized NYHA Class III heart failure patients are

MOST LIKELY TO BENEFITfrom PA pressure-guided therapy.

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Heart Failure CLASSIFICATIONbased on severity of symptoms

Adapted from American Heart Association.

CLASS IICLASS I CLASS III CLASS IV

No limitation of physical activity. Ordinary physical

activity does not cause undue fatigue, palpitation,

dyspnea (shortness of breath).

Slight limitation of physical activity. Comfortable at rest. Ordinary physical

activity results in fatigue, palpitation, dyspnea

(shortness of breath).

Marked limitation of physical activity.

Comfortable at rest. Less than ordinary activity

causes fatigue, palpitation, or dyspnea.

Unable to carry on any physical activity without

discomfort. Symptoms of heart failure at rest. If any

physical activity is undertaken, discomfort

increases.

New York Heart Association (NYHA) Functional Classification

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Valvular Heart Disease

First Transcatheter Valvular Interventions

Rubio-Alvarez V, Limon-Lason R. Arch Inst Cardiol Mex 1955 Jan-Feb;25(1):57-69.

Tricuspic Valve Valvotomy

Rubio-Alvarez V, Limon-Lason R, Soni, J. Arch Inst Cardiol Mex 1953 April;23(2):183-92.

Pulmonic Valve Valvotomy

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Mitral Clip

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Edge to Edge & MitraClip Concepts• Facilitates proper leaflet coaptation

• Degenerative - Anchor flail and prolapsed leaflets

• Functional - Coapt tethered leaflets to reduce time and force required to close valve

• Reduces LV volume overload by reducing MR

• Creates tissue bridge

• May limit dilatation of annulus

• Septal-lateral (A-P) dimension

• Supports durability of repair

• Restrains LV wall

• Limits LV dilatationPorcine model, 6M

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Everest II: Background and Purpose

• Of the 50,000 patients in the United States developing significant mitral regurgitation (MR) each year, up to 60% have functional MR

• Isolated leaflet repair for functional mitral regurgitation (FMR) has not been well characterized

• The purpose of this study is to evaluate the safety and efficacy of isolated leaflet repair using the MitraClip device in patients with FMR.

Methods: Anatomic Eligibility

• TEE evidence of FMR:• Absence of Degenerative valve disease• Presence of leaflet “tethering”

• Not exceeding 10mm

• Sufficient leaflet tissue available for mechanical coaptation

• > 2mm “vertical” leaflet tissue available• Protocol anatomic exclusions

• Coaptation depth >11mm • Coaptation length < 2mm

• Absence of severe LV dysfunction• Excluding LVID-s > 55mm or EF <25%• Ischemic or non-ischemic etiology

<2mm

>11mm

Exclusions

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5‐year Results of EVEREST IIPrimary MR

Feldman et al, JACC 2015;66:2844-54.

Survival

30 Day mortality 6%

High Surgical Risk Patients5‐year Results of EVEREST II

Primary MR

Feldman et al, JACC 2015;66:2844-54.

Survival

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TAVR Update

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The PARTNER 2A Trial NEJM On-line

Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years

Randomized Patients n = 2032

Symptomatic Severe Aortic Stenosis

ASSESSMENT by Heart Valve Team Operable (STS ≥ 4%)

The PARTNER 2A TrialStudy Design

TF TAVR (n = 775)

Surgical AVR (n = 775) VS.VS.

ASSESSMENT: Transfemoral Access

Transapical (TA) / TransAortic (TAo)Transfemoral (TF)

1:1 Randomization (n = 482)1:1 Randomization (n = 1550)

TA/TAo TAVR (n = 236)

Surgical AVR (n = 246)

Yes No

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Inclusion Criteria

Severe AS: Echo-derived AVA ≤ 0.8 cm2 (or AVA index < 0.5 cm2/m2) and mean AVG > 40 mm Hg or peak jet velocity > 4.0 m/s

Cardiac Symptoms: NYHA Functional Class ≥ II

Intermediate Risk:

1. Determined by the multi-disciplinary Heart Team

using a guideline STS ≥ 4%, and adjucated by case review committee

* Disabling stroke = CEC adjudicated stroke by a neurologist with a modifiedRankin score of 2 or greater at 30 or 90-day evaluation

Primary Endpoint

Non-hierarchical composite of all-cause mortality or disabling stroke* at two years

Intention-to-treat population is the primary analysis;

As-Treated (AT) population also a pre-specified, powered analysisTransfemoral (TF) subgroup pre-specified

All patients followed for at least 2 years

Event rates by Kaplan-Meier estimates

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1

1011 918 901 870 842 825 811 801 774

1021 838 812 783 770 747 735 717 695

Number at risk:

TAVR

Surgery

p (log rank) = 0.253

HR [95% CI] = 0.89 [0.73, 1.09]

TAVR

Surgery

0

10

20

30

40

50

19.3%

21.1%

14.5%

16.4%

0 3 6 9 12 15 18 21 24

6.1%

8.0%

Primary Endpoint (ITT)All-Cause Mortality or Disabling Stroke

Months from Procedure

All

-Cau

se M

ort

alit

y o

r D

isab

ling

Str

oke

(%

)

The PARTNER 2A Trial Conclusions (1)

In intermediate-risk patients with symptomatic severe aortic stenosis, results from the PARTNER 2A trial demonstrated that...

• TAVR using SAPIEN XT and surgery were similar (non-inferior) for the primary endpoint (all-cause mortality or disabling stroke) at 2 years.

• In the transfemoral subgroup (76% of patients), TAVR using SAPIEN XT significantly reduced all-cause mortality or disabling stroke vs. surgery (ITT: p = 0.05, AT: p = 0.04).

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Electrophysiology

Leadless Pacemaker

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Atrial Fibrillation

Atrial Fibrillation

• Random, chaotic atrial activity

• No P waves present

• Irregular heart beat

• Random, chaotic atrial activity

• No P waves present

• Irregular heart beat

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AF is a Progressive Disease

of patients progress from Paroxysmal to Persistent AF within 1 year of diagnosis

20%

Nieuwlaat R et al. Eur Heart J. 2008 May;29(9):1181-9.

First Episodeof AF

Recurrent AF Recurrent Persistent AF

Understanding AF Progression

2010

Paroxysmal AF Persistent AF Permanent AF

Scarring/fibrosis

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LA Fibrosis Staging

The DECAAF Study Marrouche NF et al JAMA. 2014;311(5):498-506

2010

Paroxysmal AF Persistent AF Permanent AF

Scarring/fibrosis

Paroxysmal AF

Persistent AF

Permanent AF

Fibrotic AtrialCardiomyopathy

+GeneticsInflammationHypertensionObesityAging

2016

Understanding AF Progression

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0

5

10

15

20

25

30

0 1 2 3 4 5

The Big Debate?Rate Control versus Rhythm Control

Mortality(%)

Years

P=0.08

Rate control

Rhythm control

AFFIRM Investigators: NEJM 347:1825, 2002

N = 4060

Pulmonary Veins Trigger Atrial Fibrillation

Haïssaguerre M et al, NEJM 1998;339(10):659

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Radiofrequency Pulmonary Vein Ablation

C.

Cryoballoon Ablation

Ablates at the point of balloon contact

1. Wire Targeted Vein 2. Inflate and Position 3. Occlude and Ablate

A.

B.C.

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Progression to Persistent AF

Proietti R et al J Am Coll Cardiol EP. 2015;1(3):105-115

Medical Therapy

Catheter Ablation

“AF ablation is associated with significantly reduced progression to persistent forms

compared with studies in the general population.”

Long-Term Effect of Goal Directed Weight Management in an Atrial Fibrillation Cohort: A Long-term Follow-Up StudY

(LEGACY Study)

Weight loss, if sustained, will be of incremental benefit in rhythm control

Weight fluctuation has detrimental effect

Dose dependent effect of long term weight loss on freedom from AF

Impact of weight fluctuation

Role of dedicated clinic

Prathak RK, et al. J Am Coll Cardiol. 2015;65(20):2159-2169

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Risk Factor Modification and Ablation Success

84%

48%

Pathak RK, et al J Am Coll Cardiol 2014;64:2222–31

Single Ablation Multiple Ablations

63

23

30

34

8

11

0 20 40 60 80Patients (%)

Non-AF(n=120)

AF(n=30)

AF and Stroke: A Healthcare Burden

• 2.7 to 6.1 million individuals in the United States had AF in 2010

• AF increases the risk for stroke ≈5-fold

• 23.5% of strokes in patients80 to 89 years old are AF related

• Strokes in patients with AF tend to be more disabling, recur, or be fatal

Mortality

Recurrentstroke

Severedisability

1-year Outcomes FollowingIschemic Stroke

Go AS et al. Circulation. 2014;129(3):e28-e292. Lin HJ et al. Stroke. 1996;27(10):1760-1764.

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Left Atrial Appendage

LAA with Thrombus

Richard P. Whitlock et al. Circulation 2009;120:1927-1932

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Warfarin for AF

Favors Warfarin Favors Placebo or Control

Study, Year Relative Risk Reduction

% % % %

From: Hart RG, et al Ann Intern Med. 2007;146:857-867

6 Trials

2,900 patients

Warfarin reduces risk of stroke by

64%

-100-50050100

All Trials

EAFT, 1993

SPINAF, 1992

CAFA, 1991

BAATAF, 1990

SPAF I, 1991

AFASAK I 1989

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AF patients without contraindications

44

58 61 57

35

0

20

40

60

80

100

<55 55-64 65-74 75-84 ≥85

Age (years)

55%

War

fari

n U

se (

%)

*Data from automated pharmacy, laboratory, and clinical administrative databases for 13,428 patients with nonvalvular AF were used to determine the prevalence of warfarin use in the 3 months before or after the identified diagnosis of AF (July 1996 – December 1997).

Using Warfarin Remains Challenging

Time in Therapeutic Range (TTR)

51

28

67

55

58

54

0 20 40 60 80

McCormick et al

Sarawate et al

Rose et al

Baker et al

Rose et al

Dlott et al

Mean TTR (%)

(N=22,237)

(N=124,551)

(N=3104)

(N=470)

(N=174)

(N=138,319)

The Novel Anticoagulants

dabigatran(Pradaxa)

rivaroxaban(Xarelto)

apixaban(Eliquis)

edoxaban(Savaysa)

Mechanism Direct Thrombin inhibitor

Factor Xa Inhibitor Factor Xa inhibitor Factor Xa inhibitor

Half-Life (t½) 14 hours 5 – 13 hours 12 hours 10-14 hours

Dosing 150mg BID (CrCl>30)75mg BID (CrCl 15-30)

20mg QD (CrCl>50)15mg QD (CrCl 30-49 or ESRD)

5mg BID2.5mg BID (age>80, Cr>1.5 or wt <60Kg)

60mg daily (CCl 50-95)30mg daily (CCl 15-50)

Population in Study

Age 71.5CHADS2 = 2.1TTR 64%

Age 73CHADS2 = 3.5TTR 57.8%

Age 70CHADS2 = 2.1TTR = 62.2%

Age 72CHADS2 = 2.8TTR = 68.4%

Stroke Risk Superior Non-inferior Superior Lower

Bleeding Risk Similar Similar Superior Superior

Mortality Reduction

12% (p=0.051) 8% (p=0.15) 11% (p=0.047) 13% (p=0.006)

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Bleeding

Thrombosis

Right Atrium Left Atrium

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Concept:Exclude the LAA from central circulation

LAA

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PROTECT AF 4-Year Results

Reddy, VY et al. JAMA. 2014;312(19):1988-1998.

• Device superior to Control: primary efficacy, CV death, hemorrhagic stroke and all-cause mortality

Device grouprate

Control grouprate

Hazard ratioWATCHMAN/

warfarin (95% CI)

P

Primary efficacy 2.3 3.8 0.61 (0.38, 0.97) 0.0348

CV death 1.0 2.4 0.40 (0.21, 0.75) 0.0045

All stroke 1.5 2.2 0.70 (0.39, 1.26) 0.2244

Hemorrhagic stroke 0.2 1.1 0.16 (0.04, 0.51) 0.0049

Ischemic stroke 1.4 1.1 1.30 (0.64, 2.84) 0.4921

Disabling stroke 0.5 1.2 0.37 (0.15, 1.00)

All-cause mortality 3.2 4.8 0.66 (0.45, 0.98) 0.0379

Primary safety 3.6 3.1 1.21 (0.78, 1.94) 0.4051

707 AF patients randomized 2:1 - Watchman vs warfarin

Watchman Long-Term Follow upPROTECT AF 4-Year Superiority

2.3

1.0

3.23.8

2.4

4.8

0

2

4

6

8

10

PS = Posterior Superiority ProbabilityReddy et al: HRS, 2013

Rat

e pe

r 10

0 pa

tient

-yea

rs

WATCHMAN (n=463)Warfarin (n=244)

Primary efficacyPS=0.96

CV or unexplaineddeath

P=0.0045

All-cause deathP=0.0379

Superior40% lower

Superior60% lower

Superior34% lower

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WATCHMANTM Device Reduces Ischemic Stroke Over No Therapy

* Imputation based on published rate with adjustment for CHA2DS2-VASc score (3.0); Olesen JB. Thromb Haemost (2011)

0

1

2

3

4

5

6

7

8

PROTECT AF PREVAIL CAP

Imputed IschemicStroke Rate*

ObservedWATCHMANIschemic Stroke Rate

Isch

emic

Str

oke

Ris

k(E

ven

ts/

100

Pat

ien

t-Y

ears

)

79%Relative

Reduction

67%Relative

Reduction

83%Relative

Reduction

Baseline CHA2DS2-VASc = 3.4



FDA Oct 2014 Panel Sponsor Presentation. Hanzel G, et al. TCT 2014 (abstract)

Watchman Indication 2016• High risk of stroke

• CHADS2 ≥ 2

• CHA2DS2VASc ≥ 3

• Suitability for short-term warfarin but deemed unable to take long term oral anticoagulation

• A formal shared decision making interaction with an independent non-interventional physician using an evidence-based decision tool on oral anticoagulation

48

Thank you!

arash karnama, do, facc oklahoma heart institute€¦ · · 2017-08-02arash karnama, do, facc...

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