Active and Passive Active and Passive Constraint DevicecsConstraint Devicecs

Stefano Nardi, MD, PhD Stefano Nardi, MD, PhD

SANTA MARIA GENERAL HOSPITAL, TERNISANTA MARIA GENERAL HOSPITAL, TERNITHORACIC SURGERY AND CARDIOVASCULAR DEPARTMENTTHORACIC SURGERY AND CARDIOVASCULAR DEPARTMENT

ARRHYTHMIA, EP CENTER AND CARDIAC PACING UNITARRHYTHMIA, EP CENTER AND CARDIAC PACING UNIT

ACHF:ACHF: Multistep, Therapeutic ApproachMultistep, Therapeutic Approach Stage AStage A

At high risk, no At high risk, no structural structural

diseasedisease

Stage BStage B

Structural heart Structural heart disease, disease,

asymptomaticasymptomatic

TherapyTherapyTreat Treat

HypertensionHypertensionTreat lipid Treat lipid

disordersdisordersEncourage regular Encourage regular

exerciseexerciseDiscourage alcohol Discourage alcohol

intakeintakeACE inhibitionACE inhibition

TherapyTherapyAll measures All measures

under stage Aunder stage AACE inhibitorsACE inhibitors in in

appropriate appropriate patientspatients

Beta-blockersBeta-blockers in in appropriate appropriate patientspatients

TherapyTherapyAll measures All measures

under stage Aunder stage ADrugs:Drugs:DiureticsDiureticsACE inhibitorsACE inhibitorsBeta-blockersBeta-blockersDigitalisDigitalis

Stage C Stage C (NYHA I-II-III)(NYHA I-II-III)

Structural heart Structural heart disease with disease with prior/current prior/current

symptoms of HFsymptoms of HF

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001

Electrical Electrical Therapy:Therapy:

CRT & ICDCRT & ICD

Stage DStage D

Refractory HF Refractory HF requiring requiring

specialized specialized interventionsinterventions

TherapyTherapyAll measures All measures

under stages A,B, under stages A,B, and Cand C

Mechanical Mechanical assist devicesassist devices

Heart Heart transplantationtransplantation

Continuous (not Continuous (not intermittent) IV intermittent) IV inotropic infusions inotropic infusions for palliationfor palliation

Hospice careHospice care

Background on Heart Failure Background on Heart Failure

• One of the few major CV diseases rising in incidence One of the few major CV diseases rising in incidence

1AHA. ’04; AHA ‘02. 2Hunt SA, ACC/AHA guidelines ‘01

Population Group Prevalence Incidence Mortality

Hospital Discharges Cost

Total Total populationpopulation 5,000,0005,000,000 550,000550,000

50% 50% within 5 within 5 yearsyears

1,000,0001,000,000 $24.3 $24.3 billionbillion

5 million people in US and 25 million people worldwide.

• More than 1 million pts hospitalized/yr More than 1 million pts hospitalized/yr

• 12 million out-pt office visits 12 million out-pt office visits

• HF-H one of largest expenses for CMSHF-H one of largest expenses for CMS 1,21,2

• Mortality rates remain very highMortality rates remain very high

Heart Failure (CHF)Heart Failure (CHF)Seeking answers, but Seeking answers, but what about unanswerable questions? what about unanswerable questions?

but many people (even some but many people (even some MD) do not realize what MD) do not realize what

really needs to be done! really needs to be done!

• CHF is a very frightening term! CHF is a very frightening term! • CHF is a very common medical problemCHF is a very common medical problem• CHF can be successfully treated CHF can be successfully treated

Heart Failure PathophysiologyHeart Failure PathophysiologyMyocardial injury Fall in LV performance

Activation of RAAS, SNS, ET,and others

Myocardial toxicityPeripheral vasoconstrictionHemodynamic alterations

Remodeling andprogressiveworsening ofLV function Heart failure symptomsMorbidity and mortality

ANPBNP

Fonarow GC. Rev Cardiovasc Med. 2001;2:7-12.

Therapeutic Goals Therapeutic Goals

• Relieve symptoms Relieve symptoms • Reverse acute hemodynamic abnormalitiesReverse acute hemodynamic abnormalities• Initiate treatments that will slow disease progression and Initiate treatments that will slow disease progression and

improve long-term survivalimprove long-term survival

• Apply treatment cost- effectivelyApply treatment cost- effectively

• Prevent end-organ dysfunctionPrevent end-organ dysfunction

Pharmacological ApproachPharmacological Approach

Digoxin, Diuretics, Idralazine ACE-I ß-blocker

and ACE-I

SOLVD CONSENSUS da -16 a -31% CIBIS II

COPERNICUS - 35%

Mortality

CHF “fiveCHF “five––drug” Rx drug” Rx

Class III-IV:Class III-IV:

40% Mortality/1 yr40% Mortality/1 yr

Class III-IV:Class III-IV:

80% Mortality/2yrs80% Mortality/2yrs

Class IV: 60% Class IV: 60% Mortality/1 yrMortality/1 yr

Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01

Growing interest for alternative Growing interest for alternative procedures for advanced HF but….. procedures for advanced HF but…..

Risk of alternative procedure

Risk of disease

progression

VSVS

Alternative Options Alternative Options

• Surgery is not often used to treat Surgery is not often used to treat pts with CHF pts with CHF

• However, it can be a logical method of treatment in However, it can be a logical method of treatment in cases in which traditional treatments are not cases in which traditional treatments are not

working for whatever reason. working for whatever reason.

• Then physicians seek to identify pts who Then physicians seek to identify pts who could have the greatest gain from surgical could have the greatest gain from surgical

intervention and with less risk.intervention and with less risk.

What about surgeryWhat about surgery??

The Unmet Need in HFThe Unmet Need in HF• Despite OMT, HF remains a progressive disease that is Despite OMT, HF remains a progressive disease that is

accompanied by progressive LV remodeling accompanied by progressive LV remodeling

• LV dilation produce a change in the morphology from LV dilation produce a change in the morphology from an ellipse to a more spherical shape an ellipse to a more spherical shape

• LV remodeling predicts mortality.LV remodeling predicts mortality.

Cardiac Support Devices (CSD)Cardiac Support Devices (CSD)

• Myosplint Myosplint ““SShape hape CChange hange TTherapy”herapy”

• Intracardiac struts. Intracardiac struts. • May prevent further LV dilation, reduce wall stressMay prevent further LV dilation, reduce wall stress

Shape Change Rx (Myosplint)Shape Change Rx (Myosplint)

Passive Cardiac Diastolic Support

“Device-based on passive LV constraint to treat DCM”. McCarthy, JTCS 2001

Objective:counteract LV remodeling in IDC less invasive surgery (?) without remove myocardial tissue

Passive Constraint Support Passive Constraint Support Devices (PCSD)Devices (PCSD)

Passive Constraint Support Passive Constraint Support Devices (PCSD) Devices (PCSD)

Provide LVEDD and LVEDV support to reduce myocardial stretch

Promote myocardial reverse remodeling

Improve functional status

PCSD

How does PCSD work ?How does PCSD work ?

IncreasedMyocyte Stretch

Increase Wall Stress

Injury

Death

Ventricular Remodeling

Decreased Cardiac Function

Heart Failure Symptoms(NYHA Class, Hospitalizations)Diastolic Wall Stress = Radius x Pressure

(Myocyte Stretch) Wall Thickness

Transmural Pressure = LVEDP – CorCap Counter Pressure

Law of LAPLACELaw of LAPLACE

PCSD

Passive Constraint Support Passive Constraint Support Devices (PCSD)Devices (PCSD)

• Highly elastic compliant nitrol structureHighly elastic compliant nitrol structure

• Delivered with special delivery system Delivered with special delivery system (minitoracotomy)(minitoracotomy)

• Self-anchoring and self-tensioning Self-anchoring and self-tensioning

• Pre sized (echo measurements)Pre sized (echo measurements)

• CRT/ICD compatibleCRT/ICD compatible

PCSDPCSD ParacorParacor

PCSD ParacorPCSD Paracor

QoL and 6MWTQoL and 6MWT Threshold AnalysisThreshold Analysis

NYHA Class NYHA Class Echo DataEcho DataPCSD ParacorPCSD Paracor

Longitudinal Load

(0.8 lbs/in)

Circumferential Load

(0.8 lbs/in)

No Load

• New mesh New mesh (multi-Filament Yarn / Knit (multi-Filament Yarn / Knit Fabric)Fabric)

PCSD CorCapPCSD CorCap

– Optimal compliance - “stretchiness”Optimal compliance - “stretchiness”– Bi-directional PropertiesBi-directional Properties

• Reshapes the heart to ellipsoidReshapes the heart to ellipsoid– 31 micro fiber construction31 micro fiber construction

• Smooth fit on surface of heartSmooth fit on surface of heart– Long term biocompatibilityLong term biocompatibility

• Reducing in MRReducing in MR• No changes in dyastolic No changes in dyastolic

properties of LV properties of LV

PCSD CorCap n=148

91 received mitral valve repair

PCSD CorCap n=148

91 received mitral valve repair

Primary Endpoint: Composite classification of improved, the same, or worse

based on occurrence of death, change in NYHA class, or cardiac procedure indicative of HF progression

Primary Endpoint: Composite classification of improved, the same, or worse

based on occurrence of death, change in NYHA class, or cardiac procedure indicative of HF progression

ACORN TrialACORN Trial

AHA 2004

Controln=152

102 received mitral valve repair

Controln=152

102 received mitral valve repair

300 pts with Heart Failure81.3% NYHA Class III, 3.7% Class IV

ischemic and non-ischemic pts, LVEF <30%, LVEDD >60 mm55% male, mean age 52.5 years, with 6-MWT < 450 m

OMT (97% received ACE-I or ARB, 85% beta-blockers, 98% diuretic)

300 pts with Heart Failure81.3% NYHA Class III, 3.7% Class IV

ischemic and non-ischemic pts, LVEF <30%, LVEDD >60 mm55% male, mean age 52.5 years, with 6-MWT < 450 m

OMT (97% received ACE-I or ARB, 85% beta-blockers, 98% diuretic)

no CABG

Acorn Clinical Trial DesignAcorn Clinical Trial Design300 Patients

Mitral Surgery Stratum

193 Patients

No Mitral Surgery Stratum

107 Patients

ControlMVR Alone102 Patients

TreatmentMVR plus CSD

91 Patients

ControlOMT Alone50 Patients

TreatmentOMT plus CSD

57 Patients

Median Follow-up of 23 mo. 504 patient years of Follow-up

(Randomized)(Randomized)

AHA 2004

Summary of PCSD effectsSummary of PCSD effectsENDPOINTSENDPOINTS FavorsFavors p-valuep-value

Primary Clinical CompositePrimary Clinical Composite CSDCSD 0.020.02 SurvivalSurvival NeutralNeutral Major Cardiac ProceduresMajor Cardiac Procedures CSDCSD 0.010.01 NYHANYHA CSDCSD 0.120.12 LVEDVLVEDV CSDCSD 0.0090.009 LVESVLVESV CSDCSD 0.0170.017 SphericitySphericity CSDCSD 0.0260.026 MLHFQMLHFQ CSDCSD 0.050.05 SF 36 (physical function)SF 36 (physical function) CSDCSD 0.0150.015 Re-HospitalizationsRe-Hospitalizations NeutralNeutral

Acorn Trial: SurvivalAcorn Trial: Survival

0102030405060708090

100

0 6 12 18 24

Months after Randomization

Perc

ent

Surv

ival CSD Treatment (n=148)

Control (n=152)

p = 0.90

PCSD “Pushing the limits”PCSD “Pushing the limits”

Batista’s Operation:Batista’s Operation: “Direct Surgical Therapy”“Direct Surgical Therapy”

• Excision of Lateral Wall with a linear closure Excision of Lateral Wall with a linear closure • Reduction of LVEDV, LVESV and wall stress Reduction of LVEDV, LVESV and wall stress

(Laplace’s law). (Laplace’s law). • High initial enthusiasm High initial enthusiasm (between ‘96 and ’00, 58 papers and editorials describe first experiences)(between ‘96 and ’00, 58 papers and editorials describe first experiences)

Wall Thickness [%]020406080100Mid

ven

tric

ula

r F

iber

Str

ess

@ E

nd

-Dia

sto

le [

kP

a]

02468101222.5%

25.1%

Wall Thickness [%]020406080100Mid

ve

ntr

icu

lar

Fib

er

Str

es

s

@ E

nd

-Sys

tole

[kP

a]

010203040506070

DCM 10% Lateral Resection 20% Lateral Resection

28.3%

29.3%

Wall Thickness [%]020406080100Mid

ven

tric

ula

r F

ibe

r S

tres

s@

En

d-S

ysto

le [

kP

a]

010203040506070

DCM 10% Lateral Resection 20% Lateral Resection

P-V RelationshipsP-V RelationshipsChange in Systolic

ElastanceChange in Diastolic

Compliance

Batista Procedure

DCM

10% Lateral Resectio

n

20% Lateral Resectio

n01020304050

Stroke Volume [ml]EF [%]1. Ratcliffe, JTCVS ‘98

LVEF is not enough1

• SD: 46% of the DeathsSD: 46% of the Deaths• CHF/Shock: 13%, CHF/Shock: 13%, • Sepsis: 6%, Sepsis: 6%, • Emergency LVAD: 20%Emergency LVAD: 20%• No SD in Survival with OMTNo SD in Survival with OMT

Improvement in Symptoms, Improvement in Symptoms, NOT Survival NOT Survival

INACTIVE AREA

Excitabile Gap

Arrhythmic Death

• The twisting ability of LV is reduced with reduction of LVEF and filling.

• As CHF progresses, the LV dilation often change both SIZE and SHAPE that becomes more spherical

• MV apparatus goes out of proper anatomical alignment, with

reduction to assist LV in the contraction MR (MR) – work-load• The distortion of LV shape reduces the force vector that moves away from AoV, resulting in inefficient pumping and turbulence in LV

Consideration

Left Ventricular Remodelling

Necrosis M.I. Normal

Infarctus Expansion

Cicatrisation Slimming Dilatation

Hypertrophy ofsound myocardium

(Compensation)L.V. globalDilatation

Progressivedeterioration

L.V. RESPONSE andREMODELING

“SVR – Dor procedure” (GOALS)

• Reconstruct a new apex • Reduce the ventricle to an optimal volume • Restore the ventricle to an elliptical shape

• Reorient the papillary muscles and muscle fibers

• The akinetic segments are excluded behind a Dacron patch, even if the muscle appears grossly normal.

• The very stiff patch is further reinforced by foldingthe residual myocardium on top of it, resulting in a dual layer patch.

Before After

Reduced Twist“Spherical”

Full Twist“Bullet”

Surgical Ventricular Restoration DOR procedure

Restore TrialRestore Trial the the RReconstructive econstructive EEndoventricular ndoventricular SSurgery returning urgery returning

TTorsion orsion OOriginal riginal RRadius adius EElliptical shape lliptical shape (~2000 pts from ’98 to ’03, 12 centres worldwide)(~2000 pts from ’98 to ’03, 12 centres worldwide)

Athanasuleus CL, JACC. ‘04

• MI in anteroseptal portion of LV• Enlarged LV• ESV index > 50ml/m2 • EDV index of > 110 ml/m2• Large area of Akinesis or Dyskinesis• Asynergy >30% of circumference or 3/10 Echo anterior segment STICH Trial • Acceptable EF of basal portion and lateral wall• Good RV function• Candidate for CABG

Schreuder, J Th C Srg ‘05

EFFECTS on STRESS

Restore TrialRestore Trial RESULTSRESULTS

Athanasuleus CL et al. JACC ‘04

Restore TrialRestore Trial SURVIVALSURVIVAL

NYHA Class EF %

Morphology ESVI ml/m2

Athanasuleus CL et al. JACC ‘04

In Hospital MortalityIn Hospital Mortality <8%<8% 1 Year Freedom from HF1 Year Freedom from HF 80%80%

Restore TrialRestore Trial RESULTSRESULTS

Overall five-year survival

Athanasuleus CL et al. JACC ‘04

“SVR – DOR procedure” CONSIDERATIONS

(Dor, Thoracic and CV, Vol.01)

• The ability to properly reshape could be a Challenge

• When surgically RE-SIZING and RE-SHAPING LV, it’s crucial to estimate the final LV morphology and volume, as well as the orientation of PAPILLARY

MUSCLES and AORTIC PLANE

• Making a too small LV it will lead to Pulmonary Hypertension, whereas a too large LV leave the pt’s heart in a state to it’s pre-operative condition

• In ‘01 was described a new technique using an Endoventricular Shaper • The Shaper is inflated to a volume based on the pts BSA and EDV

“Surgical Anterior Ventricular Endocardial Restoration - SAVER”

(TR3ISVR procedure)

• Re-sizing the ventricle around a shaper inflated ensures that a too small/large LV will not be created.

• SVR using a specific Shaper is able to reduce proportionally both short and long axis (only long-axis create a spherical LV and lead MR)

• Shaper defines the new apex.

• LV in incised in the akinetic tissue area and inspect for TR and for the border zone (akinetic and viable muscle) feeling for thin tissue or by visually identifying necrotic tissue.

• A SHAPER is inserted in the LV with the basal portion seated against the AoV and MV annuluses, and the tip that identifies the new LV apex location.

TR³ISVR Technical procedure

TR3ISVR PROCEDURE

BEFORE AFTER

HEART FAILURE & CaHEART FAILURE & Ca++++

1. Beuckelmann DJ, Basic Res Cardiol ‘’97; 2. Gomez AM, Science ‘’97

The weakened contractility of failing cardiac myocytes is The weakened contractility of failing cardiac myocytes is believed to result, in large part, from anbelieved to result, in large part, from an abnormally low abnormally low amount of Caamount of Ca++++ delivered to the myofilaments during each delivered to the myofilaments during each

beat, independent of disease etiology.beat, independent of disease etiology. 1,21,2

Φ2 – Plateau (absolute refractory)

K+

Ca++

3) Slower, inward Ca++ channels open, matching outward K+ and maintaining the membrane near 0 mV (Φ2 – Plateau)

Action Potential, Ca++ and Action Potential, Ca++ and Contractility Contractility

1.1. Reduction in the amplitude and increase in duration Reduction in the amplitude and increase in duration of APof AP

Control Control Heart FailureHeart FailureAP (EAP (Emm))

[Ca[Ca2+2+]]ii

ContractionContraction

2.2. Reduction in the upslope and downslop of the CaReduction in the upslope and downslop of the Ca++++ transient transient

3. Parallel reduction in the upslope and downslop of the peak developed tension

CaCa2+ 2+ flux in the Heartflux in the Heart

• NEC are able to prologed the AP duration due to enhanced trans-sarcolemmal Ca++ entry• Ryanodine is able to block Ca++ relase from the SR, then decrease the effects of NEC; SR is full loading with Ca++ (major contributor)

Experimental FindingSubthreshold pacing for HFSubthreshold pacing for HF

Tra

nsm

emb

ran

e P

ote

nti

al (

mV

)

Time (ms)100 200 300 400 500

Phase 2

Phase 1

Phase 3

Phase 4

-50

0

50

-100

Ph

as

e

0

Threshold Critical phase of AP Critical phase of AP for the modulation for the modulation of the E-C couplingof the E-C coupling

RV1RV2

RA

Heart FailureHeart FailureCCM – The ConceptCCM – The Concept

1- Detect localactivation

2- Apply NEC signal

NEC

Tens

ion

(% m

ax.)

50

100

Length (%∆)

Starling Law

1.5 2 2.5 µ

CCM

Increased tension

Increasedcontractility

IncreasedPressure

Remote Recruitment

Heart FailureHeart FailureCCM – Mechanisms in HumanCCM – Mechanisms in Human

CCM effectsCCM effects

CCM artifact

Immediate return to baseline

NO QT variation

LVP

(mm

Hg)

LVV ( ml)

Segment Lengt h ( mm)

060 8070 60 807 0 60 8070

15

24

16 17 18

25 26 27 24 25 26 27 24 25 26 27

120

60

LVP

(mm

Hg)

0

120

60

LVV ( ml)LVV ( ml)

15 16 1 7 18 15 16 17 18

Anterio r CCM Post erior CCM Combined CCM

Segment Lengt h ( mm) Segment Length ( mm) Segment Length ( mm)

0

120

60

Segment Length ( mm) Segment Length ( mm)

LVP

(mm

Hg)

Ante

rior Re

gio

nPoste

rior Regio

n

LVP[mmHg]

ECG

dP/dt

Dp/Dt improvement 8.7% 5’ after CCM (Millar™ in LV)

CCM

Dp/Dt Dp/Dt at IMPLANTat IMPLANT

CCM – Acute LV ResultsCCM – Acute LV Results

artifact

no change in QTc durationno change in QTc duration

RV1

RV2

RA

Basal Active signalECHO Color KinesisECHO Color Kinesis

Heart FailureHeart FailureCCM & CRT - ResultsCCM & CRT - Results

Heart FailureHeart FailureCCM – Chronic ResultsCCM – Chronic Results

Left Ventricular Ejection Fraction

0

10

20

30

40

50

60

70

80

Baseline 3-hour Phase 7-hour Phase

Study Phase

Pe

rce

nt

Peak VO2

10

12

14

16

18

20

22

Baseline 3-hour Phase 7-hour Phase

Study Phase

ml/k

g of

bod

y w

eigh

t/min

mRNA Expression for ANP

mRNA Expression for BNP

mRNA Expression of b1-Adrenergic Receptor

mRNA Expression of SERCA-2a

NL HF-Sham HF + CCMNL HF-Sham HF + CCM

mRNA Expression for aMHC

b1-AR

ANP

BNP

aMHC

Serca-2a

Therapies for Heart FailureTherapies for Heart Failure

• Natriuretic peptidesNatriuretic peptides• Endothelin antagonistsEndothelin antagonists• Vasopeptidase Vasopeptidase

inhibitorsinhibitors• Cytokine antagonistsCytokine antagonists• StatinsStatins• ErythropoietinErythropoietin

• External enhanced counter External enhanced counter pulsationpulsation

• Cardiac resynchronization Cardiac resynchronization therapy (CRT)therapy (CRT)

• Routine use of Implantable Routine use of Implantable Cardiac Defibrillators (ICD)Cardiac Defibrillators (ICD)

• Ventricular constraint Ventricular constraint devices (VCD)devices (VCD)

• Cell transplantationCell transplantation• Total artificial heart / Total artificial heart /

permanent LVADspermanent LVADs

ConclusionsConclusions

Advanced HF Advanced HF ConclusionsConclusions

• Alternative Therapeutic Options could be a logical method of Alternative Therapeutic Options could be a logical method of treatment in cases in which traditional approaches are not working treatment in cases in which traditional approaches are not working

(for whatever reason). (for whatever reason).

• Then it’s crucial to identify the right approach able Then it’s crucial to identify the right approach able to give us the greatest to gain from specific to give us the greatest to gain from specific

intervention with less risk.intervention with less risk.

Not all limitations are yet well defined, multicentric trials are ongoing (and are mandatory!) to:

optimize patients selection optimize specific (surgical) techniques

Cardiac Support Devices are an alternative option and is still developing

Always AvailableSome of them satisfying short and mid-term results

Advanced HF Advanced HF Conclusions Conclusions

DownhillDownhillIrreversibleIrreversible

High risk for SCDHigh risk for SCD

ProgressiveProgressiveNatural History of CHFNatural History of CHF

EchoEcho

My Biased ViewpointMy Biased Viewpoint• The “natural history” of CHF does not The “natural history” of CHF does not

exist and is changing. exist and is changing. • CHF could be reversible CHF could be reversible • CHF could be preventableCHF could be preventable

The Challenge……….The Challenge……….

The Challenge……….The Challenge……….

Remember that Nature has his own limits…..

Giving every single patient:•the right therapy (only one is enough??)

•at the right time (different specialists in different moments of the same disease)

Thank you for your Thank you for your attentionattention

EchoEcho

The physicianThe physicianThe The

sonographersonographerThe surgeronThe surgeron

Multidisciplinary Approach!!Multidisciplinary Approach!!

BACK-UPBACK-UP

Therapies for Advanced HFTherapies for Advanced HF• ANP, BNPANP, BNP• Endothelin antagonistsEndothelin antagonists• Vasopeptidase-IVasopeptidase-I• Cytokine antagonistsCytokine antagonists• StatinsStatins• ErythropoeitinErythropoeitin• IABPIABP• CRT/ICDCRT/ICD• Cardiac Support Cardiac Support

Devices (CSD)Devices (CSD)• Cell transplantationCell transplantation• Total artificial Heart/ Total artificial Heart/

permanent LVADpermanent LVAD

Low dose LV CCM Low dose LV CCM incorporated into standard incorporated into standard CRT deviceCRT device

Multisite LV CCMMultisite LV CCM

The next FUTURE The next FUTURE

ConclusionsConclusions Regarding the results Regarding the results HTxHTx still remains the gold still remains the gold

standard treatment for Advanced heart failurestandard treatment for Advanced heart failure

Alternative surgery limitations are not yet well defined: multicentric trial are ongoing (and are mandatory!) to:

optimize patients selection optimize surgical techniques

Alternative surgery is an effective option and is still developing

No waiting list (whenever we like)Always AvailableSatisfying mid-term results

The Challenge……….The Challenge……….•Multidisciplinary Approach!!Multidisciplinary Approach!!

Remember that Nature has his own limits…..

Giving every single patient:•the right therapy (only one is enough??)

•at the right time (different specialists in different moments of the same disease)

Pharmacological, Modulation Pharmacological, Modulation of Cardiac Contractility of Cardiac Contractility

•PDE inhibitor

•β-adrenergic agonist

•digitalis

•Benefits on hemodynamics and symptoms

•Neutral/negative effects on mortality

•Only digitalis on a chronic basis (selected pts)

Burkhoff D, Am J Phys ‘87

CANINE modelCANINE model

What does it mean CHF ?What does it mean CHF ?VO

2 (m

l/m

in/m

VO2

(ml/

min

/m22 ))

DODO22 (ml/min/m (ml/min/m22))

Critical DOCritical DO2 2

DISOXIADISOXIA

Critical VOCritical VO22

NormalNormal

Spragg DD, Circulation ’03

Regional Alterations of Protein Expression in CHF dogs

Mesenchymal Stem Cells for Mesenchymal Stem Cells for Cardiac RegenerationCardiac Regeneration

Images courtesy of Dara L. Kraitchman, V.M.D., Ph.D.

• Injection of small volumes of material can change cardiac mechanicistict properties with border zone placement the most likely to reduce pathological wall stresses.

COLOR KINESIS SYSTOLIC FUNCTION

Remote effectRemote effect

Matrix-Assisted Myocardial Matrix-Assisted Myocardial Stabilization (LVEF Model Simulation)Stabilization (LVEF Model Simulation)

Effect on Effect on LV Pressure-Volume RelationshipsLV Pressure-Volume Relationships

Effect on Ejection FractionEffect on Ejection Fraction

The Optimizer™ III The Optimizer™ III rechargable devicerechargable device

RV1

RV2

RA

Patient Patient ClassificationClassification

Any One OfAny One OfSameSameNYHANYHA

Improved Improved NYHANYHADeathDeath MCPMCP(1)(1) Worsened Worsened

NYHANYHA

WorsenedWorsened

UnchangedUnchanged

ImprovedImproved

(1) Adjudicated Major Cardiac Procedures indicative of HF Progression: Transplant, LVAD, CABG, BiV Pacing, and MV surgery (repeat)

• Pts functional status after a minimum of 12 mo FU

Acorn Clinical Trial DesignAcorn Clinical Trial Designcomposite primary end-pointcomposite primary end-point

BVP & BVP+CCMBVP & BVP+CCM

Sinergistic Effects

Therapeutic Goals Therapeutic Goals

• Relieve symptoms Relieve symptoms

1. Fonarow GC. Rev Cardiovasc Med. 2002;3(suppl 4):S18–S27.2. Stier CT Jr et al. Cardiol Rev. 2002;10:97–107.3. Masai T et al. Ann Thorac Surg. 2002;73:549–555.

• Reverse acute hemodynamic abnormalitiesReverse acute hemodynamic abnormalities

• Initiate treatments that will slow disease progression and Initiate treatments that will slow disease progression and improve long-term survivalimprove long-term survival

• Apply treatment cost- effectivelyApply treatment cost- effectively

• Prevent end-organ dysfunctionPrevent end-organ dysfunction

• Reduce dyspnea and other signs and symptoms Reduce dyspnea and other signs and symptoms of CHFof CHF

End PointsEnd Points

• Lower PCWP with adequate systemic perfusionLower PCWP with adequate systemic perfusion

• Use of ACE-I, aldosterone antagonists and β- Use of ACE-I, aldosterone antagonists and β- blockers before hospital dischargeblockers before hospital discharge

• Shorten length of stay, minimize use of ICU, Shorten length of stay, minimize use of ICU, reduce readmissionsreduce readmissions

• Inhibit RAA system Inhibit RAA system

• Monitor inflammation caused by infection Monitor inflammation caused by infection following a major surgery or traumafollowing a major surgery or trauma

Prolate Spheroidal Prolate Spheroidal CoordinatesCoordinates

Costa, Biomech Eng. ‘96 www.continuity.ucsd.edu

Ventricular Muscle Ventricular Muscle Fiber OrientationFiber Orientation

Walker et al, J Thorac CV Surg. ‘05

CHF PATHOLOGY

Definition of StressDefinition of Stress

Fung, A 1° Course in Continuum Mechanics, ‘94

LV PV loopsLV PV loops

McCulloch, Theory of Heart, ‘91

CHF PATHOLOGY

Model of Model of Shortening Shortening

DeactivationDeactivation

Guccione and McCulloch, J Biomech Eng. ‘93 Feb;115(1):72-90

Muscle Contraction Muscle Contraction Model ComparisonModel Comparison

• Non-conventional Surgical RxNon-conventional Surgical Rx• Dedicated procedures and devices Dedicated procedures and devices

Surgical Reverse Remodeling

• Passive Diastolic Support • Dynamic Cardiomioplasty• “Batista” procedure• Undersized Mitral Annuloplasty• Ventriculoplasty • Mechanical circulatory assistance

Alternative and aggrssive Rx Alternative and aggrssive Rx for advanced Heart Failurefor advanced Heart Failure

Specific Interventions

• Partial Left Ventriculectomy (J Thorac Cardiovasc Surg. 2001 Sep;122(3):592-9)

• Myocor Myosplint (Ann Thorac Surg, 0’03 Oct;76(4):1171-80; discussion 1180)

• Surgical Anterior Ventricular Restoration (Ann Thorac Surg. 2005 Jan;79(1):185-93)

• Matrix-Assisted Myocardial Stabilization (Circulation. 2006)

3+/4+ 3+/4+ MR MR due to annulus dilatationdue to annulus dilatation

No morphologic/structural valve alterationsNo morphologic/structural valve alterations

Functional Mitral RegurgitationFunctional Mitral Regurgitation

NYHA class III-IV with OMTNYHA class III-IV with OMT

E.F. E.F. <<35 % 35 %

LV VTDi LV VTDi >>110 ml110 ml

Surgical Indication in well selected pts• not favourable age for HTx.

• signs e symptoms of pulmonary congestion (congestive/backward HF) more than decreased

antegrade perfusion (forward HF)

Functional Mitral RegurgitationUndersized Mitral Annuloplasty

• Secondary MR affects up to 60% of CHF pts• Normal MV function requres maintenance of chordal, annular, subvalvular, and valvular relationships• Any etiolgy annular

Mitral RegurgitationMitral Regurgitation

Non-ischemic MR: due to annular dilation, papillary muscle displacement, loss of leaflet coaptation due to tethering,

Mitral Valve RepairMitral Valve Repair

Mitral Valve RepairMitral Valve Repair

• Ischemic MR: due to annular dilation, papillary muscle displacement, loss of leaflet coaptation due to tethering, $plus papillary muscle

dysfunction

• Dyspnea and other signs and Dyspnea and other signs and symptoms of heart failuresymptoms of heart failure11

Therapeutic Goals for ADHF Therapeutic Goals for ADHF

• Relieve symptoms Relieve symptoms Goals End Points

1. Fonarow GC. Rev Cardiovasc Med. 2002;3(suppl 4):S18–S27.2. Stier CT Jr et al. Cardiol Rev. 2002;10:97–107.3. Masai T et al. Ann Thorac Surg. 2002;73:549–555.

• Reverse acute Reverse acute hemodynamic hemodynamic abnormalitiesabnormalities

• Initiate treatments that will slow Initiate treatments that will slow disease progression and improve disease progression and improve long-term survivallong-term survival

• Apply treatment cost- Apply treatment cost- effectivelyeffectively

• Prevent end-organ Prevent end-organ dysfunctiondysfunction

• Lower PCWP with adequate Lower PCWP with adequate systemic perfusion1 systemic perfusion1 • Use of ACE-I, aldosterone Use of ACE-I, aldosterone antagonists and β-blockers antagonists and β-blockers before hospital discharge1before hospital discharge1• Shorten length of stay, Shorten length of stay, minimize use of ICU, reduce minimize use of ICU, reduce readmissions1 readmissions1 • Inhibit RAA systemInhibit RAA system• Monitor inflammation Monitor inflammation caused by infection caused by infection following a major surgery following a major surgery or trauma2,3or trauma2,3

NEJM ‘05-352NEJM ‘05-352

CRTCRT

Class III-IV: Class III-IV: 40% Mortality @ 1 Year40% Mortality @ 1 YearClass III-IV: Class III-IV: 80% Mortality @ 2 Years 80% Mortality @ 2 Years

Class IV: 60%Class IV: 60% Mortality @ 1 YearMortality @ 1 Year

Advanced Heart Advanced Heart Failure Failure Options ?Options ?

Stage DStage D

Refractory HF Refractory HF requiring requiring

specialized specialized interventionsinterventions

TherapyTherapyAll measures All measures

under stages A,B, under stages A,B, and Cand C

Mechanical Mechanical assist devicesassist devices

Heart Heart transplantationtransplantation

Continuous (not Continuous (not intermittent) IV intermittent) IV inotropic infusions inotropic infusions for palliationfor palliation

Hospice careHospice care

Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01??

Mortalità totale

Frazione di eiezione

Morte per causa aritmica

PEA

Challenges in management of CHF

NYHA II

Other24%

CHF12%

Sudden death64%

N=103

NYHA III

Sudden death59%

CHF26%

Other15%

N=232

NYHA IV

Sudden death33%

CHF56%

Other11%

N=27 MERIT-HF

Effects of CSDEffects of CSD Cell Structure and FunctionCell Structure and Function

NL CSDHF

Cell-Stretch Response Protein

NL CSDHF

CSDHFNL

p21ras

c-fos

p38 α/βMAPK

Saavedra WF, JACC ‘02; Sabbah HN, Circ Res 03

Cardiomyocyte Hypertrophy

*

* #

50

75

100

125

150

175

200

225

10

15

20

25

30

35

40

5

6

7

8

9

10

11

12

HF CSDNLHF CSDNL HF CSDNL

MCSA (µm2

) Length (µm) Width (µm)

* * *x102

** ****

Cardiomyocyte Apoptosis (per 1000)

*

* #

0.0

0.1

0.2

0.3

0.4

0.5

0

1

2

3

4

5

6

7

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

HF CSDNLHF CSDNL HF CSDNL

Overall Remote Border

**

*

NYHA Class NYHA Class Echo DataEcho Data

ParacorParacor Ventricular Support System Ventricular Support System

Natural History of DCMNatural History of DCM

1 yr Mortality ITALIAN NETWORK CHF

0

10

20

30

40

50

4,1 %4,1 %

11,7 %11,7 %

24,8 %24,8 %

36,7 %36,7 %

15,1 %15,1 %

(%)(%)

NYHA I1

NYHA II2,14

[1,33-3,44]

NYHA III3,77

[2,32-6,12]

NYHA IV5,54

[3,23-9,48]

TotalRelative Risk

ResultResult

““DDirectirect S Surgicalurgical T Therapyherapy”” Partial Left Ventriculectomy or Batista Partial Left Ventriculectomy or Batista

procedureprocedure

“Surgical Anterior Ventricular Endocardial Restoration - SAVER”

(Dor and TR3ISVR procedure)

Management of Advanced Management of Advanced CHFCHF

INACTIVE AREA

Eletrically Eletrically inactive areainactive area

Excitabile Gap

Myocor MyosplintMyocor MyosplintConclusionsConclusions

• Reduction in diastolic fiber stress was approx. Reduction in diastolic fiber stress was approx. similar to Batista.similar to Batista.

• Balanced shift of end-diastolic compliance and Balanced shift of end-diastolic compliance and end-systolic elastance.end-systolic elastance.

• As a result, there was an improvement in As a result, there was an improvement in Starling’s law that was related to the amount of Starling’s law that was related to the amount of Myosplint tension.Myosplint tension.

Partial Left Ventriculectomy Partial Left Ventriculectomy (Batista)(Batista)

ConclusionsConclusions

• LV wall Stress was reduced by approx. 25% LV wall Stress was reduced by approx. 25% • Shift in end-diastolic compliance was greater Shift in end-diastolic compliance was greater

than the reduction in end-systolic elastance.than the reduction in end-systolic elastance.• As a result there was a reduction in CO and As a result there was a reduction in CO and

decrement in Starling’s law.decrement in Starling’s law.• LVEF was not a good measure of LV function.LVEF was not a good measure of LV function.

Normal PapillaryMuscle Angle

30°-40°

Orientation of CHF pt 60-80°

• As CHF progresses, the associated dilation of the LV will often pull the MV apparatus out of proper anatomical alignment (MR)

• The misalignment also reduces the ability of MV apparatus to assist in the contraction of the LV.

• This is additional work to these muscles.

Left Ventricular Remodelling Mitral Valve

Normal PapillaryMuscle Angle

30°-40°

Orientation of CHF pt 60-80°

• As CHF progresses, the associated dilation of the LV will often pull the MV apparatus out of proper anatomical alignment (MR)

• The misalignment also reduces the ability of MV apparatus to assist in the contraction of the LV.

• This is additional work to these muscles.

Left Ventricular Remodelling Mitral Valve

(Dor, Thoracic and CV, Vol.01)

• Making a too small LV it will lead to immediate Pulmonary Hypertension

• Making a too large LV leaves the pt’s heart in a state

similar to its pre-operative condition

“SVR – DOR procedure” Limitations

• The Surgeron’s ability is to achieve a correct size (3-D)

(Dor, Thoracic and CV, Vol.01)

“SVR – DOR procedure” Limitations

• The Fontan suture, or purse string, is started at the new apex point and the suture continues along the border of the akinetic zone and the intersection of the Shaper.

• After the Fontan stitch is in place and the LV tightened around the Shaper, the patch is sutured into the LV on the rim created by the Fontan stitch.

TR³ISVR Technical procedure

• AMI in antero septal portion of the LV.• Enlarged LV between 100-180 ml/m2, EDVI• Asynergy of > 35%• Good lateral wall motion• Good basal portion of the ventricle• Good contraction• Good RV

TR3ISVR PROCEDUREIDEAL PATIENT

Contraindications

• Pulmonary pressure > 60mmHg with MR• Asynergy of >60%• Asynergy of <35%• LV volume > 180 ml/m2

TR3ISVR PROCEDURE

•  A failing right ventricle

demonstrated as a low right ventricle EF or TAPS (Tricuspid Annular Plane Systolic Movement) less than 13mm•

  Infarcts in two distinct areas of the ventricle

•  Pulmonary pressure >

60mmHg without MR

RELATIVEABSOLUTE

These CI do not rule out every pt, but alert you to the fact that they are at greater risk and need to be closely evaluated before being recommended for surgery

Cardiac Contractility Cardiac Contractility MODULATION MODULATION

(Non Exitatory Current)(Non Exitatory Current)

Subthreshold Pacing Subthreshold Pacing for Advanced Heart for Advanced Heart

FailureFailure

1Will CCM modify contractile Will CCM modify contractile function of segments remote function of segments remote

from the electrode?from the electrode?

How wide is the area where How wide is the area where contractility enhancement can be contractility enhancement can be

obtained?obtained?2

CCMNo impairment in diastolic functionNo impairment in diastolic function

COLOR KINESIS DIASTOLIC FUNCTION

mRNA Expression for ANP

mRNA Expression for BNP

mRNA Expression of b1-Adrenergic Receptor

mRNA Expression of SERCA-2a

NL HF-Sham HF + CCMNL HF-Sham HF + CCM

mRNA Expression for aMHC

b1-AR

ANP

BNP

aMHC

Serca-2aUnpublishdd dataUnpublishdd data

Heart FailureHeart FailureCCM – Mechanisms in HumanCCM – Mechanisms in Human

Baseline LV-CCMLV-CCM RV-CCMRV-CCM CCM plus CRTCCM plus CRT

Heart FailureHeart FailureCCM – Acute ResultsCCM – Acute Results

LVP

(mm

Hg)

LVV ( ml)

Segment Lengt h ( mm)

060 8070 60 807 0 60 8070

15

24

16 17 18

25 26 27 24 25 26 27 24 25 26 27

120

60

LVP

(mm

Hg)

0

120

60

LVV ( ml)LVV ( ml)

15 16 17 18 15 16 17 18

Anterio r CCM Post erior CCM Combined CCM

Segment Lengt h ( mm) Segment Length ( mm) Segment Length (mm)

0

120

60

Segment Length ( mm) Segment Length (mm)

LVP

(mm

Hg)

Ante

rior Regio

nPoste

rior Regio

nACUTE EFFECTS ON DOGSACUTE EFFECTS ON DOGS

Heart FailureHeart FailureCCM – Chronic ResultsCCM – Chronic Results

““PPassiveassive C Constraintonstraint D Devices” evices” (PCD) (PCD) (CorCap, Paracor)(CorCap, Paracor)

““DDirectirect S Surgicalurgical T Therapyherapy” (DST)” (DST) Partial Left Ventriculectomy (Batista procedure)Partial Left Ventriculectomy (Batista procedure)

“Surgical Anterior Ventricular Endocardial Restoration - SAVER”

(Dor and TR3ISVR procedure)

““SShapehape C Changehange T Therapyherapy” (SCT)” (SCT) (Myosplint)(Myosplint)

Cardiac Constraint Support (CCS)Cardiac Constraint Support (CCS)

a Vicious Cyclea Vicious Cycle

Abnormal RV-LV sequence

Mitral Regurgitation

Segmental Dyskinesia

Dysynchronous Contraction

Abnormal LV activation sequence

↑ Neurohormones

↓ LVEF

Dissynchrony RV/LV

filling flow

Surgery for HF Surgery for HF (Batista)(Batista)

“Direct Surgical Therapy”“Direct Surgical Therapy”Excision of lateral wall

Linear closure

 

DCM Model

 

 

DCM

10% Lateral Resectio

n

20% Lateral Resectio

n01020304050

Stroke Volume [ml]EF [%]1. Dickstein, 113:1032 - ‘972. Ratcliffe, JTCVS 116:566 - ‘98

LVEF is not enough1,2

Batista Procedure

• LV wall Stress was reduced ~ LV wall Stress was reduced ~ 25% 25%

• Shift in LVED compliance was Shift in LVED compliance was greater than the reduction in greater than the reduction in LVED elastance.LVED elastance.

• As a result, CO was reduce and As a result, CO was reduce and Starling’s law decrement Starling’s law decrement

Improvement in Symptoms, Improvement in Symptoms, NOT Survival NOT Survival

• Sudden Death: Sudden Death: 46% of the Deaths 46% of the Deaths

• CHF/Shock: 13%, CHF/Shock: 13%, • Sepsis: 6%, Sepsis: 6%, • Emergency LVAD: 20%Emergency LVAD: 20%• No Difference in Survival No Difference in Survival

Compared to OMTCompared to OMT

Batista Procedure

First the surgeon palpates to determine the border of the akinetic region.

A patch is sutured at that borderAnd the residual myocardium is folded over itself resulting in a thicker double-layer patch.

Surgical Anterior Ventricular Endocardial Restoration (SAVER)

New Therapies for Heart FailureNew Therapies for Heart Failure• Natriuretic peptidesNatriuretic peptides• Endothelin antagonistsEndothelin antagonists• Vasopeptidase Vasopeptidase

inhibitorsinhibitors• Cytokine antagonistsCytokine antagonists• StatinsStatins• ErythropoeitinErythropoeitin

• External enhanced counter External enhanced counter pulsationpulsation

• Cardiac resynchronization Cardiac resynchronization therapytherapy

• Routine use of Implantable Routine use of Implantable Cardiac Defibrillators (ICD)Cardiac Defibrillators (ICD)

• Ventricular constraint Ventricular constraint devicesdevices

• Cell transplantationCell transplantation• Total artificial heart / Total artificial heart /

permanent LVADspermanent LVADs

• LV dilation produce a LV dilation produce a change in the morphology change in the morphology from an ellipse to a more from an ellipse to a more spherical shape spherical shape

The Unmet Need in HFThe Unmet Need in HF

• LV remodeling predicts mortality.LV remodeling predicts mortality.

• Despite OMT, HF remains a progressive Despite OMT, HF remains a progressive disease that is accompanied by disease that is accompanied by progressive LV remodeling progressive LV remodeling

TOTAL Mortality

Ejection Fraction

Death for Arrhythmic

CausesPEA

Batista Procedure Arrhythmic Death

NYHA II

Other24%

CHF12%

Sudden death64%

N=103

NYHA III

Sudden death59%

CHF26%

Other15%

N=232

NYHA IV

Sudden death33%

CHF56%

Other11%

N=27 MERIT-HF

Athanasuleus CL et al. JACC. 2004;44:1439

Overall five-year survival

Restore TrialRestore Trial the the RReconstructive econstructive EEndoventricular ndoventricular SSurgery returning urgery returning

TTorsion orsion OOriginal riginal RRadius adius EElliptical shapelliptical shape

Stage AHigh Risk for Developing HF

Stage BAsymptomatic LV dysfunction

Stage CPast or currentSymptoms of HF

Stage DEnd-stage HF

Stages of HF

Class Isymptoms at activity levels that

would limit normal individualsClass II

symptoms of HF with ordinary exertion

Class IIIsymptoms of HF with less

than ordinary exertionClass IV

Symptoms of HF at rest

NYHA

Heart Failure (CHF)Heart Failure (CHF)

Natural History of DCMNatural History of DCM

DownhillDownhill

IrreversibleIrreversible

High risk for SCDHigh risk for SCD

ProgressiveProgressive

PCSD ParacorPCSD Paracor

Advanced Heart Advanced Heart Failure Failure

Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01

Class III-IV: Class III-IV: 40% 40% Mortality/1 yrMortality/1 yr

Class III-IV: Class III-IV: 80% 80% Mortality/2yrs Mortality/2yrs Class IV: 60% Mortality/1 yrClass IV: 60% Mortality/1 yr

ACE-I & Beta Blockade Reduce Mortality

11,5%

15,6%12,4%

7,8%

0%4%8%

12%16%

SOLVD-T MERIT-HF+ CIBIS II

1 Yea

r M

orta

lity

Placebo Treatment

Mortality Mortality

too Hightoo High

Therapies for Advanced HFTherapies for Advanced HF• ANP, BNPANP, BNP• Endothelin antagonistsEndothelin antagonists• Vasopeptidase-IVasopeptidase-I• Cytokine antagonistsCytokine antagonists• StatinsStatins• ErythropoeitinErythropoeitin• IABPIABP• CRT/ICDCRT/ICD• Cardiac Support Devices (CSD)Cardiac Support Devices (CSD)• Cell transplantationCell transplantation• Total artificial Heart/ Total artificial Heart/

permanent LVADpermanent LVAD

Stage DStage D

Refractory HF Refractory HF requiring requiring

specialized specialized interventionsinterventions

TherapyTherapyAll measures All measures

under stages A,B, under stages A,B, and Cand C

Mechanical Mechanical assist devicesassist devices

Heart Heart transplantationtransplantation

Continuous (not Continuous (not intermittent) IV intermittent) IV inotropic infusions inotropic infusions for palliationfor palliation

Hospice careHospice care

Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01

mRNA Expression for ANP

mRNA Expression for BNP

mRNA Expression of b1-Adrenergic Receptor

mRNA Expression of SERCA-2a

NL HF-Sham HF + CCMNL HF-Sham HF + CCM

mRNA Expression for aMHC

b1-AR

ANP

BNP

aMHC

Serca-2a

Heart FailureHeart FailureCCM – Mechanisms in HumanCCM – Mechanisms in Human

mRNA Expression for ANP

mRNA Expression for BNP

mRNA Expression of b1-Adrenergic Receptor

mRNA Expression of SERCA-2a

NL HF-Sham HF + CCMNL HF-Sham HF + CCM

mRNA Expression for aMHC

b1-AR

ANP

BNP

aMHC

Serca-2aUnpublishdd dataUnpublishdd data

Heart FailureHeart FailureCCM – Mechanisms in HumanCCM – Mechanisms in Human

De Gasperis Experience

6 pts: 5 IDC and 1 Ischemic NYHA class: III (5 pts) e IV (1 pt) LV preop: E.F. 34%, LVEDVi 103 mL Associate Procedures : 4 MVR, 1 MCS, 1 CABG 6 Month Mortality: 0 LV postop: E.F. 37%, LVEDVi 74 mL

PCSD CorCapPCSD CorCap

• MI in anteroseptal portion of LV• Enlarged LV• ESV index > 50ml/m2• EDV index of > 110 ml/m2• Large area of Akinesis or Dyskinesis• Asynergy >30% of circumference or 3/10 Echo

anterior segment STICH Trial • Acceptable EF of basal portion and lateral wall• Good RV function• Candidate for CABG

Inclusion CRITERIAInclusion CRITERIA“Surgical Ventricular Restoration” (SVR)

• MI in anteroseptal portion of LV• Enlarged LV• ESV index > 50ml/m2• EDV index of > 110 ml/m2• Large area of Akinesis or Dyskinesis• Asynergy >30% of circumference or 3/10 Echo

anterior segment STICH Trial • Acceptable EF of basal portion and lateral wall• Good RV function• Candidate for CABG

Inclusion CRITERIAInclusion CRITERIA“Surgical Ventricular Restoration” (SVR)

• As the LV becomes more spherical this twisting ability of LV reduced (apical counter-clockwise /basal clockwise) with reduction both of LVEF and filling.

• As CHF progresses, the associated dilation of the LV will often change both SIZE and SHAPE of LV

Left Ventricular Remodelling Size, Shape and MV apparatus

• As CHF progresses, the associated dilation of LV will often pull the MV apparatus out of proper anatomical alignment (MR)

• The misalignment reduces the ability of MV apparatus to assist LV in the contraction (additional work-load)

                                        

                                                                                                    

  Stronger Directed Vector

                                                                                                    

  Weaker

Misdirected Vector

• As the shape of the LV becomes distorted, this force vector diminishes

and its direction moves away from the AoV.

• The result is inefficient pumping and turbulence in the LV.

Left Ventricular Remodelling Aortic Valve

• Re-sizing the ventricle around a Shaper inflated ensures that a too small or too large ventricle will not be created.

• The object of SVR should be the proportional reduction of both the short and long axis, because only reducing the long axis will create a spherical LV, and lead MR.

• “Surgical Anterior Ventricular Endocardial Restoration - SAVER”

(TR3ISVR procedure)

• Shaper defines the new apex.

INACTIVE AREA

Excitabile Gap

Batista Procedure Arrhythmic Death

NYHA II

Other24%

CHF12%

Sudden death64%

NYHA III

Sudden death59%

CHF26%

Other15%

NYHA IV

Sudden death33%

CHF56%

Other11%