ISCHAEMIC CARDIOMYOPATHY REVASCULARISATION-HOW WHEN

AND WHY?

Dr. DEV PAHLAJANI (MD,FACC,FSCAI)HOD INTERVENTIONAL CARDIOLOGY BREACH CANDY

HOSPITAL AND CONSULTANT CARDIOLOGIST NANAVATI HOSPITAL

MUMBAI

Congestive Heart Failure in India

Prevalence:

18.8 million (1.76% of population)

Incidence:

1.57 million per year (0.15%)

Etiology of CHF

United States:o Ischemic (50%)o Idiopathic (50%)

Indiao Rheumatic heart disease (52.8%)o Ischemic/ hypertensive (27.2%)

Duke CVD Data-chnge

Unadjusted survival curves for CABG versus medical therapyA, overall; B, 1-vessel disease; C, 2-vessel disease; D, 3-vessel disease

Am. J. Cardiol 2002, 90, 101

Ischaemic CardiomyopathyOlder population• Usually MV Disease

• DM, CRF

• Poor LV function

• Increased LV volumes

• Regional wall motion abnormalities

• Multiple infarcts, Earlier procedures

• Conduction defects, Arrythmias

• PVD and Cer. Vascular Disease

Ischaemic Cardiomyopathy :Selection Criteria

Stitch Trial

Patient with CADEF < 35 %

Duke CVD Data Bank75 % ≥ Diameter stenosis in major coronary ArteryEF < 40 %NYHA Symptoms Class II or More

Factors Contributing to Left Ventricular Remodeling, Progression of Left Ventricular Systolic Dysfunction and Heart

Failure

LV remodeling Progression of LV

systolic dysf.Heart failure

Myocardial factors

Remote myocardiumScar tissue

HibernationIschemia / stunning

ApoptosisHypertrophy

Cardiovascularnonmyocardial

factors

Coronary artery disease extent

endothelial functionArrhythmias

Mitral valve functionVentricular synchrony

Diastolic function

Systemic and Other factors

Renin-angiotensin-aldosterone system

Sympathetic nervous system

VasodilatorsNatriuretic peptides

CytokinesDiabetes mellitus and metabolic syndrome

Sleep apneaRenal disease

Environmental Age

Dukes : CVD Data : Ischemic Cardiomyopathty – Observational Data

Am. J. Cardiol 2002, 90, 101

Duke Cardiac Catherizations

July 1969 – February 1994

N = 54,498

CHF ≥ 2n = 4129

Patients (taking first

catheterizations)

N=3630

Ejection fraction < 40 %

N=145463 patients

deleted from analysis

lost, or died within mean

time to CABGN=1391

Medical N=1052

CABG N = 339

Viability Vs HibernationAre They Same ?

NO!!! Viable myocardium = Hibernating myocardium

Myocardial Viability

Dysfunctional myocardium subtended by

disease coronary artery with limited or

absent scarring that has

POTENTIAL FOR FUNCTIONAL RECOVERY

Hibernation Myocardium

State of myocardial hypocontractility

during chronic hypoperfusion in the presence

of completely viable myocardium which

RECOVERS functionally upon REVASCULARISATION.

Duke CVD Data-chnge

Unadjusted survival curves for CABG versus medical therapyA, overall; B, 1-vessel disease; C, 2-vessel disease; D, 3-vessel disease

Am. J. Cardiol 2002, 90, 101

Duke DataIschaemic Cardiomyopathy

Am. J. Cardiol 2002, 90, 101

CABG better MED better

EF ≤ 25 %

> 25 %

Age ≤ 65

> 65

NYHA II

III

IV

Angina

No Angina

0 0.5 1 1.5

Duke CVD DataIschaemic Cardiomyopathy

Adjusted Cox Proportional-hazards Survival Estimates*

Medical Therapy CABG

1-year survival 74 % 83 %

5-year survival 37 % 61 %

10-year survival 13 % 42 %

*p<0.0001, for all comparisons. Weighted average of 1-, 2-, and 3-vessel disease used to calculate the 1-, 5-, and 10-year survival estimates

Am. J. Cardiol 2002, 90, 101

Relative Risk of Mortality for Coronary Artery Bypass Grafting Compared With Medical Therapy In Moderate to Severe Left

Ventricular Systolic Dysfunction, ranked in order of Study Quality

Study Follow-up Favors Favors Medical

(year) Surgery Treatment

Duke 5

Coronary Artery 3

Surgery Study

Mayo 2

University of Albama 5

St. Luke’s Milwaukee 6

Vanderbilt 2

Duke 10.24 0.50 0.75 1 2

Outcomes

Incomplete or short duration

Normal structure &

function

Ischemia Hibernat

ion

Complete and short

Stunning

Complete and prolonged

Low- ATP

Contractile failure

Myocardial infarction

Coronary Artery Occlusion

Influenced By Collaterals and Ischemic Preconditioning

Myo

car

dia

l T

issu

e

Surgical Revascularization Hypothesis STITCH N ENG J MED 2011

Primary Hypothesis:

In patients with HF, LVD and CAD amenable to surgical revascularization,

CABG added to intensive medical therapy (MED) will decrease all-cause

mortality compared to MED alone.

Secondary hypothesis:

Presence and extent of dysfunctional but viable myocardium, as defined

by radionuclide imaging, dobutamine stress echocardiography, or both,

will identify patients with greatest survival advantage of MED + CABG

compared with MED alone.

Important Inclusion Criteria

LVEF ≤ 0.35 within 3 months of trial entry

CAD suitable for CABG

MED eligible

– Absence of left main CAD as defined by an intraluminal

stenosis of ≥ 50%

– Absence of CCS III angina or greater

(angina markedly limiting ordinary activity)

Major Exclusion Criteria

Recent acute MI (within 30 days)

Cardiogenic shock (within 72 hours of randomization)

Plan for percutaneous intervention

Aortic valve disease requiring valve repair or replacement

History of more than 1 prior CABG

Non-cardiac illness with a life expectancy of less than 3 years or

imposing substantial operative mortality

STICH Revascularization

HF, LVD and CAD amenable to CABG

1212Randomized MED only

602

Randomized CABG610

STITCH TRIAL

N. Eng. J. Med 2011, 364, 1607- 1616

Has CABG no role in Ischemic HF ?

“We were unable to show a significant benefit for CABG in our primary analysis, but if you dive deeper, the data are much more supportive of bypass surgery,”

-Dr Eric J. Velazquez, M.D.

N. Eng. J. Med 2011, 364-1604N Engl J Med 2011; 364:1607-1616

N Engl J Med 2011; 364:1607-1616

Patients with viability tests

Patients without myocardial viability

Patients with myocardial

viability

CABG50.1%

CABG47.4%

MED49.9%

MED52.6%

601

487

243 244

114

60 54

STICH Viability

Viability testing was optional at enrolling sites and was not a prerequisite for enrollment.

SPECT protocols:

•Thallium-201 stress-redistribution-reinjection• Thallium-201 rest-redistribution•Nitrate-enhanced Tc-99m perfusion imaging

Dobutamine echo protocols:

•Staged increase in dobutamine starting at 5 μg/kg/min

N. Eng. J. Med 2011, 364-1617

STICH Viability

Implications:

In patients with CAD and LV dysfunction, assessment of myocardial viability does not identify patients who will have the greatest survival benefit from adding CABG to aggressive medical therapy

Myocardial viability testing and impact of revascularization on Prognosis in patients with

coronary artery disease and left ventricular dysfunction: A meta analysis

Kevin C. Allman , MB,BS,FRACP,FACC, * Leslee J. Shaw, PhD, Rory Hachamovitch, MD,FACC, James E. Udelson, MD,FACC

Conrod, Australia, Atlanta, Georgia and Boston, Massachusetts

JACC,2002.VOL .39. No. 7

Myocardial Viability : Meta-AnalysisAllman et al

Revasc. Medical Revasc. Medical0

5

10

15

20

3.2

16

7.7

6.2

Dea

th ra

te (%

/yr)

Viable Non-Viable

JACC Vol. 39, No. 7, 2002 April 3, 2002:1151-8

-79.6 %

x2=147p<0.0001

23.0 %

x2=1.43p<0.23

Predicted Reduction in Death Rate With Revascularization Allman et al

Relation between left ventricular ejection fraction (EF) and predicted change in mortality for patients with viable (circles) versus nonviable (triangles) myocardium based on the results of meta-regression. This demonstrates increasing potential for improved survival with lower left ventricular EF in patients with viable myocardium, p < 0.0001 (broken plot line), but not in those without viability, p = 0.11

JACC Vol. 39, No. 7, 2002 April 3, 2002:1151-8

Left Ventricular EF %25 30 35 40 45

0

-25

-50

-75

-100

Viable Non-Viable

Myocardial Hibernation : SCD

Elements of the arrhythmogenic substrate and triggers for arrhythmiain hibernating myocardium

Symptomatic stimulationAcute ischemiaMicroembolization ?Acute inflammation

Structural remodeling interstitial fibrosis

myocyte hypertrophyAltered innervation

Electrical remodeling altered conduction ?

G. Heusch

TRIGGER

SUBSTRATE

Ischaemic Cardiomyopathy Prognosis After Revascularization Relation With Improvement IN

LVEF & Viability – Rizello Y et al Heart 2009, 95, 1273

• 97 Consecutive patients• LVEF < 40 % CAD• Symptoms of Heart failure and or angina• Radionuclear ventriculography and Dobutamine Stress • Echo before Revascularization• After Revascularization : Group I – Viable patient with improved

EFGroup II – Viable

patients with no

Improvement in EFGroup III – No viability

Kaplan-Meir curves showing the cardiac event rate in the three groups of patients

Log-rank P-value 0.01

Group 1

0 1 2 3 4

40

30

20

10

0 Viable Improvement LVEF

Group 2

Viable No Improvement LVEF

Group 3Non viable

Card

iac

deat

h ra

te (%

)

Follow up (years)

Time Course of Functional Recovery After Revasc. – 26 Patients

Stunning Hibernation Nontransm scar Transm scar0

1

2

3

Baseline 3 Months 14 Months

Circulation September 18, 2001

WMS

Effect of Revascularisation On Long Term Survival In Ischaemic LV Dysfunction and Viability

SAWAD et al Am. J. Cardiol 2010, 106, 187

274 Patients : Mean LVEF 32 %

Viability In ≥ 25 % Myocardium by DSE

Primary End Point Cardiac Death

130 : Revascularization : Mean Survival 5.9 years

144 : Medical Treatment : Mean Survival 3.3 years P=0.0001

Markers of Hibernating Myocardium

Modalities and Targets Metabolism Perfusion Nonviability Scar Contractile Reserve

CMR - + + +

CT - + + -

Echocardiography - + (+) +

PET + + - -

SPECT + + - +

Assessment of functional integrity of

myocardial cells

Detection of blood flow toward the

myocardium

Exact localization and size of

necrosis/fibrosis

Assessment of contractile function

Algorithm to Assess Hibernating Myocardium With CMR

Wall Motion Abnormalities At Rest – CHR in the Presence of Coronary Artery Disease

LGE

Revascularization Transmurality

LDDSMR

Medical Therapy

Revascularization

Medical Therapy< 50 %

> 50 %

Dobutamine Study Echo In 128 Patients : Ischaemic Cardiomyopathy - EF 31 %

Heart 2006, Rizzella V et al

p = 0.015

CR-patients

CR+patients

Card

iac

deat

h ra

te (%

)

Follow up (days)0 365 730 1095 1460 1825

30

25

20

15

10

5

0

Results of Studies That Evaluated the Improvement in Function on a Segmental Basis

Sensitivity Specificity PPV NPV

CMR Contrast enhanced Dobutamine stress Total

979494

689087

738684

939287

Conventional nuclear 99mTc-sestambi SPECT FDG 201TI rest, reinjection Total

96898689

55866368

87---6973

80---8584

Echocardiography DSE DSE SRI End-diastolic wall thickness Total

76829478

81804878

66---5364

89---9390

PET PET-FDG67,70,75,79-81

Total8989

5757

7373

9090

REHEAT : Revascularization In Ischaemic Heart Failure Trial

Non Randomised case controlled

141 patients : LVEF < 40 % + CAD

Primary Outcome : Improvement in LVEF

Secondary Outcome : In-Hospital Major

Adverse Events

N=32patients allocated to

Registry group

N=141patients included

Into the study

N=55patients allocated to

PCI group

N=54patients allocated to

CABG group

30-day Follow-upN=50

(2 deaths before CABG2 deaths after CABG

up to 30 days)

30-day Follow-up

N=55

12-month Follow-upN=54

(1 death after 3 monthsfollow-up)

12-month Follow-up

N=50

Scheme of enrolling and follow-up of patients included in the study.

Results30 Days MACECABG – 40.7 %

PCI 9 % p=0.0003 Improvement in EF

CABG – 6 %PCI – 4.4 %

Functional Status Long-term Freedom From Angina

CABG was better p = 0.0013

42

40

38

36

34

32

30

28EFO EF12

p<0.01

p<0.01

p=0.38

p=0.99

LVE

F (

%) PCI

CABG

65

60

55

50

45

40Baseline after 12 months

p=0.86

p=0.78p=0.37

LVE

DD

(m

m) PCI

CABGp=0.86

50

45

40

35

30Baseline after 12 months

p=0.98

p=0.99zp=0.94

LVE

SD

(m

m) PCI

CABG

p=0.62

Symptoms and/or signs of congestive heart failure with abnormal left ventricular function

(clinical examination and echocardiography)

CADCAD

Assess myocardial viabilitywith technique available

Investigate alternativeaetiologies (DCM, valve diseases etc.

No evidence of viabilityor viability < 25 % of LV

Presence of significant viabilityin segments subtended by

stenotic coronaries

Medical treatmentCRT, ICD, LVAD

Coronary revascularizationby PCI or CABG

angina

TAKE HOME MESSAGE

• Ischemic cardiomypathy has high mortality

with medical Treatment

• Improved survival with CABG? PCI

• Effort should be made to detect viable muscle

• De,spect,cmr should be performed to detect

viable muscle