Ischaemic cardiomyopathy revascularisation how when and why

1. 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

2. Congestive Heart Failure in India Prevalence: 18.8 million (1.76% of population) Incidence: 1.57 million per year (0.15%)

3. Etiology of CHF United States : Ischemic (50%) Idiopathic (50%) India Rheumatic heart disease (52.8%) Ischemic/ hypertensive (27.2%)

4. Duke CVD Data- chnge Unadjusted survival curves for CABG versus medical therapy A, overall; B, 1-vessel disease; C, 2-vessel disease; D, 3-vessel disease Am. J. Cardiol 2002, 90, 101

5. Ischaemic Cardiomyopathy Older 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

6. Ischaemic Cardiomyopathy : Selection Criteria Stitch Trial Patient with CAD EF < 35 % Duke CVD Data Bank 75 % ≥ Diameter stenosis in major coronary Artery EF < 40 % NYHA Symptoms Class II or More

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

8. Dukes : CVD Data : Ischemic Cardiomyopathty – Observational Data Am. J. Cardiol 2002, 90, 101

9. Viability Vs Hibernation Are They Same ? NO!!! Viable myocardium = Hibernating myocardium

10. Myocardial Viability Dysfunctional myocardium subtended by disease coronary artery with limited or absent scarring that has POTENTIAL FOR FUNCTIONAL RECOVERY

11. Hibernation Myocardium State of myocardial hypocontractility during chronic hypoperfusion in the presence of completely viable myocardium which RECOVERS functionally upon REVASCULARISATION.

12. Duke CVD Data- chnge Unadjusted survival curves for CABG versus medical therapy A, overall; B, 1-vessel disease; C, 2-vessel disease; D, 3-vessel disease Am. J. Cardiol 2002, 90, 101

13. Duke Data Ischaemic 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

14. Duke CVD Data Ischaemic 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

15. 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 1 0.24 0.50 0.75 1 2

16. Coronary Artery Occlusion Influenced By Collaterals and Ischemic Preconditioning

17. Myocardial Tissue

18. 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.

19. 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)

20. 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

21. STICH Revascularization HF, LVD and CAD amenable to CABG

22. STITCH TRIAL N. Eng. J. Med 2011, 364, 1607- 1616

23. 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.

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

25. N Engl J Med 2011; 364:1607-1616

26. Patients with viability tests Patients without myocardial viability Patients with myocardial viability CABG 50.1% CABG 47.4% MED 49.9% MED 52.6%

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

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

29. 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

30. Myocardial viability testing and impact of revascularization on Prognosis in patients with coronary artery disease and left ventricular dysfunction: A meta analysis Kevi n 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

31. Myocardial Viability : Meta-Analysis Allman et al Death rate (%/yr) Viable Non-Viable JACC Vol. 39, No. 7, 2002 April 3, 2002:1151-8 -79.6 % x 2 =147 p<0.0001 23.0 % x 2 =1.43 p<0.23

32. 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 -25 -50 -75 -100 Viable Non-Viable

33. Myocardial Hibernation : SCD Elements of the arrhythmogenic substrate and triggers for arrhythmia in hibernating myocardium Symptomatic stimulation Acute ischemia Microembolization ? Acute inflammation Structural remodeling interstitial fibrosis myocyte hypertrophy Altered innervation Electrical remodeling altered conduction ? G. Heusch TRIGGER SUBSTRATE

34. 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 EF Group II – Viable patients with no Improvement in EF Group III – No viability

35. 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 Viable Improvement LVEF Group 2 Viable No Improvement LVEF Group 3 Non viable Cardiac death rate (%) Follow up (years)

36. Time Course of Functional Recovery After Revasc . – 26 Patients Circulation September 18, 2001 WMS

37. 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

38. 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

39. Algorithm to Assess Hibernating Myocardium With CMR < 50 % > 50 %

40. Dobutamine Study Echo In 128 Patients : Ischaemic Cardiomyopathy - EF 31 % Heart 2006, Rizzella V et al p = 0.015 CR-patients CR+patients Cardiac death rate (%) Follow up (days) 0 365 730 1095 1460 1825 30 25 20 15 10 5

41. Results of Studies That Evaluated the Improvement in Function on a Segmental Basis Sensitivity Specificity PPV NPV CMR Contrast enhanced Dobutamine stress Total 97 94 94 68 90 87 73 86 84 93 92 87 Conventional nuclear 99m Tc-sestambi SPECT FDG 201 TI rest, reinjection Total 96 89 86 89 55 86 63 68 87 --- 69 73 80 --- 85 84 Echocardiography DSE DSE SRI End-diastolic wall thickness Total 76 82 94 78 81 80 48 78 66 --- 53 64 89 --- 93 90 PET PET-FDG 67,70,75,79-81 Total 89 89 57 57 73 73 90 90

42. 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

43. N=32 patients allocated to Registry group N=141 patients included Into the study N=55 patients allocated to PCI group N=54 patients allocated to CABG group 30-day Follow-up N=50 (2 deaths before CABG 2 deaths after CABG up to 30 days) 30-day Follow-up N=55 12-month Follow-up N=54 (1 death after 3 months follow-up) 12-month Follow-up N=50 Scheme of enrolling and follow-up of patients included in the study.

44. Results 30 Days MACE CABG – 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

45. 42 40 38 36 34 32 30 28 EFO EF12 p<0.01 p<0.01 p=0.38 p=0.99 LVEF (%) PCI CABG

46. 65 60 55 50 45 40 Baseline after 12 months p=0.86 p=0.78 p=0.37 LVEDD (mm) PCI CABG p=0.86

47. 50 45 40 35 30 Baseline after 12 months p=0.98 p=0.99 zp =0.94 LVESD (mm) PCI CABG p=0.62

48. Symptoms and/or signs of congestive heart failure with abnormal left ventricular function (clinical examination and echocardiography) CAD CAD Assess myocardial viability with technique available Investigate alternative aetiologies (DCM, valve diseases etc. No evidence of viability or viability < 25 % of LV Presence of significant viability in segments subtended by stenotic coronaries Medical treatment CRT, ICD, LVAD Coronary revascularization by PCI or CABG angina

49. 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