4. Congestive Heart Failure in India
Prevalence:
18.8 million (1.76% of population)
Incidence:
1.57 million per year (0.15%)
5. Etiology of CHF
United States:
o Ischemic (50%)
o Idiopathic (50%)
India
o Rheumatic heart disease (52.8%)
o Ischemic/ hypertensive (27.2%)
6. 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
7. 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
8. Ischaemic Cardiomyopathy :
Selection Criteria
Duke CVD Data Bank
75 % ≥ Diameter stenosis in major coronary
Artery
EF < 40 %
NYHA Symptoms Class II or More
Stitch Trial
Patient with CAD
EF < 35 %
9. Factors Contributing to Left Ventricular Remodeling,
Progression of Left Ventricular Systolic Dysfunction and Heart
Failure
Cardiovascular
Systemic and Other
nonmyocardial factors factors
Coronary artery Renin-angiotensin-
disease extent aldosterone system
endothelial function Sympathetic nervous system
Arrhythmias Vasodilators
Myocardial factors
Mitral valve function Natriuretic peptides
Ventricular synchrony
Cytokines
Remote myocardium Diastolic function
Diabetes mellitus and
Scar tissue metabolic syndrome
Hibernation Sleep apnea
Ischemia / stunning Renal disease
Apoptosis Environmental
LV remodeling Age
Hypertrophy
Progression of
LV systolic dysf.
Heart failure
10. Dukes : CVD Data : Ischemic Cardiomyopathty –
Observational Data
Duke Cardiac
Catherizations Patients (taking first
CHF ≥ 2
July 1969 – February catheterizations)
1994 n = 4129
N=3630
N = 54,498
63 patients deleted
from analysis Ejection
Medical fraction < 40 %
lost, or died within
N=1052 mean time to CABG
N=1454
N=1391
CABG
N = 339
Am. J. Cardiol 2002, 90, 101
13. Hibernation Myocardium
State of myocardial hypocontractility
during chronic hypoperfusion in the presence
of completely viable myocardium which
functionally upon
14. 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
15. Duke Data
Ischaemic Cardiomyopathy
CABG better MED better
EF ≤ 25 %
> 25 %
Age ≤ 65
> 65
NYHA II
III
IV
Angina
No Angina
0 0.5 1 1.5
Am. J. Cardiol 2002, 90, 101
16. 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
17. 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
18. Coronary Artery Occlusion
Outcomes
Incomplete or short Complete and
Complete and short
duration prolonged
Normal structure &
function
Stunning Low- ATP
Ischemia Contractile failure
Myocardial
Hibernation infarction
Influenced By Collaterals and Ischemic Preconditioning
20. 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.
21. 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)
22. 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
23. STICH Revascularization
Randomized MED only
602
1212
Randomized CABG
HF, LVD and CAD 610
amenable to CABG
24. STITCH TRIAL
N. Eng. J. Med 2011, 364, 1607- 1616
25. 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.
26. N. Eng. J. Med 2011, 364-1604
N Engl J Med 2011; 364:1607-1616
31. 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
32. 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
33. Myocardial Viability : Meta-Analysis
Allman et al
-79.6 %
20
23.0 %
x2=147
16
Death rate (%/yr)
p<0.0001 x2=1.43
15
p<0.23
10
7.7
6.2
5 3.2
0
Revasc. Medical Revasc. Medical
Viable Non-Viable
JACC Vol. 39, No. 7, 2002 April 3, 2002:1151-8
34. Predicted Reduction in Death Rate With Revascularization
Allman et al
0
-25
-50
Viable
-75 Non-Viable
-100
25 30 35 40 45
Left Ventricular EF %
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
35. Myocardial Hibernation : SCD
G. Heusch
Symptomatic stimulation
Acute ischemia
Microembolization ?
Acute inflammation
TRIGGER
Structural remodeling
interstitial fibrosis
myocyte hypertrophy
Altered innervation
Electrical remodeling
altered conduction ?
SUBSTRATE
Elements of the arrhythmogenic substrate and triggers for arrhythmia
in hibernating myocardium
36. 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
37. Kaplan-Meir curves showing the cardiac
event rate in the three groups of patients
40
Log-rank P-value 0.01 Group 3
Cardiac death rate (%)
30 Non viable
20 Group 2
Viable
No Improvement LVEF
10
Group 1
0 Viable
0 1 2 3 4 Improvement LVEF
Follow up (years)
38. Time Course of Functional Recovery After
Revasc. – 26 Patients
3 WMS
2
1
0
Stunning Hibernation Nontransm scar Transm scar
Baseline 3 Months 14 Months
Circulation September 18, 2001
39. 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
40. Markers of Hibernating Myocardium
Modalities and Targets Metabolism Perfusion Nonviability Scar Contractile Reserve
CMR - + + +
CT - + + -
Echocardiography - + (+) +
PET + + - -
SPECT + + - +
Assessment of Detection of Exact localization Assessment of
functional blood flow and size of contractile function
integrity of toward the necrosis/fibrosis
myocardial cells myocardium
41. Algorithm to Assess Hibernating Myocardium With CMR
Wall Motion Abnormalities At Rest –
CHR in the Presence of Coronary Artery
Disease
LGE
Revascularization Transmurality
> 50 %
< 50 %
Medical
LDDSMR Therapy
Medical Therapy Revascularization
42. Dobutamine Study Echo In 128 Patients : Ischaemic
Cardiomyopathy - EF 31 %
CR-patients
30
25 p = 0.015
Cardiac death rate (%)
20
15
CR+patients
10
5
0
0 365 730 1095 1460 1825
Follow up (days)
Heart 2006, Rizzella V et al
43. Results of Studies That Evaluated the
Improvement in Function on a Segmental Basis
Sensitivity Specificity PPV NPV
CMR
Contrast enhanced 97 68 73 93
Dobutamine stress 94 90 86 92
Total
94 87 84 87
Conventional nuclear
99mTc-sestambi
96 55 87 80
SPECT FDG 89 86 --- ---
201TI rest, reinjection
Total
86 63 69 85
89 68 73 84
Echocardiography
DSE 76 81 66 89
DSE SRI 82 80 --- ---
End-diastolic wall thickness
Total
94 48 53 93
78 78 64 90
PET
PET-FDG67,70,75,79-81 89 57 73 90
Total 89 57 73 90
44. 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
45. Scheme of enrolling and follow-up of patients included in the study.
N=141
patients included
Into the study
N=55 N=54
N=32
patients allocated to patients allocated to
patients allocated to
PCI group CABG group
Registry group
30-day Follow-up 30-day Follow-up
N=50
N=55 (2 deaths before CABG
2 deaths after CABG
up to 30 days)
12-month Follow-up
N=54 12-month Follow-up
(1 death after 3 months
follow-up) N=50
46. 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
51. Symptoms and/or signs of congestive heart failure
with abnormal left ventricular function
(clinical examination and echocardiography)
CAD
CAD
Assess myocardial viability Investigate alternative
with technique available aetiologies (DCM, valve diseases etc.
No evidence of viability Presence of significant viability
or viability < 25 % of LV in segments subtended by
stenotic coronaries
Medical treatment Coronary revascularization
CRT, ICD, LVAD by PCI or CABG
52. 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