The STITCH trial evaluated the effect of CABG plus optimal medical therapy (OMT) versus OMT alone on mortality in patients with left ventricular dysfunction and coronary artery disease. A sub-study examined the role of assessing myocardial viability to identify patients who benefit most from CABG. Of 601 patients who underwent viability testing, 487 had viable myocardium and 114 did not. There was no significant interaction between viability status and treatment assignment on mortality or other outcomes. Assessing viability did not identify patients with differential survival benefit from CABG versus OMT alone.

1. STITCH TRIAL
CABG AND OMT
IN LV DYSFUNCTION
Dr AURIOM KAR
( PDT DM CARDIOLOGY)

2. BACKGROUND OF STITCH TRIAL
• CAD IS THE COMMONEST SUBSTRATE FOR HEART FAILURE,AND ROLE OF
CABG IN PT WITH CAD AND HF IS NOT BEING CLEARLY ESTABLISHED.
• THE TRIALS IN 70’S WHICH COMPARED MEDICAL THERAPY WITH CABG
ALONE WERE PREDOMINANTLY DONE IN PATIENTS WITH CHRONIC STABLE
ANGINA.
• THESE TRIAL EXCLUDED PATIENTS WITH LV SYSTOLIC DYSFUNCTION.AND
METAANALYSIS OF THESE TRIAL SHOWED THAT ONLY 7 % OF PATIENTS
WHO WENT RANDOMIZATION HAD AN EF <40 %.AND ON 4% HAD
PRIMARY SYMPTOMS OF HF RATHER THAN ANGINA.
• ALSO ALL THESE TRIALS PREDATE THE MAJOR DEVELOPMENT IN MEDICAL
THERAPHY AND CARDIAC SURGERY OF PRESENT TIME

3. HYPOTHESIS

4. 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)

5. 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
• Non-cardiac illness with a life expectancy of less than 3 years or
imposing substantial operative mortality

6. STITCH TRIAL DESIGN AND ENROLLMENT

7. SURGICAL REVASCULARIZATION
HYPOTHESIS
• IN PATIENT WITH LV DYSFUNCTION ,HF AND
CAD AMENABLE TO SURGICAL
REVASCULARIZATION,CABG ADDED TO
INTENSIVE MEDICAL THERAPHY WILL
DECREASE THE ALL CAUSE MORTALITY
COMPARED TO MEDICAL THERAPHY ALONE

8. SUBSET OF PRIMARY HYPOTHESIS
• PRESENCE AND EXTENT OF DYSFUNCTIONAL
AND VIABLE MYOCARDIUM AS DEFINED BY
RADIONUCLEOTIDE IMAGING AND
DOBUTAMINE STRESS TEST OR BOTH WILL
IDENTIFY THE PATIENTS WITH GREATEST
SURVIVAL BENEFIT WITH OMT AND CABG VRS
OMT ALONE

9. SURGICAL RESTORATION HYPOTHESIS
• IN PATIENT WITH DOMINANT ANT WALL
HYPOKINESIA OR DYSKINESIA, LV SHAPE AND
SIZE OPTIMIZATION BY SVR COMBINED WITH
CABG AND MEDICAL THERAPHY IMPROVES
LONG TERM SURVIVAL FREE OF CARDIAC
HOSPITALIZATION COMPARED WITH CABG
AND MED THERAPHY ALONE.

10. 1212
Randomized
CABG
Randomized
MED only
610602
STICH Revascularization Hypothesis
• 99 clinical sites in 22 countries
• Enrollment: July 2002 – May 2007

11. END POINTS
PRIMARY END POINTS
• DEATH FROM ANY CAUSE
SECONDARY END POINTS
• DEATH FROM
CARDIOVASCULAR CAUSES
• HOSPITALIZATION FROM
CARDIOVASCULAR CAUSES

12. All-Cause Mortality
— As Randomized
HR 0.86 (0.72, 1.04)
P = 0.123
Adjusted HR 0.82 (0.68, 0.99)
Adjusted P = 0.039

13. THE PRIMARY END POINT
• THUS AS RANDOMIZED CABG LED TO 14%
RISK REDUCTION OF ALL CAUSE MORTALITY
WHEN COMPARED TO MED THERAPHY ALONE
(WHICH WAS NOT SIGNIFICANT)

14. SO IS CABG NO ROLE IN ISCHEMIC
HEART FAILURE
• CABG FAILED TO ANY BENEFIT IN PRIMARY
ANALYSIS BUT IF WE GO DEEPER, THE DATA
ARE MUCH MORE SUPPORTIVE FOR CABG.

15. HR 0.81 (0.66, 1.00)
P = 0.050
Adjusted HR 0.77 (0.62, 0.94)
Adjusted P = 0.012
Cardiovascular Mortality
— As Randomized

16. HR 0.74 (0.64, 0.85)
P < 0.001
Adjusted HR 0.70 (0.61, 0.81)
P < 0.001
Death or Cardiovascular
Hospitalization — As Randomized

17. TIME VARYING HAZARD RATIOS
• Time dependent survival relationship between 2 treatment
arm varies according to the baseline risk.This was not studied
previously.
• Purpose of this study-
Examine the impact of key anatomical variables used in routine
clinical practice and known to be associated with prognosis on
time dependent hazard in patients randomized to OMT and
CABG in stitch trial.
• HYPOTHESIS-EARLY SURGICAL RISK IS RAPIDLY SURPASSED BY
SUBSEQUENT SURVIVAL BENEFIT AND THEN THE INDICATION
FOR CABG WILL BE MORE CLEARLY SUPPORTED.

18. .
From: Extent of Coronary and Myocardial Disease and Benefit From Surgical Revascularization in LV
Dysfunction
Time-Varying Hazard Ratios for All-Cause Mortality in Patients Randomized to Receive CABG or OMT in the STICH Trial
CABG = coronary artery bypass graft surgery; MED = medical therapy alone; OMT = optimal medical therapy; STICH = Surgical
Treatment of IsChemic Heart failure.
Figure Legend:

19. Date of download: 4/21/2016 Copyright © The American College of Cardiology. All rights reserved.
From: Extent of Coronary and Myocardial Disease and Benefit From Surgical Revascularization in LV
Dysfunction
J Am Coll Cardiol. 2014;64(6):553-561. doi:10.1016/j.jacc.2014.04.064
Kaplan-Meier Estimates of Mortality Rates
Kaplan-Meier estimates are shown for all-cause (A) and cardiovascular (B) mortality rates. In
each panel, study patients are divided according to the presence of 0 to 1 or 2 to 3 prognostic
factors, regardless of treatment allocation.
Figure Legend:

20. From: Extent of Coronary and Myocardial Disease and Benefit From Surgical Revascularization in LV
Dysfunction
J Am Coll Cardiol. 2014;64(6):553-561. doi:10.1016/j.jacc.2014.04.064
Kaplan-Meier Estimates of All-Cause Mortality Rates by Number of Prognostic Factors
Kaplan-Meier rate estimates are shown for all-cause mortality among patients with 2 to 3 (top panel) and 0 to 1 (bottom panel)
prognostic factors. In each panel, study patients are divided according to the treatment arm (CABG or OMT) to which they were
randomized. Abbreviations as in Figure 1.
Figure Legend:

21. From: Extent of Coronary and Myocardial Disease and Benefit From Surgical Revascularization in LV
Dysfunction
J Am Coll Cardiol. 2014;64(6):553-561. doi:10.1016/j.jacc.2014.04.064
Kaplan-Meier Estimates of All-Cause Mortality by Treatment Arm
Kaplan-Meier estimates are shown for all-cause mortality rates among patients randomized to OMT (top panel) or CABG (bottom
panel). In each panel, study patients are divided according to the presence of 0 to 1 or 2 to 3 prognostic factors. Abbreviations as in
Figure 1.
Figure Legend:

22. Date of download: 4/21/2016 Copyright © The American College of Cardiology. All rights reserved.
From: Extent of Coronary and Myocardial Disease and Benefit From Surgical Revascularization in LV
Dysfunction
J Am Coll Cardiol. 2014;64(6):553-561. doi:10.1016/j.jacc.2014.04.064
Schematic Representation of the Clinical Implications of the Present Study Findings
The EF and ESVI thresholds (*) are the median values of the left ventricular (LV) function variables in the present study and have not
been validated prospectively in an independent patient population. This algorithm should only be applied conceptually to support
the notion that among patients with ischemic LV systolic dysfunction, the benefit of surgical revascularization is greater when the
disease process is more advanced (see text for more detail). CAD = coronary artery disease; EF = ejection fraction; ESVI= end-
systolic volume index.
Figure Legend:

23. MYOCARDIAL VIABILITY AND
SURVIVAL IN ISCHEMIVC LV
DYSFUNCTION
SUBSTUDY OF THE STICH

24. Background
• Left ventricular dysfunction secondary in patients with coronary
artery disease is not always an irreversible process, LV function can
improve substantially in patients after CABG.
• Identifying this subgroup of patients remains the holy grail of
viability research.
• The common clinical practice of not offering CABG to patients with
LV dysfunction and nonviable scar on noninvasive studies in not
justified by published data.
• The assessment of myocardial viability has been used to identify
patients with coronary artery disease and left ventricular
dysfunction in whom CABG will provide a survival benefit. However,
the efficacy of this approach is uncertain.

25. OBJECTIVE IN THIS SUBSTUDY OF THE STICH
TRIAL(MYOCARDIAL VIABILITY AND SURVIVAL IN ISCHEMIVC LV
DYSFUNCTION)
• Reported the outcome of patients who were
randomly assigned to receive medical therapy
alone or medical therapy + CABG who also
underwent assessment of myocardial viability.

26. VIABILITY HYPOTHESIS IN THIS
PROSPECTIVE SUBSTUDY
• Tested the hypothesis that assessment of
myocardial viability identifies patients with
CAD and LV dysfunction who have the greatest
survival benefit with CABG compared to
aggressive medical therapy alone.

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

28. Viable myocardium must have the following
characteristics
1. The ability to generate PCr and ATP
2. Have an intact sarcolemma, in order to maintain
ionic/electrochemical gradients, and
3. Have sufficient perfusion, both for the delivery of
substrates and O2 and for the adequate washout of
potentially noxious metabolites
? contractility.

29. There are two tissue states that exhibit sustained
contractile dysfunction despite meeting the three
criteria
Stunned myocardium
&
Hibernating myocardium.

30. Hibernation Myocardium
STATE OF MYOCARDIAL HYPOCONTRACTILITY
DURING CHRONIC HYPOPERFUSION IN THE PRESENCE
OF COMPLETELY VIABLE MYOCARDIUM WHICH
FUNCTIONALLY UPON
IN OTHER WORDS IT CAN ALSO BE DEFINED AS defined as an exquisitely regulated
tissue successfully adapting its activity to prevailing circumstances -

31. STUNNED MYOCARDIUM
PHENOMENON OF DELAYED RECOVERY OF
REGIONAL MYOCARDIAL CONTRACTILE
FUNCTION AFTER REPERFUSION DESPITE THE
ABSENCE OF IRREVERSIBLE DAMAGE AND
DESPITE RESTORATION OF NORMAL FLOW.

33. KEY NON INVASIVE METHODS TO IDENTIFY
VIABILITY
1.Echocardiography
2.Single Photon Emission Computed
Tomography
3.Positron Emission Tomography
4.Magnetic Resonance

34. STUDY PROCEDURES INITIAL DESIGN
• Viability testing with SPECT was required for the enrollment of
patients.
• This was eventually expanded to make viability testing optional and
allow the use of either SPECT or dobutamine echocardiography.
• Investigators at all study centers were strongly encouraged to
perform viability testing in every patient, but the decision to
perform the test was left up to the recruiting investigators.
• For SPECT, patients with viability were defined as those with 11 or
more viable segments (65% OF MYOCARDIUM)on the basis of
relative tracer activity.
• For DOBUTAMINE ECHO, patients with viability were defined as
those with 5 or more segments (31% OF MYOCARDIUM)with
abnormal resting systolic function but manifesting contractile
reserve during dobutamine administration.

35. Study design
Of 601 patients
who underwent
viability testing
• 298- OMT PLUS
CABG
• 303-OMT
ALONE

36. Study design
• 487 PATIENTS WITH MYOCARDIAL VIABILITY,
1. 244 were assigned to receive medical therapy plus
CABG, and
2. 243 were assigned to receive medical therapy
alone.
• IN THE SUBGROUP OF 114 PATIENTS WITHOUT
MYOCARDIAL VIABILITY,
1. 54 were assigned to receive medical therapy
plus CABG, and
2. 60 were assigned to receive medical therapy
alone.

37. Patient Follow-up andOutcomes
• Patients were followed every 4 months for the
first year and every 6 months.
There after
Primary outcome was
• death from any cause.
Secondary end points-
• Death from cardiovascular cause
• Composite of death from any cause
• Hospitalization for cardiovascular causes

38. Kaplan–Meier Analysis of the Probability of Death, According to Myocardial Viability Status.
Bonow RO et al. N Engl J Med 2011;364:1617-1625

39. RESULTS…
• Of 487 patients with
viable myocardium
178 patients
died(37%)
• Of 114 pts with
nonviable
myocardium 58
patients died (51%)
• Association of
mortality was not
significant after
adjustment of
baseline variables.(p -
.21)

40. RESULTS COND….
• Patients with myocardial
viability also had lower rates
of the secondary end points of
death
from cardiovascular causes (P =
0.003) and a composite of death
or hospitalization for
cardiovascular causes (P<0.001)
• The relationship between
myocardial viability and death
from cardiovascular causes
was not significant on
multivariable analysis (P =
0.34),
but the relationship with the
composite of death or
hospitalization for cardiovascular
causes remained
significant (P = 0.003).

41. Kaplan–Meier Analysis of the Probability of Death According to Myocardial-Viability Status
and Treatment.
Bonow RO et al. N Engl J Med 2011;364:1617-1625

42. Kaplan–Meier Analysis of the
Probability of Death According to
Myocardial-Viability Status and
Treatment.
At 5 years in the intention-to-treat
analysis,
• The rates of death for
patients without
myocardial viability were
41.5% IN THE GROUP CABG
and 55.8% IN THE GROUP
ASSIGNED TO RECEIVE
MEDICAL THERAPY (Panel
A).
• Among patients with
myocardial viability, the
respective rates were
31.2%(CABG) and
35.4%(OMT) (Panel B).
• There was no significant
interaction between viability
status and treatment
assignment with respect to
mortality (P=0.53) (Panel C).

43. Kaplan–Meier Analysis of the
Probability of Death According to
Myocardial-Viability Status and
Treatment.
• There was no significant
interaction between
myocardial viability and
study-group assignment
with respect to death (P =
0.53)
• death from cardiovascular
causes (P = 0.70), or
• the composite of death or
hospitalization for
cardiovascular causes (P =
0.39)

44. Baseline Characteristics of Patients Who Underwent Assessment of Myocardial Viability.
Bonow RO et al. N Engl J Med 2011;364:1617-1625

45. Conclusions
1. The presence of viable myocardium was associated with a greater
likelihood of survival in patients with coronary artery disease and left
ventricular dysfunction, but this relationship was not significant after
adjustment for other baseline variables.
• The findings of this multivariable analysis do not necessarily indicate that
myocardial viability does not have pathophysiological importance in
patients with coronary artery disease and left ventricular dysfunction.
Instead, it is likely that some of the other variables in the analysis (e.g.,
left ventricular volumes and ejection fraction) are causally
determined by the extent of viable myocardium.
• The assessment of myocardial viability did not identify patients with a
differential survival benefit from CABG, as compared with medical
therapy alone.

46. LIMITATIONS
• Patients were selected for viability testing indivisually at physician
discretion.
• Patients represented only <50% of stich population.
• No of patient without viable myocardium(114 OF 601) were quite
small which limited the statistical power.
• Third, we cannot exclude the possibility that results of viability
testing could have influence subsequent clinical decision making.
• PET and CARDIAC MRI were not included.
• Use of 2 different imaging method for assessing viability . An
analysis of outcomes on the basis of a combination of these two
tests poses important limitations, given the fundamental
differences in the viability information provided by SPECT and
dobutamine echocardiography (one related to membrane integrity
and the other to contractile reserve) and the differences in analytic
approaches between the two methods.

47. THIS STUDY DIFFERS MARKEDLY FROM RESULTS
OF PREVIOUS RETROSPECTIVE STUDIES AND META-
ANALYSES.
• Low rates of death among patients with viable myocardium who were assigned to
receive medical therapy (approximately 7% per year) in this study, as compared
with previously reported rates (which exceeded 15% per year in many studies).
• Adherence to guidelines-recommended therapies was high in THIS trial, whereas
data on medical therapy are lacking in many previous retrospective analyses.
• Medical therapy, like CABG, has the potential to improve left ventricular function
in patients with dysfunctional but viable myocardium.
• The lack of interaction between myocardial- viability status and benefit from
CABG in this study indicates that assessment of myocardial viability alone should
not be the deciding factor in selecting the best therapy for these patients.
• These findings also highlight the need for prospectively designed studies to
determine the role of cardiac imaging in clinical decision making.

48. ROMERO ET AL PROVIDED A METAANALYSIS OF THE VALUE OF 3 DIFF
DIAGNOSTIC STRATIGIES WITH CMR TO PREDICT FUNCTIONAL RECOVERY
AFTER REVASCULARIZATION
Hibernating tissue is defined as a segment of
• end-diastolic wall thickness of <5.5 to 6 mm;
• with a wall motion abnormality at rest, but <50%
transmurality of scar; or
• that demonstrates functional recruitment (contractile reserve)
during low-dose dobutamine stress.

49. ALGORITHM TO ASSESS HIBERNATING MYOCARDIUM WITH
CMR

51. DISCUSSION
• Allman et al performed a meta-analysis of 24 prognostic
studies (with 3088 patients) that used various viability
techniques and that showed a 3.2% annual death rate in
patients who had viable myocardium and who underwent
revascularization, compared with a 16% annual death rate
in patients who had viable myocardium and who were
treated medically.
• Although Prior observational studies and meta-analyses
had suggested that those with viability demonstrated on
noninvasive testing fared better with revascularization than
medical therapy alone, most of these studies were based
on retrospective or cohort analyses, in addition most of the
cohort studies carried out before modern aggressive
medical therapy.

52. DISCUSSION
• The lack of randomized controlled trials (RCT) of viability testing
was addressed partly by the PARR-2 trial, the largest to date,
RCT of PET viability testing .
• PARR-2 stratified patients with severe LV systolic dysfunction
(presumed ischemic) to PET-guided management (n = 218)
versus standard care without PET (where an alternative test
could be considered [n = 212]).
• At 1 year, PARR-2 demonstrated no significant difference in the
composite primary outcome of cardiac death, myocardial
infarction (MI), or recurrent hospitalization between the 2
arms.
• Although well-conducted, PARR-2 had lower adherence to PET-
guided recommendations, which may have reduced the ability
to detect a difference in the primary outcome.

53. DISCUSSION
• The HEART (Heart Failure Revascularization Trial) was an
unblinded clinical study that aimed to randomize 800 patients with
symptomatic HF, LV ejection fraction < 35%, and evidence of
substantial myocardial viability to either conservative management
or coronary angiography with the intention of revascularization .
• Unfortunately, the study was stopped early due to problems with
recruiting and funding.
• Of the 138 patients enrolled, 69 were randomized to a strategy of
revascularization, but only 45 ultimately underwent a procedure.
• There were no differences in mortality by intention-to-treat,
suggesting a lack of benefit of revascularization therapy in patients
with viability.
• However, the trial was clearly underpowered to address this
endpoint

54. CONCLUSION
• With the publication of the stich trial (Surgical Treatment for Ischemic Heart
Failure) trial and the viability sub study , questions have arisen regarding the utility
of viability testing in patients with left ventricular systolic dysfunction and
coronary artery disease (CAD) prior to revascularization decisions.
• Stich was the first prospective randomized trial testing the hypothesis that CABG
improves survival in patients with ischemic LV dysfunction compared to outcome
with aggressive medical therapy.
• It also Provides the first opportunity to assess the interaction between myocardial
viability and survival in randomized patients who were all eligible for medical
management alone and eligible for CABG.
• Stich demonstrated a significant association between myocardial viability and
outcome, but this association is rendered non-significant when subjected to a
multivariable analysis that includes other prognostic variables.
• Stich has failed to demonstrate a significant interaction between myocardial
viability and medical versus surgical treatment with respect to mortality.
• So it concluded that 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.

55. CONCLUSION
• So far none of the prospective trials that addressed the
viability question supports the use of viability testing as
a helpful or useful test in the decision-making process
regarding revascularization in patients with ischemic
cardiomyopathy.
• This contradicts the well known biological theory that
improvement in systolic function with revascularization
(only possible in viable segments) is associated with
better prognosis.
• Hence, there is dilemma of plausible biological
concepts already incorporated into practice with the
opposing findings of recent clinical trials.

56. There are a number of possible explanations for these
discrepancies..
1. Limitations in study design and completion may have prevented
the detection of a true interaction between viability status and
the benefit of revascularization.
2. It is possible that the advances in medical and device therapy
have markedly reduced the added benefit of revascularization,
such that it is difficult to demonstrate further improvement in
clinical outcomes.
3. Furthermore patients with ischemic cardiomyopathy constitute a
heterogeneous population with an extremely complex condition
in which multiple factors play an important prognostic role. So, it
would be too simplistic to expect that a single feature like the
presence of viable myocardium would provide the answer to such
a critical question for all patients.

57. Late percutaneous coronary intervention for an occluded infarct-related artery in
patients with preserved infarct zone viability: a pooled analysis of cardiovascular
magnetic resonance studies.
Małek LA1, Silva JC, Bellenger NG, Nicolau JC, Kłopotowski M, Spiewak M, Rassi
CH, Lewandowski Z, Kruk M, Rochitte CE, Rużyłło W, Witkowski A.
• AIM OF THE STUDY was to assess the influence of late percutaneous coronary
intervention (PCI) with optimal medical therapy (OMT) vs. OMT alone on cardiac function and
remodeling in patients presenting infarct zone with preserved viability on cardiovascular
magnetic resonance (CMR).
• CONCLUSIONS: In patients with the presence of infarct zone viability, OMT with late PCI for
an occluded IRA (particularly LAD) is associated with improvement of left ventricular systolic
function and size over OMT alone.