Myocardial Viability and Long-Term Outcomes in Ischemic Cardiomyopathy

The concept of the “hibernating myocardium” gained recognition in the 1980s at a time when the role of surgical revascularization in the management of ischemic cardiomyopathy was being established through a series of seminal trials.^1-5 The hibernating myocardium was defined as tissue impaired by chronic ischemia as opposed to an acute infarct. The tissue function, although diminished, was deemed recoverable either with improved blood flow (e.g., with surgical intervention) or decreased oxygen demand (e.g., with medical therapy).

For nearly 40 years, the intuitive belief was that recovery of the hibernating myocardium through surgical revascularization underlies the benefit of bypass grafting, a finding supported by some observational studies. That view was questioned in 2011 when a substudy of the STICH (Surgical Treatment for Ischemic Heart Failure) trial was published. The STICH trial was designed to examine the role of surgical revascularization in patients with coronary artery disease and reduced ejection fraction. Approximately half the patients enrolled in STICH underwent testing for myocardial tissue viability before they were randomly assigned to surgical revascularization with medical therapy or medical therapy alone. After a median follow up of 5 years, the authors found no relation between the degree of viability and outcomes from revascularization.

Now, in a follow-up study published in the NEJM, the authors report long-term outcomes after a median of 10 years and reaffirm the lack of an association between myocardial viability and benefit from surgical revascularization. However, viable myocardium was associated with post-revascularization improvements in left ventricle systolic function, a proof-of-concept for the hibernating myocardium hypothesis. Although further research is needed, the lack of an association between cardiac viability and long-term benefit in this study raises new questions about how to decide who will benefit most from surgical revascularization.

The following NEJM Journal Watch summary provides more details of the trial and findings.

Harlan M. Krumholz, MD, SM reviewing Panza JA et al. N Engl J Med 2019 Aug 22

We cardiologists have long lived with the idea that the assessment of myocardial viability should inform decisions about revascularization, particularly in patients with ischemic cardiomyopathy, but some studies have questioned this reasonable assumption. In a substudy of the STICH trial (which compared medical therapy alone with coronary artery bypass grafting [CABG] in patients with coronary artery disease and left ventricular ejection fraction [LVEF] of ≤35%; NCT00023595), the presence of myocardial viability was not associated with a survival benefit from CABG at a median follow-up of 5.1 years (NEJM JW Cardiol May 2011 and N Engl J Med2011; 364:1462). The investigators have now analyzed associations of myocardial viability with LV function and outcomes at a median follow-up of 10.4 years.

Of the 1212 patients enrolled in STICH, 601 had myocardial viability testing, of whom 19% were classified as having no viability. The incidence of death at 10 years did not differ significantly between patients with or without myocardial viability. CABG was not more effective for patients with viability than those without viability.

LVEF was measured in 318 participants at baseline and 4 months. Patients with myocardial viability had a significant increase in LVEF at 4 months, whereas those without viability did not. Mortality did not correlate with LVEF change.

COMMENT: This study adds to the investigators' prior contributions. In this population, myocardial viability did not dictate the likelihood of benefit from surgical revascularization. Also, change in LVEF, a surrogate outcome, failed to correspond with benefit.

I have some concerns about testing for interactions in relatively small groups. We need larger studies to be certain about these findings. Nevertheless, until people can demonstrate the value of testing for myocardial viability in patients with ischemic cardiomyopathy, we should hold off using these tests for similar patients to inform decisions. 

Additional References:

1. Rahimtoola SH. A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina. Circulation 1985.
2. Braunwald E and Rutherford JD. Reversible ischemic left ventricular dysfunction: evidence for the "hibernating myocardium". J Am Coll Cardiol 1986.
3. Principal Investigators of CASS and their Associates. Coronary Artery Surgery Study: a randomized trial of coronary bypass surgery: Survival data. Circulation 1983.
4. Veterans Administration Coronary Artery Bypass Surgery Cooperative Study Group. Eleven-year survival in the Veterans Administration randomized trial of coronary bypass surgery for stable angina. N Engl J Med 1984.
5. Varnauskas E and The European Coronary Surgery Study Group. Twelve-year follow-up of survival in the randomized European Coronary Surgery Study. N Engl J Med 1988.

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Ahmad is a 2019-2020 editorial fellow at the New England Journal of Medicine. He is from Toronto, Canada where he is completing his training in pulmonary medicine at the University of Toronto.