From Pages to Practice

By Mridula Nadamuni, MD

Published November 2, 2022


When an area of the myocardium is not moving normally, it is important to realize that all may not be lost. Although ischemia can lead to infarction —or death of the cardiomyocytes— the cells may survive by “hibernating” or suspending the contractile function in order to prioritize keeping the cell metabolically active and alive until the blood supply can be restored.

The terms “stunned” and “hibernating” are sometimes used interchangeably to describe reversible myocardial dysfunction. However, stunned myocardium is typically seen after an acute ischemic episode. Disruption of coronary blood flow followed by reperfusion has been noted to cause a transient depression in left ventricular function, followed by eventual recovery of contractility. Hibernating myocardium, however, results from chronic ischemia. If the underlying cause of chronic ischemia is not treated either by reducing the oxygen demand with guideline-directed medial therapy or by increasing the blood flow with a revascularization procedure, such as coronary artery bypass grafting surgery (CABG) or percutaneous coronary intervention (PCI), the cardiomyocytes will eventually die.

Nuclear imaging is one method that helps differentiate hibernating from infarcted myocardium. Regions of the myocardium that do not contract but do show fluorodeoxyglucose uptake on a positron emission tomography (PET) scan suggest that the heart muscle is viable despite a lack of contractility, and thus has the potential for reversibility with a revascularization procedure. In another test for viability, low-dose dobutamine, an inotrope, may be administered during echocardiography or cardiac MRI. Improved contractility in response to low-dose dobutamine suggests that the myocardium is still alive and capable of restored function. It has been clinically observed that targeted reperfusion of areas of hibernating myocardium can ultimately restore contractile function.

Based on these observations, researchers of the STICH trial published in 2011 hypothesized that surgical intervention to restore flow would increase survival and improve angina and left ventricular function in patients with left ventricular systolic dysfunction, as compared with guideline-directed medical therapy. In a head-to-head comparison of CABG vs. optimal medical therapy, no difference was noted between the groups at 5 years, but at 10-year follow-up, patients who had undergone CABG had slightly improved survival. A higher rate of perioperative and postoperative complications and other hazards associated with CABG were thought to account for the 5-year outcome. Some patients with severe left ventricular systolic dysfunction experienced recovery of ejection fraction after CABG, further supporting the reversibility of hibernating myocardium and suggesting that revascularization may be able to reverse dysfunction.

In the recently published REVIVED-BCSI2 study, investigators hypothesized that PCI, like CABG, could improve survival in patients with extensive coronary artery disease and severe ischemic left ventricular dysfunction (left ventricular ejection fraction [LVEF] <35%) without the early hazards associated with CABG. Patients (mean age, 70 years) with severe ischemic left ventricular systolic dysfunction were randomized to receive PCI plus optimal medical therapy or optimal medical therapy alone. No significant difference in survival was found between the two groups after a median follow-up of 3.4 years. These results are similar to the 5-year follow up results in the STICH trial.

Although currently there does not seem to be an immediate benefit to PCI for patients with severe ischemic left ventricular systolic dysfunction, it remains to be seen whether differences between the groups emerge after longer-term follow up.

The following NEJM Journal Watch summary provides more details of the study.


No Survival Benefit of Percutaneous Revascularization for Ischemic LV Dysfunction

Fatima Rodriguez, MD, MPH, FACC, FAHA, reviewing Perera D et al. N Engl J Med 2022 Aug 27

Questions remain about optimal management for patients with coronary artery disease (CAD) and severe, ischemic left ventricular (LV) systolic dysfunction, who were excluded from the ISCHEMIA trial (NEJM JW Cardiol May 2020 and N Engl J Med 2020; 382:1395). In the REVIVED-BCIS2 trial (NCT01920048. opens in new tab), conducted at 40 U.K. centers, investigators randomized 700 patients (mean age, 70 years; 88% male; 91% white) with LV ejection fractions (LVEFs) ≤35%, extensive CAD, and demonstrable viability (without acute myocardial infarction in the prior 4 weeks) to receive percutaneous coronary intervention (PCI) plus optimal medical therapy or medical therapy alone. PCI required attempt of revascularization of all diseased proximal coronary vessels subtending areas of viable myocardium.

Incidence of the primary endpoint — death from any cause or hospitalization for heart failure — was similar in the PCI and medical-therapy-alone groups (37.2% and 38.0%, respectively; hazard ratio, 0.99) at a median follow-up of 3.4 years. The two groups also were similar in incidences of each primary-endpoint component and in LVEF measures at 6 and 12 months. An early quality-of-life advantage in the PCI group diminished by 2 years.

Comment: These surprising findings suggest that in patients with severe, ischemic LV systolic dysfunction, PCI has no added survival benefit over medical therapy alone during intermediate-term follow-up. The early observed quality-of-life advantage of PCI may be limited by the open-label study design. The biggest takeaway is that optimal medical therapy works in this patient population. Instead of rushing to the catheterization lab, clinicians should ensure that patients with ischemic cardiomyopathy are receiving appropriate treatment from the growing list of guideline-recommended medical and device therapies.

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Mridula Nadamuni, MD, is a 2022–2023 NEJM Editorial Fellow. She completed her internal medicine/pediatrics residency and chief residency at UT Southwestern Medical Center.