From bench to imagingHibernating myocardium
Introduction
Regions of hibernating myocardium are common in patients with ischemic cardiomyopathy and have a negative impact on survival rates in the absence of coronary revascularization. With the strictest definition, originally based on nuclear imaging, hibernating myocardium referred to viable regions with depressed resting flow and reduced resting function that needed to be distinguished from infarction, because functional improvement could occur after coronary revascularization. Several chronic animal models are now available that reproduce the clinical features of hibernating myocardium in the absence of infarction. These models have clarified the temporal progression from chronic stunning to hibernating myocardium as well as the relationship of these entities to the physiologic significance of a coronary stenosis. This review will primarily focus on new developments advancing the basic mechanistic understanding of the physiologic and cellular remodeling that arises from chronic repetitive myocardial ischemia. It will also highlight new mechanisms that may be responsible for the negative impact of hibernating myocardium on survival rates and the possibility that this may be related to sudden death rather than progressive left ventricular (LV) dysfunction. A historical perspective of our understanding of hibernating myocardium from basic and clinical experimental studies can be found in previous reviews.1, 2, 3, 4, 5
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Hibernating myocardium versus viable dysfunctional myocardium
The original concept of hibernating myocardium proposed that a reduction in flow was the initiating event or cause of the subsequent adaptive response to ischemia.6, 7 Early experimental studies supported this concept and confirmed that moderate levels of ischemia could be maintained over a period of hours without the development of infarction, a phenomenon that has become known as short-term hibernation and has been reviewed elsewhere.8 Many clinicians have been skeptical that such a tenuous
Development and stability of hibernating myocardium
It has not been feasible to ascertain the natural history of hibernating myocardium because this would require a longitudinal study of patients in the absence of therapeutic interventions. As a result, most clinical data have been derived from patients evaluated at a single point in time. This frequently occurs after the development of an acute coronary syndrome with viability studies performed to guide clinical decision making with regard to coronary revascularization. Despite the uncontrolled
Structural remodeling in hibernating myocardium: global versus regional changes
Myocardial biopsy specimens obtained from patients have demonstrated a broad spectrum of cellular changes that could contribute to the phenotype of hibernating myocardium. These have led to a controversy over whether the myocyte alterations represent an adaptive or maladaptive response. Many studies have demonstrated a myocyte cellular response suggesting a reversion to a fetal isoform pattern that would serve to protect cardiac myocytes from ischemic damage. These contrast with other studies
Contractile reserve in hibernating myocardium
It is generally accepted that in patients with ischemic heart disease, contractile reserve has a lower sensitivity to detect viable dysfunctional myocardium than nuclear imaging techniques yet higher specificity to predict functional improvement after coronary revascularization.71, 72 One possibility for these differences in sensitivity and specificity is that the contractile response may vary for the different types of viable dysfunctional myocardium outlined in Table 1. For example, studies
Viability testing and outcome: surrogate endpoints of functional recovery or survival?
Until now, most of the focus of clinical viability testing has been on prospectively predicting functional improvement after coronary revascularization. As a result, many clinical studies have enrolled high-risk patients with severely reduced LV function and heart failure. The presence of contractile reserve and the amount of viable dysfunctional myocardium are strong determinants of the amelioration of symptoms of heart failure. Nevertheless, it is not clear whether all of the survival benefit
Acknowledgment
We thank Anne Coe and Marsha Barber for their help in preparing the manuscript and figures.
The authors have indicated they have no financial conflicts of interest.
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2018, Trends in Cardiovascular MedicineCitation Excerpt :This biochemical mechanism has been supported by the finding of reduced resting myocardial blood flow in dysfunctional hibernating myocardial segments, with active glucose utilization as measured by PET with fluorine-18-2-deoxyglucose (FDG) and cardiac magnetic resonance (CMR) techniques [1,4,5]. In recent years, however, conflicting data have shown either reduced or normal resting blood flow suggesting that the pathogenesis of myocardial hibernation might be nonlinear [6–9]. Hibernating myocardium likely represents adaptation to reduced resting coronary blood flow [2,6].
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Supported by the Department of Veterans Affairs; American Heart Association; National Heart, Lung, and Blood Institute (HL-55324, HL-61610, and HL-76252); Mae Stone Goode Trust; John R. Oishei Foundation; and Albert and Elizabeth Rekate Fund.