A Double-Edged Sword

Ischemic heart disease remains a leading cause of morbidity and mortality. The survival after acute ischemic events has improved substantially in recent years, but new syndromes have emerged. Cardiac remodeling following a large myocardial infarction, with dilatation of the left ventricle, has deleterious hemodynamic consequences and is a major cause of chronic heart failure.1 The increased incidence of potentially lethal arrhythmias2 is related to the presence of scar tissue but also to altered properties of the surviving myocardium, as characterized in experimental studies. Myocytes in the remote myocardium are hypertrophied, and the contraction of isolated cells is reduced.3–5 This is related to a reduction in Ca transient amplitude and slower Ca removal. The changes in electrogenic Ca transport via the Na/Ca exchanger also contribute to the electrical remodeling. Indeed, the action potential profile is altered and its duration is increased because of reduced density of K currents and the changes in Ca -dependent ionic currents, and these changes are variable throughout the remaining myocardium.5–8 This remodeling process results in an increased susceptibility for arrhythmias with the myocardium as the substrate on which specific events trigger arrhythmias.2 In contrast to the extensive characterization of cellular remodeling following myocardial infarction, much less information is available on the changes in hibernating myocardium, ie, myocardium with reduced baseline blood flow and contractile dysfunction, which retains viability and recovers on revascularization.9 (This is the classical definition of hibernation,10 but others have viewed hibernation as a manifestation of repetitive stunning.11) Nevertheless, the importance of this syndrome for clinical management is increasingly recognized,12,13 more specifically the need for its diagnostic recognition and therapy by timely revascularization. This is supported by the recent meta-analysis in patients with chronic coronary artery disease and left ventricular dysfunction: in patients with evidence of myocardial viability, revascularization decreased mortality (relative to medical therapy) from 16% to 3.2% during a 25 10 month follow-up interval, whereas in patients without viability, mortality was intermediate, and neither revascularization nor medical therapy was superior in terms of mortality (7.7% versus 6.2%).14 Excess death in the population with hibernating myocardium is, to a large extent, sudden presumed arrhythmic death.15 This is also underscored by the results of the Multicenter Automatic Defibrillator Implantation Trial II demonstrating the increased survival with implantation of an automatic defibrillator in patients with ischemic cardiomyopathy16 and by similar data from the Sudden Cardiac Death in Heart Failure Trial study recently reported at the meeting of the American College of Cardiology (available at www.acc.org). The mechanisms underlying hibernation have been studied in animal models, but so far, the presence of arrhythmias has not received much attention. In this issue of Circulation Research Canty et al report on the increased incidence and characteristics of sudden cardiac death (SCD) in a retrospective analysis of their established model of repetitive stunning and hibernation in pigs.Although primarily descriptive, the study offers a first glimpse into mechanisms of arrhythmias, (ie, the substrate and potential triggers; Figure).