Pathophysiology and Risk Stratification of Sudden Cardiac Death in Ischemic Heart Disease

Sudden cardiac death accounts for approximately 360,000 annually in the United States and is the cause of half of all cardiovascular deaths. Ischemic heart disease is the major cause of death in the general adult population. Sudden cardiac death can be due to arrhythmic or non-arrhythmic cardiac causes, for example, myocardial rupture. Arrhythmic sudden cardiac death may be caused by ventricular tachyarrhythmia (ventricular tachycardia/ventricular fibrillation) or pulseless electrical activity/asystole. The majority of research in risk stratification centers on ventricular tachyarrhythmias simply because of the availability of a successful management strategy, the implantable cardioverter/ defibrillator. Currently the main criterion of primary defibrillator prophylaxis is the presence of organic heart disease and depressed left ventricular systolic function assessed as left ventricular ejection fraction. However, only one third of eligible patients benefit from the implantable defibrillator, resulting in significant redundancy in the use of the device. The cost to the health care system of sustaining this approach is substantial. Further, the current low implantation rate among eligible population probably reflects a perceived low benefit-to-cost ratio of the device. Therefore, attempts to optimize the selection process for primary implantable defibrillator prophylaxis are paramount. The present report will review the most recent pathophysiology and risk stratification strategies for sudden cardiac death beyond the single criterion of depressed ejection fraction. Emphasis will be placed on electrophysiological surrogates of conduction disorder, dispersion of repolarization, and autonomic imbalance, which represent our current understanding of the electrophysiological mechanisms that underlie the initiation of ventricular tachyarrhythmias. Further, factors that modify arrhythmic death, including noninvasive risk variables, biomarkers, and genomics will be addressed. These factors may have great utility in predicting sudden cardiac arrhythmic death in the general public.