We review the contemporary understanding of the pathophysiology of repolarization alternans and present a perspective on the use of T-wave alternans (TWA) as a risk stratification marker of malignant ventricular arrhythmias. Several studies have demonstrated a high correlation of susceptibility to ventricular arrhythmias and sudden cardiac death with the existence of TWA. We describe a number of cellular and molecular alterations in the diseased heart that may provide a link between electrical and mechanical alternans and arrhythmia susceptibility. Repolarization alternans is likely the result of distinct and diverse cellular and molecular alterations that are associated with exaggerated regional repolarization heterogeneity, which renders the heart susceptible to malignant arrhythmias.
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