Electrophysiologic basis for T wave alternans as an index of vulnerability to ventricular fibrillation

Substantial evidence indicates that T wave alternans is an intrinsic property of ischemic myocardium. The electrophysiologic basis appears to be spatial and temporal heterogeneity of repolarization resulting from changes in action potential morphology rather than in activation sequence. Ischemia-induced changes in postrepolarization refractoriness and depressed electrical restitution of action potential duration have also been implicated. The main underlying ionic basis for T wave alternans during coronary occlusion appears to be derangements in intracellular cycling of calcium. Accumulation of potassium in the extracellular space adjoining ischemic cells and disruption in electrogenic sodium-calcium exchange may also be involved. In humans, T wave alternans has been observed in Prinzmetal's and classical angina, angioplasty, and bypass graft occlusion. Under these conditions associated with acute myocardial ischemia, alternans is restricted to the ischemic zone, and alternation in action potential morphology is an underlying factor. Recently, repolarization alternans has been shown to be a statistically significant predictor of the results of electrophysiologic testing and arrhythmia-free survival in individuals with and without organic heart disease. Collectively, these observations provide a rationale for quantitation of T wave alternans magnitude for assessment of vulnerability to life-threatening ventricular arrhythmias both in response to and independent of the effects of myocardial ischemia.