Background-T-wave alternans (TWA) is an important noninvasive measure of ventricular arrhythmia vulnerability. This study tested the hypothesis that the autonomic nervous system influences TWA measurement in high-risk subjects with coronary artery disease. Methods and Results-T-wave alternans was measured in 60 patients with coronary artery disease, left ventricular dysfunction, and inducible sustained ventricular tachycardia during electrophysiological studies. All patients had TWA measured at baseline with atrial pacing at 100 bpm (600 ms), 109 bpm (550 ms), and 120 bpm (500 ms). After a 10-minute recovery period, TWA was measured again after sympathetic blockade (esmolol, nϭ20), parasympathetic blockade (atropine, nϭ20), or no intervention (control subjects, nϭ20). The prevalence of significant TWA was unchanged compared with baseline after atropine infusion and in the control group. In contrast, the amplitude of TWA in the vector magnitude lead was significantly reduced after esmolol infusion (PϽ0.001), and the number of positive TWA tests was reduced by 50% (70% versus 35%, PϽ0.05). Conclusions-Our findings have important implications for the use of TWA to risk-stratify patients for life-threatening ventricular arrhythmias and provide a new potential mechanism for the reduction in sudden cardiac death conferred by ␤-blockers among patients with coronary artery disease and congestive heart failure.

The combined use of TWA, LVEF, and PVS is a promising new approach to arrhythmia risk stratification that permits identification of high-risk and very-low-risk patients.

TWA should be measured during exercise when it is used for clinical risk stratification. EPS results may not be an adequate surrogate for spontaneous events when evaluating new risk stratification tests.

TWA is useful only for risk stratification in the absence of QRS prolongation. The presence of QRS prolongation and left ventricular ejection fraction < or = 40% may be sufficient evidence of an adverse prognosis that additional risk stratification is not useful or necessary.

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