Effects of Selective Autonomic Blockade on T-Wave Alternans in Humans

Abstract

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.

Acute volume overload elevates T-wave alternans magnitude

“…Studies in dogs and humans show that ␤-blockers suppress TWA, suggesting an etiological role for the sympathetic nervous system (3,10,11,20), although, conversely, isoproterenol may not consistently elevate TWA during constant pacing (8). Compared with baseline in our study, dogs at peak infusion exhibited sinus tachycardia, reduced total spectral power of HRV that, over 10 min, is analogous to SD of normal R-wave-to-R-wave interval and primarily reflects VLF power and nonsignificant trends for an elevated ratio of LF to HF frequency power.…”

Effects of Acute Mental Stress and Exercise on T-Wave Alternans in Patients With Implantable Cardioverter Defibrillators and Controls

“…Anger and emotional distress may precede arrhythmic episodes in a substantial number of individuals, 16,17,34,35 and controlled laboratory stress tasks can be used to assess susceptibility to electrophysiological markers of arrhythmic vulnerability. TWA is predictive of future arrhythmic events.…”

“…Adrenergic and autonomic nervous system pathways are involved in exercise-induced 33,34 and mental stress-induced 21 TWA. Patients tested while using ␤-blockade (nϭ13) had similar TWA responses to mental stress as patients tested without ␤-blockade but displayed attenuated TWA levels during rest (Pϭ0.03) and exercise (Pϭ0.02).…”

Ambulatory ECG-Based T-Wave Alternans and Heart Rate Turbulence Predict High Risk of Arrhythmic Events in Patients With Old Myocardial Infarction

“…18 Various studies have examined the influence of basal autonomic activity on TWA. Although those studies indicated that using β-blockers and amiodarone decreases the magnitude of TWA, as well as the parameters of HRT, [22][23][24][25][26] their use did not interfere with the ability of TWA to assess the risk for arrhythmic events. 21 Similarly, this finding may also be confirmed in our study.…”