Influence of heart rate and sympathetic stimulation on arrhythmogenic T wave alternans

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Abstract
We determined the temporal stability of T wave alternans (TWA) during constant rate stimulation and the dependence of alternans on heart rate (HR) and β-adrenergic stimulation. Although it is established that exercise can provoke microvolt-level TWA in patients at risk for reentrant ventricular arrhythmias, the mechanisms underlying TWA in humans are not well understood. Specifically, the temporal stability of alternans at any given HR and the influence of HR vs. sympathetic activation on alternans remain unclear. TWA was measured during prolonged fixed-rate atrial pacing at multiple cycle lengths (CLs) in 10 subjects referred for electrophysiological testing and in 14 additional subjects in whom atrial pacing was performed at identical pacing CLs with and without isoproterenol. During constant CL stimulation, TWA amplitude oscillated significantly over time (typically by 10 μV) in a quasiperiodic fashion with periodicity of ∼2–3 min. Alternans amplitude was strongly dependent on HR but not on adrenergic stimulation. There was a patient-specific threshold HR over which alternans appeared. At higher HR, alternans amplitude increased and oscillations were less prominent. Adrenergic stimulation was required to produce TWA that was not already elicited by moderate elevation of HR in only 2 of 14 (14%) patients. In conclusion, TWA 1) fluctuates spontaneously over 2–3 min and 2) increases monotonically with increased HR (without a major adrenergic contribution in most patients). These data suggest that increased HR rather than sympathetic activation is responsible for arrhythmogenic microvolt-level TWA measured during exercise.