Abstract
Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined.Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation–recovery intervals (ARI, surrogate for APD) recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge (Valsalva) and baroreceptor indices were applied to determine changes in sympathetic stimulation. Two Valsalvas were performed for each study and were repeated, both off and on bisoprolol. In addition sympathetic nerve activity (SNA) was measured from skin electrodes on the thorax using a novel validated method. Autonomic modulation significantly increased mean short-term variability in ARI; off bisoprolol mean STV increased from 3.73 ± 1.3 to 5.27 ± 1.04 ms (p = 0.01), on bisoprolol mean STV of ARI increased from 4.15 ± 1.14 to 4.62 ± 1 ms (p = 0.14). Adrenergic indices of the Valsalva demonstrated significantly reduced beta-adrenergic function when on bisoprolol (Δ pressure recovery time, p = 0.04; Δ systolic overshoot in Phase IV, p = 0.05). Corresponding increases in SNA from rest both off (1.4 uV, p < 0.01) and on (0.7 uV, p < 0.01) bisoprolol were also seen.Conclusions: Beat-to-beat variability of ventricular APD increases during brief periods of increased sympathetic activity in patients with heart failure. Bisoprolol reduces, but does not eliminate, these effects. This may be important in the genesis of ventricular arrhythmias in heart failure patients.
Highlights
Exaggerated beat-to-beat variability of repolarization (BVR) is strongly associated with pro-arrhythmia and is modulated by sympathetic activity (Shen and Zipes, 2014; Baumert et al, 2016)
We have previously reported the measurement of local ventricular action potential duration (APD) in patients with heart failure undergoing resynchronization therapy with bi-ventricular pacing (Chen et al, 2013)
Analysis of indices of sympathetic function demonstrated a mean overshoot in phase IV from baseline of 13.2 ± 11.1 mmHg and mean Pressure recovery time (PRT) of 5.26 ± 4.08 s
Summary
Exaggerated beat-to-beat variability of repolarization (BVR) is strongly associated with pro-arrhythmia and is modulated by sympathetic activity (Shen and Zipes, 2014; Baumert et al, 2016). A growing body of experimental and computational work is providing insight into the potential mechanisms underlying BVR and the modulatory role of sympathetic stimulation at the level of the ventricular action potential duration (APD) (Heijman et al, 2013; Johnson et al, 2013; Pueyo et al, 2016). While QT measurements have provided a great deal of valuable information, direct extrapolation to APD is not possible from these global recordings. Such measurements are usually made with uncontrolled cycle length which complicates interpretation in view of the strong cycle length dependence of APD (Boyett and Jewell, 1978). Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined
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