Autonomic Modulation in Patients with Heart Failure Increases Beat-to-Beat Variability of Ventricular Action Potential Duration

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.

The Benefit of Prophylactic Implantable Cardioverter Defibrillator Implantation in Asymptomatic Heart Failure Patients With a Reduced Ejection Fraction

“…It can be hypothesized that patients who are without limitation of physical activity (i.e., NYHA class I) are physically more active, thereby exposing themselves to a greater risk of exercisedinduced VTA. 19,20 Our findings are in line with a subanalysis of the DANISH Trial indicating that younger patients and patients with a lower NT-proBNP have an increased benefit of ICD implantation, 14 further supporting the hypothesis of a higher risk of exercised-induced VTA in younger and more active patients. An alternative Unadjustedvalues for time to ADT between NYHA-I and NYHA-II-III patients: HR 1.6, 95% CI 1.14 to 2.49, p = 0.009.…”

Response of Ventricular Repolarization to Simulated Microgravity Measured by Periodic Repolarization Dynamics Using Phase-Rectified Signal Averaging

“…This is in agreement with previous studies showing that low-frequency oscillations of ventricular repolarization duration are magnified following sympathetic provocation [12,13]. Potential mechanisms underlying such oscillations have been postulated [12,13]. At each phase, i.e.…”

Microgravity Exposure Alters Sympathetic Modulation of Ventricular Repolarization Quantified From the ECG via Periodic Repolarization Dynamics

“…The observed increases in PRD associated with TTT, particularly during the first part of this test, are in line with the fact that PRD is enhanced in response to sympathetic stimulus [3]. An increase in low-frequency oscillations of ventricular repolarization duration has additionally been shown to occur in response to sympathetic activation and mechanisms underlying such oscillations have been postulated, all of which would serve to support the results found in this study [9,10].…”