Atropine-induced sinus tachycardia protects against exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia

Abstract

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by exercise-induced ventricular arrhythmias, sudden death, and sinus bradycardia. Elevating supraventricular rates with pacing or atropine protects against catecholaminergic ventricular arrhythmias in a CPVT mouse model. We tested the hypothesis that increasing sinus heart rate (HR) with atropine prevents exercise-induced ventricular arrhythmias in CPVT patients.

Methods and results: We performed a prospective open-label trial of atropine prior to exercise in CPVT patients (clinicaltrials.gov NCT02927223). Subjects performed a baseline standard Bruce treadmill test on their usual medical regimen. After a 2-h recovery period, subjects performed a second exercise test after parasympathetic block with atropine (0.04 mg/kg intravenous). The primary outcome measure was the total number of ventricular ectopic beats during exercise. All six subjects (5 men, 22-57 years old) completed the study with no adverse events. Atropine increased resting sinus rate from median 52 b.p.m. (range 52-64) to 98 b.p.m. (84-119), P = 0.02. Peak HRs (149 b.p.m., range 136-181 vs. 149 b.p.m., range 127-182, P = 0.46) and exercise duration (612 s, range 544-733 vs. 584 s, range 543-742, P = 0.22) were not statistically different. All subjects had ventricular ectopy during the baseline exercise test. Atropine pre-treatment significantly decreased the median number of ventricular ectopic beats from 46 (6-192) to 0 (0-29), P = 0.026; ventricular ectopy was completely eliminated in 4/6 subjects.

Conclusion: Elevating sinus rates with atropine reduces or eliminates exercise-induced ventricular ectopy in patients with CPVT. Increasing supraventricular rates may represent a novel therapeutic strategy in CPVT.

Keywords: Arrhythmia; Atropine; Catecholaminergic polymorphic ventricular tachycardia; Heart rate; Treatment.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Flow diagram of study procedures. CPVT, catecholaminergic polymorphic ventricular tachycardia.

Figure 2

Heart rate (blue lines, left Y-axis) and ventricular ectopy (red lines, right Y-axis) are plotted against exercise time (in seconds on X-axis) throughout the baseline and atropine exercise tests in six CPVT subjects. All had ventricular ectopy during the baseline test which was eliminated (4) or reduced (2) when pre-treated with atropine to raise the sinus heart rate. Examples of ECG tracings from subject 1 (2 min into Stage 3) are shown in the bottom right. At baseline, there are couplets and non-sustained VT, after atropine only sinus rhythm. CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram.