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Accelerated sinus rhythm prevents catecholaminergic polymorphic ventricular tachycardia in mice and in patients

Michela Faggioni1, Hyun Seok Hwang, Christian van der Werf

  • 1Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0575, USA.

Circulation Research
|January 9, 2013
PubMed
Abstract

Insights

Supraventricular overdrive stimulation, like atrial pacing, can suppress ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia (CPVT) mouse models. This approach also showed promise in a subset of human CPVT patients, suggesting a potential therapy for exercise-induced ventricular tachycardia.

Area of Science:

  • Cardiology
  • Genetics
  • Electrophysiology

Background:

  • Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder linked to mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes.
  • Sinoatrial node dysfunction in CPVT patients may elevate the risk of ventricular arrhythmias (VA).
  • Understanding the relationship between heart rate and VA is crucial for managing CPVT.

Purpose of the Study:

  • To investigate whether supraventricular overdrive stimulation can suppress ventricular arrhythmias in CPVT.
  • To evaluate the efficacy of increasing sinus heart rate as a potential antiarrhythmic strategy for CPVT.

Main Methods:

  • Utilized CPVT mouse models (Casq2(-/-) and RyR2(R4496C/+)) to assess the impact of atropine and atrial overdrive pacing on ventricular tachycardia.
  • Measured ventricular arrhythmias, premature beats, and spontaneous calcium waves in isolated myocytes.
  • Analyzed heart rate dependence of CPVT in drug-naïve human patients during exercise testing.

Main Results:

  • Atropine and atrial overdrive pacing significantly suppressed ventricular arrhythmias in CPVT mouse models.
  • Rapid pacing prevented triggered beats and calcium waves in isolated CPVT myocytes.
  • In humans, a subset of CPVT patients experienced paradoxical suppression of VA as heart rates increased during exercise.

Conclusions:

  • Accelerated supraventricular rates demonstrate a suppressive effect on ventricular arrhythmias in CPVT mouse models.
  • Findings suggest that atrial overdrive pacing could be a therapeutic strategy for exercise-induced ventricular tachycardia in refractory CPVT patients.
  • Heart rate modulation represents a promising avenue for managing CPVT.

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