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CLINICAL RESEARCH: HEART RHYTHM DISORDER

Efficacy of Antiarrhythmic Drugs in Arrhythmogenic Right Ventricular Cardiomyopathy

A Report From the North American ARVC Registry

Gregory M. Marcus, MD^_*,_*, David V. Glidden, PhD, Bronislava Polonsky, MS, Wojciech Zareba, MD, PhD, Lisa M. Smith, MPH^_*, David S. Cannom, MD, N.A. Mark Estes, III, MD^||, Frank Marcus, MD^¶, Melvin M. Scheinman, MD^_* for the Multidisciplinary Study of Right Ventricular Dysplasia Investigators

^_* Division of Cardiology, Electrophysiology Section, University of California, San Francisco, California
Department of Epidemiology and Biostatistics, University of California, San Francisco, California
Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester, New York
Good Samaritan Hospital, Los Angeles, California
^|| Tufts University School of Medicine, Boston, Massachusetts
^¶ Sarver Heart Center, University of Arizona College of Medicine, Tucson, Arizona

Manuscript received February 23, 2009; revised manuscript received March 16, 2009, accepted April 3, 2009.

^_* Reprint requests and correspondence: Dr. Gregory M. Marcus, 500 Parnassus Avenue, MUE 434, San Francisco, California 94143-1354 (Email: marcusg{at}medicine.ucsf.edu).

Objectives: This study sought to examine the efficacy of empiric antiarrhythmic drugs in a rigorously characterized cohort of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.

Background: Antiarrhythmic drugs are important in protecting against ventricular arrhythmias in ARVC, but no studies have provided data in a group rigorously screened for the disease.

Methods: Antiarrhythmic medicines were examined in all subjects with implantable cardioverter-defibrillators (ICDs) enrolled in the North American ARVC Registry. A Cox proportional hazards model was used to account for time on each drug, and a hierarchical analysis was performed for repeated measures within individuals.

Results: Ninety-five patients were studied, with a mean follow-up of 480 ± 389 days. Fifty-eight (61%) received beta-blockers, and these medicines were not associated with an increased or decreased risk of ventricular arrhythmias. Sotalol was associated with a greater risk of any clinically relevant ventricular arrhythmia as defined by sustained ventricular tachycardia or ICD therapy (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.02 to 6.39, p = 0.045), but this was not statistically significant after adjusting for potential confounders. An increased risk of any ICD shock and first clinically relevant ventricular arrhythmia while on sotalol remained significant after multivariable adjustment. Those on amiodarone (n = 10) had a significantly lower risk of any clinically relevant ventricular arrhythmia (HR: 0.25, 95% CI: 0.07 to 0.95, p = 0.041), a finding that remained significant after multivariable adjustment.

Conclusions: In a cohort of well-characterized ARVC subjects, neither beta-blockers nor sotalol seemed to be protective. Evidence from a small number of patients suggests that amiodarone has superior efficacy in preventing ventricular arrhythmias.

Key Words: ARVC • ARVD • antiarrhythmic drugs • ventricular arrhythmias • ICD

Abbreviations and Acronyms   ARVC = arrhythmogenic right ventricular cardiomyopathy   CI = confidence interval   HR = hazard ratio   ICD = implantable cardioverter-defibrillator   IQR = interquartile range   VF = ventricular fibrillation   VT = ventricular tachycardia

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