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CLINICAL RESEARCH: SAFETY ISSUE

Potential Proarrhythmic Effects of Biventricular Pacing

Jeffrey M. Fish, DVM^_*, Josep Brugada, MD and Charles Antzelevitch, PhD, FACC^_*,_*

^_* Masonic Medical Research Laboratory, Utica, New York
Thorax Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain

Manuscript received May 16, 2005; revised manuscript received July 20, 2005, accepted August 1, 2005.

^_* Reprint requests and correspondence: Dr. Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York 13501-1787. (Email: ca{at}mmrl.edu).

Resynchronization therapy involving right ventricular endocardial and left ventricular epicardial pacing improves cardiac output, quality of life, and New York Heart Association functional class in patients with congestive heart failure. Although a great deal of attention has been directed at showing the mechanical benefits and in fine-tuning the biventricular pacing configuration and protocol, little attention has been focused on the consequences of reversing the direction of activation of the left ventricular wall. Recent basic science and clinical studies have shown a proarrhythmic effect of reversing the direction of activation of the left ventricular wall. Reversal of the normal activation sequence prolongs the QT interval and increases the existing transmural dispersion of repolarization, creating the substrate and trigger for re-entrant arrhythmias under long QT conditions. A number of case reports of R-on-T extrasystoles and ventricular tachyarrhythmia induction as a result of biventricular pacing support this observation, and raise concern that biventricular pacing may be proarrhythmic in select cases, particularly when associated with a prolonged QT interval. Our focus in this review is on current understanding of transmural heterogeneity of repolarization that exists across the left ventricular wall, how this dispersion of repolarization is amplified as a consequence of reversal of the normal activation sequence, and how these basic experimental findings may apply to patients receiving cardiac resynchronization therapy.

Abbreviations and Acronyms   EAD = early afterdepolarization   ECG = electrocardiogram   LV = left ventricle/ventricular   TdP = torsades de pointes   TDR = transmural dispersion of repolarization   VT = ventricular tachycardia

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