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Electrophysiological mechanism of enhanced susceptibility of hypertrophied heart to acquired torsade de pointes arrhythmias: tridimensional mapping of activation and recovery patterns

, : Electrophysiological mechanism of enhanced susceptibility of hypertrophied heart to acquired torsade de pointes arrhythmias: tridimensional mapping of activation and recovery patterns. Circulation 105(9): 1128-1134

Background-Cardiac hypertrophy is associated with increased incidence of sudden death and susceptibility to proarrhythmic effects of antiarrhythmic agents. However, the in vivo electrophysiologic mechanism of the arrhythmias has not been investigated in detail. Methods and Results-Dose-dependent susceptibility to Torsade de Pointes (TdP) by class III drug dofetilide, 3, 10, and 30 mug/kg, was compared in 6 control dogs (C) and in 5 dogs 6 to 8 weeks after induction of complete atrioventricular block (AVB) that resulted in ventricular hypertrophy (H). Tridimensional ventricular activation and repolarization (R) patterns were simultaneously analyzed from unipolar extracellular electrograms, and local R was measured from activation recovery intervals. Both R and transmural dispersion of R (TDR) were significantly greater in dogs with H compared with C. Dofetilide resulted in cycle length-dependent and dose-dependent prolongation of R, which was more marked in left ventricular endocardium/midmyocardium compared with epicardium, resulting in significant increase of TDR. These changes were more accentuated in dogs with H compared with C. All 5 dogs with H developed TdP at a dose of 3 to 10 mug/kg, whereas only 1 of 6 C dogs developed TdP at 30 mug/kg. TdP was initiated by subendocardial focal activity that infringed on TDR, resulting in functional conduction block and reentrant excitation. Conclusions-Enhanced susceptibility of hypertrophied heart to class III drugs is attributable to baseline increased TDR and greater dose-related accentuation of TDR compared with nonhypertrophied heart. This provides the electrophysiologic substrate for drug-induced TdP.


PMID: 11877367

DOI: 10.1161/hc0902.104711

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