REPOLARIZATION ABNORMALITIES, ARRHYTHMIA AND SUDDEN-DEATH IN CANINE TACHYCARDIA-INDUCED CARDIOMYOPATHY

Objectives. This study sought to determine whether the canine model of tachycardia-induced heart failure (HF) is an effective model for sudd en cardiac death (SCD) in HF. Background. Such a well established HF m odel that also exhibits arrhythmias and SCD, along with repolarization abnormalities that could trigger them, may facilitate the study of SC D in HF, which still eludes effective treatment. Methods. Twenty-five dogs were VVI-paced at 250 beats/min for 3 to 5 weeks. Electrocardiogr ams were obtained, and left ventricular endocardial monophasic action potentials (MAPs) were recorded at six sites at baseline and after HF. Weekly Holter recordings were made with pacing suspended for 24 h. Re sults. Six animals (24%) died suddenly, one with Holter-documented pol ymorphic ventricular tachycardia (VT). Holter recordings revealed an i ncreased incidence of VT as HF progressed. Repolarization was signific antly (p < 0.05) prolonged, as indexed by a corrected QT interval (mea n [+/-SD] 311 +/- 25 to 338 +/- 25 ms) and MAP duration measured at 90 % repolarization (MAPD(90)) (181 +/- 19 to 209 +/- 28 ms), and spatial MAPD(90) dispersion rose by 40%. We further tested whether CsCl inhib ition of repolarizing K+ currents, which are reportedly downregulated in HF, might preferentially prolong the MAPD(90) in HF. With 1 mEq/kg body weight of CsCl, MAPD(90) rose by 86 +/- 100 ms in dogs with HF ve rsus only 28 +/- 16 ms in control animals (p = 0.002). Similar dispari ties in CsCl sensitivity were observed in myocytes isolated from norma l and failing hearts. Conclusions. Tachycardia-induced HF exhibits mal ignant arrhythmia and SCD, along with prolonged, heterogeneous repolar ization and heightened sensitivity to CsCl at chamber and cellular lev els. Thus, it appears to be a useful model for studying mechanisms and therapy of SCD in HF. (C) 1997 by the American College of Cardiology.