Repolarization abnormalities in heart failure.

See article by Lacroix et al. [1] (pages 42 –50) in this et al. deals with both a triggering mechanism and a issue. substrate of arrhythmogenesis in heart failure: The hypothThe paper by Lacroix et al., published in this issue of eses that inspired the investigation are that (1) the Cardiovascular Research, is of interest because it deals prolongation of the action potential duration known to with the question of mechanisms underlying sudden arexist in heart failure may trigger action potentials caused rhythmic death in patients with heart failure [1]. This is a by early after depolarizations and (2) that the substrate for problem of great clinical significance, because increasing arrhythmogenesis is formed by heterogeneity in ventricular numbers of patients are suffering from heart failure and are refractoriness. The latter hypothesis is based on the idea at risk of sudden cardiac death [2], especially at moderate that heterogeneities in repolarization may cause unidirecdegrees of failure [3]. tional block, which is a pre-requisite for the initiation of a Heart failure is extremely difficult to study experimenre-entrant arrhyhtmia [10,11]. Factors favouring continuatally, not only because it is difficult to define [4], but also tion of a re-entrant arrhythmia are slow conduction and/or because a single suitable experimental model is not a short refractory period [10]. available. Several models relevant for the study of arLacroix et al. present a model of heart failure in a large rhythmogenesis in heart failure exist [5–8], but since heart mammal, the pig, where heart failure was induced by rapid failure in man results from a plethora of conditions, none pacing and which fulfils the criterion of a high loss of of these models can withstand criticism regarding its animals resulting from sudden death. They are to be clinical significance. In addition, the development of praised for the comprehensive integrative approach of the experimental models is costly as it involves the study of hypotheses, with data on ion-channel function, epicardial animals over prolonged periods of time. Another comstrips of muscle, isolated perfused hearts, as well as on in plicating factor is that, if the model is truly representative, vivo telemetric ECG recordings in the awake animals, and a high percentage of the animals will die suddenly before hemodynamic and echocardiographic documentation of they can be studied. heart failure. In the majority of cases, sudden death in heart failure is For the main results of the study, the reader is referred caused by sustained ventricular tachyarrhythmias [9]. For to the paper itself, but some of the results presented by the study of arrhythmogenic mechanisms, one should Lacroix et al. warrant comment because they may have led discriminate between the mechanism underlying the initiatto underestimation of the effect of heart failure or deserve ing beat (the ‘trigger’) and that of the continuation of the emphasis. One is the appropriateness of Bazett’s formula. arrhythmia (‘the continuator’). Favourable pre-existing With an absence of a significant difference in QT-interval, conditions (‘the substrate’) may facilitate the onset and the authors have used Bazett correction of the QT-interval. maintenance of the arrhythmia. These three mechanisms It would probably have been sufficient to point out that the may be altered by various modulating factors (e.g. circulatsame QT-interval in the heart failure group occurred at a ing catecholamines, anti-arrhythmic drugs). The presence much (110 ms) shorter cycle length. Bazett’s correction is of a single of these four mechanisms is not sufficient for a way to normalize QT-intervals to a cycle length of 1000 the onset of a sustained arrhythmia. The paper of Lacroix ms in man. It assumes a restitution curve given by a simple formula. It is known, however, that the restitution curve is altered in heart failure [8], and the use of the same *Tel.: 131-20-566-3267. E-mail address: [email protected] (R. Coronel). correction in the control animals and the failing animals (or