Spontaneous sequences of onset of torsade de pointes in patients with acquired prolonged repolarization: quantitative analysis of Holter recordings

Istituto Clinica Medica Generale e Terapia Medica, University of Milan, Italy.

OBJECTIVES. This study investigated the cycle length changes preceding the spontaneous onset of torsade de pointes in patients with acquired prolonged ventricular repolarization. BACKGROUND. Torsade de pointes is a polymorphic ventricular tachycardia generally associated with prolonged ventricular repolarization. Because torsade de pointes is not inducible by programmed electrical stimulation, quantitative analysis of Holter recordings of spontaneous episodes may clarify the mechanisms favoring the onset of torsade de pointes in actual clinical conditions. METHODS. The digitized Holter recordings of 12 patients were analyzed by a computerized Holter system (ATREC). All arrhythmias were grouped according to three classes: 1) isolated premature ventricular beats (n = 47,147, mean/patient [+/- SD] 3,929 +/- 11,571); 2) salvos of 2 to 4 consecutive beats (n = 2,003, mean/patient 167 +/- 359); 3) torsade de pointes > or = 5 beats (n = 105, mean/patient 9 +/- 11). For each patient and class of arrhythmias, six variables were computed from the 10 min and the 10 cycles preceding the event onset. RESULTS. A significant heart rate increase in the last minute (p < 0.01) and typical oscillatory short-long-short cycle length sequences preceded the onset of arrhythmias, with greater oscillation preceding torsade de pointes than salvos and premature ventricular beats. The cycle lengths preceding the onset were highly correlated with the class of arrhythmias (r = 0.65, p < 0.005) and allowed the correct classification of 69% of events by discriminant analysis (p < 0.0001). A significant negative correlation was observed between the duration of torsade de pointes and the mean length of the initial cycles (r = -0.62, p < 0.001), indicating that longer torsade de pointes had a faster rate than that at onset. CONCLUSIONS. In patients with acquired prolonged repolarization, the spontaneous onset of ventricular arrhythmias was preceded by an increasing heart rate in the last minute and escalating oscillatory "short-long-short" cycle length patterns, with greater oscillations preceding torsade de pointes than salvos and isolated ventricular beats. These findings suggest that adrenergic- and pause-dependent mechanisms (possibly inducing afterdepolarizations and triggered activity) may have a synergetic role in the genesis of complex ventricular arrhythmias associated with delayed ventricular repolarization.

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