SUMMARY To evaluate whether heart-rate-induced changes of the QT interval are dependent on autonomic tone, we studied 13 healthy subjects, mean age 67.5 years. The maximal uncorrected QT from leads I, II, V1 and V,, was determined during atrial pacing at 90 beats/min and 130 beats/min before and after i.v. administration of propranolol, 0.1 mg/kg, and atropine, 0.02 mg/kg.Significant reductions (p < 0.01) of QT were induced by the paced increases in heart rate before drugs (10%), after propranolol (10%) and after the combination of atropine and propranolol (9%). Propranolol caused no significant change in the QT interval when heart rate was held constant by pacing. In contrast, atropine produced rate-independent reductions of QT interval (5%) in subjects with ,3-adrenergic blockade (p < 0.05). Bazett's formula for heart-rate correction of the QT interval (QTc) was not applicable for atrial overdrive pacing, as it gave proportionately longer QTc values at higher heart rates.These results show that heart rate is a major determinant of the duration of the QT interval and that paced changes in heart rate induce QT-interval responses that are essentially uninfluenced by autonomic tone. The rate-independent effect of the QT interval produced by elimination of cholinergic tone suggests a direct influence of cholinergic activity on the repolarization of ventricular myocardium.INTEREST in obtaining clinical information from the QT interval of the ECG has recently increased. One reason for this is the reported association between prolonged QT intervals and serious ventricular arrhythmiasl'6 and the identification of QT prolongation as a prognostic factor for sudden death.' 7 8 Several factors influence the QT interval, including electrolyte disturbances" and drugs.9""' The effect of sympathetic nervous activity on the QT interval is well established.'2-'5 In addition, the autonomic nervous system affects the ventricular fibrillation threshold.'6, 17 Although cholinergic activity has been found to enhance ventricular electrical stability in dog experiments and the presence of cholinergic nerve fiber supplying the ventricular conducting system has been demonstrated in man,'8 an effect of cholinergic activity on the QT interval has not been reported before.Heart rate is a major determinant of the duration of the QT interval and this relation has been studied by many workers.9' [19][20][21][22] In those studies, data were collected and the QT interval was measured at the spontaneous heart rate of each subject. Consequently, the data probably include individual differences both in intrinsic properties of the ventricular myocardium and in the autonomic balance at the time of measurement and thus do not clarify whether QT is strictly ratedependent or whether it is also directly influenced by autonomic tone.We undertook the present study to determine the variation of the QT interval in the same subjects (1) spontaneous and atrially paced heart rates; (2) before and after inhibition of autonomic activity by propranolol and atropi...

SUMMARY To assess the influence of diurnal changes in the autonomic nervous system on the QT interval, 24 hour dynamic electrocardiographic monitoring was performed in six-pacemaker dependent patients with normally innervated hearts, in six cardiac transplant patients with anatomically denervated hearts (but which respond to circulating catecholamines), and in nine diabetic patients with confirmed autonomic neuropathy. QT and RR intervals from hourly intervals were measured and Bazett's formula was used to correct QT intervals during sinus rhythm. All

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443 +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74 vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24 +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs 40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.

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