QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients

Homogeneity of recovery time protects against arrhythmias whereas dispersion of recovery time is arrhythmogenic. A single surface electrocardiographic QT interval gives no information on recovery time dispersion but the difference between the maximum and minimum body surface QT interval may be relevant. This hypothesis was tested by measuring the dispersion of the corrected QT interval (QTc) in 10 patients with an arrhythmogenic long QT interval (Romano Ward and Jervell and Lange-Nielsen syndromes or drug arrhythmogenicity) and in 14 patients without arrhythmias in whom the QT interval was prolonged by sotalol. QTc dispersion was significantly greater in the arrhythmogenic QT group than in the sotalol QT group. In patients with prolonged QT intervals, QT dispersion distinguished between those with ventricular arrhythmias and those without. This supports the hypothesis that QT dispersion reflects spatial differences in myocardial recovery time. QT dispersion may be useful in the assessment of both arrhythmia risk and the efficacy of antiarrhythmic drugs.

QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death.

Death in chronic heart failure (CHF) can be from progression of disease or sudden and unexpected. We have attempted to identify factors that predict sudden death in CHF. We followed up 44 patients with CHF for 12-50 (mean 36) months. 4 patients died of non-cardiovascular causes and were excluded from analysis. There were 7 sudden deaths (symptoms for less than 1 h in a previously stable patient) and 12 from progressive CHF. Patients who died of progressive CHF had lower left-ventricular ejection fractions and higher concentrations of atrial natriuretic factor than the 21 survivors, but there were no differences in these variables between survivors and those who died suddenly. However, the sudden death group had significantly (p < 0.05) greater inter-lead variability in the QT interval on the electrocardiogram (QT dispersion; 98.6 [95% CI 79.1-118] ms1/2) than survivors (53.1 [41.9-64.3] ms1/2) or the group who died from progressive CHF (66.7 [51.8-81.6] ms1/2). QT dispersion is a marker of myocardial electrical instability. The association of increased QT dispersion with sudden death suggests that patients at high risk of such death could be identified by means of this simple, reproducible test. This group might benefit from more intensive treatment.