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Background The present study was undertaken to test the hypothesis that women are more prone than men to develop torsade de pointes (TdP) in a defined cohort of patients exposed to the QT-prolonging antiarrhythmic drug d,l -sotalol. Methods and Results In a database derived from 22 clinical trials involving 3135 adult patients who received oral d,l -sotalol (median follow-up, 164 days), TdP developed in 44 (1.9%) of 2336 men and in 33 (4.1%) of 799 women ( P P P P d,l -sotalol dose >320 mg/d ( P 1.4 mg/dL in women and >1.6 mg/dL in men was weakly predictive ( P Conclusions Women are at increased risk of developing TdP during administration of d,l -sotalol. This finding needs to be taken into account, together with other TdP risk factors, when patients are treated with this antiarrhythmic agent. Given the consistency between the present and other recent observations, greater caution in women regarding use of QT-prolonging drugs, in general, is advisable.

The Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure was designed to determine whether vasodilator drugs could alter the survival of patients with chronic congestive heart failure treated with digoxin and diuretics. Among the 642 patients entered into the study, 273 were randomly assigned to placebo, 186 were randomly assigned to the combination of hydralazine and isosorbide dinitrate, and 183 patients were randomly assigned to prazosin; all patients were followed for periods ranging from 6 months to 5.7 years. Treatment with hydralazine-nitrate produced a 28% reduction in mortality compared with that in patients receiving placebo (95% confidence interval, 3% to 46%), whereas prazosin exerted no apparent beneficial effect. Data were further examined to determine if any baseline variables had an impact on the response to treatment. Mortality in the placebo group was higher in those with coronary artery disease, with a history of antiarrhythmic drug use, and with values lower than the median for ejection fraction and exercise tolerance. A reduction in mortality with hydralazine-isosorbide dinitrate was observed in all of the above pairs of subgroups as well as in those above and below 60 years of age and those with and without a history of hypertension or excess alcohol ingestion. The benefit of hydralazine and isosorbide dinitrate was particularly prominent in younger patients with a lower ejection fraction and those with a history of hypertension and without an alcoholic history.(ABSTRACT TRUNCATED AT 250 WORDS)

The safety and end points of graded symptom-limited bicycle exercise were assessed in 607 patients before they were randomized to vasodilator or placebo in the Veterans Administration Cooperative Study-Vasodilator Heart Failure Trial. Their mean age was 58 years and left ventricular ejection fraction averaged 30%. The peak exercise responses were as follows: oxygen consumption, 14.5 +/- 3.9 ml/kg/min; heart rate, 132 +/- 24 beats/min; systolic blood pressure, 154 +/- 29 mm Hg. No major complications occurred with the baseline tests. The initial baseline test was stopped in only 10 patients (1.6%) for arrhythmias and in one patient for hypotension. Ventricular tachycardia assessed by ambulatory electrocardiographic monitoring during the second exercise test (before exercise, during exercise, and 4 hr after the test) revealed a prevalence of 5.7% during exercise and 28.8% during the rest of the monitoring period. This study has demonstrated that stable male patients with congestive heart failure can safely exercise on a bicycle ergometer to their peak effort in a well-supervised setting. In addition, we have demonstrated that ambulatory electrocardiographic monitoring is a better method than exercise testing to evaluate presence and extent of ventricular arrhythmias in patients with congestive heart failure.