benzofurans and Chagas-Cardiomyopathy

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Clinical Trials as Topic; Disopyramide; Double-Blind Method; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Random Allocation

Topics: Adult; Amiodarone; Benzofurans; Chagas Cardiomyopathy; Clinical Trials as Topic; Electrocardiography; Female; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Drug Evaluation; Humans; Prognosis

The antiarrhythmic effects of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone were compared in 14 patients with chagasic myocarditis. Drugs and placebo were administered orally in the following order: placebo and verapamil, placebo and 17-monochloracetylajmaline, placebo and mexiletine (1 week each) and placebo and amiodarone (4 weeks each). A 24 hour ambulatory electrocardiographic recording was obtained after administration of each placebo and drug. Verapamil had no effect on the number of ventricular premature complexes, ventricular couplets and runs of ventricular tachycardia. 17-Monochloracetylajmaline did not reduce the number of ventricular premature complexes and ventricular couplets but caused a moderate reduction in runs of ventricular tachycardia. Mexiletine failed to significantly reduce ventricular premature complexes but caused a moderate decrease in both ventricular couplets and runs of ventricular tachycardia. Amiodarone was the only one of the four drugs that caused a substantial reduction of ventricular premature complexes (logarithmic mean 97.8%; p less than 0.001), total suppression of runs of ventricular tachycardia in 11 of 11 patients and suppression of ventricular couplets in 8 of 14 patients and a significant reduction in the remaining 6 patients. The much greater efficacy of amiodarone as compared with the two sodium channel modifiers (17-monochloracetylajmaline and mexiletine) and one calcium channel blocker (verapamil) suggests that its potent antiarrhythmic activity is probably related to other peculiar and still undefined electrophysiologic and pharmacologic properties.

Topics: Adult; Ajmaline; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Female; Humans; Male; Mexiletine; Middle Aged; Placebos; Propylamines; Verapamil

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Chronic Disease; Dose-Response Relationship, Drug; Electrocardiography; Humans; Middle Aged

Arrhythmias may be controlled in most patients with recurrent supraventricular tachycardia or atrial fibrillation with small to moderate maintenance doses of amiodarone (100 to 400 mg/day). Moderate doses (400 mg/day) are also highly effective in suppressing "warning" ventricular arrhythmias in patients with chronic ischemic heart disease, particularly if the goal of treatment is to eliminate ventricular couplets, runs of ventricular tachycardia (VT), and the "R on T" phenomenon. Treatment and prevention of sustained recurrent VT and the malignant arrhythmias of chagasic myocarditis require, however, doses of about 800 mg/day, which may be higher than those needed for ischemic heart disease complicated by VT and ventricular fibrillation. Clinical studies suggest an elimination half-life for amiodarone of about 30 days (range 15 to 100 days). Thus there is a pretherapeutic latency period that varies according to the type of arrhythmia and the doses employed. The maximal effects (as well as the most significant adverse effects) are not attained before 90 to 150 days of treatment, and the antiarrhythmic protection may persist for varying intervals, up to 150 days or more, after the drug has been discontinued. Side effects are not negligible but are generally dose dependent. Despite these side effects, many patients have been treated by us with amiodarone for as long as 5 to 8 years--and for up to 10 years in some cases. Amiodarone appears to be one of the most promising drugs for the possible prevention of ventricular fibrillation and sudden death.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Chagas Cardiomyopathy; Dose-Response Relationship, Drug; Drug Interactions; Half-Life; Heart Ventricles; Humans; Kinetics; Wolff-Parkinson-White Syndrome

Fourteen patients with congestive heart failure due to chronic Chagas' disease had hemodynamic studies before and 20, 40 and 60 minutes and 24 hours after intravenous amiodarone. Amiodarone was given initially as a bolus (5 mg/kg); after 1 hour a continuous infusion was maintained for 24 hours (total dose 900 to 1,050 mg). During the first hour of observation, heart rate and cardiac index decreased and mean right atrial, left ventricular end-diastolic pressures and pulmonary and systemic vascular resistances increased. Except for heart rate and mean right atrial pressure, all hemodynamic variables returned to control values at 24 hours. Thus, myocardial depression occurred with a dose of 5 mg/kg within the first hour of intravenous administration. Amiodarone must be cautiously administered by bolus, especially in patients with cardiac failure.

Topics: Adult; Amiodarone; Benzofurans; Blood Pressure; Cardiac Output; Chagas Cardiomyopathy; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Infusions, Parenteral; Male; Middle Aged; Time Factors; Vascular Resistance

Topics: Adult; Amiodarone; Benzofurans; Blood Pressure; Cardiac Output; Chagas Cardiomyopathy; Echocardiography; Female; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged

Topics: Amiodarone; Benzofurans; Chagas Cardiomyopathy; Electrocardiography; Humans; Male; Middle Aged; Physical Exertion; Tachycardia

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Female; Humans; Male; Middle Aged