benzofurans and Death--Sudden

Topics: Amiodarone; Benzofurans; Cardiac Complexes, Premature; Clinical Trials as Topic; Death, Sudden; Double-Blind Method; Humans; Myocardial Infarction; Oxprenolol; Procainamide; Random Allocation

The occurrence of ventricular fibrillation after occlusion of the circumflex coronary artery in the conscious dog was examined as one preparation for sudden cardiac death arising from coronary artery disease. The incidence of ventricular fibrillation after after circumflex occlusion was reduced from 53% to 6% (p less than .01) by the infusion of prostacyclin in doses that do not alter cardiac output or peripheral resistance. This effect of prostacyclin led to the evaluation of two structurally different inhibitors of thromboxane synthase in this preparation; RO 22-4679 and U-63557A reduced ventricular fibrillation by 82% and 100%, respectively (p less than .05). The inhibition of ventricular fibrillation by U-63557A was abrogated by pretreatment with indomethacin, suggesting that a metabolite of the endoperoxide that accumulated during thromboxane synthase inhibition was responsible for the protection from ventricular fibrillation.

Topics: Animals; Benzofurans; Blood Platelets; Coronary Disease; Death, Sudden; Dogs; Epoprostenol; Imidazoles; Thromboxane-A Synthase; Ventricular Fibrillation

The relation of serum reverse T3 (rT3) to amiodarone efficacy and toxicity was studied in 31 patients with frequent and complex ventricular arrhythmias. Baseline studies included 48-hour Holter recordings and rT3 levels (normal 33 ng/dl or less). Amiodarone therapy was initiated with a 5 mg/kg infusion followed by 600 to 800 mg/day for 7 to 10 days, then 200 to 400 mg/day. Holters and rT3 levels were repeated every 1 to 3 months and amiodarone was titrated to achieve at least a 70% reduction in total ventricular premature complexes, at least a 90% reduction in couplets and abolition of ventricular tachycardia. The baseline rT3 level was 18 +/- 7 ng/dl (range 10 to 30) and patients were followed 12 +/- 9 months. Arrhythmia control was achieved in 25 patients (81%), including 21 patients with elevated rT3 levels (36 to 105 ng/dl) and 4 patients with normal rT3 (15 to 33 ng/dl). Six patients were uncontrolled with rT3 (27 to 90 ng/dl) and 14 patients had minor side effects with rT3 (27 to 123 ng/dl). Three of 4 patients in whom rT3 levels exceeded 130 ng/dl died suddenly (137 to 174 ng/dl before the event). Thus, amiodarone efficacy and minor toxicity occurs at rT3 levels less than 105 ng/dl and sudden death may be associated with levels greater than 130 ng/dl.

Topics: Aged; Amiodarone; Benzofurans; Coronary Disease; Death, Sudden; Drug Evaluation; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Monitoring, Physiologic; Thyroid Gland; Triiodothyronine, Reverse; Ventricular Fibrillation

Multivariate analysis of 11 clinical variables was performed in 104 patients with sustained, symptomatic ventricular tachycardia (VT) or ventricular fibrillation treated with amiodarone to determine variables predictive of subsequent cardiac arrest or sudden death. Twenty-five patients (24%) had fatal or nonfatal cardiac arrest after 7.3 +/- 6.2 months (mean +/- standard deviation) of therapy. Multivariate analysis identified an ejection fraction of less than 0.40, syncope or cardiac arrest before amiodarone therapy, and VT (3 or more consecutive ventricular premature complexes) during predischarge ambulatory electrocardiographic monitoring as variables associated with a high risk of subsequent fatal or nonfatal cardiac arrest (p less than 0.03). Patients who had these 3 clinical variables had a much higher predicted incidence of cardiac arrest at 6 months (62%) and 12 months (76%) than did patients with an ejection fraction greater than 0.40, without syncope or cardiac arrest before amiodarone therapy, and without VT during predischarge ambulatory electrocardiographic monitoring (2% and 5%, respectively) (p less than 0.02). Risk stratification using clinical variables can predict which patients are at high risk of recurrent cardiac arrest or sudden death during amiodarone therapy.

Topics: Aged; Amiodarone; Analysis of Variance; Benzofurans; Death, Sudden; Female; Heart Arrest; Humans; Male; Middle Aged; Recurrence; Risk; Tachycardia; Time Factors; Ventricular Fibrillation

Thirty-three consecutively referred patients with cardiac arrest from ventricular arrhythmias unassociated with a new acute myocardial infarction (AMI) were commenced on amiodarone therapy and followed for a minimum of 12 months. The dose of amiodarone was adjusted to maximum tolerance and not according to the incidence of asymptomatic ventricular premature complex activity. Eight patients died including five sudden deaths. Five out of the eight deaths occurred either within 3 months of therapy or when the dose of amiodarone was less than 400 mg/day. The majority of patients were found to have corneal microdeposits or either thyroid or liver function abnormalities, although none had any clinical manifestation. Ten patients had neurologic side effects. In summary, although the overall cardiac mortality seemed to be reduced by amiodarone therapy and the drug appears to be well tolerated by patients, its role in the prophylaxis against recurrent ventricular fibrillation may be enhanced by a regimen of higher loading and maintenance doses.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Death, Sudden; Dose-Response Relationship, Drug; Drug Evaluation; Female; Follow-Up Studies; Heart Arrest; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Time Factors

The determinants of long-term clinical outcome were studied in 42 patients with recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) who were treated with amiodarone as the sole antiarrhythmic agent. Of the 42 patients, 11 (26%) either died suddenly or had recurrent, symptomatic, sustained VT during a mean follow-up period of 10 months (range 0.3 to 45). Of the 19 patients without inducible VT/VF during electrophysiologic study while receiving amiodarone, 1 patient died suddenly but no patient had recurrent VT/VF. Ten of the 23 patients (43%) with persistently inducible arrhythmia have died suddenly or have had recurrent VT/VF. Using survival and stepwise logistic regression analyses, 2 significant independent predictors of recurrent arrhythmia were identified; persistently inducible VT during electrophysiologic testing in patients receiving amiodarone therapy (p less than 0.002) and the left ventricular ejection fraction at rest (p less than 0.05). The predictive accuracy of the response to serial electrophysiologic testing during amiodarone therapy was 67%, the sensitivity was 58% and the specificity was 91%. Thus, serial electrophysiologic testing is useful for determining the prognosis in patients with inducible VT/VF treated with amiodarone.

Topics: Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Death, Sudden; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Prognosis; Recurrence; Tachycardia; Ventricular Fibrillation

Topics: Amiodarone; Animals; Benzofurans; Consciousness; Coronary Disease; Death, Sudden; Dogs; Electrocardiography; Electrophysiology; Male; Myocardial Infarction; Time Factors; Ventricular Fibrillation

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Death, Sudden; Electrocardiography; Humans; Male; Middle Aged; Tissue Distribution