benzofurans and Tachycardia

This study aimed to review the available evidence-based literature on novel psychoactive substances and to inform health care professionals.. Internet searches were carried out using Google and Yahoo by using specific key words. For each set of key words, the first 100 websites identified by Google and Yahoo were fully assessed, together with a further 5% of random samples selected by research randomizer of the remaining websites. Thus, a list of unique web forums was identified, and qualitative information was extracted. Available evidence-based literature were reviewed along with a user's experimentation with mephedrone, NRG-1, NRG-2 and Benzofury.. It showed that when a substance (mephedrone) became controlled, the vendors aggressively promote the sale of other new compounds (NRG-1, NRG-2, Benzofury) to attract vulnerable adults. The characteristics, toxicity and suggested management of these new compounds (NRG-1, NRG-2, Benzofury) are discussed.. The arrival of hundreds of novel psychoactive substances for sale online has raised a number of public health and legal issues. Although evidence-based literature remains limited, few studies identified that most products do not contain the ingredients as advertised. Better levels of international cooperation and rapid share of available information may be needed to tackle this emerging problem.

Topics: Animals; Benzofurans; Humans; Illicit Drugs; Male; Middle Aged; Paranoid Disorders; Pentanones; Propylamines; Pyrrolidines; Random Allocation; Tachycardia

The value of programmed electrical stimulation (PES) and Holter monitoring in the assessment of amiodarone efficacy was reviewed. Many physicians have been disturbed by the persistent inducibility of arrhythmias in patients treated with amiodarone, who nevertheless do very well during the follow-up period. Noninducibility was associated with a favorable prognosis among 366 VT patients. Eighty-eight (24%) were noninducible on amiodarone, and 10% of these had recurrences, vs 39% in patients who remained inducible. Further, increased difficulty of induction with PES or induction of a slower or better tolerated VT may indicate a favorable outlook, and add to the value of PES. Few papers rigorously employed Holter monitoring in the assessment of amiodarone. In general, suppression of previously frequent arrhythmias implies excellent protection for patients with benign arrhythmias and moderate protection with malignant arrhythmias. By Holter assessment in 186 VT patients, arrhythmias were suppressed in 114 (61%), and 18% of these had recurrences vs 50% in patients whose arrhythmias were not suppressed. Studies attempting to correlate the results of PES and Holter monitoring in the same patients are lacking and may prove useful.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiac Pacing, Artificial; Clinical Trials as Topic; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Conduction System; Humans; Male; Middle Aged; Monitoring, Physiologic; Pre-Excitation Syndromes; Prognosis; Tachycardia

Topics: Amiodarone; Benzofurans; Digoxin; Drug Interactions; Humans; Kinetics; Quinidine; Tachycardia

Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.

Topics: Administration, Oral; Amiodarone; Animals; Arrhythmias, Cardiac; Atrioventricular Node; Benzofurans; Biological Availability; Drug Interactions; Electrophysiology; Eye Diseases; Half-Life; Heart Conduction System; Humans; Injections, Intravenous; Kinetics; Lung Diseases; Metabolic Clearance Rate; Photosensitivity Disorders; Purkinje Fibers; Tachycardia; Thyroid Diseases; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Heart Ventricles; Humans; Infusions, Parenteral; Kinetics; Recurrence; Tachycardia; Ventricular Fibrillation

Amiodarone, an investigational drug in the United States, has had considerable use in this country and worldwide in the treatment of cardiac arrhythmias. This article reviews the clinical pharmacology of this potentially useful antiarrhythmic agent.

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Autonomic Nervous System; Benzofurans; Bradycardia; Drug Interactions; Eye; Heart Conduction System; Heart Ventricles; Hemodynamics; Humans; Injections, Intravenous; Kinetics; Liver; Lung; Skin; Tachycardia; Thyroid Gland

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Ajmaline; Amiodarone; Anilides; Aprindine; Atrial Fibrillation; Benzofurans; Digitalis Glycosides; Disopyramide; Encainide; Female; Humans; Lidocaine; Male; Middle Aged; Procainamide; Quinidine; Tachycardia; Verapamil; Wolff-Parkinson-White Syndrome

Amiodarone, although widely studied in Europe, is a recent addition to the investigational antiarrhythmics being used in the U.S. Pharmacologically, its primary cardiac effects are to increase coronary artery blood flow, increase the effective refractory period, and produce an atropine-resistant bradycardia. Amiodarone is incompletely (approximately 50 percent) and slowly (peak serum concentration approximately 6 h) absorbed. With chronic administration, it deposits both in adipose tissue and in organs with high blood perfusion. It has an apparent elimination half-life of 15-45 days, which presents unique dosing problems. The apparent therapeutic range is 0.6-3 microgram/ml. Amiodarone is 85-95 percent effective in the treatment of atrial tachyarrhythmias and 70-80 percent effective in ventricular tachyarrhythmias. It appears to be of particular value in chronic atrial fibrillation/flutter because it may be able to maintain sinus rhythm after cardioversion. Side effects, although uncommon, may prevent the drug from becoming a standard of therapy. Drug interactions, particularly with warfarin and digoxin, as well as pulmonary fibrosis are of concern.

Topics: Amiodarone; Animals; Benzofurans; Humans; Kinetics; Tachycardia; Tissue Distribution

Topics: Amiodarone; Benzofurans; Disopyramide; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Hypertension; Middle Aged; Mitral Valve Prolapse; Pyridines; Tachycardia

Topics: Acute Disease; Administration, Oral; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiovascular System; Dose-Response Relationship, Drug; Electrophysiology; Eye Manifestations; Heart Block; Humans; Injections, Intravenous; Muscle, Smooth, Vascular; Myocardial Infarction; Skin Manifestations; Tachycardia; Thyroid Gland; Wolff-Parkinson-White Syndrome

Carzelesin (U-80244), one of the synthetic DNA minor groove binding cyclopropylpyrroloindole analogues, was selected for clinical development because of its high potency, promising antitumor activity in murine solid tumors and leukemia, and significant therapeutic efficacy against colon and rhabdomyosarcoma xenografts. In this Phase I study, carzelesin was given daily for 5 consecutive days to (a) determine the maximum tolerable dose (MTD) and the pattern of toxicity of this schedule; (b) define the pharmacokinetic profile of the parent, as was done for the intermediate compound U-76073 and the DNA-reactive agent U-76074; and (c) document any antitumor activity observed. Carzelesin was given as a 10-min infusion with a constant-rate infusion pump. Treatment was repeated every 4 weeks or when blood counts had recovered to normal values. The starting dose of 12 microgram/m2/day was escalated by 20-30% increments until the MTD (defined as the dose leading to grade 4 hematological or grade 3 nonhematological toxicity in at least two of six patients) was reached. Pharmacokinetic studies were planned on days 1 and 5 of the first cycle in at least two patients per dose level. Plasma levels of carzelesin, U-76073, and U-76074 were determined by high-performance liquid chromatography with UV detection and a detection limit of 0.5 ng/ml. Twenty-five patients were entered in the study, and 56 cycles were evaluable for hematological toxicity. Subsequent dose levels evaluated were 24, 30, 35, and 40 microgram/m2. Both neutropenia and thrombocytopenia were dose limiting and cumulative, with a high interpatient variability. Neutropenia occurred earlier (median time to neutrophil nadir and recovery, 15 and 29 days, respectively) than thrombocytopenia (median time to platelet nadir and recovery, 25 and >/=26 days, respectively); there were delays of treatment because of persisting thrombocytopenia in all patients treated at the MTD. At the MTD, the peak plasma concentrations of carzelesin were achieved at the end of the infusion and were higher than those found cytotoxic in vitro against tumor cell lines. Carzelesin was detectable up to a maximum of 1 h after the infusion. Smaller amounts of U-76073 were detectable for a maximum of 30 min only at the MTD, whereas U-76074 was never found. An 8-month partial remission was reported in one previously untreated patient with hepatocellular carcinoma at 40 microgram/m2. The MTD was fixed at 40 microgram/m2 daily; 35 and 30 micro

Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Benzofurans; Bronchial Spasm; Drug Administration Schedule; Duocarmycins; Female; Flushing; Humans; Hypersensitivity; Indoles; Male; Middle Aged; Nausea; Neoplasms; Neutropenia; Tachycardia; Thrombocytopenia; Treatment Outcome

The value of programmed electrical stimulation (PES) and Holter monitoring in the assessment of amiodarone efficacy was reviewed. Many physicians have been disturbed by the persistent inducibility of arrhythmias in patients treated with amiodarone, who nevertheless do very well during the follow-up period. Noninducibility was associated with a favorable prognosis among 366 VT patients. Eighty-eight (24%) were noninducible on amiodarone, and 10% of these had recurrences, vs 39% in patients who remained inducible. Further, increased difficulty of induction with PES or induction of a slower or better tolerated VT may indicate a favorable outlook, and add to the value of PES. Few papers rigorously employed Holter monitoring in the assessment of amiodarone. In general, suppression of previously frequent arrhythmias implies excellent protection for patients with benign arrhythmias and moderate protection with malignant arrhythmias. By Holter assessment in 186 VT patients, arrhythmias were suppressed in 114 (61%), and 18% of these had recurrences vs 50% in patients whose arrhythmias were not suppressed. Studies attempting to correlate the results of PES and Holter monitoring in the same patients are lacking and may prove useful.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiac Pacing, Artificial; Clinical Trials as Topic; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Conduction System; Humans; Male; Middle Aged; Monitoring, Physiologic; Pre-Excitation Syndromes; Prognosis; Tachycardia

Optimal loading and maintenance regimens for amiodarone are undefined. Serial electrophysiologic testing was used in 25 patients with ventricular tachycardia to assess the adequacy of a 1-week oral loading regimen at 1,200 mg/day, to modify maintenance dosing at the conclusion of loading, and to evaluate the appropriateness of maintenance dosing after 2 months of therapy. During the loading period, highly significant (p less than 0.001) increases occurred in the AH interval (88 +/- 22 vs 120 +/- 31 ms), HV interval (49 +/- 10 vs 61 +/- 11 ms), AV nodal Wenckebach cycle length (390 +/- 92 vs 537 +/- 147 ms), ventricular refractory period (247 +/- 17 vs 276 +/- 23 ms), mean ventricular tachycardia cycle length (254 +/- 38 vs 298 +/- 52 ms) and return cycle length (294 +/- 55 vs 360 +/- 87 ms). Ventricular tachycardia inducibility decreased in only a minority of cases, and when observed in association with a more than 10% increase in ventricular refractory period, resulted in a lower maintenance dose. After 2 months of maintenance therapy no additional change occurred in any of these parameters except for an increase in ventricular tachycardia cycle length (298 +/- 52 vs 330 +/- 65 ms, p less than 0.017). Ventricular tachycardia inducibility again showed no consistent response. It is concluded that patients can be discharged after 1 week of therapy with oral amiodarone loading at 1,200 mg/day and that maintenance dosing modified by electrophysiologic assessment results in steady perpetuation of the cardiac amiodarone effect, as indicated by the time course of change in electrophysiologic variables consistently affected.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Benzofurans; Clinical Trials as Topic; Drug Administration Schedule; Electrophysiology; Female; Heart Conduction System; Heart Ventricles; Humans; Male; Middle Aged; Prospective Studies; Tachycardia

The majority of sudden cardiac deaths in children occur in patients with prior arrhythmias and an abnormal heart. Amiodarone was given to 39 young patients (35 with an abnormal heart) with arrhythmias unresponsive to conventional treatment. Their age ranged from 6 weeks to 30 years with nine patients younger than 2 years of age. Atrial flutter was present in 16 patients, ventricular tachycardia in 14 patients and supraventricular tachycardia in 9 patients. The most common diagnosis (14 patients) was postoperative repair of congenital heart disease. The dose ranged from 2.5 to 21.6 mg/kg per day (mean 8.2). Elimination of arrhythmia (on 24 hour electrocardiography) occurred in 15 of 16 patients with atrial flutter, 11 of 14 with ventricular tachycardia and 5 of 9 with supraventricular tachycardia. Symptomatic side effects were: rash (three patients), headache (two patients), nausea (one patient) and peripheral neuropathy (one patient); seven patients had asymptomatic corneal microdeposits which normalized in all after the drug was discontinued. No side effects occurred in patients younger than 10 years of age. The following changed with treatment (p less than 0.05): heart rate decreased (three patients with atrial flutter and sick sinus syndrome required pacemaker implantation for bradycardia) and QTc increased; thyroxine (T4) and serum reverse triiodothyronine (T3) increased. During follow-up study (range 6 months to 3 years), 21 of the 39 patients continued to take amiodarone with complete control of arrhythmias, 9 were no longer taking the drug and 9 died (7 nonsudden and 2 sudden deaths). Amiodarone is an extremely effective treatment for infants and children with tachyarrhythmias resistant to conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Amiodarone; Atrial Flutter; Benzofurans; Child; Child, Preschool; Clinical Trials as Topic; Echocardiography; Electrocardiography; Heart Defects, Congenital; Humans; Infant; Tachycardia; Thyroid Gland

Topics: Adult; Aged; Amiodarone; Benzofurans; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Tachycardia

The role of provocation tests for the assessment of amiodarone therapy in patients with ventricular tachycardia remains a subject of controversy: recent studies seem to show that the ability to initiate VT in patients on amiodarone is compatible with a good long-term result. Eighteen patients, 16 male and 2 female, average age 56 years, were treated with amiodarone (600 mg/day in 15 cases, and 400 mg/day in 3 cases) and submitted to provocative tests before and after treatment. The mean follow-up period was 14 +/- 4 months. In Group I (5 patients), VT could not be initiated after treatment and there were no relapses of the arrhythmia. In Group II (6 patients), non-sustained VT could be initiated and only one relapse was observed after a close reduction from 600 to 400 mg/day; Group III comprised 5 patients with spontaneous recurrences. An identical VT could be initiated during electrophysiological investigation which served as a basis for selection of an effective antiarrhythmic association. Two patients could not be studied after drug impregnation (1 sudden death, 1 exacerbation of VT). The results of this study show that provocative pacing can be useful in evaluating the efficacy of amiodarone, as in Groups I and II (61% of patients) a favourable prognosis could be predicted in 91% of cases. In cases of therapeutic failure with spontaneous recurrences of VT, the same provocation tests enabled a more effective drug combination to be selected.

Topics: Adult; Aged; Amiodarone; Benzofurans; Clinical Trials as Topic; Disopyramide; Drug Therapy, Combination; Electric Stimulation; Female; Humans; Male; Middle Aged; Tachycardia; Time Factors

We examined the chronic electrophysiologic, systemic, and pharmacologic effects of chronic oral amiodarone therapy in 24 patients with refractory ventricular tachycardia and organic heart disease. Chronic amiodarone therapy resulted in significant increases in R-R interval (from 798 +/- 182 msec to 912 +/- 100 msec; P less than 0.01), P-R interval (from 205 +/- 66 msec to 221 +/- 87 msec; P less than 0.02), QRS duration (from 103 +/- 24 msec to 115 +/- 28 msec; P less than 0.001), and Q-Tc interval (from 413 +/- 48 msec to 470 +/- 46 msec; P less than 0.001). Significant increases were also noted in P-A interval (from 36 +/- 14 msec to 45 +/- 13 msec; P less than 0.05), A-H interval (from 119 +/- 61 msec to 141 +/- 87 msec; P less than 0.02), and H-V interval (from 52 +/- 12 msec to 64 +/- 11 msec; P less than 0.001). Electrophysiologic parameters showing changes included corrected sinus node recovery time (from 271 +/- 140 msec to 425 +/- 122 msec; P less than 0.01), the effective refractory period of the atrium (from 263 +/- 32 msec to 321 +/- 47 msec; P less than 0.01), the effective refractory period of the atrioventricular node (from 348 +/- 109 msec to 478 +/- 157 msec; P less than 0.001), the effective refractory period of the ventricle (from 253 +/- 21 msec to 291 +/- 28 msec; P less than 0.001), the atrial pacing cycle length producing A-V nodal Wenckebach (from 436 +/- 109 msec to 531 +/- 95 msec; P less than 0.001), and the functional refractory period of the A-V node (from 422 +/- 68 msec to 499 +/- 95 msec; P less than 0.001). Programmed electrical stimulation performed after 21-88 (mean 31) days of treatment was highly predictive of long-term results if suppression of arrhythmia induction was demonstrated (12 patients) or if the spontaneous arrhythmia was reinduced (5 patients). Induction of morphologically new ventricular tachyarrhythmias was frequent (42%) but had a low spontaneous recurrence rate (10%) during follow-up. Systemic parameters on chronic amiodarone therapy showed significant increases in total T4 and reverse T3, with no change in pulmonary function tests or left ventricular ejection fraction. Serum amiodarone levels at chronic electrophysiologic study ranged from 0.44-4.10 (mean 1.3) micrograms/ml. Long-term follow-up (2.5 to 20 months) demonstrated a marked improvement in clinical symptoms and mortality, but a significant recurrence rate of a well-tolerated slower arrhythmia persisted. Adverse effects on chronic amiodarone t

Topics: Administration, Oral; Adult; Aged; Amiodarone; Atrioventricular Node; Benzofurans; Clinical Trials as Topic; Coronary Disease; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Physical Exertion; Prognosis; Recurrence; Tachycardia; Thyroxine; Triiodothyronine

Thirty-three patients with recurrent drug-refractory ventricular tachycardia were treated with oral amiodarone during an average period of 6.1 months. In-hospital monitoring for two weeks or more, electrophysiological tests and ambulatory ECG were used to evaluate the results. Twenty patients are still using the drug with complete control of the arrhythmia. Eleven have failed the drug, ten due to recurrence of documented ventricular tachycardia. Only three patients failed after the first month of therapy. Two patients died, one suddenly. The drug was discontinued in a further two patients due to side-effects. Other side-effects were tolerable or manageable by dose adjustments alone. Five patients showed evidence of inadequate arrhythmia control between days 15 and 32 of therapy but subsequently responded to the drug for 4-9 months, giving further support to the concept that in some patients at least 30 days of therapy is necessary for the full effect of the drug to appear. In 16 of the 20 patients tested by arrhythmia induction study while on the drug, ventricular tachycardia could still be induced. Seven (44%) of these eventually failed the drug. Arrhythmia recurred in one of those four in whom tachycardia could not be induced. Amiodarone is a valuable drug in the management of recurrent ventricular tachycardia, refractory to other antiarrhythmic drugs.

Topics: Adult; Aged; Amiodarone; Benzofurans; Clinical Trials as Topic; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Tachycardia; Time Factors

Topics: Aged; Amiodarone; Benzofurans; Bradycardia; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Syndrome; Tachycardia

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 to 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Cornea; Drug Evaluation; Heart Conduction System; Humans; Tachycardia; Thyroid Gland; Ventricular Fibrillation

Eight patients with WPW syndrome were catheterised and, during the course of this investigation, the electrophysiological effects of amiodarone were assessed. By registering the potentials of the bundle of His and by using the stimulus-test technique, we were able to measure the refractory periods of the atrium and of the normal and accessory conducting pathways both before and during the first 40 minutes after an intra-atrial injection of 5 mg/kg of amiodarone chlorhydrate. The action of the conduction time was also studied. In the five cases in which we were able to measure it, the effective refractory period of the abnormal pathway increased, which led in two instances to the temporary suppression of all pre-excitation. At the same time, it was repeatedly found that the refractory periods of the A-V node were increased: the effective refractory period in 3/3 cases, and the functional refractory period in 2/2 cases. The effective refractory period of the right atrium was increased in 5 cases, and did not change in the others. The intranodal conduction time (A-H- interval) was always increased after amiodarone. Finally, in three patients runs of reciprocal tachycardia could be initiated by premature atrial stimulation. In one case, this was no longer possible after amiodarone. In the other two cases, although the attacks could still be brought on, they were slower because of the lengthening of the A-H interval. These findings explain why amiodarone is effective in controlling the tachycardia of WPW syndrome.

Topics: Action Potentials; Adult; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Bundle of His; Clinical Trials as Topic; Female; Heart Conduction System; Humans; Male; Middle Aged; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adrenergic beta-Antagonists; Adult; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Humans; Hyperthyroidism; Middle Aged; Placebos; Propranolol; Tachycardia

Topics: Aged; Benzofurans; Bradycardia; Clinical Trials as Topic; Drug Combinations; Electrocardiography; Female; Humans; Hypokalemia; Isoproterenol; Male; Monitoring, Physiologic; Oxazines; Pacemaker, Artificial; Potassium Chloride; Prenylamine; Prognosis; Quinidine; Syncope; Tachycardia; Ventricular Fibrillation

Topics: Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Benzofurans; Clinical Trials as Topic; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Tachycardia

Topics: Adult; Benzofurans; Clinical Trials as Topic; Drug Antagonism; Heart Rate; Humans; Isoproterenol; Male; Physical Exertion; Placebos; Propranolol; Rest; Sensory Receptor Cells; Statistics as Topic; Sympatholytics; Tachycardia

Amiodarone was used in the treatment of 21 patients with supraventricular or ventricular arrhythmias which were refractory to conventional antiarrhythmic drugs, individually or in combination. Six of seven patients with supraventricular arrhythmias and 12 of 14 with ventricular tachycardia were controlled with amiodarone. Although side effects were common, only one patient was removed from treatment due to pulmonary fibrosis. We conclude that amiodarone is an effective antiarrhythmic drug for refractory ventricular and supraventricular arrhythmias.

Topics: Amiodarone; Atrial Fibrillation; Benzofurans; Cardiac Complexes, Premature; Cardiomyopathy, Dilated; Coronary Disease; Coronary Vasospasm; Dose-Response Relationship, Drug; Heart Aneurysm; Heart Atria; Heart Ventricles; Humans; Recurrence; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Electrophysiology; Female; Heart; Humans; Lung; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Thirty-eight patients with refractory supraventricular and ventricular tachyarrhythmias were administered a mean oral dosage of 400 mg amiodarone daily (200-600 mg). A high-pressure liquid chromatography method was used to measure serum concentrations of amiodarone and its metabolite desethylamiodarone after one week, one month, three months, and then at 6-month intervals. In 24 patients subcutaneous fatty tissue concentrations were also measured. The mean follow-up was 9 months (4 days to 29 months). A linear correlation was found between amiodarone and its metabolite in serum (r = 0.56, p less than 0.001) as well as in subcutaneous fatty tissue (r = 0.67, p less than 0.001). While serum concentrations were dose dependent, tissue concentrations accumulated during chronic therapy (p less than 0.01, both). Clinical efficacy was achieved in 84% of the patients. No statistically significant difference was found between responders and non-responders as regards serum and subcutaneous fatty tissue concentrations. Side effects of amiodarone occurred in 63%. The incidence of adverse effects was related to significantly higher serum and subcutaneous fatty tissue concentrations of amiodarone and its metabolite (p less than 0.001, both). Thus, although the determination of serum and subcutaneous fatty tissue concentrations does not seem to be helpful for assessing clinical efficacy of this antiarrhythmic drug, these values may predict the occurrence of adverse effects.

Topics: Adipose Tissue; Adult; Aged; Amiodarone; Benzofurans; Biotransformation; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Humans; Kinetics; Male; Middle Aged; Tachycardia

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Tachycardia

Five cases of amiodarone-induced syncope due to torsades de pointes or ventricular fibrillation are described. Amiodarone was used for recurrent supraventricular tachycardia in four cases and frequent ventricular extra systoles complicating congenital QT prolongation in the remaining case. Each was associated with a marked prolongation in the QTc interval following amiodarone. Three cases had had a previous history of life-threatening ventricular arrhythmias secondary to anti-arrhythmic drugs. Hypokalemia may have been a contributory factor in two. The clinical features, predisposing factors, and treatment are discussed.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Failure; Humans; Long QT Syndrome; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Electrocardiography; Female; Humans; Male; Middle Aged; Tachycardia

Topics: Amiodarone; Benzofurans; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Tachycardia

Topics: Adult; Amiodarone; Benzofurans; Cardiomyopathy, Dilated; Female; Humans; Tachycardia

Amiodarone is an antiarrhythmic agent known to cause prolongation of action potential duration which is reflected in the electrocardiogram as a prolongation of the QT interval. Prolongation of the QT interval in patients dying suddenly was compared with that in patients who remained alive to determine whether a difference existed between these two groups. The electrocardiogram and amiodarone levels were evaluated in 33 patients who presented with cardiac arrest and symptomatic ventricular tachycardia in whom no other antiarrhythmic agent was found effective in preventing induction of ventricular tachycardia during electrophysiologic studies. There were 30 men and 3 women (mean age 52 +/- 10 years). Twenty-three are alive after a mean follow-up period of 12 +/- 7 months. Ten died: six suddenly, three of non-cardiac causes and one of congestive heart failure. Using a two-way analysis of variance, the percent change in QT, QTc, JT and JTc intervals before and after amiodarone therapy was analyzed. Marked prolongation in the QT interval was present in patients who remained alive with amiodarone therapy. A significant difference in percent QT prolongation was seen between the latter patients and those who died suddenly (p less than 0.005). No difference was observed in the percent change in QRS interval between the two groups. The levels of amiodarone (2.5 versus 3.2 micrograms/ml) and its metabolite (desethylamiodarone) were not significantly different between the living patients and those who died suddenly. These findings suggest that a prolongation of the QT interval may be a marker for the therapeutic antiarrhythmic effect of amiodarone.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Tachycardia; Time Factors

In eight patients, the right ventricular effective refractory period, rate-dependent changes in intraventricular conduction (as reflected by QRS duration during ventricular paced cycle lengths of 600 to 250 ms) and results of programmed ventricular stimulation were determined in the control state, 5 minutes after the intravenous infusion of 10 mg/kg body weight of amiodarone and after 2 months of treatment with oral amiodarone. The right ventricular effective refractory period was 230 +/- 30 ms (mean +/- SD) in the control study, 248 +/- 27 ms after intravenous amiodarone (p less than 0.001) and 296 +/- 26 ms after oral amiodarone (p less than 0.001). In the control state, QRS duration was constant at all paced cycle lengths. Intravenous amiodarone resulted in a rate-dependent prolongation of QRS duration. This rate-dependent prolongation was markedly accentuated by oral amiodarone in six patients who had an elevated serum level of reverse triiodothyronine (T3) after 2 months of oral treatment, but it was not more pronounced than the effects of intravenous amiodarone in two patients with a normal reverse T3 serum level after oral therapy. Both intravenous and oral amiodarone either suppressed or modified the induction of ventricular tachycardia by programmed stimulation in some patients, but in a discordant fashion. The relative effects of intravenous and oral amiodarone on ventricular refractoriness and conduction and on ventricular tachycardia induction did not correlate with serum amiodarone levels. Chronic amiodarone therapy results in a marked prolongation in ventricular refractoriness compared with the relatively small but significant increase that occurs after intravenous amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electric Stimulation; Electrophysiology; Female; Heart Conduction System; Heart Ventricles; Humans; Infusions, Parenteral; Male; Middle Aged; Tachycardia; Time Factors; Triiodothyronine

Topics: Aged; Amiodarone; Benzofurans; Humans; Liver Cirrhosis; Male; Tachycardia

The effects of isoproterenol on induction of circus movement tachycardia were studied in 21 patients with an accessory atrioventricular pathway. Forty-six studies were performed. Thirteen patients were studied before and during administration of isoproterenol without antiarrhythmic drugs (group A). Ten patients (including 2 from group A) were studied before and during administration of isoproterenol while receiving oral treatment with amiodarone (group B). Ability to initiate circus movement tachycardia before or during administration of isoproterenol by programmed stimulation was correlated with the relation of circus movement tachycardia to exercise in these patients. (Seven patients in group A and 7 in group B had circus movement tachycardia related to exercise.) Isoproterenol significantly shortened sinus cycle length, duration of the QRS complex during sinus rhythm, anterograde effective refractory period of the accessory pathway, and circus movement tachycardia cycle length, owing to shortening of the AH interval during the arrhythmia. Isoproterenol made initiation of circus movement tachycardia possible in patients in whom the arrhythmia could not be initiated before. However, this effect did not correlate with the relation of the spontaneously occurring circus movement tachycardia to exercise. The electrophysiologic effects produced by isoproterenol did not differ between patients with and without exercise-related tachycardia. In all patients in whom circus movement tachycardia was initiated before administration of isoproterenol, the tachycardia was still inducible during administration of that drug. It is concluded that isoproterenol facilitates initiation of circus movement tachycardia in patients with an accessory pathway, mainly by facilitating anterograde conduction over the atrioventricular node.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amiodarone; Atrioventricular Node; Benzofurans; Female; Heart Conduction System; Humans; Isoproterenol; Male; Physical Exertion; Refractory Period, Electrophysiological; Tachycardia; Time Factors

Topics: Amiodarone; Benzofurans; Electrocardiography; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Topics: Amiodarone; Benzofurans; Child, Preschool; Electrocardiography; Heart Defects, Congenital; Heart Failure; Humans; Male; Tachycardia

Over a 10-year period 130 patients with drug-resistant cardiac arrhythmias associated mainly with coronary artery disease and its complications were treated with amiodarone. The drug controlled all the tachyarrhythmias associated with the Wolff-Parkinson-White syndrome, 95% of the ventricular arrhythmias, including recurrent ventricular tachycardia and fibrillation, and 92% of the supraventricular arrhythmias. The maximum duration of therapy was 111 months and the mean 34 months. Side effects occurred in 34% of the patients, and there was one withdrawal from therapy per 15.3 patient-years of treatment. The commonest cause of withdrawal was nausea, which was significantly related (p less than 0.01) to a drug interaction with digoxin and diuretics. Reversible neurologic complications occurred in eight patients (6%), and acute myositis was recognized for the first time. Pulmonary infiltration developed in four patients (3%), who were receiving 600 mg of amiodarone per day. The rates of side effects and of withdrawal from therapy differed significantly between the patients whose maintenance doses were 600 and 200 mg/d, at 59% v. 6% (p less than 0.01) and 32% v. 0% (p less than 0.05) respectively. Thus, amiodarone is a very effective antiarrhythmic that can be administered over long periods with acceptable rates of side effects and withdrawal provided the minimal effective dose is used; 400 mg/d or less is desirable.

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Recurrence; Tachycardia; Ventricular Fibrillation

The prognostic implications of changes in ventricular ectopic activity on serial 24 hour ambulatory electrocardiographic (Holter) recordings were prospectively evaluated in 107 patients with a history of sustained ventricular tachyarrhythmias treated with amiodarone for at least 30 days. Twenty-seven patients (25%) had insufficient ventricular ectopic activity (less than 10 ventricular premature complexes/h and no repetitive forms) on baseline Holter recordings for serial statistical analysis. In 53 (66%) of the remaining 80 patients, serial 24 hour Holter monitor recordings showed efficacy of treatment, defined as a 75% decrease in ventricular premature complexes, a 95% decrease in ventricular couplets and absence of ventricular tachycardia. During a mean follow-up period of 14.2 +/- 9.9 months, 34 (32%) of the 107 patients had recurrence of a sustained ventricular tachyarrhythmia. Holter recording correctly predicted nine recurrences and correctly identified 37 patients who did not experience a recurrence. Holter efficacy failed to predict recurrence of a sustained ventricular tachyarrhythmia in 16 patients, and 18 patients remained free of recurrence despite failure to achieve Holter efficacy. The positive predictive value of Holter monitoring efficacy was 33% and the negative predictive value was 70%; however, these differences were not statistically significant by chi-square analysis. Similar results were obtained using Holter recordings performed relatively early in therapy (6 weeks and 4 months). Of the 27 patients without significant ventricular ectopic activity on the baseline Holter recording, 9 had an arrhythmia recurrence despite continued infrequent ventricular premature complexes and no repetitive forms on subsequent recordings. The recurrence rate in this group (33%) was similar to the overall recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Ambulatory Care; Amiodarone; Benzofurans; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Prospective Studies; Recurrence; Tachycardia

Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review of the hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly screened with respect to hepatic enzyme levels. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly.

Topics: Aged; Amiodarone; Benzofurans; Cholestasis, Intrahepatic; Humans; Liver Function Tests; Male; Tachycardia

Topics: Amiodarone; Benzofurans; Electrocardiography; Humans; Hypokalemia; Tachycardia

The mechanism of amiodarone-induced pulmonary toxicity is unknown. Two cases of amiodarone pulmonary toxicity are presented in which abnormal inclusion bodies containing whorls of membrane were seen on electron microscopy of extrapulmonary tissues. These cytoplasmic lysosomal inclusion bodies were observed in lymphocytes, plasma cells, granulocytes, tissue macrophages, and hepatocytes. These widespread histopathologic changes in extrapulmonary tissues and in a variety of cell types are similar to more extensively investigated findings in animal models that are thought to represent a drug-induced lysosomal storage disease, phospholipidosis.

Topics: Amiodarone; Benzofurans; Biopsy, Needle; Follow-Up Studies; Humans; Inclusion Bodies; Leukocytes; Liver; Lung; Lung Diseases; Lymph Nodes; Lysosomes; Male; Microscopy, Electron; Middle Aged; Radiography; Tachycardia

Over a five-year period 57 patients (pts) with sustained, recurrent, post-infarction ventricular tachycardia (VT) refractory to conventional antiarrhythmic treatment were evaluated. In 28 (49%) pts VT was controlled by amiodarone (A) in a dose of 3000 mg week-1. During long-term follow-up 5/28 (18%) pts died; no severe side-effects were observed with this dosage. In 17 of the 29 pts not controlled by this regimen, the dosage of A was increased to 6000-8000 mg week-1; short-term control of VT was achieved in 9/17 (53%) pts, but over a long-term follow-up 5/9 (56%) died and severe side-effects (11% pulmonary fibrosis and 11% hepatitis) occurred in 22%. Twenty pts, resistant to a low (12 pts) or high (8 pts) doses of A, underwent map-guided surgical treatment. In conclusion A is superior to conventional drugs in the treatment of sustained, recurrent, post-infarction VT, but when high doses are necessary to prevent VT, long-term results are poor and severe side-effects frequent. In pts refractory to standard doses of A, map-guided surgery is the treatment of choice.

Topics: Adult; Aged; Amiodarone; Benzofurans; Combined Modality Therapy; Endocardium; Female; Humans; Male; Middle Aged; Myocardial Infarction; Recurrence; Tachycardia

Topics: Adult; Amiodarone; Atrial Fibrillation; Benzofurans; Electrocardiography; Female; Heart; Humans; Male; Middle Aged; Refractory Period, Electrophysiological; Tachycardia; Wolff-Parkinson-White Syndrome

During treatment with amiodarone, digoxin and nadolol, asystole occurred repeatedly in a patient with chronic persistent automatic atrial tachycardia. Asystole did not occur after discontinuation of drug therapy, and rechallenge with amiodarone alone produced marked overdrive suppression of all pacemakers resulting in asystole. Amiodarone serum level was within therapeutic range. The possible electrophysiologic mechanisms by which amiodarone might suppress both normal and abnormal pacemakers are discussed. The occurrence of asystole at therapeutic serum concentration of amiodarone suggests that this drug should be used with caution.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Atria; Heart Rate; Humans; Nadolol; Propanolamines; Tachycardia

Forty-two patients with refractory, recurrent life-threatening ventricular tachycardia and spontaneous ventricular tachycardia (greater than or equal to 3 beats, heart rate greater than 100 beats/min) on baseline 24 hour Holter recording were treated with amiodarone. After 1 week of amiodarone therapy and during the follow-up period (22 +/- 11 months, mean +/- SD), patients had serial 24 hour Holter recordings (10.6 +/- 3.8 per patient). Twenty-four hour, 48 hour or 72 hour Holter monitoring was performed during the second week of therapy. Ventricular tachycardia was suppressed on all follow-up serial Holter recordings in 17 patients (40%). Ventricular tachycardia was suppressed in 34 (81%) of 42 patients with 24 hour Holter recordings, 21 (72%) of 29 patients with 48 hour recordings and 20 (69%) of 29 patients with 72 hour recordings during the second week of therapy. At follow-up 24 patients (57%) were free of clinical arrhythmic events (Sustained ventricular tachycardia or sudden death). The sensitivity, specificity, positive and negative predictive values and predictive accuracy of ventricular tachycardia on 24, 48 and 72 hour Holter recordings during the second week of therapy for predicting subsequent events were analyzed. The positive and negative predictive values were 100 and 71% for 24 hour Holter recordings, 88 and 71% for 48 hour recordings and 89 and 75% for 72 hour recordings. Overall predictive accuracy was 76, 76 and 79%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amiodarone; Benzofurans; Electrocardiography; Humans; Long-Term Care; Monitoring, Physiologic; Tachycardia

Ventricular tachycardia induced by programmed electrical stimulation during amiodarone therapy often does not preclude a good clinical response. The purpose of this study was to determine whether use of discriminant analysis could distinguish patients who remained asymptomatic from those who subsequently developed symptomatic ventricular tachycardia or cardiac arrest. Studies were performed in 37 patients with sustained ventricular tachycardia who still had ventricular tachycardia induced during programmed electrical stimulation during amiodarone therapy. The mean follow-up time was 14.1 +/- 1.3 months (+/- SEM). Twenty-three patients remained asymptomatic, whereas 14 patients had symptomatic recurrence of their ventricular tachycardia. In patients with recurrence of arrhythmia compared with asymptomatic patients, administration of amiodarone caused a longer ventricular effective refractory period (296 +/- 8 versus 271 +/- 7 ms, p less than 0.05) and a greater change in corrected QT [QTc] interval (90 +/- 18 versus 44 +/- 9 ms, p less than 0.02), but no difference in the decrease in premature ventricular complexes after treatment with amiodarone. During amiodarone therapy, nonbundle branch reentrant repetitive ventricular responses were induced by a single ventricular extrastimulus during sinus rhythm in 9 of 14 patients with recurrent arrhythmias compared with 2 of 21 asymptomatic patients (p = 0.001). Also, less aggressive pacing techniques were required to induce ventricular tachycardia in 9 of 14 symptomatic patients compared with 4 of 23 asymptomatic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiodarone; Benzofurans; Electrocardiography; Electrophysiology; Female; Humans; Long-Term Care; Male; Middle Aged; Recurrence; Risk; Tachycardia

The prognostic importance of electrophysiologic studies in patients with sustained ventricular tachyarrhythmias treated with amiodarone was prospectively studied in 100 consecutive patients. Sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) was inducible in all patients before amiodarone therapy. After amiodarone administration 2 groups of patients were identified. In group 1 patients the ventricular tachyarrhythmia was no longer inducible and in group 2 patients the arrhythmia remained inducible. In group 1, no recurrent arrhythmia occurred during a follow-up of 18 +/- 10 months. In group 2, 38 of 80 patients (48%) had arrhythmia recurrence during a follow-up of 12 +/- 9 months. The difference between group 1 and 2 could not be explained by clinical variables, amiodarone doses or plasma concentrations, or electrocardiographic variables. In patients in whom cardiovascular collapse or other severe symptoms where noted during electrophysiologic study after amiodarone treatment, recurrences caused sudden death (n = 12). However, in patients in whom the induced arrhythmia produced moderate symptoms, the recurrent arrhythmia was nonfatal VT (n = 26). Electrophysiologic testing provides clinical guidance and predicts prognosis in patients treated with amiodarone as it does for the evaluation of other antiarrhythmic agents.

Topics: Adult; Aged; Amiodarone; Benzofurans; Coronary Disease; Electrophysiology; Female; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Tachycardia; Time Factors; 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

Thirteen patients with refractory, recurrent, life-threatening ventricular tachycardia (VT) underwent electrophysiologic testing before and after long-term amiodarone therapy. Nine patients (69%) had coronary artery disease, 3 (23%) had nonischemic cardiomyopathy and 1 patient (8%) had mitral valve prolapse. At control electrophysiologic study, programmed electrical stimulation (PES) induced VT in all patients: sustained VT in 11 and nonsustained VT in 2 (9 beats and 31 beats). After oral loading with amiodarone, 1200 mg/day for 14 days, followed by maintenance therapy with 408 +/- 20 mg/day (mean +/- standard error of the mean), repeat PES at 6 +/- 1.6 months revealed inducible VT in 12 of 13 patients: sustained VT in 11 and nonsustained VT (32 beats) in 1 patient. Inducible VT was suppressed in only 1 patient. Amiodarone significantly increased sinus cycle length, PR interval, QRS duration and right ventricular effective refractory period. Insignificant increases in AH, HV and QTc intervals were noted. At 24 +/- 2 months, 8 patients (62%) (all with inducible VT at late PES) were free of clinical arrhythmic events (syncope or sudden death), compared with 5 patients (38%) (4 with inducible VT at late PES) with events. There were no significant differences in the induced VT cycle length, VT cycle length change, ease of inducibility or hemodynamic response to induced VT at late PES in patients with and without arrhythmic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electric Stimulation; Electrophysiology; Female; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Recurrence; Tachycardia; Time Factors

Topics: Adult; Amiodarone; Benzofurans; Humans; Liver; Lysosomes; Male; Middle Aged; Tachycardia

In 65 patients a single oral dose of amiodarone (30 mg/kg) produced an antiarrhythmic effect on supraventricular or ventricular arrhythmias within 3 to 8 hours and lasted for 17 to 19 hours. On the second day a 15-mg/kg dose reproduced this effect within 3 to 9 hours. Plasma concentration of amiodarone increased to a maximum (2.2 +/- 1.7 mg/liter) mean +/- standard deviation) at 6 +/- 3.5 hours and plasma levels of N-desethylamiodarone (NDA) rose to 0.2 +/- 0.08 mg/liter at 12 +/- 6.4 hours. Sixty-one other patients were given a single 30-mg/kg dose 7 hours to 4 days before open heart surgery. Biopsies of the right atrial and left ventricular walls were taken during surgery. Myocardial concentration of amiodarone was maximal in the atrium after 7 hours (13 +/- 8 mg/kg) and in the ventricle after 24 hours (17 +/- 11 mg/kg). NDA myocardial concentration increased progressively until 24 hours and then remained stable over 4 days (1.5 mg/kg). The amiodarone myocardial to plasma concentration ratio was similar in the atrium and in the ventricle and averaged 22 and 10 for amiodarone and NDA, respectively. A significant relation existed between amiodarone concentration and the effect on ventricular premature complexes (r = 0.74, p less than 0.001) and between amiodarone plasma concentration and the effect on the atrioventricular conduction (r = 0.58, p less than 0.001). The plasma concentration of amiodarone corresponding to a 60% decrease in arrhythmias averaged 1.5 to 2 mg/liter.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrioventricular Node; Benzofurans; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Myocardium; Tachycardia; Time Factors

A dose-dependent cutaneous leukocytoclastic vasculitis developed in a 34 year old man who was given amiodarone for supraventricular tachycardias resistant to other drugs. This adverse reaction disappeared within 2 weeks after discontinuation of amiodarone despite its very long half-life of 52 days in this patient. During previous treatment periods with amiodarone, the patient had experienced photosensitivity and dose-dependent polyserositis. Since high doses of amiodarone have been recently proposed for the treatment of resistant cardiac arrhythmias, dose-dependent adverse effects as described here may be encountered with increasing frequency.

Topics: Adult; Amiodarone; Benzofurans; Humans; Male; Necrosis; Photosensitivity Disorders; Serositis; Tachycardia; Vasculitis, Leukocytoclastic, Cutaneous

A 61 year old man with mild aortic stenosis and chronic depression took 12.5 mg digoxin in a suicide attempt. Ventricular tachycardia and fibrillation were resistant to lignocaine and to phenytoin but responded to intravenous amiodarone, with restoration of pacing. Because of persistent hyperkalaemia he was also treated with Fab fragments of digoxin specific antibody, which bound most of the ingested digoxin. It is suggested that the treatment of choice in severe digoxin poisoning is amiodarone for ventricular arrhythmias followed by pacing if necessary and the use of Fab antibody fragments if hyperkalaemia persists.

Topics: Amiodarone; Benzofurans; Digoxin; Electrocardiography; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Tachycardia

This study was performed to ascertain whether intravenous amiodarone would revert supraventricular tachycardias to sinus rhythm, and if so, whether this effect depended upon the underlying mechanism of the arrhythmia. Fourteen patients were studied. Seven had Wolff-Parkinson-White (WPW) syndrome, 1 had dual atrioventricular nodal pathways and 1 an ectopic atrial tachycardia. Five patients had atrial fibrillation without accessory pathways. An atrial electrode was inserted to initiate tachycardias and record the electrogram. If tachycardias were stable for more than 5 min, amiodarone (5 mg/kg) diluted with dextrose saline was infused intravenously over 5 min. Two electrocardiographic leads and the right atrial electrogram were monitored. In 7 patients with atrial fibrillation (2 with accessory pathways), 6 did not revert to sinus rhythm, 1 reverted only after 1 hr. In 5 cases without accessory pathways the ventricular rate fell 5-10 min after commencing amiodarone. Four of the 5 patients with WPW syndrome and re-entrant tachycardias returned to sinus rhythm within 6 min of commencing the infusion (atrioventricular and ventriculoatrial times increased by 0-38% and 0-14% respectively). (Tachycardias terminated in the anterograde limb.) Three patients underwent intermittent right atrial stimulation for 1 hr. No tachycardias could be initiated for 30 min post amiodarone. The ectopic atrial tachycardia and that due to dual atrioventricular nodal pathways terminated within 7 and 2 min, respectively, of commencing intravenous amiodarone. Thus the use of intravenous amiodarone would be appropriate in the acute management of sustained supraventricular tachycardias.

Topics: Adolescent; Adult; Aged; Amiodarone; Atrial Fibrillation; Atrioventricular Node; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Ventricles; Humans; Injections, Intravenous; Male; Middle Aged; Tachycardia; Wolff-Parkinson-White Syndrome

A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.

Topics: Adult; Amiodarone; Atrial Fibrillation; Atrial Flutter; Benzofurans; Combined Modality Therapy; Exercise Test; Humans; Male; Motor Neurons; Neural Conduction; Neuromuscular Diseases; Pacemaker, Artificial; Pericardial Effusion; Pleural Effusion; Pneumonia, Aspiration; Pneumonia, Lipid; Tachycardia

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Electrocardiography; Female; Humans; Injections, Intravenous; Male; Middle Aged; Tachycardia

Topics: Amiodarone; Benzofurans; Humans; Hypokalemia; Tachycardia

We report two patients who developed symptomatic life-threatening ventricular tachyarrhythmias with changing QRS axes (resembling torsades de pointes), during treatment of their supraventricular tachycardias with oral amiodarone. Like other effects of amiodarone on the body, the arrhythmias became evident several days after initiating therapy, at which time electrocardiographic QT prolongation was present. The arrhythmias subsided after amiodarone treatment was withdrawn. No other drugs or electrolyte disturbances could be incriminated as a cause.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Digoxin; Electrocardiography; Female; Humans; Tachycardia

Amiodarone hydrochloride is an antiarrhythmic drug which produces a keratopathy and anterior subcapsular lens opacities that are usually asymptomatic. Serial observations for eye findings were made in 21 patients on a daily dosage of 200-600 mg for periods ranging from six months to three years. Corneal deposits developed in all 21 patients and anterior lens opacities developed in 12 of 20 phakic patients. Resolving keratopathy was present in three patients for periods of at least seven to 20 months after amiodarone was discontinued.

Topics: Adult; Aged; Amiodarone; Benzofurans; Cataract; Corneal Opacity; Follow-Up Studies; Humans; Middle Aged; Risk; Tachycardia

Topics: Aged; Amiodarone; Atrioventricular Node; Benzofurans; Humans; Injections, Intravenous; Male; Tachycardia

Previous studies have shown that amiodarone prevents sustained ventricular arrhythmias in 77% to 93% of patients. To date, a study using statistical analysis to verify the drug's effectiveness has not been reported. Amiodarone was given to 17 patients with drug refractory sustained ventricular arrhythmias. All patients had serious underlying heart disease including coronary artery disease (15 patients) or cardiomyopathy (two patients). Ten patients had angiographic evidence of a left ventricular aneurysm. All patients had left ventricular dysfunction. The mean left ventricular ejection fraction was 33%. In the 5.5 +/- 8.3 months prior to amiodarone, these 17 patients had documented sustained ventricular arrhythmias requiring countershock (41 episodes), overdrive pacing (four episodes), or intravenous drugs (three episodes). Amiodarone was given as a loading dose (1 gm/day for 10 days) and a maintenance dose (200 to 600 mg/day). During a follow-up period of 8.9 +/- 5.7 months, only eight episodes occurred requiring countershock (5) or overdrive pacing (2); one patient died suddenly. A statistical test constructed for this problem showed a significant (p greater than 0.001) reduced risk of experiencing a sustained ventricular arrhythmia after amiodarone. This statistical model confirms previous studies showing that amiodarone prevents sustained ventricular arrhythmias and prevents sudden cardiac death.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Cardiomyopathies; Coronary Disease; Drug Resistance; Female; Follow-Up Studies; Heart Aneurysm; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Tachycardia; Ventricular Fibrillation

The clinical significance of sustained nonclinical ventricular tachycardia (VT) induced during electrophysiologic studies was studied in 10 amiodarone-treated patients. Nine patients had previous myocardial infarction while 1 patient had right ventricular dysplasia. All patients had only a single morphologic type of VT recorded during the multiple spontaneous episodes of tachycardia. After serial pharmacological electrophysiologic testing, the patients were placed on antiarrhythmic regimens which included amiodarone in all cases. These drugs did not prevent the induction of nonclinical VT in any of the 10 patients and of sustained clinical VT in 7 patients. Nonclinical VT was sustained, requiring cardioversion (7 patients) or rapid ventricular pacing (3 patients) for termination. After a mean follow-up period of 27 +/- 10 months (range 12 to 36 months), 4 patients did not exhibit recurrent VT, 3 patients with inducible clinical VT experienced a recurrent episode of clinical VT after 16, 27 and 49 months, respectively, 2 patients had nonarrhythmia related deaths after 11 and 12 months, and 1 patient died suddenly after 17 months. These results suggest that laboratory induction of sustained nonclinical VT in amiodarone-treated patients does not imply the likelihood of their future spontaneous occurrence and, therefore, their prevention may not be required.

Topics: Adult; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Electrophysiology; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Tachycardia; Time Factors

In 23 patients with symptomatic severe supraventricular and ventricular tachyarrhythmias the effectiveness and the side effects of a long-term therapy with the class III antiarrhythmic drug Amiodarone (Cordarone) in a dosage of 100-800 mg/die in monotherapy and combination therapy were investigated. In these cases it proved to be an excellently effecting antiarrhythmic drug in tachycardiac dysrhythmias at atrial and ventricular level with an altogether good tolerance. In 16 patients side effects appeared and above all concerned corneal micro-deposition without any clinical symptoms (10 patients). In 3 patients nuclear-medically insignificant changes of the function of the thyroid gland were found--also without clinical relevance. Three times a photosensitisation was conspicuous, only in one patient the therapy was finished on account of epigastric trouble after three months. Av-blockings of higher degree, particularly with bundle-branch block and severe sinus bradycardias as well as disturbances of the thyroid function are regarded as contraindications without preceding pacemaker implantation.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Bradycardia; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Tachycardia; Thyroid Gland; Thyroxine; Triiodothyronine

The effect of amiodarone on survival was assessed in patients with hypertrophic cardiomyopathy and ventricular tachycardia in a drug trial with historical controls. During 1976 and 1977, 24 hour (seven) or 48 hour (79) electrocardiographic monitoring was performed in 86 consecutive patients; 24 had ventricular tachycardia and received conventional antiarrhythmic agents. Nineteen clinical, echocardiographic, and haemodynamic features were assessed. Seven patients died suddenly during follow up of three years; of these, five had continued to have ventricular tachycardia and two had no documented ventricular tachycardia. During 1978 and 1979, ventricular tachycardia was detected during 48 hour electrocardiographic monitoring in 21 of the next 82 consecutive patients with hypertrophic cardiomyopathy. They received amiodarone (150-400 mg/day, median 300); ventricular tachycardia was suppressed in all during repeat 48 hour electrocardiographic examination. Two patients died suddenly during a three year follow up, but neither belonged to the amiodarone treated group with ventricular tachycardia. The clinical and haemodynamic variables were similar in patients taking amiodarone and conventional agents. The fact that control of ventricular arrhythmia with amiodarone is significantly associated with improved survival suggests that amiodarone may prevent sudden death in patients with hypertrophic cardiomyopathy and ventricular tachycardia.

Topics: Amiodarone; Benzofurans; Cardiomyopathy, Hypertrophic; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Prognosis; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Polyneuropathies; Tachycardia

The role that the new antiarrhythmic agents, such as verapamil and amiodarone, might play in the therapeutic strategy of tachycardia-induced fetal heart failure remains to be determined.

Topics: Adult; Amiodarone; Benzofurans; Female; Fetal Diseases; Fetal Heart; Heart Failure; Heart Rate; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Tachycardia; Verapamil

Topics: Amiodarone; Benzofurans; Cardiomyopathy, Hypertrophic; Humans; Tachycardia

The refractory periods during cardiac pacing were studied in 13 patients with the Wolff-Parkinson-White syndrome. The right atrial and right ventricular refractory periods and refractory period of the accessory pathway (anterogradely and retrogradely) were studied at 2 pacing cycle lengths before and after therapy with oral amiodarone (8,400 to 11,200 mg given in 4 to 6 weeks). The right atrial and right ventricular effective refractory period shortened significantly when the pacing rate was increased during the control study, and also after oral amiodarone administration. The anterograde and retrograde effective refractory period of the accessory pathway also shortened significantly at control study, but not during treatment with oral amiodarone. This indicated that amiodarone blunted the rate-dependent shortening in the refractory period of the accessory pathway. The rate-dependent increase in refractoriness of the accessory pathway could not be predicted or determined in all patients. In 5 patients a rate-dependent increase in the effective refractory period of the accessory pathway was observed in the anterograde direction and in 3 patients in the retrograde direction while they were receiving oral amiodarone therapy. When these data were correlated with the mode of induction and termination of tachycardia, however, a possible effect was found in only 1 patient. Further investigation of new antiarrhythmic drugs should include the development of components resulting in a reliable and predictable increase in refractoriness when the heart rate increases. This would result in prompt termination of reentrant tachycardia by creating block for the circulating impulse.

Topics: Administration, Oral; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electrophysiology; Heart Atria; Heart Conduction System; Heart Ventricles; Humans; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Female; Follow-Up Studies; Humans; Infusions, Parenteral; Male; Middle Aged; Tachycardia

Intravenous amiodarone has a clear anti-arrhythmic effect on induced sustained ventricular tachycardia (VT) in pigs with subacute myocardial infarction. Degeneration of the VT into ventricular fibrillation is almost abolished, and conversion of VT into sinus rhythm by programmed stimulation is enhanced.

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Benzofurans; Female; Swine; Tachycardia; Ventricular Fibrillation

Topics: Adult; Amiodarone; Benzofurans; Epididymitis; Humans; Male; Middle Aged; Tachycardia

We report the case of a patient who developed a life-threatening polymorphous ventricular tachycardia ( PVT ) after six weeks of treatment with amiodarone. The Q-T interval was markedly prolonged at 0.86 second. The drug induction of PVT was strongly suggested by the fact that PVT resolved four days after withdrawal of amiodarone when the Q-T interval had shortened to 0.60 second; the arrhythmia has not recurred in the nine months of follow-up since then. Amiodarone, though a very effective antiarrhythmic agent, may induce serious PVT .

Topics: Aged; Amiodarone; Benzofurans; Electrocardiography; Heart Ventricles; Humans; Male; Tachycardia

A patient with automatic atrial tachycardia refractory to all conventional therapies is described. Amiodarone controlled the tachycardia by causing a progressive decrease in the rate of discharge from the atrial focus. We conclude that 1) amiodarone was effective therapy for automatic atrial tachycardia, avoiding the need for nonmedical therapy; and 2) amiodarone appeared to act by decreasing spontaneous automaticity.

Topics: Amiodarone; Atrioventricular Node; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Heart Atria; Humans; Male; Middle Aged; Tachycardia

Using His bundle electrograms and programmed ventricular stimulation, the effects of chronic amiodarone treatment on induction, morphology, and the rate of ventricular tachycardia (VT) were studied in 17 consecutive patients treated with amiodarone for control of recurrent sustained VT or ventricular fibrillation. Studies were done before and after treatment with amiodarone for an average duration of 5.3 (range 2 to 18) months. During the control study, sustained VT could be induced in 16 patients. VT was initiated by single or double right ventricular (RV) extrastimuli in 14 patients, by double left ventricular (LV) extrastimuli in 1 patient, and by RV burst pacing in 1 patient. Only one pattern (morphology) of VT similar to that of spontaneous VT was induced in 12 patients and two patterns of VT in 4 patients. The average cycle length (CL) (mean +/- SD) of induced VT was 325.8 +/- 61.2 ms. After amiodarone, VT could be induced in 7 of 17 patients and was initiated by single RV extrastimuli in 5 patients, double RV extrastimuli in 1 patient, and RV burst pacing in 1 patient. In 3 of 5 patients in whom VT could be initiated by single RV extrastimuli, initiation of VT required double RV or double LV extrastimuli in the control study; in 1 of 5 patients VT could not be induced in the control study. Amiodarone induced nonclinical, polymorphic VT in 4 patients in whom only clinical VT could be induced during the control study. Compared to control, the CL of induced VT was significantly longer (322 +/- 65.7 vs 416 +/- 41.5 ms; P less than 0.001).+

Topics: Adult; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Electrophysiology; Follow-Up Studies; Heart Conduction System; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia

Topics: Amiodarone; Benzofurans; Half-Life; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Tachycardia

Sudden death in Wolff-Parkinson-White syndrome (WPW) is related to a very fast ventricular response to spontaneous atrial fibrillation (AF) conducted via accessory pathway (AP). The effect of oral amiodarone was studied in 12 patients with WPW syndrome and life-threatening rapid ventricular response via an AP during spontaneous AF. The effective refractory period of the AP in the anterograde direction was 280 ms or less during control study in all patients. After amiodarone therapy, the effective refractory period remained 280 ms or less in 7 of the 12 patients. During incremental atrial pacing, the longest atrial pacing cycle length that produced block over an AP ranged from 200 to 310 ms (mean 261 +/- 42) during the control period and 240 to 980 ms (mean 377 +/- 198) after amiodarone therapy. During AF the shortest ventricular response via the AP could be measured in 10 of 12 of the patients both before and after amiodarone treatment and ranged from 200 to 290 ms (234 +/- 30) and 250 to 500 (mean 302 +/- 75), respectively (p less than 0.01). The average RR interval during AF before and after the drug ranged from 200 to 390 ms (mean 280 +/- 55) and 280 to 650 ms (mean 396 +/- 116), respectively (p less than 0.01). Thus, the safety of amiodarone in the WPW syndrome should be established by electrophysiologic studies and induction of AF, because amiodarone is not protective in all patients with WPW.

Topics: Adolescent; Adult; Amiodarone; Atrial Fibrillation; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Conduction System; Humans; Male; Middle Aged; Prospective Studies; Tachycardia; Wolff-Parkinson-White Syndrome

The clinical efficacy and electropharmacologic effects of continuous intravenous (i.v.) amiodarone infusion (10 to 20 mg/kg/day for 4 to 7 days) followed by chronic oral amiodarone therapy (400 to 800 mg/day for 24 to 53 days) were evaluated in 17 patients with refractory sustained ventricular tachycardia (VT) or ventricular fibrillation. Intravenous amiodarone infusion prolonged the RR interval (from 754 +/- 85 to 860 +/- 157 ms, p less than 0.05), PR interval (from 192 +/- 53 to 212 +/- 54 ms, p less than 0.01) QRS duration (from 103 +/- 21 to 117 +/- 25 ms, p less than 0.001) and QTc interval (from 423 +/- 22 to 466 +/- 31 ms, p less than 0.001). Chronic oral amiodarone treatment had similar but more pronounced effects on electrocardiographic intervals. The ventricular effective refractory period tended to prolong after i.v. amiodarone infusion (p less than 0.1 to greater than 0.05) but prolonged significantly after chronic oral amiodarone (p = 0.025). Mean serum amiodarone concentration was 1.7 +/- 1.0 mg/liter with infusion and 1.5 +/- 0.6 mg/liter with oral therapy. Intravenous amiodarone infusion suppressed spontaneous VT in 5 of 9 patients with frequent VT recurrences, but had no effect on cycle length of spontaneous VT. Chronic amiodarone therapy either suppressed spontaneous VT recurrences or prolonged cycle length during VT recurrences. VT induction after i.v. amiodarone was not predictive of VT induction or spontaneous VT recurrences after chronic oral amiodarone treatment. Thus, i.v. amiodarone has limited value in acute control of VT and clinical or electrophysiologic response to it is not predictive of long term therapeutic results with amiodarone.

Topics: Administration, Oral; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Ventricles; Humans; Infusions, Parenteral; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Although amiodarone has been used for the suppression of complex ventricular arrhythmias since the early 1970s, there is a paucity of information regarding the relation of serum concentration to arrhythmia suppression. To investigate this relation, 25 patients receiving chronic amiodarone therapy for complex ventricular arrhythmias were retrospectively studied. At each visit a blood sample for determination of trough serum amiodarone concentration and a 24-hour 2-channel ambulatory electrocardiogram (ECG) were obtained. Dosage was adjusted, based on the ambulatory ECG, to maintain arrhythmia suppression at the lowest possible amiodarone dose and, hence, because of the extremely long half-life of amiodarone, patients were rarely in a true steady state. Over 17 months, 218 ambulatory ECGs with corresponding serum samples were analyzed. Negative correlations between serum amiodarone concentration and the frequencies of premature ventricular complexes (PVCs), paired PVCs and ventricular tachycardia were found (p less than 0.005, p less than 0.005 and p less than 0.05, respectively). No correlations existed between amiodarone dose and these arrhythmias. Trough serum amiodarone concentrations greater than 2.0 micrograms/ml were associated with significant reductions in the frequencies of PVCs (p less than 0.01) and paired PVCs (p less than 0.02) when compared with serum concentrations below this level. A reduction in ventricular tachycardia was seen with serum concentrations greater than 1.5 micrograms/ml (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiodarone; Benzofurans; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Retrospective Studies; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis; Tachycardia

The relationship of apparent steady-state serum concentrations of amiodarone and its metabolite, desethylamiodarone, to therapeutic and toxic effects was assessed in 127 patients who had treatment-resistant ventricular or supraventricular arrhythmias or were intolerant to other agents. After at least 2 months (mean, 9.8) of treatment with daily maintenance doses of 200 to 600 mg, arrhythmias were effectively suppressed in 78% of patients. Arrhythmias recurred in 47% of patients with serum amiodarone concentrations of less than 1.0 mg/L, whereas only 14% of patients with higher concentrations had recurrences (p less than 0.005). Side effects, most of them mild, occurred in 57%; only 9 patients required discontinuation of drug therapy. The risk of developing adverse reactions was related to serum amiodarone concentrations (p less than 0.0001). Adverse reactions were common in patients with serum values exceeding 2.5 mg/L, although pulmonary complications did occur at lower concentrations. Monitoring serum amiodarone concentrations may differentiate failure of drug therapy from suboptimal dosing and reduce the incidence of concentration-related side effects.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Tachycardia; Ventricular Fibrillation

Amiodarone is a potent new antiarrhythmic drug that has multiple effects on thyroid function, including inhibition of extrathyroidal triiodothyronine production and rarely, iodine-induced hypothyroidism. This report describes a man with recurrent ventricular tachycardia in whom hypothyroidism developed during amiodarone therapy and who died of probable myxedema coma. Parenteral and oral thyroxine therapy promptly reduced serum thyroid-stimulating hormone concentrations without increasing the patient's very low serum triiodothyronine concentration. This response to thyroxine suggests that thyroxine itself may have biologic activity and participate directly in regulation of thyrotropin secretion. Because amiodarone-induced hypothyroidism may be life-threatening, thyroid function should be monitored before and during amiodarone therapy, and the drug discontinued or appropriate therapy instituted if hypothyroidism develops.

Topics: Aged; Amiodarone; Benzofurans; Coma; Humans; Male; Myxedema; Tachycardia; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

Topics: Amiodarone; Antipyrine; Benzofurans; Drug Interactions; Heart Ventricles; Humans; Kinetics; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pneumonia; Pulmonary Alveoli; Radiography; Tachycardia

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Middle Aged; Tachycardia

We report a patient with fibrosing alveolitis associated with amiodarone therapy. Review of the literature suggests that amiodarone induced pulmonary disease generally occurs on a maintenance dose of at least 400 mg of amiodarone daily; there is however a wide range in the duration of therapy or total dose administered prior to presentation.

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis; Tachycardia; Time Factors

Topics: Acenocoumarol; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Drug Synergism; Female; Humans; Middle Aged; Tachycardia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Tachycardia

Amiodarone and a metabolite, desethylamiodarone, were measured in plasma of 55 patients and in both plasma and red blood cell (RBC) in 28 patients who received chronic amiodarone treatment. The assay for amiodarone and desethylamiodarone was performed by high-pressure liquid chromatography. During chronic treatment, median plasma concentration of amiodarone was 2.80 micrograms/ml and desethylamiodarone was 2.20 micrograms/ml. In matched samples, plasma amiodarone concentration exceeded RBC amiodarone concentration (p less than 0.001) and the RBC-to-plasma concentration ratio averaged 0.31. The plasma desethylamiodarone concentration was not significantly different from its RBC concentration, and the RBC-to-plasma concentration ratio averaged 1.29. There was a linear correlation between plasma concentrations of amiodarone and desethylamiodarone (r = 0.82) and between RBC concentrations of drug and metabolite (r = 0.71). Drug or metabolite concentrations in plasma and RBCs correlated directly with daily dosage of amiodarone. Adverse side effects during chronic amiodarone therapy were related most strongly to RBC drug and metabolite concentrations. The group with adverse side effects had a significantly higher RBC concentration of amiodarone, 150 vs 0.75 micrograms/ml (p less than 0.001), than did patients free of adverse effects. After dosage reduction, side effects abated and plasma and RBC concentrations of drug and metabolite decreased. These data indicate that there is an expected range of amiodarone and desethylamiodarone concentrations during chronic treatment and that adverse side effects correlate best with RBC concentrations of drug and metabolite. Red cell concentrations may reflect the amount of unbound, free amiodarone and desethylamiodarone in plasma.

Topics: Amiodarone; Anorexia; Benzofurans; Erectile Dysfunction; Erythrocytes; Humans; Male; Nausea; Saliva; Tachycardia; Ventricular Fibrillation

The time course and the mode of antiarrhythmic action of Amiodarone was studied after acute i.v. injection of the drug (5 mg/kg in 5 min) to four patients with junctional reciprocating tachycardia. Electrophysiological studies were performed before and 1 and 2 hours after Amiodarone injection. It was impossible or considerably more difficult to induce junctional reciprocating tachycardia after Amiodarone, and the drug's effect was detectable mainly on the AV node. Kinetic analysis of blood levels of Amiodarone during the electrophysiological study did not support a direct association between blood concentration and its effects.

Topics: Adult; Aged; Amiodarone; Atrioventricular Node; Benzofurans; Cardiac Catheterization; Electrophysiology; Heart Conduction System; Humans; Injections, Intravenous; Middle Aged; Tachycardia

In 12 patients (nine with Wolff-Parkinson-White syndrome and three with ventricular tachycardia) the electrophysiologic effects of intravenous (5 mg/kg body weight in 1 min) and oral (total dose 9800 to 11,200 mg) amiodarone were studied with programmed stimulation of the heart. Intravenous and oral amiodarone had a similar (p less than .05) effect of lengthening on the effective refractory period of the atrioventricular node. Only intravenous amiodarone prolonged (p less than .05) the AH interval. Oral amiodarone was more effective than intravenous amiodarone in lengthening the anterograde effective refractory period of the accessory atrioventricular pathway. Only oral amiodarone prolonged the effective refractory period of atrium and ventricle and the HV interval, all significantly (p less than .05). Intravenous amiodarone slowed (p less than .05) the rate of circus-movement tachycardia in patients with Wolff-Parkinson-White syndrome, and further slowing was observed after oral amiodarone. Termination of tachycardia by intravenous amiodarone predicted prevention of reinitiation of tachycardia during oral amiodarone. These data indicate that intravenous and oral amiodarone do not have the same electrophysiologic effects. It is not clear whether cumulative effects, active metabolites, or both are responsible for these differences.

Topics: Administration, Oral; Adolescent; Adult; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Child; Electrocardiography; Electrophysiology; Female; Heart Conduction System; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Tachycardia; Wolff-Parkinson-White Syndrome

This study evaluates whether the electrophysiologic effects of i.v. amiodarone in patients with reentrant supraventricular tachycardia (SVT) can predict the efficacy of long-term oral therapy with this drug. The effects of oral and i.v. amiodarone were studied in 27 patients with SVT. In 14 the SVT circuit involved a concealed atrioventricular bypass for retrograde conduction (Group I), and in 13 a concealed atrio-His bypass (Group II). Intravenous amiodarone induced significant prolongation of the AH interval, the refractory periods of the atrium, atrioventricular node, His-Purkinje system and ventricular myocardium. The ventriculoatrial interval was slightly prolonged in Group I patients and did not change in Group II patients after i.v. administration of the drug. In both groups, the effective refractory period (ERP) of the concealed bypass was prolonged by i.v. amiodarone. During control state, SVT could be induced in all patients; after i.v. administration of the drug, SVT was presented in 6 patients in Group I and in 8 patients in Group II. In all cases, in which i.v. amiodarone prolonged the ERP of the concealed bypass to more than 350 ms, the drug always prevented SVT even when given orally. All but 2 patients--1 from Group I and 1 from Group II--remained asymptomatic after oral amiodarone. In the patient from Group I, SVT had been prevented by i.v. amiodarone, whereas in the patient from Group II SVT could not be induced by ventricular stimulation during the control state, but appeared after i.v. administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Amiodarone; Atrioventricular Node; Benzofurans; Child; Electrocardiography; Electrophysiology; Female; Heart Conduction System; Humans; Male; Middle Aged; Tachycardia

Electrophysiologic studies were performed in nine patients with reentrant paroxysmal supraventricular tachycardia (PSVT) during a control period and following 5 mg/kg body weight of intravenous amiodarone (Cordarone, Labaz) administered as a slow continuous infusion over 15 to 20 minutes. All nine patients had induction of sustained PSVT during control studies. In seven of nine patients (group 1) the tachycardia was due to atrioventricular (AV) nodal reentry, and in two of nine patients (group 2) a concealed retrograde bypass tract was incorporated in the reentrant process. In group 1, following amiodarone, all seven patients lost the ability to sustain PSVT with either absence of atrial echoes (one patient) or induction of less than or equal to 3 echo beats (six patients) with termination of PSVT in the antegrade pathway (three patients) or retrograde pathway (two patients) or both (one patient). In group 2, following amiodarone, both patients lost the ability to sustain PSVT with absence of atrial echoes (one patient) on induction of a single echo beat (one patient) with block in the retrograde pathway (i.e., the concealed retrograde bypass tract). Amiodarone significantly increased (1) atrial cycle length for AV nodal Wenckebach block, (2) antegrade functional refractory period of the AV node, (3) antegrade effective refractory period of the AV node, (4) ventricular paced cycle length for ventricular atrial block, and (5) the retrograde functional refractory period of the ventricular-atrial conducting system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Amiodarone; Benzofurans; Cardiac Catheterization; Depression, Chemical; Electrocardiography; Heart Conduction System; Heart Ventricles; Humans; Infusions, Parenteral; Male; Middle Aged; Tachycardia; Time Factors

Twenty-four mongrel dogs were divided into two equal groups to determine the effects of orally administered amiodarone on left ventricular function. Measurements of left ventricular function included left ventricular contractility as denoted by maximum rate of rise of left ventricular pressure (dP/dtmax), cardiac index (CI), left ventricular stroke work index (LVSWI), and peripheral vascular resistance (PVR). Left ventricular function was measured in 6 of the 12 animals in Group 1 before and after 14 days of amiodarone administered orally; the remaining animals served as controls. The dP/dtmax was reduced from 2,855 to 1,291 mm Hg/sec (p less than 0.01), and LVSWI fell from 1.6 to 0.74 gm-m/beat/kg (p less than 0.05) in the 6 animals given amiodarone. The 12 animals in Group 2 underwent 30 minutes of ischemic arrest. Six animals in Group 2 underwent 30 minutes of ischemic arrest. Six animals were given amiodarone orally for 14 days prior to cardiopulmonary bypass and ischemic arrest; the other 6 served as controls. Before cardiopulmonary bypass, the dogs administered amiodarone had significantly greater depression of dP/dtmax (p less than 0.01) and LVSWI (p less than 0.05). Thirty minutes of ischemia produced significant depression of left ventricular function in all animals in Group 2. However, a significantly greater reduction in dP/dtmax and LVSWI occurred in those animals receiving amiodarone. Furthermore, 4 of the 6 dogs receiving amiodarone were unable to sustain sufficient cardiac output following cardiopulmonary bypass to permit long-term survival (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Amiodarone; Animals; Benzofurans; Cardiopulmonary Bypass; Dogs; Heart; Heart Function Tests; Heart Ventricles; Hemodynamics; Models, Biological; Stroke Volume; Tachycardia; Vascular Resistance; Ventricular Function

Mild pleuroparenchymal fibrosis associated with amiodarone pulmonary toxicity is reported in a 63-year-old white man; partial radiographic resolution and complete symptomatic resolution with decreasing the daily dosage to 200 mg permitted continued anti arrhythmic therapy.

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases; Male; Middle Aged; Tachycardia

Ten patients with refractory recurrent supraventricular tachycardia were found by electrophysiologic study to have bypass tracts and orthodromic atrioventricular reentrant tachycardia. All had failed to respond to conventional antiarrhythmic therapy and were therefore treated with oral amiodarone (1,600 to 2,000 mg/day for 2 weeks, then 800 to 1,200 mg/day for another 2 weeks with subsequent 200 to 600 mg/day maintenance doses). During or after the fourth week of therapy, electrophysiologic study was repeated. In 9 of 10 patients, supraventricular tachycardia could not be reinduced by programmed stimulation. In the remaining patient, nonsustained supraventricular tachycardia (greater than 10 beats, lasting less than 30 seconds) with a slower basic cycle length than that during the control period was provoked. Significant increases in the effective refractory period of the accessory pathway in both the anterograde (+26%, p less than 0.05) and retrograde (+40%, p less than 0.02) directions were noted, the magnitude of change being independent of the control effective refractory period. There were also significant increases in the effective refractory period of the right atrium (+24%, p less than 0.01) and the right ventricle (+15%, p less than 0.01) during long-term therapy with amiodarone. Over a mean follow-up period of 20 months, symptomatic control of the arrhythmia occurred in all patients; in only one patient treatment with amiodarone could not be continued because of side effects. These data establish the electrophysiologic basis for the effectiveness of amiodarone in the prophylactic control of refractory paroxysmal supraventricular tachycardia complicating the bypass tract syndromes.

Topics: Adult; Aged; Amiodarone; Benzofurans; Digoxin; Electrocardiography; Heart Conduction System; Humans; Male; Middle Aged; Propranolol; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Benzofurans; Electric Countershock; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia

We studied the effects of intravenous amiodarone administration (5 mg/kg) on reproducible repetitive ventricular responses and ventricular tachycardia (VT) induced by programmed electrical stimulation of the heart in 32 patients. Intravenous amiodarone prevented induction of bundle branch reentry in only 2 of 11 patients (18.2%) and did not change His-Purkinje conduction and refractoriness in the remaining 9 of 11 (81.8%) patients. In contrast to the small effect of intravenous amiodarone on bundle branch reentry, the drug completely abolished intraventricular reentry in three of nine (33.3%) patients and in the remaining six of nine (66.7%) patients decreased the number of intraventricular reentrant beats from up to five beats in control to one to two beats after the drug. The drug also prevented induction of VT (greater than or equal to 5 ventricular ectopic beats in a row) in three of five (60%) patients with nonsustained VT and in three of seven (42.9%) patients with sustained VT. In two of seven (28.6%) patients with sustained VT, only nonsustained tachycardia could be induced after drug administration. In another two of seven (28.6%) patients, sustained VT with slower rates was induced after the drug. In 11 of 12 (91.7%) patients with VT the coupling interval between the last stimulus and the first ventricular beat increased after drug administration. These effects of intravenous amiodarone occurred in the absence of effect on ventricular effective refractory period. These findings suggest that intravenous amiodarone might have greater effect on diseased ventricular tissue, the site of reentry in VT, than on healthy ventricular tissue.

Topics: Aged; Amiodarone; Benzofurans; Blood Pressure; Bundle of His; Electric Stimulation; Electrocardiography; Humans; Infusions, Parenteral; Male; Middle Aged; Purkinje Fibers; Tachycardia

Topics: Amiodarone; Benzofurans; Female; Humans; Hypokalemia; Middle Aged; Tachycardia

Amiodarone is a new and powerful antiarrhythmic agent currently under investigation in North America. In the past two years, there have been increasing reports of serious side effects associated with its use, including 14 cases of pneumonitis or pulmonary fibrosis. This report describes a case of acute necrotizing pneumonitis, a complication that has not been observed previously with amiodarone therapy. Amiodarone also appeared to alter carbohydrate metabolism in this patient. Metabolic changes induced by this drug may be mediated by superoxide radicals. A high index of suspicion for pulmonary complications should be maintained in patients taking amiodarone, and nonspecific respiratory complaints should be investigated carefully.

Topics: Acute Disease; Aged; Amiodarone; Benzofurans; Humans; Hyperglycemia; Lung; Male; Necrosis; Pneumonia; Radiography; Tachycardia

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

The effects of long term treatment with oral amiodarone on retrograde conduction ( S2H2 interval) and refractoriness of the His-Purkinje system were studied in 11 patients using His bundle electrograms and the ventricular extrastimulus method. Ten patients had ventricular tachycardia and one supraventricular tachycardia. Electrophysiological studies were carried out before and after the patients had been taking their maintenance dose for a mean duration of 84 days. After amiodarone treatment the HV interval was prolonged in seven patients and unchanged in four. At comparable S1S2 intervals, the S2H2 intervals were longer after treatment with amiodarone in all patients than before. Similarly, the longest S2H2 intervals achieved after amiodarone were longer than the control values. Amiodarone significantly increased the relative, effective, and functional refractory periods of the His-Purkinje system. Thus amiodarone exerts important effects on the His-Purkinje system.

Topics: Adult; Aged; Amiodarone; Benzofurans; Bundle of His; Electrocardiography; Heart Conduction System; Humans; Male; Middle Aged; Neural Conduction; Purkinje Fibers; Refractory Period, Electrophysiological; Tachycardia; Time Factors; Ventricular Fibrillation

Although the antiarrhythmic aspect of amiodarone has been extensively studied, its effects on His-Purkinje system conduction and refractoriness have not been systematically investigated in human beings. In 24 patients, anterograde His-Purkinje system conduction (HV intervals) and variables of His-Purkinje system refractoriness using the ventricular extrastimulus (V2) technique were analyzed before and after long-term therapy with amiodarone. The mean duration of amiodarone therapy at the time of repeat study was 16.2 +/- 7.7 weeks (range 11 to 42). The anterograde His-Purkinje system conduction time (HV interval) measured 49.6 +/- 9.5 ms (range 40 to 80) before and 60.6 +/- 10.7 ms (range 45 to 90) after amiodarone (p less than 0.005). During retrograde refractory period studies, the longest V1V2 interval at which a retrograde His bundle potential (H2) emerged from the V2 electrogram (relative refractory period of the His-Purkinje system) was consistently longer after amiodarone as compared with the control period (376.4 +/- 46.6 versus 318.8 +/- 33.1 ms, p less than 0.005). Similarly, the shortest and longest His-Purkinje system conduction times ( V2H2 interval) at comparable V1V2 intervals were uniformly and significantly prolonged after administration of the drug. Amiodarone also abolished macroreentry in the His-Purkinje system in six of the nine patients who showed such reentry during the control period. The effective refractory period of the ventricular myocardium was also increased from a mean of 227.1 +/- 13.9 to 259.2 +/- 20.2 ms (p less than 0.005) in this series of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Bundle of His; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Conduction System; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Purkinje Fibers; Tachycardia

Administration of amiodarone (600 to 1,600 mg/day) to 28 patients during long-term digoxin therapy (0.25 +/- 0.05 mg/day) increased serum digoxin level from 0.97 +/- 0.45 to 1.98 +/- 0.84 ng/ml (p less than 0.001). Gastrointestinal side effects occurred in nine patients, central nervous system reactions occurred in five and cardiovascular reactions occurred in four. Pharmacokinetic studies in six patients with a 1 mg intravenous digoxin dose before and during amiodarone therapy increased serum digoxin level at 30 minutes from 8.59 +/- 1.68 to 10.07 +/- 1.70 ng/ml (p less than 0.05). Amiodarone caused a 31% prolongation of digoxin elimination half-life from 49.5 +/- 8.8 to 65.0 +/- 28.8 hours, but the increase in half-life was not statistically significant. Total body clearance was reduced significantly (29%, p less than 0.05) from 2.05 +/- 0.76 to 1.46 +/- 0.64 ml/min per kg. Nonrenal clearance also showed a significant decrease (33%, p less than 0.05) from 1.20 +/- 0.46 to 0.80 +/- 0.30 ml/min per kg. The renal clearance decreased by 22% and the volume of distribution decreased by 11% after amiodarone therapy, but these changes were not significant. The data show that the mechanism of digoxin-amiodarone interaction is multifactorial and emphasize the need for close monitoring of serum digoxin levels and clinical features during concurrent digoxin-amiodarone therapy.

Topics: Adult; Aged; Amiodarone; Benzofurans; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Kinetics; Male; Middle Aged; Tachycardia

A major disadvantage of conventional amiodarone therapy is the long delay between initiation of therapy and arrhythmia suppression. In this study, the hypothesis was tested that complex ventricular arrhythmias would be suppressed rapidly by an intravenous amiodarone infusion designed to achieve and maintain a therapeutic serum concentration. Eleven patients were studied. Each underwent a single intravenous dose kinetic study, followed by a two stage infusion of amiodarone that achieved and maintained a serum concentration of 2 to 3 micrograms/ml. In seven patients, arrhythmias during hours 24 to 48 after the infusion were compared with arrhythmias without therapy. Amiodarone therapy reduced episodes of ventricular tachycardia by 85% (p less than 0.01), paired premature ventricular complexes by 74% (p less than 0.01) and premature ventricular complexes by 60% (p less than 0.05). Four patients could not tolerate a control period without therapy because of symptomatic arrhythmias. In three patients, symptomatic arrhythmias were abolished during the 24 hour evaluation period. Two of 11 patients, both with severe left ventricular dysfunction, developed significant hypotension during the loading phase of the infusion. It is concluded that the achievement and maintenance of a therapeutic serum concentration of intravenous amiodarone are effective in the rapid suppression of life-threatening ventricular arrhythmias. Caution should be employed when using large intravenous doses in patients with severely impaired left ventricular function.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Benzofurans; Female; Heart Ventricles; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Recurrent atypical ventricular tachycardia, with a long QT interval, was documented in a 56-year-old patient 16 days after discontinuing amiodarone 200 mg and 400 mg on alternate days. Tachycardia and variable prolongation of myocardial repolarization were abolished by temporary cardiac pacing and correction of mild hypokalaemia.

Topics: Amiodarone; Benzofurans; Bradycardia; Cardiac Pacing, Artificial; Electrocardiography; Female; Humans; Hypokalemia; Middle Aged; Substance Withdrawal Syndrome; Tachycardia

Topics: Adult; Amiodarone; Benzofurans; Female; Fetus; Heart Atria; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Tachycardia

There are a number of important drug interactions with amiodarone. This agent appears to have a marked effect on the kinetics of some commonly used cardiovascular drugs, such as warfarin, digoxin, quinidine, and procainamide, and has dynamic interactions with others, such as the beta blockers and some calcium antagonists. Bleeding has been reported, apparently caused by a potentiation of the anticoagulant effect of warfarin by amiodarone. Torsades de pointes has been observed when quinidine, propafenone, or mexiletine is given together with amiodarone. Furthermore, amiodarone may interact with beta-blocking agents and some of the calcium antagonists to produce symptomatic sinus bradycardia and sinus arrest, especially in a latent or overt sick sinus syndrome. During surgery, amiodarone may induce hypotension and an atropine-resistant bradycardia, possibly by interacting with anesthetic agents. A knowledge of the time of onset, extent, duration, and possible mechanisms of the interactions of amiodarone with other cardioactive drugs is still incomplete, but further studies are of great therapeutic importance.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Benzofurans; Blood Coagulation Disorders; Calcium; Digoxin; Drug Interactions; Drug Synergism; Heart Arrest; Humans; Kinetics; Quinidine; Tachycardia; Warfarin

Fifty-eight patients with symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF) were treated with amiodarone. All had clinical episodes of VT/VF or inducible VT during electropharmacologic testing despite treatment with maximum-tolerated doses of conventional antiarrhythmic agents. Chronic treatment with amiodarone was begun at a dose of 800-1000 mg per day. Thirty-two patients were also treated with a previously ineffective conventional agent. Thirty patients underwent programmed ventricular stimulation after 2.6 +/- 1.7 months (mean +/- S.D.) of treatment with amiodarone at a mean daily dose of 588 +/- 155 mg. VT was induced in 25 patients (sustained in 20, nonsustained in five). Seventeen patients had a recurrence of VT or VF after 0.5-9 months of treatment with amiodarone (fatal in seven, non-fatal in 10). Forty-one patients (71%) had no recurrence of symptomatic VT or VF while being treated with amiodarone (mean follow-up period, 17.1 +/- 12.4 months). Among the 25 patients who had inducible VT with programmed ventricular stimulation while being treated with amiodarone, 19 patients (76%) have had no recurrence of symptomatic VT or VF over a follow-up period of 21.5 +/- 7.3 months. Ambulatory electrocardiographic recordings obtained after one week of treatment with amiodarone were not helpful in predicting clinical response. Twenty-two patients (38%) developed ataxia and/or an intention tremor which improved with a decrease in the amiodarone dose. Amiodarone, either by itself or in combination with conventional antiarrhythmic drugs, has a significant therapeutic effect in high risk patients with refractory VT. The finding of inducible VT during electropharmacologic testing in patients taking amiodarone does not preclude a favorable clinical response. Neurologic toxicity is common in patients treated with 600-800 mg per day of amiodarone.

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

Our use of amiodarone in 200 patients during an 8-year period confirms our previous experience which indicated that the drug was close to being the ideal antiarrhythmic agent in children's arrhythmias. Its absence of cardiac toxicity, its powerful antiarrhythmic properties, its depressive effect on the AV nodal conduction, combined with its beta-inhibitory effect makes it effective and harmless in practically all forms of atrial, junctional and ventricular arrhythmias, whatever the reentrant or automatic mechanism of the arrhythmia. The metabolism is much faster in children than in adults, making the drug active in a few hours, with a lesser prolonged duration of action. Though there is practically no limitation for its use on a short- or mean-term basis, the long-term use must be limited to truly refractory arrhythmias, a situation which is rarely encountered. In such cases, combining amiodarone with conventional therapy allows a decrease in the maintenance dosage and a lower incidence of extracardiac side effects.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Bundle-Branch Block; Child; Electrocardiography; Heart Conduction System; Heart Defects, Congenital; Heart Valve Diseases; Heart Ventricles; Humans; Infant; Tachycardia

The purpose of the present report is to review the available pharmacokinetic information on amiodarone with an emphasis on our own experience in monitoring serum amiodarone concentrations. We have found that 400 mg should be the maximal maintenance dose; if that treatment fails, careful addition of other antiarrhythmic agents is preferable over an increase in amiodarone dosage. Serum concentrations below 2.5 mg/L will significantly improve amiodarone's benefit-to-risk ratio.

Topics: Amiodarone; Animals; Benzofurans; Biological Availability; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Dogs; Half-Life; Humans; Kinetics; Rats; Tachycardia

Fifteen patients aged 59.3 +/- 11.5 years (mean +/- standard deviation [SD]) had recurrent symptomatic ventricular tachycardia (VT) refractory to at least 2 conventional antiarrhythmic drugs. All patients had organic heart disease; 4 had an acute myocardial infarction. The mean ejection fraction was 0.30 +/- 0.09. TWelve patients had overt congestive heart failure. Five had bundle branch block. Before treatment with intravenous amiodarone, the patients had had 6 to 40 episodes of symptomatic VT over 1 to 8 days of hospitalization. All patients received an initial bolus of 5 mg of amiodarone/kg over 15 minutes. Seven patients also received a continuous infusion of 600 to 1,000 mg of amiodarone over 12 to 24 hours. Additional doses depended on the patients' clinical responses. In 11 of 15 patients, antiarrhythmic drugs that had failed to suppress VT were continued during administration of amiodarone. In 12 of 15 patients acute control of VT was obtained with intravenous administration of amiodarone either alone or in combination with previously ineffective drugs. Three patients continued to have frequent episodes of VT while being treated with intravenous amiodarone. Mobitz type I atrioventricular block developed in 1 patient. No patient had high degree atrioventricular block, symptomatic hypotension, or a clinically apparent worsening of congestive heart failure. The use of intravenous amiodarone represents a significant advance in the acute treatment of frequent life-threatening VT refractory to other drugs. With appropriate monitoring, it can be used safely in patients with congestive heart failure, bundle branch block, or acute myocardial infarction.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Heart Block; Heart Failure; Humans; Infusions, Parenteral; Injections, Intravenous; Long-Term Care; Male; Middle Aged; Recurrence; Sinoatrial Node; Tachycardia

Topics: Amiodarone; Benzofurans; Humans; Infusions, Parenteral; Tachycardia

Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for ventricular tachycardia or fibrillation and 31 for supra-ventricular arrhythmias. The mean (range six days to 51 months), permitting a total of 100 patient years of observation. Adverse reactions were observed in 69 patients. Severe side effects were encountered in 13: four patients developed interstitial pneumonitis, four patients developed incessant ventricular tachycardia, three patients taking amiodarone and digoxin sustained sinus node arrest with depression of escape foci, one patient developed hepatitis, and one patient developed hypercalcaemia with renal failure. Furthermore, a rise in the serum concentration of digoxin and potentiation of warfarin anticoagulation occurred in cases in which these agents were combined with amiodarone. Amiodarone was stopped in 14 patients because of side effects. Although amiodarone is effective in suppressing arrhythmias in most patients in whom extensive use of antiarrhythmic drugs has been unsuccessful, it is associated with diverse and serious toxicity. These observations suggest that at present the use of amiodarone should be reserved for patients with life threatening or seriously disabling arrhythmias in whom longer established drugs have been ineffective or are contraindicated.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Pulmonary Fibrosis; Recurrence; Respiratory Function Tests; Tachycardia

Amiodarone is an investigative antiarrhythmic drug in the United States. However, it has been used successfully in European countries for the past 14 years. Amiodarone is effective in the long-term management of resistant supraventricular and ventricular arrhythmias. Although a very useful addition to the antiarrhythmic drugs currently in use, it has potential side effects that have delayed its acceptance by the Food and Drug Administration. The consensus of opinion among the clinical investigators of amiodarone is that it will be released for limited clinical use in the near future. Cardiovascular nurses involved in the design, coordination, and conduction of clinical investigations need to be vigilant in objectively monitoring and documenting both the potential efficacy and possible adverse effects of all interventions in research subjects.

Topics: Amiodarone; Benzofurans; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia

Amiodarone was used in 40 patients with life-threatening or refractory tachyarrhythmias. Eighteen patients had recurrent ventricular tachycardia of whom 13 had suffered a cardiac arrest. Control has been excellent or good in 17 of these 18 patients during an average follow-up period of 10 months. A further 22 patients had supraventricular arrhythmias, including three with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation. In 20 of these control has been excellent or good. The mean daily maintenance dose of amiodarone was 300 mg for patients with ventricular tachyarrhythmias and 200 mg for those with supraventricular tachyarrhythmias. Side-effects were common and included corneal microdeposits, skin rash and discolouration, alteration in thyroid function, and symptomatic bradycardia. Serious adverse effects were uncommon however and necessitated discontinuation of the drug in only two patients. Amiodarone did not appear to precipitate or exacerbate cardiac failure in any patient although many had severe left ventricular dysfunction. We conclude that amiodarone is effective in the therapy of life-threatening or refractory cardiac arrhythmias.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Kinetics; Male; Middle Aged; Tachycardia; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

The antiarrhythmic effects of amiodarone hydrochloride 200 to 600 mg/daily were studied in 25 patients with ventricular tachycardia (VT). The arrhythmia was registered on a 24 hours two channel Holter recording. This study was performed before and after one month treatment with the drug. The adequate suppression of the VT was observed in 25 patients. The drug showed a total suppression of ventricular ectopic activity in 10 patients (40%) (4 at a dose of 200 mg/daily, 5 at 400 mg/daily and 1 at 600 mg/daily) and a satisfactory reduction (total suppression of couplets and VT and more than 85% reduction of premature ventricular beat frequency) in 12 patients (48%) (6 at a dose of 200 mg/daily, 5 at a dose of 400 mg/daily and 1 at a dose of 600 mg/daily). After a mean follow up of 15.9 months on continuous amiodarone therapy there have been no recurrences of arrhythmia on Holter recordings. No patient died during the study. Side effects were minimal and limited to corneal microdeposits at slit lamp examination without impairment of visual acuity. According to our results amiodarone is an excellent and safe agent for the treatment of complex ventricular arrhythmias.

Topics: Adult; Aged; Amiodarone; Benzofurans; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia

Three infants with junctional automatic ectopic tachycardia (JET) were seen over an 8-month period. Each had decreased left ventricular function. Two were treated with amiodarone, which together with propranolol reduced the tachycardia rate 10 to 40 bpm, but did not result in sinus rhythm. One patient died suddenly at home, as had 50% of our patients with JET treated with conventional medication. Two patients were treated by transcatheter ablation of the bundle of His and implantation of an atrial synchronous pacemaker. Neither has had subsequent tachycardia or required drugs. One patient resumed sinus rhythm and does not use his pacemaker. The other patient has complete AV block and continues to use her pacemaker. This aggressive approach to this lethal dysrhythmia offers hope for prevention of the former bad prognosis.

Topics: Amiodarone; Benzofurans; Bundle of His; Cardiac Catheterization; Electrocardiography; Heart Conduction System; Humans; Infant; Pacemaker, Artificial; Tachycardia

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Drug Interactions; Heart Atria; Heart Ventricles; Humans; Tachycardia; Warfarin

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.

Topics: Aged; Amiodarone; Anorexia; Ataxia; Benzofurans; Female; Heart Arrest; Humans; Lung Diseases; Male; Middle Aged; Nausea; Recurrence; Tachycardia; Thyroid Diseases; Time Factors; Tremor; Ventricular Fibrillation; Vision Disorders

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Female; Humans; Myocardial Infarction; Pulmonary Fibrosis; Tachycardia

Oral amiodarone was administered to ten children aged 3 months to 15 years who had recurrent SVT associated with the Wolff-Parkinson-White syndrome. In nine patients, amiodarone was used following failure of oral digoxin, quinidine, propranolol, and verapamil. Each patient received an oral loading dose of 10 to 15 mg/kg followed by 5 mg/kg daily. All children became asymptomatic of tachyarrhythmias within five days of therapy and remained asymptomatic for 5 to 36 months. In one patient, amiodarone therapy was discontinued because of generalized urticaria after a positive initial response. After high-dose oral verapamil failed to eliminate recurrent bouts of SVT, the patient was again given amiodarone and he had a complete recovery. All ten children had normal results on thyroid function tests, and no other adverse effects were detected. Amiodarone has been shown to be highly effective and well tolerated in this series of children. Therefore, we recommend its use for the control and prevention of sustained arrhythmias in pediatric patients with Wolff-Parkinson-White syndrome when the traditional antiarrhythmic drugs fail.

Topics: Administration, Oral; Adolescent; Amiodarone; Benzofurans; Child; Child, Preschool; Electrocardiography; Female; Humans; Infant; Male; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adolescent; Amiodarone; Benzofurans; Child; Child, Preschool; Humans; Infant; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Child; Drug Evaluation; Female; Humans; Injections, Intravenous; Male; Middle Aged; Tachycardia

A clinical investigation was carried out in 13 patients in order to answer the question of a possible interaction between amiodarone (A) and digoxin (D) and to study the extent to which plasma digoxin levels (PDL) may be influenced by A. Combined therapy with A + D was instituted in patients with supraventricular tachyarrhythmia where treatment with D alone was insufficient. All patients had normal renal function. Amiodarone was added to the treatment regimen of patients receiving D at doses ranging from 0.125 to 0.5 mg daily on a long term basis. The initial dosage of A was 1200 mg daily for 5 days to achieve saturation, followed by a maintenance dose of 200-400 mg daily. 3 PDL were measured before therapy with A was added and during combined A and D treatment at weeks 1, 2 and 3 and 3 months after the addition of A. In 11 patients a significant increase in PDL occurred as early as the 1st and 2nd weeks following the addition of A. In one patient PDL was elevated only after 3 months and in one other patient it remained unchanged. In 4 patients the PDL increase was associated with nausea. No other subjective or objective symptoms of digitalis intoxication were observed. This investigation has demonstrated a clinically relevant interaction between A and D. Regular monitoring of PDL is recommended during the first 3 weeks of combined treatment with A + D, and the D doses should be adjusted accordingly.

Topics: Adult; Aged; Amiodarone; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Tachycardia

Serum levels of amiodarone (A) and desethylamiodarone (D) were determined by HPLC in 34 adults receiving loading (2 g) or maintenance doses (200 mg daily) of amiodarone. Serum levels of A after i.v. loading doses were much higher (1.35 micrograms/ml) than after equivalent oral doses (0.51 microgram/ml), suggesting low bioavailability. During maintenance therapy, very low levels of A were measured during the first 3 months of treatment (0.31 microgram/ml), after which they tended to rise (0.53 microgram/ml), as did the ratio of D/A. Among 4 children under maintenance therapy, one had high serum levels of A (1.50 micrograms/ml) and D (2.50 micrograms/ml) and showed nervous and cutaneous signs of toxicity.

Topics: Aged; Amiodarone; Benzofurans; Child; Female; Humans; Male; Middle Aged; Tachycardia

Topics: Amiodarone; Benzofurans; Electrocardiography; Heart Ventricles; Humans; Tachycardia

Amiodarone hydrochloride, used for prophylaxis of recurrent ventricular tachyarrhythmias that are resistant to other agents, may cause toxic pulmonary reactions associated with abnormal chest radiographs. The authors review four new cases of amiodarone-induced toxicity and eight cases reported in the literature. Peripheral areas of consolidation, predominantly in the upper lobes and resembling chronic eosinophilic pneumonia or tuberculosis, and diffuse interstitial disease were seen. Clinical symptoms included dyspnea on exertion, weakness, and occasionally pleuritic pain. Radiographic abnormalities developed after a median latency period of six months on the drug (600 to 800 mg daily). Pathologic findings suggested a possible toxic effect of the drug on phospholipid metabolism in the lung. Amiodarone toxicity may lead to significant pulmonary insufficiency. The clinical symptoms and radiographic abnormalities were completely reversible upon cessation of drug use and institution of corticosteroid treatment. Resolution generally occurs within three months.

Topics: Adult; Aged; Amiodarone; Benzofurans; Biopsy; Humans; Lung; Lung Diseases; Male; Middle Aged; Radiography; Tachycardia; Time Factors

Ninety-six patients with life-threatening ventricular arrhythmias refractory to two or more conventional agents were treated with amiodarone and followed for 6 to 40 months (mean, 15 months). Currently, 75 are alive and well. Seven patients died from nonarrhythmic and five from arrhythmic causes. Nonfatal arrhythmias recurred in four patients, one with early and three with late onset. Intolerable side effects occurred in five patients but heart failure was not aggravated by the drug. On 24-hour Holter recordings done before and serially during therapy in 72 patients, amiodarone eliminated episodes of ventricular tachycardia and complex ectopy and reduced total ectopic beat counts by 90% or more in all but 4 patients. In contrast, ventricular tachycardia inducible by programmed electrical stimulation was suppressed in only 50% of patients, but failure of such suppression did not compromise an excellent clinical outcome. Thus, amiodarone is highly effective in the prophylaxis of recurrent refractory life-threatening ventricular arrhythmias.

Topics: Acute Disease; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Follow-Up Studies; Gastrointestinal Diseases; Heart Ventricles; Humans; Male; Middle Aged; Prognosis; Recurrence; Sleep Initiation and Maintenance Disorders; Tachycardia

Topics: Amiodarone; Benzofurans; Heart Ventricles; Humans; Tachycardia

Topics: Amiodarone; Benzofurans; Digoxin; Drug Interactions; Humans; Tachycardia

Topics: Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Electrophysiology; Humans; Tachycardia

Five cases of amiodarone-induced polymorphous ventricular tachycardia (torsade de pointes) are presented. All patients had recurrent syncope or dizziness due to polymorphous ventricular tachycardia and in all cases the QT interval was prolonged. In two cases hypokalemia was present at the time the arrhythmia was first recorded, but in both cases polymorphous ventricular tachycardia persisted despite correction of the electrolyte imbalance. Standard treatment for polymorphous ventricular tachycardia (isoproterenol, ventricular pacing, or both) was successful in all patients, however, therapy had to be continued for 5 to 10 days, most probably because of the long elimination half-life of amiodarone.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Half-Life; Humans; Isoproterenol; Male; Middle Aged; Syncope; Tachycardia

Using a high-pressure liquid chromatographic assay, we measured serum amiodarone concentrations serially in 122 patients treated with amiodarone for 1.5-53 months (mean 9.3 months) for control of refractory symptomatic atrial or symptomatic and life-threatening ventricular tachyarrhythmias. The atrial tachyarrhythmias were successfully controlled in 45 of 54 patients (83%) during a mean follow-up of 10.0 months. In the ventricular tachyarrhythmia group, which included 22 survivors of sudden cardiac death, 38 of 50 patients (76%) responded to amiodarone during a mean follow-up of 10.9 months. Although the mean serum amiodarone concentration did not differ between responders and nonresponders, eight responders relapsed when their serum concentration fell below 1.0 mg/l. Side effects resulted in withdrawal of amiodarone in only 10 of 122 patients (9%) despite a 30% overall incidence of side effects. Central nervous system and gastrointestinal side effects became more frequent with serum concentrations greater than 2.5 mg/l, although only central nervous system side effects achieved statistical significance. Absorption and disposition kinetics of a single oral 800-mg dose of amiodarone were studied in eight patients. Serum values were measured for 24 hours in five patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated in three patients. The tissue concentration of amiodarone was determined in two patients who died during long-term amiodarone therapy and an attempt was made in 14 patients to correlate serum concentrations with daily dosages during maintenance therapy. The pharmacokinetics of oral amiodarone support the practice of using high loading dosages until arrhythmia suppression or apparent steady state is achieved (usually 2-4 weeks), followed by low-dose maintenance therapy (200-600 mg once a day) for treatment of symptomatic atrial and ventricular tachyarrhythmias.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Female; Heart Atria; Heart Ventricles; Humans; Kinetics; Male; Middle Aged; Tachycardia; Time Factors; Tissue Distribution

Ninety-six patients with recurrent, drug-refractory tachyarrhythmias were treated with amiodarone for 8.0 +/- 7.5 months (range 1 day to 27 months): 77 for recurrent ventricular tachycardia or ventricular fibrillation (VT/VF), two for complex ventricular ectopy, and 17 for supraventricular tachyarrhythmias. The actuarial incidence of successful amiodarone therapy was 52 +/- 7% at 12 months and 28 +/- 9% at 24 months for patients with VT/VF. Neither patient with complex ventricular ectopy was successfully treated. Among the patients with supraventricular tachyarrhythmias, 64.7% were successfully treated for 7.7 +/- 7.6 months (range 1 to 22 months). Amiodarone toxicity occurred in 66 of 91 patients (72.5%) treated for more than 1 week. Fourteen patients had therapy-limiting toxicity. Of these 14, six had pulmonary toxicity, four had arrhythmia exacerbation, one had hepatitis, one had renal toxicity, one had rash, and one had erythema nodosum. The actuarial incidence of therapy-limiting side effects was 27 +/- 7% at 15 months. We conclude that amiodarone is useful in the treatment of refractory tachyarrhythmias but that the rate of efficacy in VT/VF is lower and the incidence of significant toxicity is higher than has been generally appreciated.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Topics: Adult; Aged; Amiodarone; Benzofurans; Electrophysiology; Female; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrophysiology; Heart Ventricles; Humans; Tachycardia; Ventricular Fibrillation

A patient with sustained ventricular tachycardia was operated on after an unsuccessful trial of amiodarone. Profound myocardial depression and low cardiac output became evident as he was weaned from cardiopulmonary bypass. Despite inotropic support, use of the intra-aortic balloon pump and left heart assist device, he died. Because of this experience, the authors developed a canine model to determine the effects on left ventricular function of amiodarone given orally. Left ventricular stroke work, cardiac output, ventricular contractility (maximum dP/dt) and peripheral vascular resistance were measured in 12 mongrel dogs at a heart rate of 150 beats/min and at a constant preload of 10 mm Hg. Six animals received the drug orally and the remaining animals were used as sham-operated controls. Maximum dP/dt decreased from 2855 mm Hg/s to 1291 mm Hg/s (p less than 0.01) and left ventricular stroke work was reduced from 48.7 g-m/beat to 21.8 g-m/beat (p less than 0.05) after the administration of amiodarone. Cardiac output and peripheral vascular resistance did not differ significantly. Amiodarone severely depressed left ventricular function in this experiment. The prolonged half-life of this antiarrhythmic combined with its adverse effect on myocardial function suggests that it should not be used in patients with refractory life-threatening ventricular tachycardia who are good candidates for electrophysiologic evaluation and endocardial resection.

Topics: Amiodarone; Animals; Benzofurans; Cardiac Output; Cardiac Output, Low; Cardiac Surgical Procedures; Dogs; Female; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia; Vascular Resistance

4 children, ages 11-14 years, were diagnosed as having primary ventricular arrhythmias (3 ventricular tachycardia, 1 multifocal premature ventricular contractions) without underlying heart disease. All 4 patients were treated initially with standard antiarrhythmic drugs (quinidine, propranolol, procainamide) and either did not respond (3 patients) or experienced drug toxicity (quinidine - 1 patient) necessitating withdrawal of antiarrhythmic therapy. Amiodarone, a new antiarrhythmic agent, was initiated in a single oral daily dose of 10 mg/kg/day. All patients have shown a significant clinical response to oral amiodarone with either complete suppression of ventricular tachycardia in 2 patients, near complete suppression in 1 and abolition of multifocal premature ventricular contractions in the fourth patients. 2 patients have had corneal microdeposits detected by slitlamp examination and are receiving methylcellulose eye drops; no other adverse reactions have been encountered during the follow-up of 6 months to 3 years.

Topics: Adolescent; Age Factors; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Corneal Diseases; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Male; Prognosis; Propranolol; Quinidine; Retrospective Studies; Tachycardia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Male; Middle Aged; Pneumonia; Tachycardia

Topics: Adult; Aged; Amiodarone; Benzofurans; Electrocardiography; Female; Heart Conduction System; Humans; Male; Middle Aged; Tachycardia; Thyroid Gland

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Humans; Male; Middle Aged; Quinidine; Tachycardia

We evaluated the electrophysiologic effects of amiodarone and its ability to control ventricular arrhythmia in a selected group of 51 patients with refractory sustained ventricular arrhythmia. Amiodarone in doses of 400 to 800 mg/day prolonged refractoriness in the atria, atrioventricular (AV) node, and ventricle as well as conduction through the AV node and His-Purkinje system. Although it had no effect on measurements of sinus nodal function (sinus nodal recovery time and sinoatrial conduction time), it prolonged the sinus cycle length and 2 patients required a permanent pacemaker for symptomatic sinus bradycardia. Amiodarone did not alter the ease of inducibility in any consistent manner, and only 5 of 43 patients (12%) who had inducible ventricular tachycardia before amiodarone therapy had none induced during amiodarone treatment. The clinical effectiveness of amiodarone could be evaluated in 46 patients followed up for 8.6 +/- 6 months (range 0.5 to 22). It provided effective therapy in 23 patients (50%), partly effective therapy in 13 (28%), and was ineffective in 10 (22%). Adverse effects were noted in 28 of 51 patients (55%), and in 11 of these (22%) the drug had to be discontinued because of adverse effects. We conclude that amiodarone is a useful agent for the treatment of refractory sustained ventricular arrhythmia. Its use should be reserved for patients with life-threatening sustained arrhythmia because of the significant incidence of adverse effects. Furthermore, good clinical response can be observed in patients receiving amiodarone in spite of continued inducibility.

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Chemical and Drug Induced Liver Injury; Corneal Diseases; Electrophysiology; Female; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Peripheral Nervous System Diseases; Photosensitivity Disorders; Pulmonary Fibrosis; Stroke Volume; Tachycardia; Ventricular Fibrillation

Topics: Adult; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Drug Eruptions; Heart Ventricles; Humans; Rabbits; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Heart Arrest; Humans; Male; Middle Aged; Tachycardia

Topics: Administration, Oral; Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Male; Recurrence; Tachycardia; Time Factors

Amiodarone has proved to be a valuable drug in atrial fibrillation associated with the Wolff-Parkinson-White syndrome. When it was administered to a patient with this syndrome in atrial fibrillation, who had previously suffered an inferior myocardial infarction, the ventricular rate accelerated from 170 to 230 beats/minute.This unusual case emphasises the need for full electrophysiological assessment of patients with the Wolff-Parkinson-White syndrome for whom amiodarone treatment is being considered.

Topics: Aged; Amiodarone; Atrial Fibrillation; Benzofurans; Electrocardiography; Humans; Male; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adult; Aged; Amiodarone; Benzofurans; Chronic Disease; Female; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia

Ventricular tachycardia, especially in its apparently primary form, is rare in children and difficult to treat, often requiring aggressive methods of reduction or antiarrhythmic drugs unsuited for paediatric practice. Therefore, we investigated the use of amiodarone whose efficacity in the treatment of resistant ventricular tachycardia and good tolerance in children have been established. Three infants, aged from 9 to 15 months, and two children aged 6 and 7 years with apparently primary VT were selected. Etiological investigations were negative in four cases but in one of the older children a left ventricular fibroma was diagnosed and removed surgically. Amiodarone was administered orally at a dose of 500 mg/m2/24 hrs for 5 to 15 days, and then 250 mg/m2/24 hrs for one month in the surgical patient and for 9 to 39 months in the four "idiopathic" cases. Reduction of VT was obtained in all cases 8 to 48 hours after the first dose. There was only one recurrence, attributed to an over-rapid reducing in dosage; it quickly regressed after returning to the initial dosage. Stable sinus rhythm was maintained at long-term: 18 months, 2 years and 5 years after tailing off a course of 20, 40 and 1 month's treatment in 3 children. These cases are considered to be cured, but in one of these children two courses of amiodarone were required, the second for a relapse 3 months after stopping a 9 month's course of therapy. The other two children are still under treatment after 9 and 15 months with no recurrences. There were no hemodynamic, ocular or thyroid side effects. On the other hand, three cases of photosensitivity, two minor and one major requiring termination of therapy after a 20 months course, were observed. In conclusion, amiodarone would appear to be the treatment of choice for ventricular tachycardia in children, reduction of the arrhythmia being obtained in all cases even by oral administration within reasonable limits: its prophylactic value is excellent and clinical tolerance very satisfactory: a definitive cure can be hoped for an idiopathic VT providing that maintenance therapy has been sufficiently prolonged (2 years).

Topics: Amiodarone; Benzofurans; Child; Electrocardiography; Female; Follow-Up Studies; Humans; Infant; Male; Tachycardia

Topics: Adult; Aged; Amiodarone; Benzofurans; Bradycardia; Female; Follow-Up Studies; Humans; Male; Middle Aged; Sinoatrial Node; Syndrome; Tachycardia

A 44-year-old woman is described in whom amiodarone, disopyramide, and quinidine, administered alone separately, induced atypical ventricular tachycardia (AVT, torsade de pointes). Following a closed mitral valvotomy, she received quinidine, 1.2 g/day, without interruption for 17 years. Because of a recurrence of paroxysmal atrial fibrillation, the dose of the drug was increased to 1.4 g/day; 24 hours later AVT with syncope developed but responded promptly to atropine. Two years later, 24 hours following an increase in the dose of disopyramide from 300 to 600 mg/day, AVT with syncope occurred; isoproterenol abolished the arrhythmia instantly. Amiodarone was the third drug to induce AVT in this patient; she received 200 mg/day six days per week for six months. The dose was subsequently increased to 200 and 400 mg/day on alternate days, six days per week, and two months later AVT occurred. That time the only effective treatment was ventricular pacing.

Topics: Adult; Amiodarone; Atrial Fibrillation; Benzofurans; Disopyramide; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Ventricles; Humans; Prajmaline; Pyridines; Quinidine; Tachycardia

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Electrophysiology; Heart Rate; Humans; Male; Middle Aged; Tachycardia

We studied the antiarrhythmic effects of amiodarone, 600-1400 mg/day, in 18 patients with refractory arrhythmias, and related to drug efficacy and side effects to serum levels of T4, reverse T3 (rT3) and the QTc interval. In the 11 patients with ventricular arrhythmias, premature complexes were reduced by 90-98%, and complex ectopy and runs of ventricular tachycardia were abolished; in the seven patients with paroxysmal atrial flutter, there were no recurrences on stable drug therapy. The QTc lengthened by 11.6% (p less than 0.01), T4 increased by 31.6-63.3% (p less than 0.001) and rT3 increased by 82.9-176.8% (p less than 0.001) as a function of dose and duration of amiodarone therapy. A close correlation was found between rT3 (normal up to 50 ng/dl) and drug efficacy and some of the drug side effects; arrhythmia suppression occurred at levels of 55-100 ng/dl, and some of the known side effects at levels of 100-110 ng/dl. When amiodarone was stopped in nine patients, the changes in QTc, T4 and rT3 regressed toward normal and arrhythmia recurred in eight 2-20 weeks (mean 7.4 weeks) and when rT3 levels fell below 55 ng/dl; arrhythmia resuppression was achieved 3-28 days (mean 11 days) after resumption of amiodarone therapy. The indirect therapeutic half-life of amiodarone in seven patients, computed from the semilogarithmic plots of plasma rT3 after cessation of amiodarone therapy, ranged from 25 to 55 days (mean 35 days). The data suggest that rT3 levels may be useful in monitoring the efficacy and certain side effects of amiodarone.

Topics: Adult; Aged; Amiodarone; Atrial Flutter; Benzofurans; Electrocardiography; Heart Ventricles; Humans; Male; Middle Aged; Recurrence; Tachycardia; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Electrophysiology; Exercise Test; Humans; Male; Middle Aged; Myocardial Infarction; Tachycardia

Topics: Amiodarone; Benzofurans; Electrocardiography; Humans; Male; Middle Aged; Tachycardia; Tachycardia, Paroxysmal

Trans-placental passage of amiodarone has not yet been demonstrated, even if it has been suspected from the observation of some cases of congenital mixedema in babies born of amiodarone-treated women. A pregnant woman, suffering from recurrent episodes of resistant high frequency, 1:1 atrial tachycardia, with severe hypotension, was treated with oral amiodarone 200 mg daily during the last three months of pregnancy. The arrhythmia was satisfactorily controlled and pregnancy was carried on well. At birth, the baby was normal on physical examination and routine blood exams. Particularly, thyroid function was normal. After delivery, the plasma level of the drug and its electrocardiographic effects both in the mother and the newborn were determined. High pressure liquid chromatography (HPLC) method was used for the pharmacologic determinations and led to demonstrate the presence of amiodarone and one of its metabolites in the newborn plasma. Placental permeability for the metabolite resulted to be higher than for amiodarone, comparing mother versus newborn drug concentrations. Electrocardiographic changes due to amiodarone (i.e. lengthening of QT interval) were observed in both the ECGs of the mother and the newborn, but in the latter lenghthening of QT was much more evident. The authors briefly report another personal case of amiodarone-treatment during pregnancy and conclude, on the basis of their experience, that amiodarone can be used in pregnancy, but strictly in refractory, life-threatening arrhythmias and limitedly to the last three months.

Topics: Adult; Amiodarone; Benzofurans; Female; Fetus; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Tachycardia

Topics: Administration, Oral; Adult; Aged; Amiodarone; Benzofurans; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neurocirculatory Asthenia; Tachycardia

Six patients treated with a combination of amiodarone and class I antiarrhythmic agents for a minor arrhythmia developed atypical ventricular tachycardia "en torsades de pointe". All patients had QT-interval prolongation in the ECG. Combined administration of quinidine and amiodarone in a normal volunteer resulted in an increase in plasma quinidine concentration and in QT prolongation, thus confirming the clinical observation of a clinically relevant interaction between the two drugs.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Quinidine; Tachycardia

Topics: Adrenergic beta-Antagonists; Ajmaline; Amiodarone; Benzofurans; Drug Therapy, Combination; Humans; Quinidine; Tachycardia; Verapamil; Wolff-Parkinson-White Syndrome

The authors observed 127 patients with different disorders of the cardiac rhythm treated with ethmozine, cordarone and rhythmodan. To assess the efficacy of the therapy circadian ECG was recorded on a magnetic tape with a portable cardiomonitor, exercise tests (bicycle ergometry, treadmill and walking under ECG control) were conducted. Good effect was seen after a course of treatment in patients with ventricular and atrial extrasystolae, paroxysms of supraventricular, ventricular tachycardia and auricular fibrillation. Cordarone was found effective in the Wolff-Parkinson - White syndrome and paroxysms of supraventricular tachycardia.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Benzofurans; Cardiac Complexes, Premature; Coronary Disease; Disopyramide; Drug Evaluation; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Moricizine; Morpholines; Phenothiazines; Pyridines; Tachycardia

Twenty-three patients with sustained, recurrent, symptomatic ventricular tachycardia were treated with oral amiodarone. Initial doses were 600-2000 mg/day and maintenance doses were 200-1200 mg/day. Amiodarone was highly effective in 20 patients (87%), seven of whom had a follow-up of 30 months or longer, including two who were followed for 5 years. Three patients died within the first 45 days, three died suddenly after a follow-up of 33.5 months, and four had a nonarrhythmic death after a follow-up of 25 months. Fifteen patients (65%) had no recurrence during a follow-up of 21.5 months, while five (22%) had isolated recurrences during a follow-up of 32.2 months. The average maintenance dose was 713 mg/day in the 15 patients who did not have recurrences and 375 mg/day in the five patients who had recurrences (p less than 0.001). Both short- and long-term tolerance were excellent and there was not a single case in which treatment had to be discontinued. The main disadvantage of amiodarone was that it took an average of 9.5 days to reach anti-arrhythmic efficacy. The main advantages were prolonged duration of action (recurrences occurred only 15-60 days after the drug was discontinued or the dose lowered, virtual absence of contraindications, doses as high as 2000 mg/day were safe and patient compliance was excellent.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Corneal Diseases; Humans; Long-Term Care; Male; Middle Aged; Photosensitivity Disorders; Recurrence; Skin Diseases; Tachycardia; Time Factors

We evaluated the effects of amiodarone in 45 patients with recurrent ventricular tachycardia or ventricular fibrillation. At a mean follow-up time of 12.7 +/- 8.8 months (range, three to 36), amiodarone was successful in nine of 16 patients with recurrent ventricular fibrillation and 21 of 29 with recurrent ventricular tachycardia. During amiodarone therapy, ventricular tachycardia could be induced in 18 of 19 patients in whom it had been induced before therapy, but only six of these 19 had spontaneous recurrence during follow-up. Side effects included corneal microdeposits, hyperthyroidism, blue skin, nausea, and symptomatic bradycardia. Pulmonary fibrosis occurred in three patients. Doses of up to 2000 mg a day did not produce cardiac toxicity, but neurologic side effects precluded long-term therapy at this dose. We conclude that amiodarone is effective for long-term therapy of recurrent ventricular tachyarrhythmias, that induction of arrhythmia during therapy does not always predict efficacy, and that side effects are frequent but do not usually limit therapy.

Topics: Adult; Aged; Amiodarone; Benzofurans; Drug Evaluation; Electric Stimulation; Electrophysiology; Female; Follow-Up Studies; Heart Conduction System; Humans; Long-Term Care; Male; Middle Aged; Pulmonary Fibrosis; Recurrence; Tachycardia; Ventricular Fibrillation

Amiodarone was used in 30 patients with tachyarrhythmias refractory to treatment with several antiarrhythmic agents. In 18 patients with supraventricular arrhythmias (recurrent atrial tachycardia in seven; atrial fibrillation, recurrent in four and persistent in five; Wolff-Parkinson-White syndrome in two), complete control was obtained in eight and marked improvement in eight patients. Conversion of persistent atrial fibrillation to sinus rhythm was documented in three patients. Congestive heart failure improved markedly in three patients who had persistent atrial fibrillation during amiodarone therapy. In 12 patients with tachycardia of ventricular origin effective control was obtained in nine. The incidence of side effects was low. Amiodarone is effective in maintaining sinus rhythm in many patients with both supraventricular and ventricular tachyarrhythmias when standard antiarrhythmic agents have failed.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Recurrence; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Benzofurans; Coronary Artery Bypass; Heart Block; Humans; Male; Middle Aged; Postoperative Period; Risk; Tachycardia; Vascular Resistance

Amiodarone was utilized in 70 patients with symptomatic, sustained refractory tachyarrhythmias. Of these, 29 had atrial arrhythmia (20 recurrent atrial fibrillation and nine sustained supraventricular tachycardia). Control was achieved in eight with supraventricular tachycardia and in 16 with atrial fibrillation. Recurrence has been prevented in these 24 patients (83%) during an average follow-up of 13.4 months. An additional 41 patients had recurrent ventricular tachycardia. In 19 with symptoms consisting of dizziness of lightheadedness without syncope or clinically apparent hemodynamic compromise, treatment was limited to amiodarone. Of these, 14 responded (74%) and have been free of arrhythmia during an average follow-up of 13 months. In 22 who had experienced either syncope or life-threatening hemodynamic impairment, amiodarone was added to those agents which had only partially suppressed advanced grades of ventricular premature beats. Fourteen of these patients (64%) have remained free pf recurrent ventricular arrhythmia during an average follow-up of 12 months. After drug loading, maintenance therapy consisted of a daily dose ranging from 200 to 600 mg. Only mild side effects have been encountered in the 17 patients (23%) with any untoward responses. This experience confirms that oral amiodarone is an effective and safely applied agent against recurrent refractory atrial tachyarrhythmia and sustained intractable ventricular tachycardia with moderate symptoms. While also efficacious in refractory sustained life-threatening ventricular tachyarrhythmia, usage of the agent is often difficult in this condition owing in part to insufficient information concerning amiodarone pharmacokinetics.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Tachycardia; Time Factors; Wolff-Parkinson-White Syndrome

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

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Heart; Heart Ventricles; Humans; Middle Aged; Tachycardia; Thyroid Gland

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Female; Humans; Longitudinal Studies; Male; Middle Aged; Tachycardia

A 25 year old man had experienced virtually incessant ventricular tachycardia since the age of 16 years, and complained of increasing lethargy and shortness of breath over the past 5 years. Despite medical therapy with numerous conventional antiarrhythmic agents, no single drug or combination of drugs had successfully controlled the tachycardia. Isotope and contrast angiography revealed an enlarged left ventricle with poor function. Electrophysiological studies demonstrate earliest endocardial activation at the left ventricular apex. No electrical procedure terminated tachycardia. Following institution of amiodarone, continuous ECG monitoring revealed periods of sinus rhythm alternating with periods of ventricular bigeminy. Repeat isotope angiography indicated a considerable improvement in L.V. function. There was a corresponding reduction in heart size on the chest radiograph. Clinical improvement was evidenced by disappearance of lethargy and shortness of breath. This report demonstrates that amiodarone, a new antiarrhythmic agent, may suppress long standing incessant ventricular tachycardia resistant to other antiarrhythmic agents. The marked reduction in heart size on amiodarone may suggest that the associated cardiomegaly is secondary to tachycardia.

Topics: Adult; Amiodarone; Benzofurans; Cardiomegaly; Electrocardiography; Humans; Male; Radiography; Tachycardia

Amiodarone, 600 mg orally daily, was used in an attempt to control supraventricular tachyarrhythmias in a patient with the sick sinus syndrome. Twenty days from the onset of therapy the Q-T interval lengthened. Episodes of ventricular flutter, ventricular fibrillation and self-terminating ventricular tachyarrhythmia (torsade de pointes) developed on the 28th day of amiodarone therapy. Temporary cardiac pacing prevented further episodes of ventricular fibrillation. Despite the suggestion that this drug may be given in large doses for long periods of time since it has a wide safety margin, we feel that the risk of lethal arrhythmias is such that caution is required in its use.

Topics: Amiodarone; Benzofurans; Bradycardia; Cardiac Pacing, Artificial; Electric Countershock; Electrocardiography; Female; Humans; Middle Aged; Sick Sinus Syndrome; Tachycardia; Ventricular Fibrillation

A combined mexiletine and amiodarone treatment was applied in nine cases with recurrent refractory ventricular tachycardia. During the first two days of treatment, mexiletine and amiodarone were perfused intravenously at a dose of 1,000 mg. and 1,500 mg. per 24 hours, respectively. Simultaneously amiodarone was also given orally at a dose of 600 mg. per 24 hours. From the third day onwards, the intravenous administration was interrupted and both drugs were continued orally at a dose of 600 mg. daily. The first three patients were very critically ill and had had at least five episodes of ventricular tachycardia per 24 hours during the last 10 days in the intensive care unit. The treatment resulted in total suppression of the tachycardic episodes within three days after initiation of therapy. In the remaining six cases, ventricular tachycardia was easily initiated by programmed electrical stimulation of the heart. No arrhythmia could be elicited by repeated testing on the seventh day of treatment. The mean follow-up period was 6 months. Two patients with poor left ventricular function died in intractable heart failure. Another one died suddenly 4-1/2 months after his release from the hospital. He had a large aneurysm and whether he continued his treatment is unknown. A fourth patient had an aneurysmectomy; he suffered a recurrence, and died at his second operation. All the others presently remain asymptomatic. The association of a class I (mexiletine) with a class III (amiodarone) agent is theoretically attractive for the treatment of refractory ventricular arrhythmias. The present findings corroborate this hypothesis, but show that this association is not able to protect individuals with severe underlying myocardial damage.

Topics: Adult; Amiodarone; Benzofurans; Drug Therapy, Combination; Electric Stimulation; Follow-Up Studies; Humans; Male; Mexiletine; Middle Aged; Propylamines; Recurrence; Tachycardia

Oral amiodarone was given to 135 children (mean age, 10.2 years) for a mean duration of 4.1 months (range, 1 day to 6 years) for mainly idiopathic (25%) and postoperative (61%) arrhythmias. Complete ECG control or partial ECG control with clinical improvement was obtained in 60% and 33% of cases, respectively, regardless of the arrhythmia location (atrial 69%, junctional 16%, and ventricular 15%), mechanism, resistance (55%) or sensitivity (45%) to other drugs, and presence of cardiomegaly (40%) or clinical signs of heart failure (27%). The only factor favoring improvement was a short history (< 2 months in 54%). The rapid onset of drug effect (4.1 days), the early relapses after treatment discontinuation (3.3 weeks), and the absence of side effects due to drug accumulation reflect a faster metabolism than that in adults, with no cardiac toxicity and a low incidence of thyroid dysfunction (2 hyperthyroid, 1 hypothyroid).

Topics: Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Drug Tolerance; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Infant; Infant, Newborn; Male; Tachycardia; Time Factors

Amiodarone hydrochloride was used to treat 19 patients with symptomatic arrhythmias refractory to quinidine sulfate, procainamide hydrochloride, disopyramide phosphate, antazoline hydrochloride, lidocaine hydrochloride, bretylium tosylate, propranolol hydrochloride, phenytoin sodium, and practotol acetanilide given to the limit of tolerance. In 17 patients, attacks were completely controlled. Arrhythmias treated successfully included recurrent supraventricular tachycardias, recurrent supraventricular tachycardias with Wolff-Parkinson-White syndrome, and refractory ventricular arrhythmias including recurrent ventricular tachycardia and ventricular fibrillation complicating acute coronary heart disease. Control was confirmed by continuous ECG monitoring both in the hospital and when ambulatory and was maintained for up to four years. Attacks of supraventricular tachycardia were reduced from 7.9/mo to one attack every 53.5 months on amiodarone. Hospital admissions for arrhythmias were reduced from 34 the year before treatment to none the year after. Therefore, amiodarone is an excellent drug for control of many refractory arrhythmias, but two patients with recurrent atrial fibrillation were refractory to this treatment.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Recurrence; Tachycardia

Topics: Amiodarone; Benzofurans; Bradycardia; Humans; Tachycardia

Topics: Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Humans; Tachycardia

Five patients with the bradycardia-tachycardia syndrome have been treated successfully with the antiarrhythmic agent amiodarone. Three patients were treated for over nine months and one of these patients had corneal micro deposits. One patient had to be taken off the drug because of side effects. Amiodarone should be tried in patients suffering from the bradycardia-tachycardia syndrome before resorting to cardiac pacing.

Topics: Aged; Amiodarone; Benzofurans; Bradycardia; Corneal Diseases; Female; Humans; Male; Middle Aged; Syndrome; Tachycardia

A long Q-T interval syndrome is described, followed by "torsade de pointe" and by irriducible ventricular fibrillation that is ascribed to a badly conducted therapy with amiodarone, in a patient affected by mitral valve disease, microcitaemia and hemolitic intercurrent moderate jaundice.

Topics: Amiodarone; Benzofurans; Female; Humans; Middle Aged; Mitral Valve Insufficiency; Syncope; Tachycardia; Ventricular Fibrillation

Topics: Aged; Amiodarone; Benzofurans; Bradycardia; Electrocardiography; Exercise Test; Humans; Male; Middle Aged; Tachycardia

The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.

Topics: Adolescent; Adult; Amiodarone; Atrial Fibrillation; Atrioventricular Node; Benzofurans; Electrocardiography; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Neural Conduction; Pacemaker, Artificial; Refractory Period, Electrophysiological; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Administration, Oral; Amiodarone; Benzofurans; Child; Humans; Male; Remission, Spontaneous; Tachycardia

Topics: Amiodarone; Benzofurans; Humans; Tachycardia

L 9146 or 2-methyl-3(3,5 dimethyl-4-gamma-di-n-butylaminopropoxy-benzoyl)-benzo [b] thiophene is a substance belonging to the amiodarone series which induces in the anaesthetized dog a decrease of myocardial oxygen consumption which is mainly due to slowing of the heart rate and reduction in systemic blood pressure. L 9146 also enhances coronary blood flow. L 9146 has also antiadrenergic properties since catecholamine-induced hypertension, tachycardia and increase of myocardial oxygen consumption are markedly antagonized; these antiacrenergic effects are not due to a competitive blockade of the beta-adrenoceptors. L 9146 does not decrease cardiac output, but increases it appreciably in the initial phase of its action. Several findings indicate that when the intensity of certain properties is considered, l9146 is more active than aniodarone since only half the dose used with aniodarone is required to achieve a given level of action. The overall haemodynamic properties of L 9146, which are similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris.

Topics: Adrenergic beta-Antagonists; Amiodarone; Angina Pectoris; Animals; Benzofurans; Blood Pressure; Cardiac Output; Coronary Circulation; Depression, Chemical; Dogs; Electrocardiography; Epinephrine; Female; Heart Rate; Hemodynamics; Hypertension; Isoproterenol; Male; Oxygen Consumption; Propylamines; Tachycardia; Thiophenes; Vascular Resistance

Topics: Amiodarone; Benzofurans; Coronary Disease; Electrocardiography; Heart Ventricles; Humans; Male; Middle Aged; Recurrence; Tachycardia

Topics: Adult; Antihypertensive Agents; Benzofurans; Child; Child, Preschool; Diagnosis, Differential; Digoxin; Drug Synergism; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Infant; Infant, Newborn; Male; Prenylamine; Tachycardia; Time Factors

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Digitalis Glycosides; Electric Countershock; Lidocaine; Phenytoin; Potassium; Procainamide; Quinidine; Tachycardia; Verapamil

Topics: Angina Pectoris; Animals; Anti-Arrhythmia Agents; Benzoates; Benzofurans; Blood Flow Velocity; Blood Pressure; Cardiac Output; Dogs; Ethylamines; Heart Rate; Hypertension; Iodobenzoates; Oxygen Consumption; Propylamines; Tachycardia; Thiophenes; Time Factors

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Benzofurans; Heart Ventricles; Humans; Tachycardia

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Female; Humans; Male; Middle Aged; Tachycardia

Topics: Angina Pectoris; Antihypertensive Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Cardiac Complexes, Premature; Humans; Tachycardia; Tachycardia, Paroxysmal

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Barium; Benzofurans; Cardiac Complexes, Premature; Chlorides; Dogs; Rabbits; Strophanthins; Tachycardia

Topics: Adult; Aged; Angina Pectoris; Antihypertensive Agents; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Tachycardia

Topics: Animals; Antihypertensive Agents; Benzofurans; Blood Pressure; Coronary Disease; Dogs; Epinephrine; Femoral Artery; Heart Rate; Hypertension; Myocardium; Norepinephrine; Oxygen Consumption; Tachycardia; Ventricular Function

Ethyldimethyl(7-methylcoumaran-3-yl)ammonium iodide (SK&F 90,109) and its guanidine analogue [N-(7-methylcoumaran-3-yl)guanidine nitrate] (SK&F 90,238) abolish the effects of adrenergic nerve stimulation in cats, as do xylocholine and bretylium. SK&F 90,109 has slight sympathomimetic actions; these are less marked than in SK&F 90,238. Large doses of SK&F 90,109 have an action, dependent on local noradrenaline stores, that delays the appearance of adrenergic-neurone blockade in conscious cats. Responses to adrenaline are, in general, enhanced by each drug, but SK&F 90,238 transiently antagonizes tachycardia induced by adrenaline and isoprenaline. Both drugs inhibit the release of noradrenaline from the spleen during splenic nerve stimulation, but the release of catechol amines from the adrenal glands, in response to electrical or chemical stimulation, is unimpaired. In contrast to the prolonged adrenergic-neurone blocking action, any inhibition of the effects of cholinergic nerve stimulation is transient. Large intravenous doses produce neuromuscular blockade. The compounds have a slight central depressant action. In contrast to reserpine and guanethidine the noradrenaline content of rat hearts is not appreciably lowered 24 hr after a single dose of either drug. Unlike xylocholine they are not local anaesthetics. Related compounds also block the effects of adrenergic-nerve stimulation. The possible modes of action of these drugs are discussed.

Topics: Adrenergic Agents; Adrenergic Neurons; Animals; Autonomic Nerve Block; Benzofurans; Blood Flow Velocity; Catecholamines; Cats; Coumarins; Electric Stimulation; Epinephrine; Female; Gastrointestinal Motility; Guanethidine; Guanidines; Heart Rate; Humans; Isoproterenol; Myocardium; Neurophysiology; Nictitating Membrane; Norepinephrine; Pharmacology; Rats; Research; Salivation; Splanchnic Nerves; Spleen; Stomach; Sympathetic Nervous System; Sympatholytics; Sympathomimetics; Tachycardia; Uterus