Gene B. Trobaugh

Toxic and therapeutic effects of amiodarone in the treatment of cardiac arrhythmias

Amiodarone was used to treat cardiac arrhythmias that had been refractory to conventional medical therapy. The first 70 consecutive patients treated with amiodarone in this study had at least 6 months of follow-up (range 6 to 24, mean 11) and form the basis for this report. Sixty-six patients were treated for ventricular arrhythmias and four for supraventricular tachycardias. Amiodarone therapy consisted of a loading dose of 600 mg orally twice a day for 7 days, and 600 mg daily thereafter. Doses were reduced only if side effects occurred. Because of frequent side effects, the dose was reduced from 572 +/- 283 mg per day (mean +/- standard deviation) at 45 days to 372 +/- 174 mg per day at 6 months. With a mean follow-up of 11 months in the 54 patients who continued to take amiodarone, only 4 patients had ventricular fibrillation. Three additional patients experienced recurrent sustained ventricular tachycardia in long-term follow-up. All 70 patients had extensive clinical and laboratory evaluation in follow-up. Side effects were common, occurring in 93% of patients. Thirteen patients (19%) had to discontinue the medication because of severe side effects. Fifty-six patients had gastrointestinal side effects, most commonly constipation. All patients but 1 eventually developed corneal microdeposits, and 43 patients were symptomatic. Cardiovascular side effects were uncommon. Symptomatic pulmonary side effects occurred in seven patients, with unequivocal pulmonary toxicity occurring in five. Neurologic side effects, most commonly tremor and ataxia, occurred in 52 patients. Thyroid dysfunction occurred in 3 patients, and 32 patients had cutaneous abnormalities. Miscellaneous other side effects occurred in 32 patients. Amiodarone appears to be useful in the management of refractory arrhythmias. Because virtually all patients develop side effects when given a maintenance daily dose of 600 mg, lower maintenance doses should be used. It is unknown if the more severe side effects are dose-related. Amiodarone is difficult to administer because of its narrow toxic-therapeutic range and prolonged loading phase. More importantly, the first sign of antiarrhythmic failure may be manifest as sudden cardiac death.

Myocardial imaging with intravenously injected thallium-201 in patients with suspected coronary artery disease: Analysis of technique and correlation with electrocardiographic, coronary anatomic and ventriculographic findings

Myocardial imaging was performed after intravenous injection of thallium-201 at rest in 50 patients with suspected coronary artery disease and the results were compared with electrocardiographic, ventriculographic and coronary arteriographic findings. The thallium-201 myocardial images were of good quality and compared favorably with images previously obtained with intracoronary particle injection. Myocardial to background ratios averaged 2:1, a considerable improvement over ratios reported with potassium-43. There was complete intra- and interobserver agreement in the interpretation of images in 90 and 82 percent of cases, respectively. Major disagreement occurred in less than 5 percent of cases. Overall, 15 (30 percent) had an abnormal, 10 patients (20 percent) a borderline abnormal and 25 patients (50 percent) a normal myocardial image. Of patients with electrocardiographic Q waves, 91 percent had an image defect. Of 39 patients without Q waves, 13 percent had an image defect. All 30 patients with a normal or borderline abnormal thallium-201 image had a normal ventricular contraction pattern. All patients with a segmental ventriculographic abnormality had an image defect. In all cases, the area of electrocardiographic or ventriculographic abnormality corresponded to the area of the thallium-201 image defect. The systolic ejection fraction was depressed (0.49 +/- 0.18 [mean +/- standard deviation]) in patients with an image defect compared with that in patients with a normal image (0.64 +/- 0.06, P less than 0.005). Coronary arterial lesions were present and usually of high grade in all patients with an abnormal image; however, the presence of high grade coronary stenosis or occlusion as such correlated with image defects only to the extent that prior myocardial infraction was associated. Thus, satisfactory myocardial images at rest appear to be obtained with intravenously administered thallium-201 and electrocardiographic, ventriculographic and coronary arteriographic data suggest that image defects denote regions of prior myocardial infarction.

Ventricular Fibrillation Causes Sudden Death in Southeast Asian Immigrants

Young, male, Southeast Asian immigrants living in the United States have a high incidence of unexplained, sudden, nocturnal death. We report the cases of three patients, two Laotians and one Filipino, who were resuscitated and subsequently studied extensively. Each patient was having ventricular fibrillation when first examined by paramedics outside the hospital, and episodes of fibrillation recurred in the early hospital course. Clinical evaluation found no significant coronary atherosclerosis or structural cardiac disease. One patient is asymptomatic after 2 years; the second patient died suddenly at 4 months; and the third is asymptomatic but had inducible ventricular tachycardia on electrophysiologic testing 6 months after resuscitation. The mechanism of sudden death in young Southeast Asian men appears to be ventricular fibrillation. The cause of the arrhythmia is unclear, although in our patients the arrhythmia was not an isolated event; underlying predispositions to further cardiac arrest persisted.

Prolongation of cardiac refractory times in man by clofilium phosphate, a new antiarrhythmic agent☆

The electrophysiologic effects of clofilium phosphate, a new quaternary ammonium antiarrhythmic agent, were evaluated in 15 patients with a variety of cardiac dysrhythmias. Ten patients had ventricular dysrhythmias and five patients had supraventricular dysrhythmias. Clofilium was administered as a single bolus intravenously in doses ranging from 60 to 300 micrograms/kg during electrophysiologic testing. Blood pressure and heart rate were unchanged, and there were no significant side effects. Conduction time was unchanged in atrial tissue, ventricular tissue, atrioventricular node, and in the His-Purkinje system. QT intervals lengthened, atrial effective refractory period increased, and ventricular effective refractory period increased. The effective refractory period of the AV node was unchanged. Refractoriness of the bundle branches or His-Purkinje system was increased in eight patients. Inducible supraventricular arrhythmias were improved in four of four patients, and inducible ventricular arrhythmias were improved in at least five of nine patients. Clofilium is a model for an antiarrhythmic drug which should be useful in interrupting or suppressing reentrant arrhythmias because it increases refractoriness without major changes in conduction time.