Jeffrey A. Werner

STENT PLACEMENT COMPARED WITH BALLOON ANGIOPLASTY FOR OBSTRUCTED CORONARY BYPASS GRAFTS

BACKGROUND Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts. METHODS A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later. RESULTS As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate of procedural efficacy, defined as a reduction in stenosis to less than 50 percent of the vessel diameter without a major cardiac complication (92 percent vs. 69 percent, P<0.001), but they had more frequent hemorrhagic complications (17 percent vs. 5 percent, P<0.01). Patients in the stent group had a larger mean (+/-SD) increase in luminal diameter immediately after the procedure (1.92+/-0.30 mm, as compared with 1.21+/-0.37 mm in the angioplasty group; P<0.001) and a greater mean net gain in luminal diameter at six months (0.85+/-0.96 vs. 0.54+/-0.91 mm, P=0.002). Restenosis occurred in 37 percent of the patients in the stent group and in 46 percent of the patients in the angioplasty group (P=0.24). The outcome in terms of freedom from death, myocardial infarction, repeated bypass surgery, or revascularization of the target lesion was significantly better in the stent group (73 percent vs. 58 percent, P = 0.03). CONCLUSIONS As compared with balloon angioplasty, stenting of selected venous bypass-graft lesions resulted in superior procedural outcomes, a larger gain in luminal diameter, and a reduction in major cardiac events. However, there was no significant benefit in the rate of angiographic restenosis, which was the primary end point of the study.

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.

Effect of amiodarone on serum quinidine and procainamide levels

Serum levels of quinidine or procainamide were measured in patients who had amiodarone added to their antiarrhythmic regimen. Dosages of quinidine or procainamide were held constant. Eleven of 11 patients had an increase in the serum quinidine level, and 11 of 12 other patients had an increase in the serum procainamide level. The dose requirement to maintain a stable plasma level of quinidine or procainamide decreased by 37% and 20%, respectively. Clinical toxicity occasionally occurred with the increase in serum levels of quinidine and procainamide, and the dose of these drugs should be decreased when amiodarone is administered concurrently.

Sensitivity of various extrastimulus techniques in patients with serious ventricular arrhythmias

Abstract One hundred seventeen consecutive patients with a history of sudden cardiac death (group I = 62 patients) or recurrent symptomatic ventricular tachycardia (group II = 55 patients) as well as 11 control subjects (group III) were studied with programmed electrical stimulation over the past year. Programmed right ventricular stimulation included premature stimulation during atrial pacing (A1V2 mode) and during ventricular pacing (V1V2 mode), double ventricular extrastimuli during ventricular pacing (V1V2V3), and brief bursts of rapid ventricular pacing (Vburst). Repetitive ventricular responses were defined as two or more ventricular premature beats produced by the final ventricular pacing stimulus occurring by intraventricular reentry. All but 13 patients were on antiarrhythmic therapy at the time of study. The incidence of repetitive ventricular responses induced by A1V2 pacing mode was 22% (22 of 104 patients) and that of sustained ventricular tachycardia was 1%. The sensitivity of inducing repetitive ventricular responses with V1V2 stimulation was 44% and that of sustained ventricular tachycardia was 7%; the sensitivity with V1V2V3 pacing mode was significantly higher at 77% and 25%, respectively. When V1V2V3 and Vburst stimulation were directly compared, the incidence of induction of repetitive ventricular responses and sustained ventricular tachycardia were comparable. The incidence of induction of repetitive ventricular responses and sustained ventricular tachycardia in groups I and II was similar; no repetitive ventricular responses were induced in group III patients. There was no significant difference in the sensitivity of either repetitive ventricular response or sustained ventricular tachycardia induction in patients with coronary disease compared with those with the diagnosis of noncoronary disease. We conclude that, contrary to an earlier report from our group, the incidence of induction of repetitive ventricular responses to single ventricular extrastimuli during atrial pacing is low in patients with a history of sudden death or recurrent ventricular tachycardia. The incidence of induction of repetitive ventricular responses and sustained ventricular tachycardia is highest using the V1V2V3 and Vburst modes of stimulation.

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.

Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans.

OBJECTIVES This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty. BACKGROUND Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models. METHODS In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon. RESULTS The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 +/- 0.44 vs. 1.49 +/- 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables. CONCLUSIONS Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis.