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. (C) 2000 by the American College of Cardiology.

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.

The purpose of this interim analysis of the SAVED Restenosis Trial was to assess the acute results of balloon angioplasty (PTCA) and elective PalmazSchatz coronary stent placement in the treatment of de novo venous bypass graft lesions. As of August 1, 1994, 128 patients (60 PTCA, 68 Stent) have been enrolled at 13 centers. Baseline demographics were similar in both groups. Mean graft ages in the PTCA and Stent groups were 9.8 ± 4.2 vs 9.7 ± 4.5 years (p = ns). Initial angiographic results by core laboratory analysis and clinical events from 0 to 30 days were as follows:Angiographic resultsPICAStentClinical Events (%)PICAStentVessel diameter (mm)3.213.18Death3.35.9Baseline mid (mm)0.980.93O-wave MI1.71.5Final mid (mm)2.122.85Bypass Surgery6.70**Final % diam stenosis3312*Closure: ≥24 hrs332.9Procedure success (%)8596**>24 hrs1.70*p < 0.01**p < 0.05 vs PICA p < 0.01 p < 0.05 vs PICA One or more major clinical events occurred in 11.7% of PTCA patients vs 5.9% of Stent patients (p = ns). Crossover from assigned to alternative therapy (including bypass surgery) was 13.3% for the PTCA group vs 1.5% for the Stent group (p < 0.01). In conclusion, the preliminary findings of this prospective trial indicate: (1) Elective stent placement in de novo saphenous vein bypass graft lesions achieves a superior initial angiographic result compared to balloon angioplasty; (2) Stents confer a salutary effect on early clinical events with less frequent need for alterna1e therapies including coronary bypass surgery.

Myocardial size and contractility were measured by gated radionuclide ventriculography in 70 patients before and a mean of 66 days after beginning amiodarone therapy. The mean dose of amiodarone at the time of the second study was 481 mg. The mean left ventricular (LV) ejection fraction (EF) increased slightly, from 40% to 43% (p = 0.001). The mean right ventricular EF remained unchanged (38% to 39%, difference not significant [NS]). The LV end-diastolic volume (count-based method) increased by 9% (p = 0.01), but no change could be demonstrated for end-systolic volume (4%, NS). The LV stroke volume increased 19% (p = 0.001), but cardiac output remained unchanged (5%, NS) because the heart rate decreased by 9 beats/min (p = 0.001). The right ventricular end-diastolic volume increased by 12% (p = 0.01) and end-systolic volume increased by 11% (p = 0.03). Stroke volume increased by 18% (p = 0.005). There was no significant correlation between the change in LVEF and the pre-amiodarone LVEF, the time interval between studies, or with indexes of amiodarone effect (change in heart rate, QRS, QTc, TSH, amiodarone dosage). In 5 patients (7%), LVEF decreased significantly, requiring discontinuation of amiodarone therapy in 1 patient. At the time of the second study congestive heart failure was manifest in 19%, and there was a trend suggesting that congestive heart failure was more likely if the initial LVEF was less than or equal to 35% (p = 0.10). Thus, amiodarone may rarely adversely affect contractility, although myocardial contractility is typically unchanged. There is an associated small increase in the size of both ventricles.

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.

Gated radionuclide angiography (RVG) in orthogonal projections was used to evaluate left ventricular volume, ejection fraction, and segmental wall motion. Images of the left ventricle at end-diastole and endsystole were outlined in two projections using a simple manual method. The perimeter drawings were digitized on a desktop computer, interfaced to an XY recorder and left ventricular volumes and ejection fraction calculated. The results were compared to contrast left ventriculography (CVG) in the same projections. RVG and CVG gave similar results for end-diastolic volume (r = .87, P < 0.001), end-systolic volume (r = .95, P < 0.001), and ejection fraction (r = .89, P < 0.001) over a wide range of values. In 92% of all left ventricular segments analyzed, RVG and CVG showed only minor differences in the analysis of wall motion. Reproducibility of the method by a trained observer was excellent. Interobserver trials demonstrated that less well-trained observers consistently over- or underestimated volumes, emphasizing the need for prior experience in RVG analysis. Use of this manual method for analysis of gated equilibrium RVG in orthogonal projections appears to be a reasonably accurate, reproducible method for evaluating left ventricular function.

The influence of left ventricular filling pressure on the atrial contribution to cardiac output was evaluated in 18 patients. An inverse relationship between filling pressure and atrial contribution was seen in studies done at baseline (PCW (r = −.53, p < .025), as well as in studies done after PCW was modified by volume expansion and/or nitrates (r = −.53, p < .005). At baseline, atrial contribution averaged 9.3 ± 1.3 c.c./M.2 in patients with PCW < 20 mm. Hg, while it was only 2.4 ± 1.2 c.c./M.2 in patients with PCW ≥ 20 mm. Hg (p < .005). Atrial contribution was significantly greater in patients who had no history of heart failure when they were volume loaded to a PCW above 20 mm. Hg than in patients with impaired ventricular function whose baseline PCW was above 20 mm. Hg. Thus, atrial contribution tends to be less effective in augmenting cardiac output when filling pressure is already elevated, particularly in patients with impaired left ventricular function.

Myocardial scintigraphy with technetium-99m pyrophosphate has proved to be a sensitive technique for diagnosing acute transmural myocardial infarction and has also been considered reliable in the recognition of nontransmural or subendocardial infarction. To assess the accuracy of pyrophosphate scintigraphy in diagnosing this latter entity, this procedure was studied in 31 patients with a confirmed nontransmural infarct, 43 with a transmural Infarct and 40 with stable angina pectoris. Radionuclide uptake was graded on a scale of 0 to 4+ and classified as discrete or diffuse. Diffuse uptake appeared to be nonspecific, occurring in 19 percent of patients with a subendocardial infarct and in 10 percent of those with stable angina pectoris; neither rate was significantly different from the 14 percent prevalence rate reported among patients without heart disease undergoing routine bone scan. Discrete uptake was highly specific for acute infarction but occurred in only 32 percent of patients with a nontransmural infarct compared with 84 percent of patients with a transmural infarct ( P < 0.001). In both patient groups, scintigrams showing discrete uptake occurred in those with higher levels of creatine kinase MB level ( P < 0.025), whereas scintigrams showing diffuse uptake occurred in patients whose enzyme level was similar to that of patients with negative scintigrams. It is concluded that discrete radionuclide uptake is a specific indicator of acute necrosis in patients with either transmural or nontransmural infarction, whereas diffuse uptake is nonspecific. However, discrete uptake occurs in only a minority of patients with subendocardial infarction, and therefore pyrophosphate scintigraphy is an insensitive technique in these patients.

To determine the utility of thallium-201 stress scintigraphy in assessing the results of coronary bypass surgery, chest paln, stress electrocardiograms and sclntigrams were evaluated in 27 patients postoperatlvely. These findings were compared with coronary angiographie data in which a significant postoperative lesion was defined as 75 percent or more stenosis in a graft, its distal vessel or in an ungrafted native vessel. As an indicator of postoperative coronary lesions, chest pain lacked sensitivity (60 percent) and was nonspecific (20 percent). The stress electrocardiogram had poor sensitivity (60 percent) and good specificity (86 percent) but was not helpful in six patients who had equivocal or suboptimal tests. The scintigram had good sensitivity (77 percent) and was highly specific for the diagnosis of coronary stenosis. It was significantly more specific than chest pain (P < 0.01), gave excellent localizing information and added to the accuracy of both conclusive and inconclusive stress tests. In nine patients with preoperative stress scintigrams, comparison of pre- and postoperative studies reflected the éffects of bypass surgery on coronary perfusion. Scintigraphy is a useful technique for the noninvasive evaluation of the patient after coronary bypass surgery, and postoperative scintigraphy alone is of great value in documenting surgical results.

Echocardiograms from 562 patients were examined for evidence of the pattern of tricuspid valve prolapse. Criteria for the diagnosis can be established similar to those applicable to mitral prolapse. In 500 consecutive patients without mitral valve prolapse, there were no cases of isolated tricuspid valve prolapse. Eleven of 53 (21 per cent) patients with mitral valve prolapse also had tricuspid valve prolapse. Four of six (67 per cent) patients with Marfan's syndrome and mitral valve prolapse also had tricuspid valve prolapse. The occurrence of this echocardiographic pattern as an isolated finding as well as associated with mitral valve prolapse was significantly less than previous angiographic reports. Patients with both these findings tended to be older than those with mitral valve prolapse alone, but clinically differed in no other way. Use of standardized technique can minimize errors in diagnosis.