R Balcon

Long-term Effects of Angiopeptin Treatment in Coronary Angioplasty Reduction of Clinical Events but Not Angiographic Restenosis

Background Angiopeptin is a cyclic octapeptide analogue of somatostatin that has been shown to limit myointimal thickening of arteries in balloon injury models and to restore the vasodilating response to acetylcholine. A randomized, double-blind placebo controlled trial was conducted to assess the effect of angiopeptin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Methods and Results Patients received a continuous infusion of either placebo or angiopeptin subcutaneously 6 to 24 hours before PTCA and for 4 days after PTCA (3 mg per 24 hours before PTCA followed by 6 mg per 24 hours after PTCA and for the remaining period). A 1.5-mg bolus dose of placebo or angiopeptin was given at PTCA. Aspirin (acetylsalicylic acid, 150 mg/d) was administered throughout the study period. Coronary angiograms obtained before and after PTCA and at 6-month follow-up were subjected to computerized quantification. Clinical follow-up was performed after 12 months. Primary clinical end points were death, myocardial infarction, coronary artery bypass surgery, or repeat PTCA. In total, 553 patients with 742 lesions were randomized. Clinical follow-up was available for all 553 patients. Angiopeptin decreased the clinical events during 12 months of follow-up from 36.4% in the placebo-treated group to 28.4% in the angiopeptin-treated patients ( P =.046). Quantitative angiography after PTCA and at follow-up was available in 423 of 455 patients who underwent successful PTCA. The minimal lumen diameter at follow-up was 1.52±0.64 mm in the angiopeptin-treated group compared with 1.52±0.64 mm in the placebo-treated patients ( P =.96). The late losses were 0.31±0.59 and 0.30±0.62 mm ( P =.81) and the restenosis rates (>50% diameter stenosis at follow-up) were 36% and 37% ( P =.85) in the angiopeptin- and placebo-treated groups, respectively. Conclusions In this study, angiopeptin significantly decreased the incidence of clinical events, principally the rate of revascularization procedures. In contrast, no significant effect was seen on angiographic variables.

Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion.

Treatment with the combination of aspirin and dipyridamole is believed to reduce the incidence of coronary vein graft occlusion. A double blind randomised controlled trial was carried out in which aspirin 990 mg and dipyridamole 225 mg daily or placebo were added to the routine postoperative management (warfarin for three months) of 320 patients undergoing coronary bypass grafting. The trial treatment was given for 12 months, after which the results were assessed by coronary and graft angiography. The two randomised groups, each of 160 patients, were comparable in age, sex, symptomatic state, angiographic findings, and operative procedure. Repeat coronary arteriography was carried out on 266 patients, 133 in each group. All grafts and distal anastomoses were patent in 68% (91/133) of the placebo patients and in 75% (100/133) of those receiving active treatment. Overall graft patency was 87% (306/352) and 89% (342/385) respectively. Retrospective subgroup analysis showed patency rates of 72% (26/36) and 78% (39/50) of grafts to vessels requiring preliminary endarterectomy, and 80% (36/45) and 91% (40/44) of distal anastomoses to vessels measured at operation to have a diameter of less than or equal to 1 mm. None of these differences was significant at the 5% level. Thus in this group of patients with high graft patency rates, treatment with aspirin and dipyridamole conferred no appreciable advantage.

Irregular coronary lesion morphology after thrombolysis predicts early clinical instability

After successful thrombolytic treatment for acute myocardial infarction, recurrent ischemia and infarction may occur with little warning. Coronary lesion morphology was analyzed from angiograms performed in 72 consecutive patients at 1 to 8 days after streptokinase treatment for acute myocardial infarction and the data were evaluated in relation to the subsequent clinical course. All patients were clinically stable at the time of angiography and continued to receive heparin infusion for greater than or equal to 4 days after thrombolysis. The infarct-related artery was patent in 55 patients (76%). In the 10 days after angiography, 15 patients developed prolonged episodes of angina at rest; the condition of 4 stabilized with medical treatment, but 11 required urgent medical intervention (coronary angioplasty in 8 and bypass surgery in 3). There were no differences in age, gender, left ventricular function or extent of coronary artery disease between those patients who developed unstable angina and those who had a stable in-hospital course. However, the median plaque ulceration index of the infarct-related lesion was 6.7 (95% confidence limits 6.3, 10) in the 15 patients with an unstable course versus 3.3 (2, 4.4) in those with a stable course (p less than 0.001). There were no differences between the two patient groups in the severity of stenosis, length of diseased segment, symmetry/eccentricity, presence of a shoulder, location at branch point or bend, presence of globular or linear filling defects, contrast staining or collateral supply. These data show that after thrombolysis, the degree of irregularity of the infarct-related artery is a critical determinant of early clinical instability.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced pulmonary microvascular permeability in severe chronic left heart failure

Pulmonary edema is a serious complication of heart failure, but often patients with chronic heart failure resist pulmonary edema despite elevated pulmonary venous pressures. This protection might be a result of decreased pulmonary microvascular permeability. Double-isotope scintigraphy with 113mindium-labeled transferrin and 99mtechnetium-labeled erythrocytes allows noninvasive estimation of pulmonary microvascular permeability; an index of transferrin accumulation is calculated that reflects microvascular permeability. Fourteen patients with severe chronic left ventricular dysfunction were compared with a control group of 15 patients with mild coronary artery disease. In the control group the transferrin accumulation index was 0.35 (range -0.3 to 1.0) x 10(-3)/min, and in patients with heart failure the index was 0.0 (range -1.0 to 0.7) x 10(-3)/min, which was significantly lower (p less than 0.01). The reduction in the transferrin accumulation index correlated weakly with the duration of heart failure (R = -0.5, p less than 0.02). These data indicate reduced protein efflux consistent with a decrease in pulmonary microvascular permeability in patients with severe chronic heart failure. Similar changes have been observed in severe mitral stenosis and may reflect a generalized adaptation to chronic pulmonary venous hypertension.

Coronary lesion morphology in acute myocardial infarction: Demonstration of early remodeling after streptokinase treatment

Coronary lesion morphology was analyzed in 72 patients 1 to 8 days after streptokinase treatment for acute myocardial infarction and compared with lesion morphology in a control group of 24 patients with stable angina. In the streptokinase group the infarct-related artery was patent in 55 patients (76%). Compared with stenoses in the stable angina group, there were no differences in the stenosis length, severity, calcification or in the proportion located at an acute bend or at a branch point. However, lesions in the streptokinase group were more often irregular (p less than 0.005) and eccentric (p less than 0.01), had a shoulder (p less than 0.0001), globular filling defects (p less than 0.01), linear filling defects (p less than 0.00005) and contrast staining (p less than 0.05). Plaque ulceration index was higher in the streptokinase than in the stable angina group (6.2 +/- 7.9 versus 3.5 +/- 3.4, p less than 0.001). Of the 72 streptokinase-treated patients, 35 were maintained on heparin infusion until angioplasty 2 to 10 days later. At repeat angiography before angioplasty, globular lesion filling defects seen in eight patients had disappeared, whereas linear filling defects persisted in 7 of 14 cases. Fewer lesions were irregular (p less than 0.0001) and the ulceration index decreased from 7.4 +/- 10.4 to 3.0 +/- 1.6 (p less than 0.001). These data show that the lesion in the infarct-related artery after streptokinase treatment is irregular and often associated with filling defects, perhaps corresponding to plaque fissuring and intraluminal thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of heart rate/ST slope and coronary angiographic findings.

The heart rate/ST slope was evaluated in 49 patients undergoing routine investigation for possible coronary artery disease. The slope correctly predicted the absence of any 75% stenoses in the seven patients to whom this applied; it was, however, correct for only four of 30 with one stenosis, one of 10 with two, and neither of the patients with three. Distinct slope ranges were not found, and the previously published ranges said to be specific for no significant stenosis and one, two, and three vessel disease were not.

What proportion of patients with myocardial infarction are suitable for thrombolysis

Four hundred and three patients were considered for entry into a trial of intravenous streptokinase in suspected myocardial infarction. Three hundred and sixty seven (91%) were excluded. Two hundred and sixty (65%) did not meet the inclusion criteria and 45 of the remaining 143 (35%) patients had contraindications to thrombolysis. This left 98 (24%) patients who were suitable for thrombolysis and 42 of them were over 70 years, the upper age limit. Thus according to this trial protocol 56 (14%) patients were eligible for recruitment; 36 (9%) patients were finally randomised. These data suggest that treatment with intravenous streptokinase may be applicable to only a small proportion of patients with myocardial infarction.

Isolated disease of left anterior descending coronary artery. Angiocardiographic and clinical study of 218 patients.

The angiocardiographic and clinical findings in 218 patients with significant obstruction confined to the left anterior descending coronary artery were reviewed to study the influence of the site of obstruction and of the collateral circulation on clinical presentation and prognosis. One hundred and fifty-six patients had been managed medically, 51 had had aortocoronary bypass operations, and 11 had had left ventricular aneurysms excised. The artery was divided into three segments: left anterior descending 1 (LAD1) from its origin to the first septal branch, left anterior descending 2 (LAD2) from the first septal to the first diagonal branch, and left anterior descending 3 (LAD3) the remaining distal vessel. Cardiogenic shock occurred only in patients with LAD1 lesions, but apart from this the clinical presentation bore no consistent relation to the site of disease. Patients with proximal lesions were more likely to have a positive exercise test, had more severely impaired left ventricular function, and had a worse prognosis than those with more distal disease. Non-visualisation of collateral vessels in patients with left anterior descending occlusion was associated with extensive infarction, and patients who presented with infarction had more severely impaired ventricular function than those who presented with angina and subsequently had an infarction. Left ventricular function was poor at the time of angiography in 11 of 12 of those who subsequently died; it is therefore unlikely that the prognosis of patients with isolated left anterior descending obstruction could be improved by expanding the indication for aortocoronary bypass from that of severe angina.

Emergency surgical revascularisation for coronary angioplasty complications.

OBJECTIVES--To evaluate trends in referrals for emergency operations after percutaneous transluminal coronary angioplasty (PTCA) complications; to analyse morbidity and mortality and assess the influence of PTCA backup on elective surgery. DESIGN--A retrospective analysis of patients requiring emergency surgical revascularisation within 24 hours of percutaneous transluminal coronary angioplasty. PATIENTS--Between January 1980 and December 1990, 75 patients requiring emergency surgery within 24 hours of percutaneous transluminal coronary angioplasty. SETTING--A tertiary referral centre and postgraduate teaching hospital. RESULTS--57 patients (76%) were men, the mean age was 55 (range 29-73) years, and 30 (40%) had had a previous myocardial infarction. Before PTCA, 68 (91%) had severe angina, 59 (79%) had multivessel disease, and six (8%) had a left ventricular ejection fraction of less than 40%. A mean of 2.1 grafts (range one to five) were performed; the internal mammary artery was used in only one patient. The operative mortality was 9% and inhospital mortality was 17%. There was a need for cardiac massage until bypass was established in 19 patients (25%): this was the most important outcome determinant (P = 0.0051) and was more common in those patients with multivessel disease (P = 0.0449) and in women (P = 0.0388). In 10 of the 19 cases a vacant operating theatre was unavailable, the operation being performed in the catheter laboratory or anaesthetic room. These 19 patients had an operative mortality of 32% and inhospital mortality of 47%, compared with 2% and 7% respectively for the 56 patients who awaited the next available operating theatre. Complications included myocardial infarction, 19 patients (25%); arrhythmias, 10 patients (3%); and gross neurological event, two patients (3%). The mean intensive care unit stay was 2.6 days (range 1 to 33 days) and the mean duration of hospital admission was 13 days (range 5-40 days). CONCLUSIONS--Patients undergoing emergency surgery after PTCA complications have a substantially increased inhospital mortality and morbidity. PTCA in this unit continues to require surgical cover. Delays in operating on stable patients in centres which operate a next available theatre backup policy may not differ from some units performing PTCA with offsite cover for PTCA complications. Particularly in the presence of multivessel disease, however, PTCA complications may be associated with the need for crash bypass and such patients are unlikely to survive hospital transfer. The proportion of patients requiring crash bypass has increased during the period reviewed because of the extent of disease in the emergency surgical group increased. These results indicate that surgery should not be denied to these patients.

Significance of "reciprocal" ST segment depression: left ventriculographic observations during left anterior descending coronary angioplasty.

To evaluate the significance of reciprocal ST segment depression resulting from coronary occlusion, 27 patients with single vessel coronary disease were studied with intravenous digital subtraction left ventriculography before and during angioplasty of the left anterior descending coronary artery. During balloon inflation, 13 patients developed inferior lead ST depression in addition to anterior lead ST elevation (Group 1), whereas the remaining 14 patients did not (Group 2). The degree of anterior lead ST elevation in Group 1 (5 mm) was greater than that in Group 2 (1.5 mm, p less than 0.001) as was the reduction in left ventricular ejection fraction (24% versus 13%, respectively; p less than 0.02). Anterior and apical regional shortening decreased in both groups similarly, but an additional decrease in anterobasal shortening was confined to Group 1 (from 38% to 21%; p less than 0.002). Despite the presence of inferior lead ST depression in Group 1, inferior regional shortening did not change and inferobasal contraction was enhanced (from 4% to 29%; p less than 0.01). Inferior lead ST segment depression during anterior descending coronary angioplasty reflects a greater degree of anterior wall ischemia. The concurrent preservation of inferior wall contraction and the augmentation of infero-basal shortening confirm that this electrocardiographic feature is a reciprocal phenomenon rather than a manifestation of remote ischemia.