Prospective, randomized trial of prolonged intracoronary urokinase infusion for chronic total occlusions in native coronary arteries.

OBJECTIVES: The purpose of this study was to determine the safety and efficacy of three dosing regimens of intracoronary urokinase for facilitated angioplasty of chronic total native coronary artery occlusions. BACKGROUND: Percutaneous transluminal coronary angioplasty of chronically occluded (>3 months) native coronary arteries is associated with low initial success secondary to an inability to pass the guide wire beyond the occlusion. METHODS: Patients were enrolled if a chronic total occlusion >3 months old could not be crossed with standard angioplasty equipment. Of the 101 patients enrolled, 41 had successful guide wire passage and were excluded from urokinase treatment. The remaining 60 patients were randomized to receive one of three intracoronary dosing regimens of urokinase over 8 h (group A = 0.8 million U; group B = 1.6 million U; group C = 3.2 million U), and angioplasty was again attempted after completion of the urokinase infusion in 58 patients. RESULTS: Coronary angioplasty was successful in 32 patients (53%) (group A 52%, group B 50%, group C 59%, p = 0.86). This study had a 90% power to detect at least a 50% difference between dosing groups at alpha 0.05. Bleeding complications requiring blood transfusion did not differ significantly among the dosing groups (A 0%, B 15%, C 6%, p = 0.14), although major bleeding episodes were less common in group A (p < 0.05). There were no major procedural or in-hospital complications. Angiographic follow-up in 69% of the patients with successful angioplasty revealed target vessel patency in 91% but an angiographic restenosis rate of 59%. CONCLUSIONS: A prolonged supraselective intracoronary infusion of urokinase can be safely administered and may facilitate angioplasty of chronic total occlusions. Lower doses of urokinase are equally effective and result in fewer bleeding complications than do higher dosage regimens. Vessel patency is frequently maintained, but restenosis remains a problem.

Ankle/arm pressure index in asymptomatic middle-aged males: an independent predictor of ten-year coronary heart disease mortality.

PURPOSE OF THE STUDY: to evaluate the predictive power of a reduced ankle/brachial pressure index (ABPI) (< or = .90) in an asymptomatic middle-aged male working population free of coronary heart disease. MATERIALS AND METHODS: 2023 subjects forty to fifty-five years old were screened at their work place. Standard techniques were used. Blood was drawn in the fasting state. Ankle and brachial blood pressures were measured by Doppler signals and all measures were done by one observer, duly trained in epidemiologic methodology. RESULTS: in univariate analysis, an ABPI < or = .90 was significantly associated with age, total serum cholesterol, body mass index, smoking, and awareness of diabetes. In multivariate analysis, it was associated with awareness of diabetes, age, Ln triglycerides (P = .073), and smoking (P = .088). Relative risks for reduced versus normal ABPI are 2.77 (P = .010), 4.16 (P = .011) and 4.97 (P = .006) for ten-year all causes, cardiovascular, and coronary mortality, respectively. In a multiple logistic regression analysis, the following variables were significant independent predictors of coronary mortality: smoking (odds ratio [OR] = 4.84), reduced ABPI (OR = 3.63), and low density lipoprotein cholesterol (OR for 1 SD = 1.69). Reduced ABPI is also an independent predictor of cardiovascular mortality. CONCLUSION: a reduced ABPI is an independent risk factor for coronary and cardiovascular mortality in asymptomatic middle-aged Belgian males.

New recombinant glycosylated prourokinase for treatment of patients with acute myocardial infarction. Prourokinase Study Group.

OBJECTIVES: Three dosage regimens of a new recombinant glycosylated prourokinase (A-74187) were evaluated by measuring coronary artery patency at 90 min in patients with acute myocardial infarction. BACKGROUND: Prourokinase is a thrombolytic drug with unique pharmacologic properties that may be clinically advantageous. METHODS: Aspirin (325 mg), intravenous heparin and prourokinase (60- or 80-mg monotherapy or 60 mg "primed" with a preceding bolus dose of 250,000 IU of recombinant urokinase) were administered to 128 patients. Coronary angiography was performed at 60 min (wherever possible), 90 min (primary end point) and 24 h to determine arterial patency and reocclusion rates. Plasma was collected serially to measure fibrinogen, plasminogen, thrombin antithrombin III and fibrinopeptide A. Clinical events until hospital discharge were recorded. RESULTS: The coronary artery patency rate at 90 min was similar for all three regimens, averaging 73% (95% confidence interval [CI] 64% to 80%); Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow rates averaged 52% (95% CI 42% to 61%). Arterial patency at 60 min was 62% (95% CI 50% to 73%), and reocclusion occurred in 1.4% (95% CI 0.1% to 4.1%). Prourokinase demonstrated relative fibrin specificity at all doses studied. Fibrinopeptide A and thrombin antithrombin III levels were elevated at baseline and declined rapidly during the 1st 12 h. There was no difference in the baseline values of these thrombin markers between patients with patent versus closed arteries at 90 min. There was one death; no strokes occurred. CONCLUSIONS: A-74187 prourokinase is a rapid-acting, effective fibrin-specific thrombolytic agent. Reocclusion was unusual, possibly because of aggressive anticoagulation with intravenous heparin or unique features of the drug. Full definition of the clinical effectiveness of this drug merits examination in future randomized trials evaluating clinical and angiographic effectiveness.

Intravenous diltiazem versus nitroglycerin for silent and symptomatic myocardial ischemia in unstable angina pectoris.

For 18 patients consecutively admitted to the coronary care unit for unstable angina, 48-hour electrocardiographic Holter monitoring was performed after they were randomly assigned in a single-blind fashion to 1 of 2 treatment groups. The first group was treated with acetylsalicylic acid (ASA) and intravenous nitroglycerin, the second with ASA and intravenous diltiazem. All of the patients treated with nitroglycerin still had ischemic episodes after 48 hours (33% were symptomatic), in contrast with 11% of the diltiazem group (11% asymptomatic). Maximal ST-segment depressions of symptomatic and asymptomatic episodes were significantly different; and no significant increases in heart rate were observed either during the 15 seconds before ischemia began or during the ischemic episode. During the 48 hours, the diltiazem group had significantly fewer ischemic episodes (17) than did the nitroglycerin group (145). We concluded that "on-line" ST-segment observation is of prime importance for monitoring unstable angina; that the majority of the ischemic episodes associated with unstable angina are silent; and that intravenous diltiazem could be an effective pretreatment for patients who must undergo mechanical or surgical therapy.

Hemodynamic effects of SIN-1 in acute left heart failure.

To assess the hemodynamic effects of SIN-1, the active metabolite of the venodilator molsidomine, after acute as well as chronic intravenous administration, ten patients with exacerbation of chronic heart failure were studied. After a mean bolus dose of 2 mg of SIN-1, mean right atrial pressure (MRAP), mean pulmonary artery pressure (MPAP), and pulmonary capillary wedge pressure (PCAP) decreased significantly up to the 60th minute; pulmonary vascular resistance (PVR) decreased significantly up to the 30th minute, while cardiac index (CI) and systemic vascular resistance (SVR) remained unchanged. During a 24-hour continuous infusion of SIN-1, MRAP, MPAP, and PCAP decreased significantly, while CI, PVR, and SVR remained largely unaltered. No dose adjustment was required to maintain the hemodynamic effects over 24 hours. The absence of noteworthy side effects and tolerance during this prolonged administration indicate that SIN-1 is a potentially useful drug in the management of patients admitted with exacerbation of heart failure.

Secondary prevention after myocardial infarction: effects of beta blocking agents and calcium antagonists.

Therapeutic interventions in patients with myocardial infarction, whether during the first hours after coronary occlusion or several days later, aim to reduce mortality and morbidity by several mechanisms: Prevention of fatal ventricular fibrillation, limitation of infarct size, and inhibition of platelet aggregation are some examples of such mechanisms. Results from early intervention trials with beta blocking agents, particularly from ISIS-I, suggest that 1-year mortality is significantly lower in selected patients randomized to active treatment. Late intervention studies also suggest a significant reduction in coronary mortality and morbidity with beta blockade, particularly when data are pooled. Studies with the calcium channel blockers nifedipine and verapamil were unable to demonstrate any beneficial effects of these drugs on mortality or reinfarction. In this review article, attention will be directed to the most recent information about the preventive value of beta adrenergic blocking drugs and slow calcium channel inhibitors.

Physical fitness does not reflect physical activity patterns in middle-aged workers.

Questionnaires and a sub-maximal exercise test were used to assess occupational and leisure time physical activity as well as physical fitness in a standardized prospective study in 2,565 Belgian and Slovakian middle-aged healthy workers. Less than 5% of the subjects engaged in strenuous work requiring an energy expenditure above 31.5 kJ.min-1. One-third of the Belgians and 50% of the Slovakians reported no heavy leisure time activity during the preceding 12 months. Physical fitness, defined as the workload at heart rate 150 beats.min-1 (standardized for body weight), was significantly higher in Slovakians as compared to Belgians (1.52 +/- 0.28 W.kg-1 and 1.48 +/- 0.28 W.kg-1; P less than 0.001). Occupational physical activity in Belgians and heavy leisure time activity in Slovakians were independently related to fitness levels. However, each activity score explained less than 1% of the variance of physical fitness. We conclude that in these mainly sedentary, middle-aged subjects, fitness levels are independent from the usual physical activity patterns.

Protection against ischemic heart disease in the Belgian Physical Fitness Study: physical fitness rather than physical activity?

Occupational and leisure time physical activity and conventional risk factors were determined in the Belgian Physical Fitness Study, a prospective study of 2,363 healthy male factory workers who were aged 40-55 years at entry in 1976-1978 and who were followed for five years. Physical fitness, defined as the interpolated physical working capacity at heart rate 150 beats per minute, was measured in 2,109 subjects. In this subgroup, there were 31 myocardial infarctions and sudden deaths. Smoking, physical fitness, and high density lipoprotein cholesterol (HDL cholesterol) were independent risk indicators for subsequent ischemic heart disease, while both physical activity scores were not. It is concluded that in this healthy, predominantly sedentary population, the fitness level, but not the physical activity pattern, is an independent protective factor against ischemic heart disease.

[Hemodynamic effects of microencapsulated delayed-release nitroglycerin in acute myocardial infarction]. / Effets hémodynamiques de la nitroglycérine microencapsulée à libération prolongée dans l'infarctus aigu du myocarde.

The hemodynamic effects following an oral dose of 19.5 mg of nitroglycerin microencapsulated to give prolonged release have been studied in 10 patients during the 48 hours which followed the establishment of a myocardial infarct complicated by moderate left cardiac insufficiency. The right auricular pressure and the pulmonary capillary pressure diminished significantly 20 minutes after the dose; 4 hours later the persistence of these effects is significant. A transient diminution of the systolic arterial pressure was observed initially (p less than 0.05). We observed that the cardiac index tends to increase although the increase did not attain the threshold of significance. No difference was observed in cardiac frequency, diastolic and mean arterial pressure and in the systemic vascular resistance. We conclude that in the patient presenting an acute myocardial infarct, 19.5 mg of NTG, microencapsulated to give prolonged release, essentially produce a reduction of the preload, with an early onset of action and a hemodynamic efficacy lasting at least 4 hours.

Anomalous origin of an accessory coronary artery from the main pulmonary artery: report of a case with arrhythmia, precordial pain and left heart failure.

Anomalous origin of the coronary arteries from the main pulmonary artery is a rare congenital malformation. While this anomaly rarely produces cardiac symptoms, the more frequently encountered anomalous left coronary artery arising from the main pulmonary artery is poorly tolerated, the majority of patients dying in infancy. This report describes a symptomatic sixty-year old man with anomalous posterior descending coronary artery arising from the pulmonary trunk and details the angiographic findings.

Effects of molsidomine on left ventricular dimensions and cardiac function in patients with chronic heart failure.

The effects of molsidomine were studied in seven patients with refractory congestive heart failure by means of two-dimensional echocardiography. Four milligrams of molsidomine or placebo was sublingually administered in a double-blind crossover manner. End-diastolic dimension, end-systolic dimension, and mean velocity of circumferential fiber shortening were measured just below the mitral valve before drug or placebo administration and 1 hour later. No significant changes were observed with placebo. Heart rate and mean arterial pressure were not significantly modified with Molsidomine (80 to 83 bpm and 100 to 97 mm Hg, respectively). The reduction in end-diastolic dimension (67 to 61 mm; 9%; P less than 0.01) was slightly greater than the decline in end-systolic dimension (59 to 54 mm; 8%; p less than 0.01). The mean velocity of circumferential fiber shortening increased from 0.4 to 0.5 sec-1 but did not achieve statistical significance. Thus sublingual administration of molsidomine in patients with chronic heart failure reduces end-diastolic more than end-systolic dimension without effect on blood pressure, suggesting a predominant action on cardiac preload.

The new long-acting coronary artery dilator molsidomine and its metabolite SIN-1.

We studied the effects of intracoronary injections of SIN-1 (0.8 mg), the active metabolite of molsidomine, on coronary artery diameters and coronary stenoses. In nine patients with abnormal angiograms measurements were made 4 and 8 minutes after SIN-1 administration. There was a statistically significant increase in coronary luminal diameter in proximal, medial, and distal segments as well as at the level of the stenoses. At 4 minutes after administration distal segments showed a mean increase in diameter of 50%, compared to a mean increase of 26% in proximal segments. In six patients with normal angiograms SIN-1 abolished three of four coronary spasms induced by ergonovine maleate. A protective effect of SIN-1 against the vasoconstrictor effects of ergonovine was still present at 8 minutes after administration. Heart rate and blood pressure remained unchanged throughout the study. We conclude that the vasodilation induced by SIN-1 in normal and stenotic coronary arteries is probably an important contribution to the antianginal efficacy of molsidomine and suggests that molsidomine may be effective in the prophylaxis of variant angina.

[Physical activity, physical fitness and coronary disease]. / Activité physique, aptitude physique et affections coronariennes.

The relationship between physical activity on and off the job, physical fitness and coronary artery disease was investigated in a prospective study involving 2 363 men, 40 to 55 years old. Sudden death and myocardial infarction occurred in 31 subjects during a 5-year follow-up. Preliminary data are reported. There was no significant correlation between quartiles of physical activity on and off the job and incidence of coronary events. Physical fitness was significantly inversely correlated with incidence of coronary events (p less than 0.05) and was significantly lower in the 31 new cases (p less than 0.03). Multivariate analysis showed that HDL-cholesterol, smoking and physical fitness significantly and independently discriminate between coronary prone patients and healthy subjects. We conclude that physical fitness is an independent, inverse risk indicator of new coronary events.