Short- and long-term effects of molsidomine retard and molsidomine nonretard on exercise capacity and clinical status in patients with stable angina: a multicenter randomized double-blind crossover placebo-controlled trial.

A multicenter, randomized, double-blind, crossover, placebo-controlled study was conducted in 90 isosorbide dinitrate responders showing stable angina to compare the efficacy of molsidomine retard, 8 mg b.i.d., with that of molsidomine, 4 mg t.i.d., for 6 weeks. Total work performance (workload x min) was significantly improved, compared with baseline and placebo until 8 and 12 h after molsidomine and molsidomine retard administration, respectively. ST-segment depression decreased significantly under the two treatments at 60 W as well as at maximal exercise. The rate-pressure product (heart rate x systolic blood pressure) decreased and increased significantly at submaximal and maximal exercise level, respectively. All these effects remained significant after 6-week treatment, with only the ST segment showing a nonsignificant tendency to improvement at maximal work. The frequency of anginal attacks and of sublingual nitroderivative-tablets consumption decreased significantly with molsidomine, 4 mg, and molsidomine retard, 8 mg. However, overall results showed that the latter form reduces myocardial ischemia more efficiently at submaximal exercise level, has a more prolonged effect on exercise tolerance, and maintains it at a somewhat higher level after 6-week treatment.

Acute and chronic effect of molsidomine extended release on exercise capacity in patients with stable angina, a double-blind cross-over clinical trial versus placebo.

A double-blind, placebo-controlled, cross-over study was performed in 50 patients with ischemic heart disease and stable angina to determine the duration of efficacy of 8 mg molsidomine in extended-release form. Exercise testing was performed at baseline and 2, 4, 6, 8, and 10 h after intake of either the medication or the placebo. Total duration of exercise (in minutes) and total work performance (workload x min) was significantly improved in the molsidomine retard group, not only compared with baseline but also with placebo for all time-points. ST segment depression at 60 W and at maximal exercise improved similarly until 10 h after molsidomine retard treatment. The rate-pressure product (heart rate x systolic blood pressure) showed significant improvement only at 60 W. No attenuation of the obtained effects was observed after 14 days of treatment. The number of anginal attacks and the consumption of sublingual nitroderivates were significantly reduced with molsidomine retard 8 mg as compared with placebo. Molsidomine retard 8 mg is effective until at least 10 h after oral (p.o.) intake. A dose schedule of molsidomine retard 8 mg twice daily definitely reduces anginal symptoms.

[Sudden death in athletes]. / La mort subite chez l'athlète.

In France, about one of ten thousand athletes die suddenly each year. Although this is a small proportion of the number of total deaths, it is a striking one because of the subjects it concern e.g: healthy and physically trained. Age is the major determinant cause of sudden death: coronary heart disease in victims over 35 years, hypertrophic cardiomyopathy, congenital disease and aortic rupture before. Positive predictive value of usual tests is given; high value of echocardiography is to be noted, in comparison with low value of the traditional stress test for detection of subjects at risk.

[Short- and long-term prognosis of myocardial infarct. Contributions and limitations of the clinical aspects and non-invasive technics]. / Pronostic à court et à long terme de l'infarctus du myocarde. Apports et limitations de la clinique et des techniques non invasives.

Clinical variables and those obtained by non-invasive techniques were recorded in a series of 306 patients discharged from hospital after an acute myocardial infarction. We studied the prognostic value at 2 and 12 months of these variables (alive/dead). The results of simple clinical data were as discriminant as those from more elaborated techniques. When the prognostic value of the same data at 12 months was studied in those surviving for two months, most of the predictive variables lost their discriminant power. The study shows that the predictive value of many of the predischarge variables usually taken into account in the assessment of long term risk, does not extend beyond the first two months.

Diastolic function and modifications of left ventricular architecture in ultraendurance athletes.

Although diastolic function is altered in left ventricular hypertrophy due to aortic stenosis or systemic hypertension, it has been shown to be normal in athletes. To analyze the reason for this discrepancy, we have studied left ventricular masses and volumes and diastolic flow velocities in 13 ultraendurance athletes and in 8 sedentary subjects as a control group by M-mode (TM), two-dimensional (2D) and Doppler echocardiography. Significant differences in the measurements of mass and volume have been found depending upon the method used. Considering that two-dimensional echocardiography is more appropriate for estimations of LV mass and LV volume, especially when the shape of the left ventricle is modified, overestimation of LV mass and underestimation of LV volume in ultraendurance athletes by TM could be explained by an elongation of LV cavity in athletes. Doppler velocimetry showed similar results in athletes and control subjects. We suggest that those LV configurational changes partly explain the preservation of diastolic function in athletes by restoring in diastole the energy stored in systole.

[Early exercise test after myocardial infarction]. / Epreuve d'effort précoce aprés infarctus du myocarde.

Exercise tests of coronary function at the tenth day of an uncomplicated myocardial infarction offer objective evaluation of short-term benefits of an early accelerated physical retraining program. They also allow better individual adaptation of exercises prescribed at the start of convalescence at home. Exercise test results show significant correlation with clinical data and bicycle ergometer tests carried out two months after infarction, with respect to physical aptitude, reasons for discontinuation of test and lethality risk two months after infarction. This suggests that exercise tests performed after the acute phase of myocardial infarction are of diagnostic and prognostic value.

Exercise tolerance in coronary patients: randomized trial of two-week treatment with molsidomine versus placebo.

Using a randomized, double-blind, crossover protocol, we compared the effects of oral molsidomine (Corvaton, 6 mg/day) and placebo, administered alternately for two 14-day periods, on the exercise tolerance of 25 outpatients with coronary heart disease. Resting heart rate and oxygen consumption increased by 6.8% (p less than 0.005) and 12.6% (p less than 0.01), while peripheral systolic blood pressure was reduced by 5.1% (p less than 0.05). At submaximal workloads, systolic and diastolic blood pressures were reduced by 5.6% (p less than 0.001) and 6.1% (p less than 0.001), the pressure-rate product was reduced by 8.5% (p less than 0.05), and ST segment depression was reduced by 40.0% (p less than 0.005). At maximal exercise level, mechanical power increased by 32.4% (p less than 0.001) and oxygen consumption by 15.5% (p less than 0.005), while ST segment depression was reduced by 30.6% (p less than 0.001). No alteration was found in postexercise lung function tests. It is concluded that molsidomine reduces myocardial ischemia at both submaximal and maximal work levels and increases exercise tolerance significantly. These effects could be related to reduced myocardial oxygen requirements, reflected in a lower pressure-rate product at submaximal exercise and perhaps enhanced by a lower preload, which, moreover, would favor coronary flow in subendocardial layers. The drug has no adverse bronchopulmonary effects.

Influence of age on functional recovery after myocardial infarction.

Two age-groups of patients, of 45-59 and 65-69 years respectively, were investigated 10 days and 2 months after myocardial infarction. Left ventricular performance at rest was evaluated by radionuclide ventriculography, working capacity by submaximal heart rate-limited stress testing at discharge from the coronary care unit and maximal testing 2 months after the coronary attack. Resting ejection fraction remained unchanged while exercise tolerance increased in both age groups between the first and second examination but remained systematically lower in the elderly. The author conclude that although functional recovery after myocardial infarction is independent of age, physical capacity is lower in older patients during the acute phase as well as after early convalescence; resting ejection fraction remains, however, unchanged.

Effects of molsidomine on exercise tolerance in patients with coronary heart disease.

We performed a double-blind crossover study with molsidomine in 10 patients with coronary heart disease. A single dose of molsidomine and placebo were given sublingually 1 hour before an exercise tolerance test. Molsidomine significantly reduced systolic blood pressure at rest and at all work-loads. There was also a significant reduction in electrocardiographic ST-segment depression at submaximal exercise. At maximal exercise the drug significantly increased symptom-limited oxygen consumption and total mechanical work. Molsidomine could prove useful in the treatment of angina pectoris. It has no adverse effects on pulmonary function.

Postinfarction exercise capacity after lidoflazine treatment or physical training.

44 male postinfarction volunteers were divided into 4 groups and submitted to performance tests. Groups I and II consisted of 24 patients, 12 of whom followed a 2-month physical training program, while the other 12 served as controls. Groups III and IV (10 patients each) were included in a 10-month double-blind crossover study with lidoflazine 240 mg/day vs. placebo. The cardiovascular adaptation of the patients treated for 5 months with lidoflazine had two features in common with that observed after 2 months of physical training, namely an increase in maximal exercise capacity and, during submaximal exercise tests, a decrease in heart rate compensated for by an increase in stroke volume. In contrast to physical training, treatment with lidoflazine did not improve the peripheral oxygen consumption by the muscles.

Influence of short-term physical training on exercise tolerance after myocardial infarction.

14 patients with stabilized myocardial infarction were submitted to a functional evaluation before and after 3 sessions of interval training on the bicycle ergometer. With submaximal exercise, myocardial load decreases after short-term training, the heart rate and the blood pressure--heart rate product being significantly lower for the same oxygen consumption. Maximal working capacity, expressed in watts or oxygen consumption, increases significantly after short-term training, the benefit being one-third of that obtained after 6 weeks' training. These early changes in functional capacity are positively correlated with those obtained by a more prolonged rehabilitation program. Leg muscular blood flow during submaximal and maximal exercise tends to increase after short-term training, although this change is not systematic and thus not significant.