Improved exercise tolerance after propranolol, diltiazem or nifedipine in angina pectoris: comparison at 1, 3 and 8 hours and correlation with plasma drug concentration.

Exercise tolerance 1, 3 and 8 hours after 80 mg of propranolol, 120 mg of diltiazem and 20 mg of nifedipine, and after 20 minutes of 0.6 mg of sublingual nitroglycerin were compared with placebo in 15 men who had chronic stable angina pectoris. Three hours after drug ingestion, the exercise time was prolonged by 72 +/- 26, 162 +/- 27 and 161 +/- 30 seconds (p less than 0.05) for propranolol, diltiazem and nifedipine, respectively, and by 123 +/- 35 seconds (p less than 0.001) 20 minutes after sublingual nitroglycerin compared with placebo. The onset of ST-segment depression greater than or equal to 0.1 mV was delayed by 120 +/- 34, 203 +/- 29 and 189 +/- 35 seconds (p less than 0.05) and by 79 +/- 23 seconds (p less than 0.05), respectively. After propranolol, the peak rate-pressure product decreased compared with placebo (15.1 +/- 1.1 U [10(-3)] vs 20.0 +/- 1.5 U, p less than 0.01). In contrast, the peak rate-pressure product was greater after diltiazem and nifedipine than after placebo (22.2 +/- 1.3 U [p less than 0.05] and 23.8 +/- 1.4 U [p less than 0.01]). The maximal increase in exercise tolerance was most marked for each drug at 3 hours, but was also significant at 1 hour for nifedipine and at 8 hours for diltiazem. At 3 hours, an increase in exercise time of more than 2 minutes was observed in 4 of 6 patients who had plasma propranolol concentrations greater than 40 ng/ml, 8 of 9 who had a plasma diltiazem concentration greater than 150 ng/ml, and in 7 of 7 who had a plasma nifedipine concentration greater than 90 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris.

Diltiazem is a calcium slow-channel blocking drug that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy 3 hours after a single oral dose of 120 mg, 12 men with chronic stable angina pectoris performed a maximal exercise test on a bicycle ergometer after ingesting either placebo or diltiazem administered in a double-blind fashion. During submaximal exercise at a fixed work load, diltiazem decreased the average heart rate response from 119 +/- 17 to 107 +/- 14 beats/min (p less than 0.01), systolic blood pressure from 182 +/- 15 to 175 +/- 15 mm Hg (p less than 0.05) and the rate-pressure product from 21.8 +/- 4.2 to 18.8 +/- 3.2 x 10(-3) units (p less than 0.01). The average submaximal work load at which significant ST-segment depression (0.1 mV) first appeared was increased from 355 +/- 142 to 525 +/- 143 seconds (p less than 0.01) after diltiazem. At peak exercise after diltiazem, the average depth of ST-segment depression in any one lead and the extent of myocardial ischemia observed in all 12 ECG leads were decreased (p less than 0.01), even though the average work load was increased by 29% (p less than 0.01). Peak heart rate, systolic blood pressure and rate-pressure product were similar with placebo and diltiazem. The plasma diltiazem concentration was 13.9 +/- 29 ng/ml 3 hours after ingestion and was significantly (p less than 0.05) related to the increased time to the onset of important ST-segment depression (r = 0.65) and to the decrease in the extent of myocardial ischemia observed in all 12 ECG leads (r = -0.61) compared with placebo. Thus, diltiazem is effective in treating chronic stable angina pectoris. It decreases myocardial oxygen requirements during upright exercise and appears to increase myocardial oxygen delivery.

Diagnostic accuracy of exercise ECG lead systems in clinical subsets of women.

The diagnostic accuracy of 14-lead exercise electrocardiography was evaluated in 112 women who had no history of myocardial infarction and underwent coronary angiography. The sensitivity of ST-segment displacement of 0.1 mV or more in any of 14 ECG leads was 0.79 for coronary artery stenosis of at least 70%; the specificity was 0.66. Results were similar using bipolar ECG leads CC5 and CM5 or 11 standard ECG leads. The ST-segment shifts that occurred only during exercise were associated with a 77% false-positive rate (10 of 13). Downsloping ST-segment depression did not provide more diagnostic information than horizontal ST-segment depression in the three clinical subsets of women. In women with typical angina pectoris, ST-segment depression of at least 0.15 mV for 0.08 second after the J point or a final treadmill time less than 360 seconds was predictive of proximal left or multivessel coronary artery disease. In the women with probable angina or nonspecific chest pain, this finding was not of diagnostic value. ST-segment elevation of 0.1 mV or more in leads V1-2 or a VL predicted proximal stenosis of at lest 80% in the left anterior descending coronary artery in all six women with typical angina pectoris. Maximal exercise testing in women with typical angina provides important diagnostic information when 11 standard ECG leads are recorded. In women with probable angina or nonspecific chest pain, diagnostic exercise testing is less useful and bipolar leads CC5 and CM5 are sufficient for most clinical purposes.

Increased plasma catecholamines in patients with Friedreich's ataxia.

We studied free plasma catecholamines in 23 patients with Friedreich's ataxia, having a mean age of 22 +/- 9.6 (SD) years. Conjugated catecholamines were also studied in 10 patients. Mean plasma norepinephrine and epinephrine were significantly higher than controls both in the supine and standing positions. In total 15 out of 23 patients (65%) had increase free and/or conjugated plasma catecholamines. The increased in plasma catecholamines was more marked in patients with severe neuromotor impairment. Among the patients with left ventricular concentric hypertrophy (wall thickness greater than 12 mm), only 3 had no demonstrable sympathetic hyperfunction. Since the high local concentrations of norepinephrine at the site of release from sympathetic nerve terminals may serve as a trigger for the hypertrophic response of the myocardial cell, it is suggested that early pharmacological intervention could prevent or limit the cardiomyopathic process or its clinical consequences.

A simple exercise test in borderline and sustained essential hypertension.

We measured blood pressure and heart rate at rest and during exercise on a bicycle ergometer in 19 patients with borderline hypertension, in 58 with sustained essential hypertension and in a group of 30 healthy subjects of the same age. On each subject, we determined the systolic blood pressure/heart rate curve during exercise and calculated the slope and intercept. In patients with borderline hypertension, blood pressure was elevated in basal conditions but was within the normal range at the end of exercise. This caused an increased intercept (P less than 0.001) and a reduced slope (P less than 0.05) of the curve. In patients with sustained hypertension, blood pressure was elevated throughout the exercise test. This caused an increased slope (P less than 0.001) of the blood pressure/heart rate curve. The slope of the curve correlated negatively with basal heart rate in borderline hypertensive patients (P less than 0.01) and correlated positively with basal total peripheral resistance in sustained hypertensive patients (P less than 0.01). Exercise testing can help one diagnose borderline and sustained hypertension and predict the evolution of borderline hypertension toward fixed hypertension.

[Methyl-ergometrin maleate test during coronary arteriography in spontaneous chest pain]. / Le test au maléate de méthyl-ergométrine au cours de la coronarographie dans les douleurs thoraciques spontanées.

This coronary spasm provocation test with methyl-ergometrine maleate was carried out during coronary arteriography in 47 patients presenting with spontaneous chest pain. Coronary spasm was triggered in 16 cases, reproducing the chest pain in 11 patients, and accompanied by electrical changes in 15 cases, 12 subepicardial ischaemias and 3 subendocardial ischaemias. This test is not without danger to the patient as arrhythmias and conduction defects were recorded in 6 cases although the spasm was readily reversible on injection of intravenous glyceryl trinitrate. Of 7 patients with Prinzmetal variant angina, the test was positive 6 times, in three of which on pre existing severe organic lesions, so confirming the mechanism of this syndrome and the reliability of the test. Of 40 patients presenting with spontaneous chest pain, 10 had a positive test. In 2 of these cases the chest pain was subsequently observed with subepicardial ischaemic electrical changes, so confirming the screening value of this test. In the 7 cases where coronary spasm gave rise to electrical changes with or without pain, the logical diagnosis would appear to be spastic angina. In the 30 cases where the test was negative the subsequent outcome did not provide any proof in favour of a coronary origin of the chest pain.

[Prospective etiologic survey on apparently primary nonobstructive myocardiopathies in adults. 57 cases, excluding ischemic cardiopathies]. / Enkquête étiologique prospective sur les myocardiopathies non obstructives présumées primitives de l'adulte. 57 observations, cardiopathies ischémiques exclues.

A prospective study into the aetiology of presumed primary non-obstructive cardiomyopathy was carried out in 57 patients who had no lesions of the trunk of the coronary artery; one case of haemochromatosis and one of amyloidosis were found. Excluding these two cases of cardiomyopathy which were in fact secondary, most of the others were associated with manifestations or with complications of myocardial diseases (two pulmonary emboli and one case of jaundice) or pathology associated with it. Investigation into possible infection, biochemical abnormalities and dietary indiscretion (alcohol, colza oil), were unfruitful. Electromyographic changes of the "myositic" type were very common. The bicycle ergometry test was often interrupted through fatiguing of the peripheral muscles. These findings suggest that the muscular abnormalities may not be limited to the heart. The cost of an enquiry of this type has been investigated.

[Arterial pressure changes during exertion in the normal subject]. / Variations de la pression artérielle à l'effort chez le sujet normal.

The exercice electrocardiogram, carried out in 160 normal subjects, has allowed us to witness the physiological mechanisms of adaptation to exercise as a function of age and sex. The relationship between systolic arterial pressure (SAP) and cardiac rate (CR) is very narrow (R = 0.97), and is a linear function. Its slope increases with age in both sexes, and differs significantly in the male and female (P less than 0.001). Systolic pressure is related to the relative cardiac rate (CR%) by the formula SAP = 1.55.CR% + 70.

Improved efficiency of treadmill exercise testing using a multiple lead ECG system and basic hemodynamic exercise response.

One hundred consecutive men with a normal ECG at rest had a maximal treadmill test using 14 leads during and post-exercise. Coronary arteriography performed the following day revealed coronary stenoses greater than or equal to 70% in 66 patients. Test results obtained from a V5 lead were compared to different lead combinations and were correlated with arteriographic findings. A positive exercise test occurred in 37 men using an isolated V5 lead compared to 50 men (P less than 0.05) using 11 leads, 52 men (P less than 0.05) using a combined CM5, CC5, Cl (inferior) lead system and 58 (P less than 0.001) men using all 14 leads. The predictive value of a positive test varied between 89-95% and was not changed significantly by the addition of multiple leads. The 14 lead ECG was positive in 43/45 (96%) patients with multivessel disease. Parameters which helped to predict multivessel disease using 14 leads were 1) the time that ischemia first appeared 2) the pressure-rate product at the time ischemia first appeared, and 3) the maximum workload that could be attained. In general, the magnitude of ST-segment depression and the time required for a positive ECG to return to normal postexercise were not useful predictors of multivessel disease. We conclude that the use of multiple leads improves the sensitivity and efficiency of the maximal treadmill exercise test. The usefulness of exercise test results can be further improved if multiple leads are combined with physiologic data collected during exercise.

[Value of the exercise test after aortocoronary bypass]. / Valeur de l'épreuve d'effort aprés pontage aorto-coronaire. A propos de 100 cas.

The 100 patients who underwent an exercise test and a follow-up coronary arteriogram at a mean interval of 10.1 months after an aorto-coronary bypass had suffered preoperatively from incapacitating angina 50%), a threatened infarction syndrome (35%), or Prinzmetal's angina (15%). The majority had a single bypass graft (72%), but 28% had two or three grafts. The exercise test was positive 39 times, negative 51 times, and indeterminate in 10. Correlation with the clinical picture shows that 27% of the patients in functional category I had a positive exercise test. Correlation with coronary arteriography shows that a positive test is reliable evidence for a defect or occlusion of the graft. On the other hand, a negative exercise test is a less reliable indicator of a good result. No instances of positive exercise tests were found when there was complete alleviation of the coronary condition.