Effects of nisoldipine and/or enalapril on left ventricular function and exercise capacity in patients with recent anterior myocardial infarction and mild cardiac dysfunction.

Treatment of abnormal remodeling and dysfunction of left ventricle after myocardial infarction is one of the major goals of recent therapeutic interventions. The current study, the Nisoldipine Enalapril Anterior Myocardial infarction Study pilot investigation, was designed to investigate the effects of 12 weeks of treatment with enalapril or nisoldipine or their combination on left ventricular (LV) function and exercise capacity in patients with recent (< 1 month) anterior myocardial infarction and mild LV dysfunction (LV ejection fraction [EF] 38% to 48%). Forty-six patients were studied and received, by random assignment, enalapril (5 mg once per day) plus placebo (n = 14) or nisoldipine (10 mg two times per day) plus placebo (n = 18) or enalapril (5 mg once per day) plus nisoldipine (10 mg two times per day) (n = 14). All patients received aspirin (325 mg) throughout the study. Data on LV EF and peak filling rate at rest and LV EF during exercise were collected during radionuclide ventriculography. In addition, the product of heart rate and systolic blood pressure (rate-pressure product) and exercise time were determined during exercise stress testing. The analyzed parameters were not significantly modified after treatment with enalapril or with nisoldipine. In contrast, the combination of enalapril and nisoldipine significantly raised LV EF at rest (from 43% +/- 3% to 48% +/- 6%, p < 0.01) and during exercise (from 45% +/- 8% to 50% +/- 9%, p < 0.01) and raised peak filling rate at rest (fraction of end-diastolic volume per second) from 1.57 +/- 0.3 to 1.67 +/- 0.3 (p < 0.05). In addition, the combined administration of the two drugs increased the rate-pressure product (values x 10(3)) (from 20.7 +/- 5 to 22.7 +/- 4, p < 0.05) and increased exercise time (from 573 +/- 173 seconds to 668 +/- 178 seconds, p < 0.05). These results show that in patients with recent anterior myocardial infarction and mild LV dysfunction, the combination of the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine nisoldipine improves resting LV systolic and diastolic function and exercise LV systolic function and exercise capacity.

Different protocols generate variations in systolic blood pressure response after exercise in patients with coronary artery disease.

Some patients with coronary artery disease (CAD) and exercise-induced myocardial ischemia demonstrate no change or a paradoxical increase in systolic blood pressure (SBP) during recovery following exercise. Previous studies have investigated the significance and clinical usefulness of analysis of recovery SBP response in detecting CAD, but conflicting data have been reported. Different protocols were used for the time of SBP recording and either bicycle or treadmill testing. We studied the exercise response in 64 male patients investigated for CAD who underwent symptom-limited treadmill stress testing during electrocardiographic monitoring and serial recording of blood pressure. Forty-three patients showed on or more stenoses of at least 70% at angiography (CAD). Twenty-one patients with normal coronary tree or slight lesions served as controls. The sensitivity (true positive/all CAD patients), specificity (true negative/all CAD-free patients), and the correct classification rate (correct diagnoses/all subjects) were assessed by standard ST segment analysis and two recovery SBP ratios calculated by dividing the first minute recovery SBP by the immediate postexercise value (RR/R) or by the true peak exercise value (RR/P). ST segment analysis achieved 53% sensitivity, 57% specificity, and 54% correct classification, the RR/R ratio achieved 73%,23%, and 60%, and the RR/P ratio 53%, 71%, and 59%, respectively. There were significant differences in results using these ratios. Time of SBP recording generated discrepancies in recovery SBP ratios. Therefore, differences in the timing of SBP measurement may generate conflicting clinical indications.

Abnormal recovery systolic blood pressure response for detecting coronary artery disease in men and women investigated by upright bicycle exercise.

We investigated the clinical significance of recovery systolic blood pressure (SBP) ratio, obtained dividing the recovery SBP at 1st (R1/A) or 3rd min (R3/A) by the peak exercise SBP (before stopping), during upright bicycle exercise in 530 subjects (ranging from 17 to 73 years). Our results may be summarized as follows: 1) we found a higher value of R1/A in control subjects with exercise induced ST depression; 2) the normal range in women was higher than in men; 3) the use of recovery SBP ratios gives a lower sensitivity and a higher specificity than ST segment analysis in detection of CAD; 4) this pattern may be useful particularly in patients with previous myocardial infarction and not detectable ST segment analysis during exercise.

Recovery systolic blood pressure response after treadmill exercise procedures. Evidence against its usefulness in detecting coronary artery disease.

We compared the response of the systolic blood pressure (SBP) recovery ratio (obtained by dividing the SBP recovery values by the peak exercise values) during a treadmill exercise test in patients with chest pain and an angiographically normal coronary tree (n = 18) (C group), one or more greater than or equal to 70% stenosed major coronary vessel and normal resting ejection fraction (n = 26) (CAD group) or depressed left ventricular function (ejection fraction less than 40%) (n = 15) (CAD DYS group). The mean values of SBP recovery ratios were, in the three groups: 0.93 +/- 0.07, 0.97 +/- 0.07, 0.95 +/- 0.09, respectively, at the 1st min and 0.83 +/- 0.08, 0.88 +/- 0.09, 0.86 +/- 0.08, at the 3rd min. There are no significant differences in the CAD or CAD DYS group versus the C group, because of large overlapping of points in the plot. The post-exercise SBP response during treadmill procedures cannot provide the opportunity for differentiation of CAD patients with or without left ventricular dysfunction at rest from subjects with chest pain and normal coronary tree, while upright bicycle exercise, as we previously observed, can.

Exercise time: a possible source of misleading results during long-term pharmacological studies by multiple stress testings in coronary artery disease.

The assessment of chronic pharmacological treatment of stable angina requires serial exercise stress testings. It is well known that exercise tolerance can be improved by the training effect of performing repeated testings. Our study investigated the values of heart rate, systolic blood pressure, rate-pressure product, and duration of exercise at 0.1 mV ST depression during exercise and the same parameters plus the maximal ST-segment depression at peak exercise, collected from three different tests. The first and second were performed at one-week intervals before, and the third (75 days after the first), was performed after a double-blind study with a drug versus placebo. We found a significant increase of exercise duration at 0.1 mV ST depression and at peak exercise, while 6 of 12 patients increased exercise duration from the second to the third test. Individual variability of exercise duration showed increasing values, ranging from 0 to 71% (first vs. third test). In contrast, the ratio of heart rate and systolic blood pressure did not differ between the tests. Our data criticized the use of mean values of exercise time for pharmacological studies; moreover, individual variability could affect results independently of drug or placebo administration. These findings should be taken into account in order to exclude misleading results.

Atenolol and/or nifedipine in effort angina: which is the treatment of choice for exercise coronary protection?

The authors performed a long-term, double-blind, crossover, randomized study on the effects of two drugs (atenolol, 100 mg/day, or nifedipine, 10 mg t.i.d.) when administered alone or in combination on the exercise tolerance in 10 patients with stable angina on effort (mean age 52 +/- 4 years, 8 males and 2 females) and documented significant (greater than or equal to 70%) obstructive coronary lesions at angiography. None of the drug treatments improved exercise duration or maximal sustained work load. Atenolol decreased significantly ST segment depression to -1 +/- 0.8 from -1.91 +/- 0.7, baseline and -2.05 +/- 0.5, placebo. Nifedipine was not better than placebo. The atenolol plus nifedipine treatment was better than placebo (p less than 0.001) or nifedipine alone (p less than 0.05) but was not more significantly efficacious than atenolol alone. Long-term management of exertional angina can be usefully performed using atenolol. The use of nifedipine at the present dose of 10 mg, although well tolerated, did not improve the ST signs of ischemia.

Long-term management of exercise-induced myocardial ischemia. Diltiazem versus propranolol, a double-blind, crossover study.

The authors performed a long-term, double-blind, crossover study on the effect of two drugs (propranolol, 40 mg t.i.d. or diltiazem, 60 mg t.i.d., each administered for 2 months) on their exercise tolerance in 13 patients with stable angina (mean age 52 +/- 7 years, 9 males and 4 females), after exertion and documented significant (greater than or equal to 70%) obstructive coronary lesions at angiography. Only propranolol, by decreasing heart rate and rate-pressure product, improved maximal sustained work load and duration of exercise (measured by a bicycle ergometer) versus the placebo (p less than 0.05). In both cases, however, they did not find any significant difference between propranolol and diltiazem. ST segment depression was decreased by both drugs (-1.73 +/- 0.95, baseline, vs -0.94 +/- 1.01, propranolol, and -0.95 +/- 0.76, diltiazem, p less than 0.5, for both). Long-term management of stable angina on effort therefore, can be usefully performed using propranolol or diltiazem.