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.

Cardiopulmonary exercise response in patients with left ventricular dysfunction or heart failure: a noninvasive study by gas exchange and impedance cardiography monitoring.

We investigated the upright bicycle exercise cardiopulmonary response in 20 patients with left ventricular dysfunction (LVD, secondary to previous myocardial infarction, left ventricular ejection fraction range 18-44%). Ten patients (48 +/- 7 years) asymptomatic (I NYHA class) without drug treatment (LVD group). The others (n = 10) (50 +/- 1 years) complained of dyspnea and/or fatigue despite therapy (NYHA II-III). They represented the heart failure (HF) group. Eight sedentary men (40 +/- 10 years) served as controls. Controls and patients performed stress testings under drug treatment, when administered. Anaerobic ventilatory threshold (ATge) was considered as an index of submaximal exercise while peak exercise VO2 (Peak VO2) was considered the maximal volitional exercise capacity. The ratio between minute ventilation (VE) to carbon dioxide release (VCO2) (VE/VCO2) was assessed to evaluate the ventilatory response during exercise. We coupled gas exchange assessment (2001, MGC) with noninvasive monitoring of stroke volume (SV) by impedance cardiography (NCCOM3, BOMED) and total systemic vascular resistances (TSVR; by auscultatory blood pressure measurement). In controls VO2 increase during exercise was related to higher heart rate (HR) and SV both from resting to ATge and from this point to the peak. TSVR declined during both steps. In patients with HF VO2 rose from resting to ATge (by faster HR and unchanged SV). VO2 increased slightly from this point to Peak VO2. This result was related to flat HR increase and unchanged SV as well as TSVR. In patients with LVD VO2 increased similarly to controls from resting to ATge and less above the threshold. In these patients both HR and SV increased during submaximal exercise. From ATge to Peak VO2 only HR increased. TSVR declined significantly similarly to controls. The VE/VCO2 ratio was higher at peak exercise in patients with HF compared to controls. Different determinants were demonstrated in patients with left ventricular dysfunction with mild or symptomatic chronic heart failure (CHF). These findings and the increased ventilatory response in patients with CHF can explain different changes of VO2 in these patients during submaximal and maximal voluntary exercise and contribute to explain exercise-induced exertion in these subjects.

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.

Incidence and complexity of ventricular ectopy during Holter monitoring in patients with exercise-induced myocardial ischemia and normal or mildly reduced left ventricular function.

We aimed to assess the relationship between frequent and complex ventricular ectopy by continuous electrocardigraphic 24-hours Holter monitoring in patients with coronary artery disease and inducible ischemia during exercise procedures. We investigated 609 consecutive patients. They were referred for chest pain (28% with a previous myocardial infarction, older than 6 months). In all population patients radionuclide ventriculography showed a global normal or mildly reduced left ventricular function (ejection fraction > 45%). All patients showed exercise-induced myocardial ischemia (ST depression) and exercise thallium-201 reversible defects. During Holter monitoring, in study population, divided according to incidence of premature ventricular complexes (PVC), we found a higher prevalence of complex ventricular arrhythmias (CVA) (bigeminy, couplets, ventricular tachycardia, multiformity) in patients with high incidence of PVC. The relationship between frequent and complex ventricular ectopy has been observed also during ischemic ST shifts occuring during 24-hours monitoring. In contrast, the R on T phenomenon was not related to incidence of PVC. Therefore, in patients with exercise-induced myocardial ischemia and global normal or mildly reduced left ventricular function there is a relationship between frequent and complex ventricular ectopy, as previously suggested in CAD patients with depressed left ventricular function.