Reduced peak aerobic capacity in asymptomatic left ventricular systolic dysfunction. A substudy of the studies of left ventricular dysfunction (SOLVD). SOLVD Investigator. Studies of Left Ventricular Dysfunction.

BACKGROUND: Peak oxygen consumption is reduced in patients with symptomatic congestive heart failure, but functional capacity of patients with asymptomatic left ventricular systolic dysfunction has not been assessed by measurement of peak oxygen consumption attained during graded exercise testing. METHODS AND RESULTS: Peak oxygen consumption, that is, aerobic capacity (VO2, mL/kg per minute), was determined during graded treadmill exercise using the modified Naughton protocol in 40 patients with left ventricular systolic dysfunction (mean ejection fraction ranging from 14% to 35%; mean, 29%) who, while not receiving any cardiac medications, were totally asymptomatic, and in 41 age-matched normal subjects. Peak exercise duration and VO2 were significantly lower in patients with asymptomatic left ventricular systolic dysfunction than in normal subjects (948 +/- 273 versus 1239 +/- 372 seconds, P < .001, and 22.1 +/- 5.9 versus 29.8 +/- 7.7 mL/kg per minute, respectively, P < .001), while asymptomatic patients and normal subjects reached similar respiratory equivalents (1.14 +/- 0.11 versus 1.11 +/- 0.11 [NS]) and level of perceived exertion, using the modified Borg scale (7.4 +/- 2.6 versus 8.1 +/- 1.5 [NS]). Heart rate, systemic blood pressure, and oxygen pulse response to peak exercise were significantly lower in asymptomatic patients than in normal subjects. CONCLUSIONS: Although patients with left ventricular systolic dysfunction can be totally asymptomatic in their daily activities, they have experienced a substantial reduction in peak aerobic capacity when compared with normal subjects of similar age.

Comparison of nifedipine gastrointestinal therapeutic system and atenolol on antianginal efficacies and exercise hemodynamic responses in stable angina pectoris.

A gastrointestinal therapeutic system (GITS) of nifedipine has been developed to provide a once-daily dosing, and predictable, relatively constant plasma concentrations. This study compared the antianginal efficacy of nifedipine GITS with a once-a-day beta-receptor blocker, atenolol. Seventeen patients with documented coronary artery disease and stable stress-induced angina pectoris were studied during a 2-week, single-blind, placebo baseline phase and a 12-week randomized, double-blind, active drug crossover efficacy phase, using the bicycle exercise test and ambulatory electrocardiographic recordings. Patients exercised significantly longer with nifedipine GITS (883 +/- 47 seconds) and atenolol (908 +/- 44 seconds) than with placebo (794 +/- 41 seconds). Nifedipine GITS reduced systolic blood pressure at all stages of exercise compared with placebo but, because heart rate tended to increase more during nifedipine therapy, there was no difference in rate-pressure products between the placebo and nifedipine GITS periods. In contrast, atenolol reduced heart rate, systolic blood pressure and rate-pressure product during exercise compared with placebo. Whereas left ventricular ejection fractions (by radionuclide angiocardiography) increased with exercise, the maximal increase was smaller with atenolol than with placebo and nifedipine. The net increase in left ventricular ejection fraction at the end of exercise was greater with nifedipine than with placebo or atenolol. Ambulatory electrocardiograms showed only a small number of ischemic events. Neither nifedipine GITS nor atenolol reduced the number of ischemic events or total duration of ST-segment deviations significantly. It is concluded that nifedipine GITS is as effective an antianginal agent as atenolol, but the hemodynamic effects of the 2 agents differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of peak aerobic capacity in symptomatic and asymptomatic subjects with left ventricular dysfunction. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators.

Expired gas analysis was used to determine the aerobic exercise performance of subjects with depressed left ventricular (LV) systolic function and congestive heart failure (CHF). To determine whether subjects with no or minimal CHF have better aerobic exercise performance than do those with overt CHF, oxygen consumption (VO2) at anaerobic threshold (AT) and peak exercise was measured in 184 subjects with LV ejection fraction less than or equal to 0.35 who participated in the Studies of Left Ventricular Dysfunction. Subjects were divided into those with overt CHF needing treatment (treatment trial; n = 20) and those who had neither overt CHF nor treatment for CHF (prevention trial; n = 164). Treatment trial subjects had a lower LV ejection fraction (0.25 +/- 0.07) than did prevention trial ones (0.29 +/- 0.05; p = 0.001), but there were no differences in age, gender, body weight, resting heart rate and blood pressure. Treadmill exercise testing was performed after 2 to 3 weeks of placebo (no angiotensin-converting enzyme inhibitor) treatment. Treatment trial subjects exercised for a shorter time (493 +/- 160 seconds) and attained a lower peak VO2 (13 +/- 4 ml/kg/min) and VO2 at AT (11 +/- 4 ml/kg/min) than did prevention trial ones (842 +/- 277 seconds, and 20 +/- 6 and 16 +/- 5 ml/kg/min, respectively). Analysis of covariance showed that the differences in peak VO2 and VO2 at AT were statistically significant between the 2 trials after adjusting for age, gender, LV ejection fraction and New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute hemodynamic effects of pinacidil in hypertensive patients with and without propranolol pretreatment.

To study the systemic and regional hemodynamic effects of the new antihypertensive agent pinacidil, the authors administered intravenously two doses of pinacidil (0.1 mg/kg) to patients with hypertension after 3 days of randomized, double-blind pretreatment with either propranolol or placebo. Pinacidil administration decreased systemic arterial pressure and total peripheral vascular resistance in both groups of patients. It also decreased pulmonary artery wedge pressure, and increased cardiac output, heart rate, and plasma norepinephrine levels; the changes in cardiac output and heart rate were attenuated by propranolol pretreatment. In addition, propranolol-pretreated patients responded to pinacidil with a decrease in forearm blood flow. In contrast, pinacidil administration exerted no significant effects on right atrial pressure, stroke volume, or mean pulmonary arterial pressure alone or in combination with propranolol. The results show that pinacidil is a potent arterial dilator but has little effect on the venomotor tone in patients with hypertension.

Comparison of antianginal efficacies and exercise hemodynamic effects of nifedipine and diltiazem in stable angina pectoris.

The antianginal efficacies of nifedipine (40 to 120 mg/day) and diltiazem (120 to 360 mg/day) were studied in 21 normotensive patients with chronic stable angina pectoris, using a randomized, double-blind, crossover design. Patients received each agent titrated to maximum tolerated doses for 6 weeks, after a 2-week placebo baseline period. The maximum tolerated dose for nifedipine was 72 +/- 8 (standard error) mg/day and for diltiazem 297 +/- 20 mg/day. Two patients discontinued nifedipine early because of side effects. Duration of symptom-limited treadmill exercise was longer during the nifedipine (556 +/- 43 seconds) and diltiazem periods (546 +/- 39 seconds) compared with placebo baseline (474 +/- 41 seconds, p less than 0.02). Compared with placebo, nifedipine caused a significant increase in heart rate both at rest standing and at peak exercise. Nifedipine decreased resting systolic blood pressure but had no effect at peak exercise. In contrast, diltiazem caused a significant decrease in heart rate at rest but had no effect on blood pressure at rest or at peak exercise. Thus, nifedipine and diltiazem have differential effects on heart rate and systolic blood pressure suggesting different modes of action. However, despite the increase in exercise duration, neither nifedipine nor diltiazem increased the heart rate-systolic pressure product during maximum exercise. This suggests that the antianginal effects of the 2 agents probably are mediated via reduction of myocardial oxygen demand at submaximal exercise. In addition, diltiazem appears to be better tolerated than nifedipine.