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Correlates and prognostic implication of exercise capacity in chronic congestive heart failure

Previous studies have shown poor correlations between exercise tolerance and measurements of left ventricular (LV) function during rest in patients with congestive heart failure (CHF). To further evaluate the determinants of exercise tolerance and their relation to prognosis, we performed rest and exercise hemodynamic measurements and blood pool scintigraphy in 27 patients with CHF. All patients were treated with digitalis and diuretic drugs, but not vasodilator drugs. Exercise capacity was assessed by maximal oxygen consumption (VO2max) during upright bicycle ergometry. Both right ventricular (RV) and LV ejection fractions were measured by radionuclide techniques, and arterial, right atrial and pulmonary artery pressures, cardiac output, and derived hemodynamic indexes were determined. As a group, patients with severely impaired exercise tolerance (group 1, VO2max less than 10 ml/min/kg) had significantly higher rest pulmonary capillary wedge and right atrial pressures (30 +/- 4 vs 23 +/- 6 and 12 +/- 4 vs 7 +/- 2 mm Hg, respectively) than those with a VO2max of 10 to 18 ml/min/kg (group 2). They also had lower LV and RV ejection fractions (16 +/- 4% vs 21 +/- 4% and 19 +/- 12% vs 27 +/- 7%, respectively). However, overlap among individual patients was considerable, and only pulmonary capillary wedge pressure at rest correlated significantly (r = 0.69, p less than 0.001) with VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study.

Although many studies have shown acute hemodynamic improvement in patients with congestive heart failure treated with vasodilating drugs, long-term controlled studies with both hemodynamic and exercise capacity measurements are not available. We studied the converting-enzyme inhibitor captopril in 16 ambulatory patients in New York Heart Association functional class II-IV heart failure who were clinically stable on digoxin and diuretics. The acute response to open-label captopril was quantified by blood pool scintigraphy, right-heart catheterization at rest and during exercise, and measurements of exercise capacity. The patients were then randomized to maintenance therapy with captopril or matching placebo and were restudied after 3 months. The two groups were similar in their clinical characteristics and pretreatment rest and exercise hemodynamic measurements. Both displayed similar acute beneficial responses to captopril at rest, with a mean reduction in left ventricular filling pressure from 24 9 to 14 6 mm Hg (p < 0.001) and increases in cardiac index, from 2.1 0.5 to 2.5 + 0.61/min/m2 (p < 0.01), and stroke index, from 25 8 to 34 + 8 mI/M2 (p < 0.001). Directionally similar hemodynamic improvement was noted during exercise.After 3 months, these beneficial hemodynamic changes were sustained only in the patients randomized to captopril. Concomitantly, the captopril patients increased their exercise capacity as measured by the duration of bicycle exercise (9.0 2.2 vs 11.7 1.4 min, p < 0.01), maximal work load (360 80 vs 460 50 kpm/min, p < 0.005) and oxygen consumption (12.9 2.3 vs 15 + 1.8 ml/kg/min). The placebo group showed either no change or a worsening over the 3 months compared to their pretreatment measurements.These findings demonstrate that captopril is an effective adjunctive agent for the treatment of chronic heart failure and that it produces long-term hemodynamic improvement together with an increase in exercise capacity.

Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure

Enalapril is a recently developed angiotensin-converting enzyme inhibitor that improves cardiac function at rest in patients with congestive heart failure. This study investigated the acute effects of enalapril on the cardiovascular response to exercise, and then evaluated the long-term effects of enalapril on exercise capacity and functional status during a 12 week placebo-controlled trial in patients with heart failure. Ten patients underwent hemodynamic monitoring while at rest and during incremental bicycle exercise before and after 5 to 10 mg of enalapril orally. At rest, enalapril decreased mean blood pressure 13% (p less than 0.01) and systemic vascular resistance 20% (p less than 0.05) and increased stroke volume index 21% (p less than 0.01). During maximal exercise, enalapril decreased systemic vascular resistance and increased both cardiac and stroke volume indexes. Enalapril acutely increased exercise duration (p less than 0.05) and maximal oxygen consumption (p less than 0.001). These 10 patients and an additional 13 patients were then randomized to either placebo or enalapril treatment and followed up for 12 weeks. Of the 11 patients assigned to active treatment, 73% considered themselves improved compared with 25% of the patients assigned to placebo treatment (p less than 0.02). During long-term treatment, exercise capacity increased in patients receiving enalapril (p less than 0.001) but was unchanged in patients receiving placebo (intergroup difference, p less than 0.05). During long-term treatment, no adverse effects of enalapril occurred. Thus, enalapril improves cardiac function at rest and during exercise. Compared with placebo, maintenance therapy with enalapril results in symptomatic improvement and increased exercise capacity.

Lack of relationship between the short-term hemodynamic effects of captopril and subsequent clinical responses.

The role of hemodynamic monitoring during the initiation of vasodilator therapy for heart failure remains to be defined, despite the tremendous potential socioeconomic and clinical ramifications. We therefore performed resting and exercise hemodynamic studies before and during the initial 48 hr of captopril therapy in 14 stable patients with New York Heart Association Class II or III chronic congestive heart failure. Their clinical response to therapy was determined by evaluating changes in clinical status and the measured changes in exercise tolerance, heart size, and ejection fraction after 3 months. Significant improvement in each of these indexes was found for the group as a whole, but the baseline hemodynamics and the hemodynamic responses to captopril differed little between the patients showing marked improvement and those exhibiting little or no change. Correlations between the hemodynamic measurements and the changes in clinical class, exercise tolerance, heart size, and ejection fraction were generally poor. Even when they achieved significance, these correlations were too loose to allow prediction of the clinical efficacy of captopril in individual subjects. These findings indicate that the routine use of invasive hemodynamic monitoring during the initiation of captopril is unnecessary and potentially misleading, although such measurements remain valuable for diagnosis, the management of patients with complex conditions, and for investigation. The response to captopril may be best evaluated by serial measurements of exercise tolerance and heart size in addition to clinical assessment.

Hemodynamic and radionuclide effects of acute captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg or oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responses at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml (p less than 0.01) and from 52 +/- 26 to 43 +/- 20 volume units (p less than 0.01), respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg (both p less than 0.001). Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22 +/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively (both p less than 0.01). During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. Thus, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.

Ejection fraction response to supine exercise in asymptomatic aortic regurgitation: Relation to simultaneous hemodynamic measurements

The change in ejection fraction during exercise is frequently employed as a measure of left ventricular functional reserve in patients with aortic regurgitation. However, little information is available about its relation to invasive measurements of cardiac performance. Therefore, simultaneous hemodynamic measurements and supine exercise blood pool scintigraphy were performed in 14 patients with severe, asymptomatic or minimally symptomatic aortic regurgitation associated with cardiomegaly but preserved left ventricular function at rest. Their hemodynamic measurements at rest were normal and their exercise capacity was excellent. When the patients were categorized into those patients whose ejection fraction increased or did not decrease by more than 0.05 (Group 1) and those whose ejection fraction decreased by more than 0.05 (Group 2), important differences were apparent. Echocardiographic, radionuclide and hemodynamic measurements at rest in the two patient groups were similar, but Group 1 exhibited a greater increase in cardiac index during supine exercise (2.8 +/- 0.4 to 10.0 +/- 1.8 versus 2.7 +/- 0.5 to 6.9 +/- 1.0 liters/min per m2; p less than 0.005) and a lesser increase in pulmonary capillary wedge pressure (13 +/- 4 to 19 +/- 7 versus 12 +/- 4 to 31 +/- 8 mm Hg; p less than 0.01). The severity of regurgitation decreased during exercise in all patients, but end-diastolic volume decreased and end-systolic volume decreased or was unchanged in Group 1, whereas end-diastolic volume was unchanged and end-systolic volume increased in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic differences between supine and upright exercise in patients with congestive heart failure.

Although the differences in hemodynamic responses to supine and upright exercise have been studied in normal subjects and in patients with angina pectoris, no such comparison has been made in patients with congestive heart failure. Many investigators measure exercise hemodynamics in heart failure patients to assess the effect of vasodilator and inotropic drugs. Both modes of exercise have been used and have often yielded differing results.We compared the hemodynamic response to supine and upright exercise in 14 patients with stable, New York Heart Association class III chronic heart failure. During upright exercise, peak heart rate was higher (124 ± 15 vs 115 ± 18 beats/min, p < 0.025) and peak mean arterial pressure was lower (102 15 vs 95 17 mm Hg, p < 0.25), yielding similar double products. Although the peak left ventricular filling pressure was slightly lower during upright exercise (40 ± 7 vs 35±10 mm Hg, p < 0.05), the maximum cardiac and stroke indexes were not significantly different (3.6 ± 0.8 vs 3.4 ± 0.8 I/min/m2 and 30 ± 8 vs 30 ± 6 ml/m2, upright vs supine exercise). In contrast to these relatively similar hemodynamic responses, exercise capacity was significantly greater during upright exercise (peak work load 336 ± 84 vs 293 ± 73 kpm/min, p < 0.1; maximum oxygen consumption 12.1 ± 2.4 vs 9.8 ± 1.9 ml/min/kg, p < 0.001). We conclude that either exercise method may be used to assess the hemodynamic effects of drugs, but that exercise capacity should be measured in the upright position.

Long-term captopril therapy for chronic congestive heart failure

Although the short-term hemodynamic and clinical responses to angiotensin-converting enzyme inhibition in patients with congestive heart failure (CHF) are well known, little information is available about the long-term results of captopril therapy. In the present study, 15 stable outpatients received captopril therapy and were followed for a mean of 19 months (range 6 to 27) with serial clinical assessments and measurements of exercise tolerance, ejection fraction (EF) and cardiothoracic ratio. Exercise tolerance on a modified Naughton protocol improved from 10.5 +/- 2.7 to 12.7 +/- 2.4 minutes (mean +/- standard deviation) at 3 months (p less than 0.001), tended to increase progressively up to 12 months and remained significantly increased even after 24 months (9.7 +/- 1.8 vs 13.5 +/- 4.0 minutes, p less than 0.05). However, individual responses were variable; 4 patients did not show measurable improvement. Left ventricular EF increased from 0.20 +/- 0.06 to 0.25 +/- 0.06 (p less than 0.01) at 3 months and remained higher (0.30 +/- 0.12, p less than 0.02) at latest follow-up. Cardiothoracic ratio decreased from 0.59 +/- 0.04 to 0.56 +/- 0.05 (p less than 0.02) at 3 months and remained significantly lower at 12 months and at latest follow-up, although again individual responses were variable. Clinical responses generally correlated with these objective measurements, with clinical classification on a scale modified from the New York Heart Association classification improving from 3.0 +/- 0.6 to 2.3 +/- 0.5 (p less than 0.01) at 3 months and remaining improved throughout the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Monotherapy in mild to moderate hypertension: Comparison of hydrochlorothiazide, propranolol and prazosin

There has been recent interest in using nondiuretic drugs as initial antihypertensive therapy. Therefore, a study was designed to compare the efficacy and the effects on left ventricular function of hydrochlorothiazide, propranolol and prazosin in 13 patients with mild to moderate hypertension. After a 4-week washout period, patients were treated serially with each drug in a randomized order for 2 months each. Dosages were titrated until the patient showed a sitting diastolic blood pressure less than or equal to 90 mm Hg or to a maximum dosage of 100 mg/day of hydrochlorothiazide, 320 mg of propranolol and 20 mg of prazosin. Blood pressure was measured, plasma catecholamine concentrations were assayed and radionuclide determinations of rest and exercise left ventricular function and volume were made at the end of each period as well as after a second 1-month washout period at the end. In the sitting and standing positions, systolic and diastolic blood pressure control was equivalent for all 3 drugs. Goal blood pressure was achieved in 10 of 13 patients receiving hydrochlorothiazide, in 8 of 12 receiving propranolol and in 9 of 13 on prazosin. Importantly, 3 of 4 patients not controlled with prazosin, 5 of 6 uncontrolled with propranolol and 2 of 3 whose blood pressure was not reduced by hydrochlorothiazide were controlled when receiving 1 of the other medications. None of the drugs changed rest or exercise ejection fraction or volume, and side effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)