Controlled clinical trial of a novel hemostatic agent in cardiac surgery. The Fusion Matrix Study Group.

BACKGROUND: We performed a prospective randomized trial to compare FloSeal Matrix (Fusion Medical Technologies, Inc, Mountain View, CA), a gelatin-based hemostatic sealant, with Gelfoam-Thrombin (Gelfoam, Pharmacia and Upjohn, Kalamazoo, MI; Thrombin, Gentrac Inc, Middeton, WI) (control group) to control perioperative bleeding. METHODS: A total of 93 patients undergoing cardiac operations were randomized into the FloSeal or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after applying the hemostatic agent. If bleeding stopped within 10 minutes, the application was considered to be successful. In the case of a failure, the surgeon could use any means preferred (except FloSeal) to achieve hemostasis. All bleeding sites in a patient were treated with the hemostatic agent to which the patient was randomized. Follow-up evaluation was performed at 12 to 36 hours and 6 to 8 weeks after operation. RESULTS: FloSeal stopped bleeding in 94% of the patients (first bleeding site only) within 10 minutes, compared to 60% in the control group (p = 0.001). At 3 minutes, successful hemostasis was achieved in 72% of the FloSeal group compared with 23% in the control group (p = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: FloSeal Matrix demonstrated efficacy superior to that of Gelfoam-Thrombin and had a safety profile similar to that of Gelfoam-Thrombin when used as a topical hemostatic agent during cardiac surgery procedures.

Chronic aortic insufficiency: factors associated with progression to aortic valve replacement.

STUDY OBJECTIVE: To determine whether the initial measurement of clinical variables in patients with chronic stable aortic insufficiency is helpful in identifying patients at risk for earlier progression to aortic valve replacement. DESIGN: Prospective analysis of a cohort of patients for a median follow-up time of 44 months (range, 8 to 57). SETTING: Referral-based cardiology clinics at two university hospitals and their affiliated Veterans Administration medical centers. PATIENTS: Cohort of 50 asymptomatic or minimally symptomatic patients with chronic aortic insufficiency and left ventricular enlargement. Patients had preserved left ventricular ejection fraction at rest and no evidence of coronary artery disease or significant noncardiac illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Baseline evaluation included a history and physical examination, chest roentgenogram. M-mode echocardiogram, treadmill test, and radionuclide angiogram done at rest and during supine bicycle exercise. Ten patients progressed to surgery because of the onset of limiting symptoms or objective evidence of left ventricular dysfunction, or both; the overall rate was 4% +/- 3% per year. The Breslow and Mantel-Cox statistics were used to compute survival (surgery-free) dichotomized by prognostic variables. The progression to surgery was earlier in patients with left ventricular end-diastolic volume indices of 150 cc/m2 or more, end-systolic volume indices of 60 cc/m2 or more, a left ventricular ejection fraction at maximal exercise of less than 0.50, or an end-systolic wall stress of 86 dynes/cm2 or more. CONCLUSIONS: Patients at higher and lower risk for early progression to aortic valve replacement can be identified through the measurement of left ventricular size and function. This information can be used to decide the frequency and intensity of follow-up evaluation in these patients.

Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial.

Although vasodilator drugs acutely reduce regurgitation and improve cardiac performance in aortic insufficiency, their long-term effects on left ventricular size and function are uncertain. Consequently, we performed a double-blinded, placebo-controlled trial using hydralazine in 80 minimally symptomatic patients who had clinically stable, moderate-to-severe aortic insufficiency. Patients randomized to hydralazine displayed a progressive reduction in left ventricular end-diastolic volume index (LVEDVI) measured by radionuclide angiography, the predetermined end point of the study. At 24 months, mean LVEDVI had been reduced by 30 +/- 38 ml/m2, an 18% reduction from baseline. In contrast, LVEDVI changed minimally in patients randomized to placebo, and the intergroup differences over time were statistically significant (p less than 0.03). The hydralazine group also experienced reductions in left ventricular end-systolic volume index and increases in ejection fraction that were significantly different (both p less than 0.01) from changes in placebo-treated patients. These findings show that long-term treatment with hydralazine reduces the volume overload in aortic insufficiency and suggest that such therapy may have a beneficial effect on the natural history of the disease.

Combined hemodynamic and scintigraphic assessment of piroximone (MDL 19,205) and comparison with dobutamine and nitroprusside.

The acute hemodynamic responses to intravenous infusion of piroximone (MDL 19,205), a nonglycoside, noncatecholamine agent with positive inotropic activity in vitro, were compared with those of intravenous dobutamine and sodium nitroprusside, respectively, in 2 groups of patients with New York Heart Association class III or IV symptoms. Each drug was titrated to optimal dosage (dobutamine, 12.5 +/- 3.9 micrograms/kg/min; nitroprusside, 2.5 +/- 0.6 micrograms/kg/min; piroximone 1.4 +/- 0.6 mg/kg) and simultaneous hemodynamic and scintigraphic values were measured. In group 1, the increase in cardiac index was slightly greater with piroximone than with dobutamine (from 1.6 +/- 0.5 to 2.7 +/- 0.6 vs 2.4 +/- 0.6 liters/min/m2, p less than 0.025) and only piroximone significantly decreased left ventricular (LV) filling pressure (from 29 +/- 7 to 22 +/- 8 mm Hg, p less than 0.05). Both agents increased heart rate and systolic blood pressure. In group 2, cardiac index increased similarly with nitroprusside and piroximone (1.5 +/- 0.6 to 2.6 +/- 0.8 and 1.6 +/- 0.5 to 2.6 +/- 0.5 liters/min/m2, difference not significant), whereas LV filling pressure decreased slightly less with piroximone (29 +/- 7 to 24 +/- 10 vs 30 +/- 7 to 20 +/- 11 mm Hg, difference not significant). Only nitroprusside reduced mean arterial pressure (88 +/- 13 to 72 +/- 12 mm Hg, p less than 0.001 between drugs). In group 1, systolic blood pressure to end-systolic volume ratio increased in 9 of 10 patients taking both piroximone and dobutamine, whereas in group 2, this ratio increased in 7 of 8 patients taking piroximone and declined in 7 of 8 taking nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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)

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)

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.

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)

Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension.

This study was undertaken to determine the prevalence and significance of diastolic left ventricular (LV) dysfunction in mild to moderate systemic hypertension. Rest and exercise equilibrium blood pool scintigraphy was performed in 39 hypertensive subjects (mean systolic blood pressure [BP] 156 +/- 14 mm Hg [+/- standard deviation]; mean diastolic BP 103 +/- 5 mm Hg) and 11 normal control subjects. These studies were analyzed for ejection fraction (EF), segmental wall motion, peak filling rate (PFR), time to PFR and filling fraction in the first third of diastole normalized for cycle length (first-third filling fraction). EF at rest was similar in the hypertensive patients and control subjects (0.63 +/- 0.09 versus 0.65 +/- 0.07); only 2 patients had a reduced EF. The EF response to exercise was normal in every hypertensive patient (increasing to a mean of 0.74 +/- 0.08); only 1 patient had asynergy. In contrast, even when the 2 patients with abnormal systolic function were excluded, each index of diastolic filling was significantly different from the control group. PFR was lower (2.29 +/- 0.49 vs 2.63 +/- 0.39 end-diastolic volumes per second [EDV/s], p less than 0.05), time to PFR was longer (199 +/- 47 versus 158 +/- 17 ms/s), p less than 0.01) and first-third filling fraction was smaller (0.38 +/- 0.11 vs 0.60 +/- 0.07, p less than 0.001). The latter index fell below the lowest normal value in 84% of the hypertensive patients. The degree of diastolic filling abnormality was not related to the patients' age, heart rate, BP, duration of systemic hypertension or systolic function.(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)

Converting-enzyme inhibitor therapy for chronic heart failure.

In congestive heart failure, acute administration of the converting enzyme inhibitor captopril leads to a decrease in arterial pressure, systemic vascular resistance, left ventricular filling pressure, and the end-diastolic volumes of both ventricles, as well as to an increase in cardiac index, stroke volume index, right and left ventricular ejection fractions. The mechanism of action appears not only attributable to a decrease in angiotensin II but, possibly, may also be accounted for by central and peripheral sympathicolytic effects diminished degradation of bradykinin and an increase in synthesis of vasoactive prostaglandins. During continued treatment with captopril over three months a further decrease in left ventricular filling pressure and an increase in cardiac output can be observed. While the exercise tolerance is not meaningfully affected at the beginning of treatment, a significant increase may be seen during long-term use. After three months of therapy an increase in the acutely-lowered mean arterial pressure can be noted. As compared with placebo-treated control patients, a more favorable clinical course was seen in those receiving captopril. There does not appear to be a relationship, however, between the initial hemodynamic effects and the clinical response. On combined use of captopril and hydralazine, as compared to treatment with captopril only, there is a greater increase in cardiac output and stroke volume without marked additional fall in pulmonary capillary pressure and a further decrease in systemic arterial pressure, incurred without symptomatic hypotension in the majority of patients. The adverse effect is hypotension which precludes long-term treatment in about 10% of patients. Proteinuria, neutropenia and renal insufficiency occur only rarely, usually in patients who are maintained on daily dosages above 300 mg or who have preexisting renal disease. Skin rashes and taste alterations are more common but are frequently well-tolerated and, generally, do not warrant discontinuation of treatment.

Acute and long-term effects of captopril on exercise cardiac performance and exercise capacity in congestive heart failure.

Although many studies have shown that captopril (CPT) provides acute hemodynamic improvement in patients with severe congestive heart failure (CHF) at rest, little information is available concerning exercise hemodynamic responses to CPT or the effect of this drug on exercise tolerance in CHF. Therefore, we evaluated the hemodynamic effects of CPT at rest and during upright bicycle exercise in 15 patients with stable CHF. CPT (25 to 50 mg) reduces both resting heart rate and mean arterial pressure (84 +/- 11 to 78 +/- 7 bpm, p less than 0.025 and 85 +/- 9 to 64 +/- mm Hg, p less than 0.001). Concomitantly, left ventricular filling pressure dropped dramatically (26 +/- 9 to 15 +/- 7 mm Hg, p less than 0.001), while cardiac and stroke indices rose (2.0 +/- 0.5 to 2.5 +/- 0.6 L/min/m2, p less than 0.001, and 25 +/- 8 to 33 +/- 7 ml/m2, p less than 0.001). Similar directional changes occurred during exercise, with heart rate, mean arterial pressure, and left ventricular filling pressure at maximum exercise being less (123 +/- 15 to 115 +/- 16 bpm, p less than 0.01; 93 +/- 17 to 86 +/- 14 mm Hg, p less than 0.05; and 35 +/- 10 to 30 11 mm Hg, p less than 0.001, respectively) after CPT ingestion. Peak exercise cardiac index rose slightly (3.6 +/- 0.7 to 3.9 +/- 0.6 L/min/m2) but not significantly. Six patients followed long term on CPT underwent elective recatheterization after 3 months. In these, the beneficial hemodynamic changes seen acutely persisted or further improvement was noted, both at rest and during exercise. Most impressively, peak exercise cardiac index rose from 3.6 +/- 0.7 to 4.6 +/- 1.0 L/min/m2 (p less than 0.05), and this was associated with an increase in exercise duration (8.0 +/- 2.2 to 11.5 +/- 1.4 minutes, p less than 0.05) and exercise work load (332 +/- 32 to 468 +/- 52 kp-m/min, p less than 0.05). These findings indicate that in patients with severe CHF, oral CPT provides markedly beneficial augmentation of cardiac function during activity as well as at rest; moreover, chronic CPT therapy substantially increases exercise capacity in this setting.

Acute and long-term effects of captopril on left and right ventricular volumes and function in chronic heart failure.

To more fully delineate the effects of captopril (CPT) on cardiac size and function in patients with chronic congestive heart failure (CHF), we performed blood pool scintigraphy in conjunction with hemodynamic measurements during the initiation of vasodilator therapy and repeat scintigraphy after 2 and 12 weeks. Measurements of both right and left ventricular volumes and ejection fraction were made before and 90 minutes after the first 25 mg dose of CPT in 14 patients. Overall, heart rate fell modestly, from 82 +/- 10 to 77 +/- 11 bpm (p less than 0.01), while mean arterial pressure dropped considerably, from 86 +/- 10 to 73 +/- 13 mm Hg (p less than 0.01). Left ventricular end-diastolic and end-systolic volumes fell from 388 +/- 81 to 350 +/- 77 and 319 +/- 75 to 271 +/- 75 ml (both p less than 0.01). Right ventricular end-diastolic and end-systolic volumes also decreased. The left ventricular ejection fraction rose modestly but significantly, from 19 +/- 6% to 22 +2- 5% (p less than 0.01), as did right ventricular ejection fraction (25 +/- 9% to 29 +/- 11%, p less than 0.01). Simultaneous hemodynamic measurements demonstrated corresponding decreases in left and right ventricular filling pressures (24 +/- 10 to 17 +/- 9 to 10 +/- 5 to 6 +/- 5 mm Hg, respectively, both p less than 0.001). The slight increase in cardiac and stroke indices at 90 minutes, from 2.0 +/- 0.5 to 2.1 +/- 0.4 and 25 +/- 8 to 27 +/- 7 ml/m2, respectively, were not significant, although both indices rose significantly at the time of each individual's peak effect. Six patients were discharged on CPT and underwent follow-up nuclear studies: the acute decrease in ventricular volumes were sustained, as was the slight improvement in ejection fractions. These findings indicated that the major acute effect of CPT in CHF is a reduction in the preload of both ventricles. This reduction in diastolic volumes and pressures persists during chronic therapy.

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 less than 0.025) and peak mean arterial pressure was lower (102 +/- 15 vs 95 +/- 17 mm Hg, p less than 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 less than 0.05), the maximum cardiac and stroke indexes were not significantly different (3.6 +/- 0.8 vs 3.4 +/- 0.8 l/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 less than 0.1; maximum oxygen consumption 12.1 +/- 2.4 vs 9.8 +/- 1.9 ml/min/kg, p less than 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.

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.