Barry Kramer

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.

Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty

To assess the incidence and clinical significance of elevated total plasma creatine kinase (CK) and MB isoenzyme fraction after apparently successful coronary angioplasty, a prospective study of 272 consecutive elective procedures was undertaken. Total CK (normal less than 100 IU/liter) and CK MB isoenzyme (normal less than 4%) were measured immediately after successful completion of the procedure and every 6 h for 24 h. All nonelective procedures and results not fulfilling all American Heart Association/American College of Cardiology Task Force guideline criteria for a successful result were excluded from analysis. Of the 272 elective procedures, 249 (92%) were successfully; abnormally elevated CK or CK MB serum levels, or both, were found in 38 (15%) of the successful outcomes. Three patterns of abnormal enzymes were identified: 15 patients with CK greater than or equal to 200 IU/liter and CK MB greater than or equal to 5% (group 1), 4 patients with CK greater than or equal to 200 IU/litter and CK MB less than or equal to 4% (group 2) and 19 patients with CK less than 200 IU/liter and CK MB greater than or equal to 5% (group 3). The three groups were distinguishable by the nature of the complications causing the enzyme release (in particular, the etiology and clinical manifestations). There were significantly more clinically apparent events in group 1 than in the other groups (13 of 15 versus 11 of 23, p less than 0.01) and more events associated with persistent electrocardiographic changes (p = 0.05) and chest pain (p less than 0.05). However, no clinically important sequelae were recognizable in any group at hospital discharge. Thus, abnormal cardiac serum enzyme release after apparently successful coronary angioplasty is 1) relatively common; 2) has many possible causes, including both minor complications and early reversibility of impending major complications; and 3) results in no permanent clinical sequelae.

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.

Radionuclide measurement of left ventricular volume: comparison of geometric and counts-based methods.

Radionuclide measurements of left ventricular volume were determined in 20 patients by geometric and nongeometric, counts-based techniques using data from first-pass and equilibrium blood pool scintigraphy. Two geometric analytic approaches were used: directly measured long and short axes and the arealength method. Each approach was applied to the single-plane right anterior oblique images obtained by the first-pass technique and to biplane data, using the right anterior oblique first-pass, and left anterior oblique blood pool data together. For the nongeometric determinations, background-corrected left ventricular counts were related to blood counts. This ratio was converted to volume by means of a linear regression relationship with angiographic volumes. All methods yielded high correlation coefficients (r > 0.93), but the standard errors of the estimates for the geometric techniques were high, and therefore the 95% confidence limits were wide. The use of biplane data improved the correlations, but area-length analysis of digitized data was no better than direct measurement of short axes from the analog images. The counts-based, nongeometric method provided the highest correlation and lowest standard error. These findings indicate that nongeometric left ventricular volume measurements using equilibrium blood pool scintigrams are the most accurate radionuclide technique. This approach also permits multiple determinations with a single dose of radiotracer.

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.

Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance.

The acute hemodynamic response to vasodilators in patients with chronic heart failure has been well characterized, but less is known about the long-term hemodynamic effects of vasodilator therapy. We measured hemodynamic variables at rest and during upright exercise in 11 patients during the initiation of therapy with oral hydralazine and sublingual isosorbide dinitrate and, in eight of these, after 3 months of continuous treatment. Marked initial increases in resting cardiac output and stroke volume and reductions in wedge pressure were sustained during chronic therapy. Similarly, the early improvement in exercise hemodynamic measurements persisted in most subjects.Exercise tolerance, quantified as the maximum duration of treadmill exercise, increased modestly (7.7 2.6 to 8.9 ± 3.3 minutes, 0.05 < p < 0.10) after several days on vasodilators and further (10.2 ± 3.7 minutes, p < 0.01) during long-term treatment. The acute hemodynamic effects of vasodilator therapy at rest or during exercise did not correlate well with the changes in exercise tolerance.Our findings suggest that the combination of hydralazine and isosorbide dinitrate improves cardiac performance at rest and during exercise in patients with chronic heart failure and that this improvement persists during chronic therapy. In most patients, this hemodynamic improvement is accompanied by greater exercise tolerance.

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.