Improvement of cardiac performance by intravenous infusion of L-arginine in patients with moderate congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate the hemodynamic effect of L-arginine infusion in patients with congestive heart failure. BACKGROUND: Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. Nitric oxide, which was identified as endothelium-derived relaxing factor, is generated by nitric oxide synthase from L-arginine. Our hypothesis was that administration of L-arginine in patients with congestive heart failure may increase nitric oxide production and have a beneficial hemodynamic effect. METHODS: Twelve patients with congestive heart failure (New York Heart Association class II or III) due to coronary artery disease (left ventricular ejection fraction < 35%) were given 20 g of L-arginine by intravenous infusion over 1 h at a constant rate. Stroke volume, cardiac output and left ventricular ejection fraction were determined with Doppler echocardiography at baseline and at 30 and 60 min and 1 h after the end of infusion. Blood and urinary levels of nitrite/nitrate (NO2/NO3), stable metabolites of nitric oxide, were measured and clearance was calculated. RESULTS: One hour of infusion of L-arginine resulted in a significant increase in stroke volume (from 68 +/- 18 ml to 76 +/- 23 ml [mean +/- SD], p = 0.014) and cardiac output (from 4.07 +/- 1.22 liters/min to 4.7 +/- 1.42 liters/min, p = 0.006) without a change in heart rate. Mean arterial blood pressure decreased (from 102 +/- 11 mm Hg to 89 +/- 9.5 mm Hg, p < 0.002), and systemic vascular resistance decreased significantly. Within 1 h after cessation of L-arginine infusion, blood pressure, stroke volume, cardiac output and systemic vascular resistance were statistically not different from baseline values. Clearance of NO2/NO3 increased significantly during L-arginine administration (from 13.28 +/- 0.42 ml/min to 29.97 +/- 1.09 ml/min, p < 0.001). CONCLUSIONS: Infusion of L-arginine in patients with congestive heart failure results in increased production of nitric oxide, peripheral vasodilation and increased cardiac output, suggesting a beneficial hemodynamic and possibly therapeutic profile.

One-year clinical and echocardiographic follow-up of patients with congestive cardiomyopathy treated with captopril compared to placebo.

The beneficial hemodynamic and clinical effects of angiotensin-converting enzyme (ACE) inhibition in patients with severe congestive heart failure has recently been documented in large-scale studies. This mode of therapy when added to digitalis and diuretics improves survival. To evaluate the clinical effect and the changes in cardiac dimensions of captopril compared to placebo we followed 50 patients with severe congestive heart failure over 1 year using echo-Doppler cardiography. After randomization, 25 patients were started on captopril and 25 patients on placebo. At baseline and at 6 and 12 months, each patient underwent exercise tolerance test, radionuclide angiography to estimate left and right ventricular ejection fraction, M mode and two-dimensional echocardiography and Doppler cardiography to calculate cardiac dimensions and stroke volumes. During follow-up two patients in the captopril group and four in the placebo group died. Due to clinical deterioration nine patients in the placebo group had to be started on open-label captopril. Treatment with captopril was associated with a more significant improvement in functional class and exercise duration compared to placebo. Forward stroke volume estimated from Doppler echocardiography increased significantly by captopril from 47 +/- 3 to 55 +/- 3 ml and decreased in the placebo-treated patients from 49 +/- 5 to 44 +/- 4 ml. This improvement was associated with a trend towards reduced heart rate by captopril. Left ventricular end diastolic volume tended to increase in the placebo group and did not change in the captopril group. Calculated mitral regurgitant volume at 6 and 12 months tended to be lower in the captopril-treated patients. Thus captopril therapy proved efficacious in patients with severe congestive heart failure and resulted in increased forward stroke volume; it may have a beneficial effect on cardiac dimensions and on mitral regurgitation.

Left ventricular filling dynamics by Doppler echocardiography in dilated cardiomyopathy: one-year follow-up in patients treated with captopril compared to placebo.

The role of impaired diastolic function in determining the pathophysiology of congestive cardiomyopathy was only recently appreciated. In the present study, echocardiography and Doppler cardiography were used to determine changes in cardiac size and transmitral filling dynamics over a 1-year period in patients with congestive cardiomyopathy and determine the effect of captopril on these changes. The study population consisted of 27 patients with congestive heart failure in spite of therapy with digitalis and diuretics (NYHA class 3.2). Fifteen patients were started on placebo and 12 on captopril. Noninvasive evaluation was performed at 6-month intervals. Left ventricular size and left ventricular ejection fraction did not change significantly in either group. Forward stroke volume improved significantly only in patients on captopril compared to placebo (p < 0.05). No significant changes in transmitral flow dynamics were observed in the placebo group whereas the captopril-treated group showed a decrease in the peak velocity, flow velocity integral and rate of rapid filling wave (E) and an increase in the peak, integral and rate of filling during atrial contraction (A). The E/A ratio did not change significantly over time in the placebo group, whereas a reduction in the ratio was noted in the captopril-treated patients. These changes are sustained over 1 year with concomitant improvement in stroke volume, exercise duration and functional class.