This randomized, double-blind, placebo-controlled, multicenter trial compared the effects of treatment with ibopamine with those of placebo in patients with severe heart failure who still showed symptoms although they were receiving standard therapy with digitalis and diuretics. The results showed a significant and sustained improvement in exercise tolerance (+70% about in average), clinical condition, and NYHA functional class and a decrease in cardiothoracic ratio and left ventricular end-systolic wall stress in patients treated with ibopamine, digitalis, and diuretics (group 1) compared with patients treated with digitalis, diuretics, and placebo (group 2).
Hypertrophy represents a frequent but inconstant response of the heart to hypertension and probably other nonhemodynamic factors are involved. We have performed 2D and Doppler echocardiography and assessed of neurohumoral pattern in 85 untreated patients with hypertension (diastolic blood pressure: 101 +/- 12.8 mmHg). Left ventricular hypertrophy was defined as a mass index greater than 134 g/m2 in males and 110 g/m2 in females. Doppler evaluation of left ventricular filling pattern was performed to detect the possible association of hypertrophy and diastolic dysfunction. In all patients the following neurohumoral substances were sampled and tested: plasmatic renin activity (PRA), aldosterone and norepinephrine. At Doppler echocardiography, 27 patients had hypertrophy and diastolic dysfunction, 15 only hypertrophy and 43 only diastolic dysfunction. The presence or absence of morpho-functional anomalies were independent of age, duration of hypertension and blood pressure levels. The mean value of neurohumoral substances were: norepinephrine 323.3 +/- 245 pg/ml, PRA 2.5 +/- 4 ng/ml/h, aldosterone 153.58 +/- 102 pg/ml. A significant correlation was found between PRA and blood pressure, and between aldosterone and all the Doppler-derived parameters of diastolic dysfunction. In conclusion, left ventricular hypertrophy seems to be related to alteration in ventricular geometry rather than to hemodynamic factors. Among nonhemodynamic factors, aldosterone may be the most responsible for abnormal filling, presumably through the activation of collagen matrix growth.
Long-term beta-blocker therapy may be useful in some patients affected by chronic heart failure. In a group of 15 patients with chronic heart failure of different origin we evaluated clinical, hemodynamic and neurohormonal features after 1 year of therapy. All patients were treated with atenolol at dosage of 50 mg/die. We observed a better ejection fraction by radionuclide angiography after 1 year of treatment. There was an increase of exercise time and VO2 max evaluated by cycloergometer test. There was a decrease of mean pulmonary artery pressure, of pulmonary vascular resistance and of right atrial pressure. Plasmatic norepinephrine decreased from 1294 +/- 568 to 574 +/- 33 pg/l. Our results suggest that patients who well tolerated chronic beta-blockade show an improvement of performance parameters.
The aim of this study was to investigate whether long-term treatment with ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, in patients with severe symptomatic congestive cardiomyopathy is associated with an improvement in cardiovascular conditions. The investigation was carried out in 18 outpatients with idiopathic or post-ischemic dilated cardiomyopathy and chronic severe heart failure (NYHA (New York Heart Association) Class III-IV). Patients were randomly assigned to a protocol in which either digitalis and diuretics (8 patients, Group 2) or the same treatment plus ibopamine (10 patients, Group 1) were given. There were no significant differences between the two groups in age, weight, height, functional class and duration of symptoms. The results obtained showed that cardiovascular conditions worsened dramatically in the group of controls during the 10-week period, irrespective of the treatment with digitalis and diuretics. Some of the parameters deteriorated significantly (p less than 0.05 or less than 0.01) such as systolic and diastolic left ventricular diameters, fractional shortening, end-systolic stress and pressure/diameter ratio, and other parameters showed a tendency to become worse (exercise time, cardiothoracic ratio). On the contrary, in patients of group 1, ibopamine in association with digitalis and diuretics appeared to preserve left ventricle function from a progressive worsening. None of the parameters deteriorated with ibopamine by contrast with a sharp decrease in the control group. Some of the parameters (fractional shortening, pressure/diameter ratio, exercise time) showed a tendency to improve although not significantly. The data suggest than 10 weeks treatment with ibopamine may prevent any deterioration or even produce a mild improvement in patients with very severe congestive heart failure.
