Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM 14.478 in patients with congestive heart failure

Abstract : The benzimidazol analogue BM 14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II‐IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM 14.478. There was a significant decrease of mean pulmonary artery pressure (28±11 vs. 23±11 mmHg; p>0.05), mean right atrial pressure (8.6±5.2 vs. 5.0±4.7 mmHg; p>0.02), and systemic vascular resistance (1651±484 vs. 1206±252 dynes$$s$$cm –5 ; p>0.05) as early as 10 min after injection of BM 14.478. Pulmonary vascular resistance also was reduced (128±86 vs. 61±39 dynes$$s$$cm –5 , 30 min after injection; p>0.02). Simultaneously there was a significant increase of cardiac index (2.3±0.7 vs. 3.1±0.8 1$$min –5 $$m –2 , 10 min after injection; p>0.02), and stroke volume index (28.8±11.7 vs. 33.9±8.5 ml$$min –1 $$m –2 ; 30 min after injection; p>0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51±20 vs. 41±21 pg/ml; p>0.02; 30 min after injection) and atrial natriuretic peptide (229±283 vs. 121±168 pg/ml; p>0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM 14.478. Response of plasma renin activity and plasma vasopressin levels to BM 14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM 14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short‐term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.