Neurohormonal activation in severe heart failure: relations to patient death and the effect of treatment with flosequinan.

摘要: Abstract Background Flosequinan is a direct-acting vasodilator that exerts beneficial hemodynamic effects and improves the exercise tolerance of patients with heart failure. However, multicenter trial has demonstrated long-term administration flosequinan associated increased mortality rate. To explore possible role neurohormonal activation on this adverse outcome, we conducted substudy to examine plasma levels 3 systems known have prognostic implications in Methods At 20 participating Canadian centers, paired samples at baseline 1 month after randomization for measurement N-terminal atrial natriuretic peptide (N-ANP), angiotensin II, norepinephrine were obtained 234 (114 receiving 120 placebo). Results Treatment was decline median N-ANP (2139 pmol/L 1625 [ P = .0001]), unchanged II (40 50 .2700]), modest increase (391 439 pg/mL .002]). These changes not observed placebo group. Multivariate analysis variables revealed level predicted patients' death whereas incorporating both 1-month indicated death. Furthermore, group, significant survivors only. On multivariate data, did predict rate use flosequinan, suggesting 2 might be mediated by separate mechanisms. Conclusions our study demonstrate severe failure, predicts increases these through mechanisms override its effects. Our reinforces concept direct actions pharmacologic agent may more profound impact prognosis than