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

作     者：Moe, GW Rouleau, JL Charbonneau, L Proulx, G Arnold, JMO Hall, C de Champlain, J Barr, A Sirois, P Packer, M 

作者机构：St Michaels Hosp Terrence Donnelly Heart Ctr Toronto ON M5B 1W8 Canada 

出 版 物：《AMERICAN HEART JOURNAL》 (美国心脏杂志)

年 卷 期：2000年第139卷第4期

页      面：587-595页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：血管紧张素Ⅱ/生理学 心钠素/生理学 死亡原因 队列研究 去甲肾上腺素/生理学 预后 蛋白质前体/生理学 喹啉类/治疗应用 存活率 血管舒张药/治疗应用 老年人 女(雌)性 人类 男(雄)性 中年人 

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