Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide.
Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide.
复制标题
DOI：
10.1016/j.jacc.2012.07.056
复制
发表时间：
2012-12-04
影响因子：
24
通讯作者：
Burnett, John C., Jr.
中科院分区：
文献类型：
--
作者：
Chen, Horng H.;Glockner, James F.;Schirger, John A.;Cataliotti, Alessandro;Redfield, Margaret M.;Burnett, John C., Jr.
本研究的目的是将我们的实验室研究转化为慢性SQ BNP给药8周在人类C期心衰中的安全性和有效性。B型利钠肽(BNP)是一种心脏激素，具有扩张血管、利钠、抑制肾素-血管紧张素(RAS)和促血管生成作用。我们先前已经证明，在实验性心力衰竭(HF)中，慢性心脏激素替代联合BNP皮下注射(SQ)可以改善心血管功能。我们进行了一项随机双盲安慰剂对照概念验证研究，比较了EF<；35%和NYHAII-III级心衰患者服用SQ BNP(10μg/kg Bid)(n=20)和安慰剂(n=20)8周的疗效。主要结果是心脏MRI确定的左心室体积和左心室质量。次要结果包括超声心动图的左心室充盈压、体液功能和肾功能。与安慰剂相比，长期服用SQ BNP 8周后，LV收缩和舒张期容量指数和LV质量指数的下降幅度更大。与安慰剂相比，明尼苏达州心力衰竭(MLHF)评分、左心室充盈压(E/e‘)和左房容量指数(LA)的下降明显改善。用SQ BNP保存GFR，以及激活血浆cGMP的能力。(P<；0.05 vs安慰剂)在这项概念验证的先导性研究中，服用SQ BNP的慢性蛋白质疗法在最佳疗法下改善了收缩心衰稳定患者的左室重构、左室充盈压力和MLHF评分。RAS被抑制，GFR被保留。SQ BNP代表了一种新的、安全有效的人类心力衰竭蛋白质治疗策略。有必要进行进一步的研究，以确定这些生理观察是否可以转化为改善临床结果，并最终延缓心力衰竭的进展。
The objective of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SQ BNP administration in human Stage C HF. B-Type natriuretic peptide (BNP) is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin (RAS) inhibiting and lusitropic properties. We have previously demonstrated that chronic cardiac hormone replacement with subcutaneous (SQ) administration of BNP in experimental heart failure (HF) resulted in improved cardiovascular function. We performed a randomized double-blind placebo-controlled proof of concept study comparing eight weeks of SQ BNP (10 μg/Kg bid) (n=20) with Placebo (n=20) in patients with EF<35% and NYHA class II–III HF. Primary outcomes were LV volumes and LV mass determined by cardiac MRI. Secondary outcomes include LV filling pressure by Doppler echo, humoral function and renal function. Eight weeks of chronic SQ BNP resulted in a greater reduction of LV systolic and diastolic volume index and LV mass index as compared to placebo. There was a significantly greater improvement of Minnesota Living with Heart Failure (MLHF) score, LV filling pressure as demonstrated by the reductions of E/e′ ratio and decrease in LA volume index as compared to placebo. GFR was preserved with SQ BNP, as was the ability to activate plasma cGMP. (p<0.05 vs placebo) In this pilot proof of concept study, chronic protein therapy with SQ BNP improved LV remodeling, LV filling pressure and MLHF score in patients with stable systolic HF on optimal therapy. RAS was suppressed and GFR preserved. SQ BNP represents a novel, safe and efficacious protein therapeutic strategy in human HF. Further studies are warranted to determine if these physiologic observations can be translated into improved clinical outcomes and ultimately delay the progression of HF.
登录
查看更多内容
影响因子：
120.7
作者：
Redfield, MM;Jacobsen, SJ;Rodeheffer, RJ
通讯作者：
Rodeheffer, RJ
影响因子：
20.1
作者：
Tsuruda, T;Boerrigter, G;Burnett, JC
通讯作者：
Burnett, JC
影响因子：
15.9
作者：
BROWN, LA;NUNEZ, DJR;WILKINS, MR
通讯作者：
WILKINS, MR
影响因子：
18.2
作者：
Chen, Horng H.;Schirger, John A.;Burnett, John C., Jr.
通讯作者：
Burnett, John C., Jr.
DOI：
10.1073/pnas.0508782102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Hawkridge, AM;Heublein, DM;Muddiman, DC
通讯作者：
Muddiman, DC