Atrial Natriuretic Peptide and Treatment With Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction,JACC: Heart Failure

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Atrial Natriuretic Peptide and Treatment With Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction
JACC: Heart Failure ( IF 13.0 ) Pub Date : 2020-11-11 , DOI: 10.1016/j.jchf.2020.09.013
Sean P Murphy ₁ , Margaret F Prescott ₂ , Alexander Camacho ₁ , Seethalakshmi R Iyer ₃ , Alan S Maisel ₄ , G Michael Felker ₅ , Javed Butler ₆ , Ileana L Piña ₇ , Nasrien E Ibrahim ₈ , Cheryl Abbas ₂ , John C Burnett ₃ , Scott D Solomon ₉ , James L Januzzi ₁₀

Affiliation

Massachusetts General Hospital, Boston, Massachusetts, USA.
Novartis Pharmaceuticals, East Hanover, New Jersey, USA.
Mayo Clinic, Rochester, Minnesota, USA.
University of California, San Diego School of Medicine, San Diego, California, USA.
Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina, USA.
University of Mississippi Medical Center, Jackson, Mississippi, USA.
Detroit Medical Center, Detroit, Michigan, USA.
Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA; Brigham and Women's Hospital, Boston, Massachusetts, USA.
Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Baim Institute for Clinical Research, Boston, Massachusetts, USA.

Objectives

This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).

Background

Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP.

Methods

In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment.

Results

Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p < 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p < 0.001 for both).

Conclusions

Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183)

中文翻译：

心房利钠肽和沙库巴曲/缬沙坦治疗射血分数降低的心力衰竭

目标

本研究旨在评估射血分数降低的心力衰竭 (HFrEF) 患者开始使用沙库巴曲/缬沙坦后心房利钠肽 (ANP) 的纵向变化与逆转心脏重构之间的关联。

背景

脑啡肽酶抑制导致几种血管活性肽的增加，这些肽可能介导沙库巴曲/缬沙坦的有益作用，包括 ANP。

方法

在 HFrEF 患者开始和滴定沙库巴曲/缬沙坦的前瞻性研究中，在预定的时间点将血液收集到含有蛋白酶抑制剂的试管中。这项预先指定的探索性分析包括在基线和连续 12 个月的治疗期间测量 ANP 的患者。

结果

在 144 名参与者中（平均年龄：64.5 岁；左心室射血分数：30.8%），在开始使用沙库巴曲/缬沙坦后，ANP 早期显着增加，其中大部分从基线时的 99 pg/ml 上升至 156第 14 天 pg/ml (p < 0.001)。从第 30 天到第 45 天还有第二次增加的趋势（p = 0.07）。在最大上升时，ANP 翻了一番。在纵向分析中，ANP 早期升高之后，尿循环单磷酸鸟苷随后升高。ANP 早期较大的增加与左心室射血分数和左心房容积指数的较大后期改善相关（两者 p < 0.001）。