Vergaro Giuseppe, Sciarrone Paolo, Prontera Concetta, Masotti Silvia, Musetti Veronica, Valleggi Alessandro, Giannoni Alberto, Senni Michele, Emdin Michele, Passino Claudio
Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana Gabriele Monasterio, Via Moruzzi 1, Pisa, 56127, Italy.
ESC Heart Fail. 2021 Feb;8(1):719-724. doi: 10.1002/ehf2.13085. Epub 2020 Nov 20.
Clinical trials and observational cohorts show that beneficial effects of sacubitril/valsartan are less strong in an appreciable proportion of patients with heart failure with reduced ejection fraction (HFrEF). Lower blood pressure and impaired renal function predict suboptimal sacubitril/valsartan titration and a less favourable response. Circulating renin encompasses neurohormonal activation, intravascular volume, and renal function. We hypothesized that renin may predict response to sacubitril/valsartan, assessed by changes in N-terminal fraction of pro-brain natriuretic peptide (NT-proBNP).
We performed a prospective, open-label, real-life cohort study. The study population consisted of 80 consecutive HFrEF patients (age 66 ± 10 years, 83% men) planned to initiate sacubitril/valsartan. Clinical and biohumoral assessment, including a full neurohormonal panel, was performed at baseline and at 1, 3, and 6 month follow-up. Response to sacubitril/valsartan was defined as ≥30% reduction in NT-proBNP levels from baseline to 6 months. Patients in the lower renin tertile had higher blood pressure and plasma sodium concentration (all P < 0.05). At follow-up, 38 patients (48%) were classified as responders. Circulating renin was lower in the responder group compared with non-responders (19.8 mU/L, IQR 3.7-78.0 mU/L vs. 55.0 mU/L, IQR 16.4-483.1 mU/L; P = 0.004). After adjustment for age, renal function, and blood pressure, renin was independently associated to response to sacubitril/valsartan (P = 0.018).
In our preliminary study, we show that circulating renin predicts reduction in NT-proBNP levels after sacubitril/valsartan initiation in HFrEF patients. Renin assessment might be useful to discriminate potential responders from the subgroup with a weaker expected benefit, thus needing a closer, tailored management strategy.
临床试验和观察性队列研究表明，在相当一部分射血分数降低的心力衰竭（HFrEF）患者中，沙库巴曲缬沙坦的有益作用较弱。血压较低和肾功能受损预示着沙库巴曲缬沙坦滴定效果欠佳且反应较差。循环肾素涉及神经激素激活、血管内容量和肾功能。我们假设肾素可能预测沙库巴曲缬沙坦的反应，通过脑钠肽前体N端片段（NT-proBNP）的变化来评估。
我们进行了一项前瞻性、开放标签、真实生活队列研究。研究人群包括80例连续的计划开始使用沙库巴曲缬沙坦的HFrEF患者（年龄66±10岁，83%为男性）。在基线以及随访1、3和6个月时进行了临床和生物体液评估，包括完整的神经激素检测。沙库巴曲缬沙坦的反应定义为从基线到6个月时NT-proBNP水平降低≥30%。肾素三分位数较低的患者血压和血浆钠浓度较高（所有P<0.05）。在随访时，38例患者（48%）被归类为反应者。与无反应者相比，反应者组的循环肾素较低（19.8 mU/L，IQR 3.7 - 78.0 mU/L vs. 55.0 mU/L，IQR 16.4 - 483.1 mU/L；P = 0.004）。在调整年龄、肾功能和血压后，肾素与沙库巴曲缬沙坦的反应独立相关（P = 0.018）。
在我们的初步研究中，我们表明循环肾素可预测HFrEF患者开始使用沙库巴曲缬沙坦后NT-proBNP水平的降低。肾素评估可能有助于从预期获益较弱的亚组中区分出潜在反应者，因此需要更密切、量身定制的管理策略。
