Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
PLoS One. 2021 May 14;16(5):e0249674. doi: 10.1371/journal.pone.0249674. eCollection 2021.
Circulating Neprilysin (sNEP) has emerged as a potential prognostic biomarker in heart failure (HF). In PARAGON-HF benefit of sacubitril/valsartan was only observed in patients with left ventricular ejection fraction (LVEF) ≤57%. We aimed to assess the prognostic value of sNEP in outpatients with HF and LVEF >57%, in comparison with patients with LVEF ≤57%.
Consecutive HF outpatients were included from May-2006 to February-2016. The primary endpoint was the composite of all-cause death or HF hospitalization and the main secondary endpoint was the composite of cardiovascular death or HF hospitalization. For the later competing risk methods were used.
sNEP was measured in 1428 patients (age 67.7±12.7, 70.3% men, LVEF 35.8% ±14), 144 of which had a LVEF >57%. sNEP levels did not significantly differ between LVEF groups (p = 0.31). During a mean follow-up of 6±3.9 years, the primary endpoint occurred in 979 patients and the secondary composite endpoint in 714 (in 111 and 84 of the 144 patients with LVEF >57%, respectively). sNEP was significantly associated with both composite endpoints. Age- and sex- adjusted Cox regression analyses showed higher hazard ratios for sNEP in patients with LVEF >57%, both for the primary (HR 1.37 [1.16-1.61] vs. 1.04 [0.97-1.11]) and the secondary (HR 1.38 [1.21-1.55] vs. 1.11 [1.04-1.18]) composite endpoints.
sNEP prognostic value in patients with HF and LVEF >57% outperforms that observed in patients with lower LVEF. Precision medicine using sNEP may identify HF patients with preserved LVEF that may benefit from treatment with sacubitril/valsartan.
循环脑啡肽酶（sNEP）已成为心力衰竭（HF）的潜在预后生物标志物。在 PARAGON-HF 研究中，沙库巴曲缬沙坦的获益仅见于左心室射血分数（LVEF）≤57%的患者。我们旨在评估 sNEP 在 LVEF>57%的 HF 门诊患者中的预后价值，并与 LVEF≤57%的患者进行比较。
连续纳入 2006 年 5 月至 2016 年 2 月期间的 HF 门诊患者。主要终点是全因死亡或 HF 住院的复合终点，主要次要终点是心血管死亡或 HF 住院的复合终点。对于后者，采用竞争风险方法。
共纳入 1428 例患者（年龄 67.7±12.7 岁，70.3%为男性，LVEF 为 35.8%±14%），其中 144 例 LVEF>57%。两组间 sNEP 水平无显著差异（p=0.31）。中位随访 6±3.9 年后，共有 979 例患者发生主要终点事件，714 例患者发生次要复合终点事件（144 例 LVEF>57%的患者中分别有 111 例和 84 例）。sNEP 与两个复合终点均显著相关。年龄和性别校正的 Cox 回归分析显示，在 LVEF>57%的患者中，sNEP 的风险比更高，在主要终点（HR 1.37[1.16-1.61] vs. 1.04[0.97-1.11]）和次要终点（HR 1.38[1.21-1.55] vs. 1.11[1.04-1.18]）中均如此。
sNEP 在 LVEF>57%的 HF 患者中的预后价值优于 LVEF 较低患者。使用 sNEP 的精准医学可能会识别出保留 LVEF 的 HF 患者，这些患者可能从沙库巴曲缬沙坦治疗中获益。
