Background:Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain.Methods:In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index.Results:Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m², respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged −27.9% (95% CI, −35.1% to −20.7%; P<0.001) for NT-proBNP; −6.7% (95% CI, −8.8% to −4.7%; P<0.001) for hs-cTnT; and −1.6% (95% CI, −2.9% to −0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures.Conclusions:Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.

中文翻译：

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射血分数降低的心力衰竭患者血管紧张素受体-脑啡肽酶抑制、心血管生物标志物和心脏重构之间的关联

背景：沙库巴曲/缬沙坦 (S/V) 治疗与心脏重构逆转和反映心室壁应力和心肌损伤的生物标志物减少有关，例如 NT-proBNP（N 端前 B 型利钠肽）、hs-cTnT （高敏心肌肌钙蛋白 T）和致瘤性可溶性抑制剂 2 (sST2)。这些共同分析的生物标志物的纵向变化如何与 S/V 治疗的射血分数降低的心力衰竭患者的心脏重构相关尚不确定。 方法：在射血分数降低的心力衰竭患者的 S/V 前瞻性研究中，这项预先指定的探索性分析包括在 12 个月的治疗中具有连续收集的生物标志物和心脏重构的超声心动图测量值的患者。多变量潜在生长曲线模型评估了生物标志物同时变化与左心室射血分数和左心房容积指数之间的关联。结果：包括 794 名研究参与者中的 715 名（平均年龄 65 岁，73% 为男性）。平均基线左心室射血分数和左心房容积指数分别为 29% 和 40 mL/m²、分别。调整后的生物标志物几何平均基线浓度包括 649 pg/mL 的 NT-proBNP、15.9 ng/L 的 hs-cTnT 和 24.7 ng/mL 的 sST2。S/V 开始后，NT-proBNP、hs-cTnT 和 sST2 的循环浓度在 30 天内显着降低，并且在所有后续时间点与基线保持显着差异。从基线到第 12 个月，NT-proBNP 的调整后生物标志物浓度平均降低 -27.9%（95% CI，-35.1% 至 -20.7%；P <0.001）；hs-cTnT 为-6.7%（95% CI，-8.8% 至 -4.7%；P <0.001）；和 -1.6%（95% CI，-2.9% 至 -0.4%；P<0.001) 对于 sST2。NT-proBNP 浓度可预测 hs-cTnT 的后期变化。NT-proBNP 和 hs-cTnT 浓度的降低幅度与左心室射血分数和左心房容积指数的改善有关。sST2 的变化与其他指标的变化之间没有关联。结论：在 S/V 开始后，NT-proBNP、hs-cTnT 和 sST2 浓度显着降低。NT-proBNP 和 hs-cTnT 的纵向变化与左心房和左心室反向重构相关。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT02887183。