Robles-Mezcua Ainhoa, Januzzi James L, Pavón-Morón Francisco Javier, Rodríguez-Capitán Jorge, López-Garrido Miguel A, Cruzado-Álvarez Concepción, Robles-Mezcua María, Gutiérrez-Bedmar Mario, Couto-Mallón David, Rueda-Calle Eloy C, Barreiro-Pérez Manuel, Sánchez Pedro L, Gómez-Doblas Juan José, Jiménez-Navarro Manuel F, García-Pinilla José M
Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), Málaga, Spain; Área del Corazón, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Unidad de Insuficiencia Cardíaca y Cardiopatías Familiares, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatología, Facultad de Medicina, Universidad de Málaga, Spain.
Massachusetts General Hospital, Harvard Medical School and Baim Institute for Clinical Research, Boston, MA, USA.
Biomed Pharmacother. 2025 Feb;183:117874. doi: 10.1016/j.biopha.2025.117874. Epub 2025 Jan 30.
Treatment of heart failure and reduced ejection fraction (HFrEF) using angiotensin receptor-neprilysin inhibitor demonstrates beneficial effects on cardiac remodeling (CR). We assessed the impact of sacubitril/valsartan on the concentrations of HF biomarkers in relation to parameters of CR using imaging techniques in patients with HFrEF. In a prospective single-center open-label study, 68 patients with symptomatic HFrEF were treated with sacubitril/valsartan and followed-up every three months for 12 months. Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin I (hs-cTnI) were measured in blood samples. Additionally, echocardiography and cardiac magnetic resonance imaging (cMRI) were performed to assess heart structural and functional changes. Following treatment initiation, follow-up visits revealed an improved NYHA functional class in these patients, alongside significant decreases in all circulating biomarkers, increases in left ventricular ejection fraction (LVEF), and reductions in volume- and diameter-related LV parameters. Sustained gradual decreases in sST2 concentrations over time correlated with NT-proBNP concentrations (rho=+0.26, P < 0.001). Both biomarkers were inversely correlated with LVEF, and positively correlated with volume- and diameter-related LV parameters from echocardiography and cMRI. However, NT-proBNP concentrations exhibited stronger correlations with these LV parameters and were associated with the number of LV segments showing fibrosis, unlike sST2. Sacubitril/valsartan treatment in HFrEF leads to reduced sST2 and NT-proBNP concentrations with distinct decreasing curves, which are linked to reverse CR through LV-related parameters. In contrast to sST2, NT-proBNP is also associated with fibrosis, suggesting that both biomarkers unveil distinct mechanisms during CR in patients treated with sacubitril/valsartan.
使用血管紧张素受体脑啡肽酶抑制剂治疗射血分数降低的心力衰竭（HFrEF）对心脏重塑（CR）具有有益作用。我们使用成像技术评估了沙库巴曲缬沙坦对HFrEF患者HF生物标志物浓度与CR参数的影响。在一项前瞻性单中心开放标签研究中，68例有症状的HFrEF患者接受了沙库巴曲缬沙坦治疗，并每三个月随访一次，为期12个月。在血样中测量了可溶性肿瘤抑制因子2（sST2）、N端前脑钠肽（NT-proBNP）和高敏心肌肌钙蛋白I（hs-cTnI）。此外，进行了超声心动图和心脏磁共振成像（cMRI）以评估心脏结构和功能变化。治疗开始后，随访显示这些患者的纽约心脏协会（NYHA）功能分级有所改善，同时所有循环生物标志物均显著下降，左心室射血分数（LVEF）增加，与左心室体积和直径相关的参数降低。随着时间的推移，sST2浓度持续逐渐下降与NT-proBNP浓度相关（rho=+0.26，P<0.001）。两种生物标志物均与LVEF呈负相关，与超声心动图和cMRI中与左心室体积和直径相关的参数呈正相关。然而，与sST2不同，NT-proBNP浓度与这些左心室参数的相关性更强，并且与显示纤维化的左心室节段数量相关。HFrEF患者接受沙库巴曲缬沙坦治疗可降低sST2和NT-proBNP浓度，且下降曲线不同，这通过与左心室相关的参数与逆向CR相关。与sST2不同，NT-proBNP也与纤维化相关，这表明在接受沙库巴曲缬沙坦治疗的患者的CR过程中，这两种生物标志物揭示了不同的机制。
