Liberale Luca, Duncker Dirk Jan, Hausenloy Derek John, Kraler Simon, Bøtker Hans Erik, Podesser Bruno Karl, Heusch Gerd, Kleinbongard Petra
Department of Internal Medicine, University of Genoa, Genoa, Italy.
IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy.
Nat Rev Cardiol. 2025 Jun 22. doi: 10.1038/s41569-025-01163-w.
Heart failure (HF) is not confined to contractile failure of cardiomyocytes or myocardial fibrosis. Coronary and systemic vascular dysfunction contributes to the initiation and progression of HF with or without reduced ejection fraction. Furthermore, HF compromises vascular function, creating and sustaining a vicious cycle with deranging effects on coronary blood flow, cardiac metabolism and cardiac function. In HF, systemic arterial dysfunction, characterized by increased arterial stiffness and resistance, raises cardiac afterload and impedes myocardial contractile function. Reduced coronary blood flow impairs myocardial oxygen delivery and consequently cardiomyocyte metabolism and function. Coronary microvascular dysfunction is heterogeneous in its pathogenesis and manifestations, complicating the diagnosis and management across different HF phenotypes. Understanding the alterations in function in different segments of the vasculature, from the aorta to the capillary level, offers mechanistic insights into disease drivers and therapeutic interventions. Interventional approaches can improve vascular haemodynamics, whereas established and emerging pharmacotherapies target the neurohumoral axis and reduce extravascular compression, inflammation, and oxidative stress, thereby improving vascular function and HF-related outcomes. In this Review, we provide a mechanistic framework of vascular dysfunction in the pathogenesis of HF with or without reduced ejection fraction, pointing towards integrated therapies that consider the vascular implications of contemporary HF management across HF phenotypes.
心力衰竭（HF）并不局限于心肌细胞的收缩功能衰竭或心肌纤维化。无论射血分数是否降低，冠状动脉和全身血管功能障碍都会促使HF的发生和发展。此外，HF会损害血管功能，形成并维持一个恶性循环，对冠状动脉血流、心脏代谢和心脏功能产生紊乱影响。在HF中，以动脉僵硬度和阻力增加为特征的全身动脉功能障碍会增加心脏后负荷并阻碍心肌收缩功能。冠状动脉血流减少会损害心肌氧供，进而影响心肌细胞代谢和功能。冠状动脉微血管功能障碍在发病机制和表现上具有异质性，使不同HF表型的诊断和管理变得复杂。了解从主动脉到毛细血管水平的不同血管段功能变化，有助于深入了解疾病驱动因素和治疗干预措施。介入方法可以改善血管血流动力学，而现有和新兴的药物疗法则针对神经体液轴，减少血管外压迫、炎症和氧化应激，从而改善血管功能和HF相关结局。在本综述中，我们提供了一个关于射血分数降低或未降低的HF发病机制中血管功能障碍的机制框架，指出了综合治疗方法，该方法考虑了当代HF管理对不同HF表型的血管影响。
