Ono Ryohei, Menezes Falcão Luiz
Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba Japan.
Academic Medical Center of Lisbon (CAML), Cardiovascular Center of the University of Lisbon (CCUL@RISE), Faculty of Medicine of the University of Lisbon, Lisbon, Portugal.
Rev Port Cardiol. 2025 Jul;44(7):445-456. doi: 10.1016/j.repc.2025.02.007. Epub 2025 Jun 3.
Heart failure with preserved ejection fraction (HFpEF) is characterized by diverse underlying pathophysiological mechanisms and can be divided into two subgroups based on the identification of the specific cause: primary and secondary HFpEF. Primary HFpEF is caused by primary impairments in myocardial relaxation or compliance with the contribution of several risk factors. Therefore, we have reviewed current literature on pathophysiology and treatment in patients with primary HFpEF. Patients with primary HFpEF represent specific "phenotypes" and are usually elderly, more commonly women, and often with a history of arterial hypertension, obesity, iron deficiency (ID), coronary artery disease (CAD), sleep apnea, diabetes, chronic kidney disease (CKD), and chronotropic incompetence. Some of the main pathophysiological mechanisms for each phenotype of primary HFpEF are as follows: arterial hypertension, which promotes left ventricular hypertrophy and fibrosis; obesity, which contributes through systemic inflammation and metabolic dysregulation; aging, which leads to ventricular-vascular stiffening; gender differences, with women experiencing changes due to smaller heart size and hormonal shifts; ID, which affects mitochondrial function; CAD, which impairs myocardial blood flow; diabetes, which is associated with hyperglycemia, lipotoxicity, insulin resistance, and microvascular rarefaction; CKD, which leads to hypertension, metabolic disturbance, systemic inflammation, and endothelial dysfunction; sleep apnea, which induces cardiac changes through pressure swings and hypoxia; and chronotropic incompetence, which is due to reduced cardiac β-receptor responsiveness. In conclusion, each factor intricately contributes to the complex pathophysiology of HFpEF. Understanding these interrelated mechanisms is critical for tailoring management strategies to improve outcomes in HFpEF patients.
射血分数保留的心力衰竭（HFpEF）具有多种潜在的病理生理机制，根据特定病因可分为两个亚组：原发性和继发性HFpEF。原发性HFpEF由心肌舒张或顺应性的原发性损害以及多种危险因素共同作用引起。因此，我们回顾了目前关于原发性HFpEF患者病理生理学和治疗的文献。原发性HFpEF患者具有特定的“表型”，通常为老年人，女性更为常见，且常伴有动脉高血压、肥胖、缺铁（ID）、冠状动脉疾病（CAD）、睡眠呼吸暂停、糖尿病、慢性肾脏病（CKD）和变时性功能不全病史。原发性HFpEF各表型的一些主要病理生理机制如下：动脉高血压促进左心室肥厚和纤维化；肥胖通过全身炎症和代谢失调起作用；衰老导致心室-血管僵硬；性别差异，女性因心脏较小和激素变化而出现改变；缺铁影响线粒体功能；CAD损害心肌血流；糖尿病与高血糖、脂毒性、胰岛素抵抗和微血管稀疏有关；CKD导致高血压、代谢紊乱、全身炎症和内皮功能障碍；睡眠呼吸暂停通过压力波动和缺氧引起心脏变化；变时性功能不全是由于心脏β受体反应性降低。总之，每个因素都错综复杂地促成了HFpEF复杂的病理生理学。了解这些相互关联的机制对于制定管理策略以改善HFpEF患者的预后至关重要。
