Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35139 Padova, Italy.
Clinical Cardiology, Department of Medical Science and Public Health, University of Cagliari, 09125 Cagliari, Italy.
Rev Cardiovasc Med. 2021 Mar 30;22(1):97-104. doi: 10.31083/j.rcm.2021.01.277.
Heart failure with preserved ejection fraction (HFEF) is one of the greatest unmet needs in modern medicine. The lack of an appropriate therapy may reflect the lack of an accurate comprehension of its pathophysiology. Coronary microvascular rarefaction in HFEF was first hypothesized in an autopsy study that showed how HFEF patients had lower microvascular density and more myocardial fibrosis than control subjects. This was later confirmed when it was noted that HFEF is associated with reduced myocardial flow reserve (MFR) at single photon emission computed tomography (SPECT) and that coronary microvascular dysfunction may play a role in HFEF disease processes. HFEF patients were found to have lower coronary flow reserve (CFR) and a higher index of microvascular resistance (IMR). What is the cause of microvascular dysfunction? In 2013, a new paradigm for the pathogenesis of HFEF has been proposed. It has been postulated that the presence of a proinflammatory state leads to coronary microvascular endothelial inflammation and reduced nitric oxide bioavailability, which ultimately results in heart failure. Recently, it has also been noted that inflammation is the main driver of HFEF, but via an increase in inducible nitric oxide synthase (iNOS) resulting in a decrease in unfolded protein response. This review summarizes the current evidence on the etiology of coronary microvascular dysfunction in HFEF, focusing on the role of inflammation and its possible prevention and therapy.
射血分数保留的心力衰竭（HFpEF）是现代医学中最大的未满足需求之一。缺乏适当的治疗方法可能反映出对其病理生理学认识不足。HFpEF 中冠状动脉微血管稀疏首先在一项尸检研究中提出，该研究表明 HFpEF 患者的微血管密度低于对照组，心肌纤维化更多。当发现 HFpEF 与单光子发射计算机断层扫描（SPECT）时心肌血流储备（MFR）降低有关，并且冠状动脉微血管功能障碍可能在 HFpEF 疾病过程中起作用时，这一点得到了进一步证实。HFpEF 患者的冠状动脉血流储备（CFR）较低，微血管阻力指数（IMR）较高。微血管功能障碍的原因是什么？2013 年，提出了 HFpEF 发病机制的新范式。据推测，促炎状态的存在导致冠状动脉微血管内皮炎症和一氧化氮生物利用度降低，最终导致心力衰竭。最近，人们还注意到炎症是 HFpEF 的主要驱动因素，但通过诱导型一氧化氮合酶（iNOS）的增加导致未折叠蛋白反应减少。本文综述了目前关于 HFpEF 中冠状动脉微血管功能障碍病因的证据，重点关注炎症及其可能的预防和治疗作用。
