Heart failure with preserved ejection fraction (HFpEF) is a major, worldwide health-care problem. Few therapies for HFpEF exist because the pathophysiology of this condition is poorly defined and, increasingly, postulated to be diverse. Although perturbations in other organs contribute to the clinical profile in HFpEF, altered cardiac structure, function or both are the primary causes of this heart failure syndrome. Therefore, studying myocardial tissue is fundamental to improve pathophysiological insights and therapeutic discovery in HFpEF. Most studies of myocardial changes in HFpEF have relied on cardiac tissue from animal models without (or with limited) confirmatory studies in human cardiac tissue. Animal models of HFpEF have evolved based on theoretical HFpEF aetiologies, but these models might not reflect the complex pathophysiology of human HFpEF. The focus of this Review is the pathophysiological insights gained from studies of human HFpEF myocardium. We outline the rationale for these studies, the challenges and opportunities in obtaining myocardial tissue from patients with HFpEF and relevant comparator groups, the analytical approaches, the pathophysiological insights gained to date and the remaining knowledge gaps. Our objective is to provide a roadmap for future studies of cardiac tissue from diverse cohorts of patients with HFpEF, coupling discovery biology with measures to account for pathophysiological diversity.

射血分数保留的心力衰竭 （HFpEF） 是一个重大的全球性医疗保健问题。HFpEF 的治疗方法很少存在，因为这种情况的病理生理学定义不明确，并且越来越多地假设是多样化的。尽管其他器官的扰动有助于 HFpEF 的临床特征，但心脏结构、功能改变或两者兼而有之是这种心力衰竭综合征的主要原因。因此，研究心肌组织对于提高 HFpEF 的病理生理学认识和治疗发现至关重要。大多数关于 HFpEF 心肌变化的研究都依赖于来自动物模型的心脏组织，而没有（或有限）对人类心脏组织进行验证研究。HFpEF 的动物模型是根据理论 HFpEF 病因学演变而来的，但这些模型可能无法反映人类 HFpEF 的复杂病理生理学。本综述的重点是从人类 HFpEF 心肌研究中获得的病理生理学见解。我们概述了这些研究的基本原理、从 HFpEF 患者和相关对照组获取心肌组织的挑战和机遇、分析方法、迄今为止获得的病理生理学见解以及仍然存在的知识差距。我们的目标是为来自不同 HFpEF 患者队列的心脏组织的未来研究提供路线图，将发现生物学与解释病理生理多样性的措施相结合。