Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging–sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, “gero-centric” approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.

运动不耐受（EI）是射血分数保留的慢性心力衰竭（HFpEF）的主要表现，是老年人中最常见的心力衰竭形式。最近认识到 HFpEF 可能是一种系统性多器官疾病，与其他常见的、难以治疗的、与衰老相关的疾病具有共同的特征，这表明通过结合衰老和心血管疾病学科的知识和概念可以获得新的见解。这项最先进的审查基于国家老龄化研究所主办的关于 HFpEF 中老龄化和 EI 的工作组会议的结果。我们讨论了 HFpEF 中 EI 的衰老相关因素和心外因素，并提供了跨学科、“以老年人为中心”的方法的基本原理，以增进我们对 HFpEF 中 EI 的理解，并确定有前途的新治疗靶点。我们还提供了一个框架，用于确定未来研究的优先顺序，包括开发统一、全面的 HFpEF 表型表征方法，阐明治疗的关键老年科学目标，以及进行概念验证试验来修改这些目标。