Heart failure and preserved ejection fraction: pathophysiology, clinical assessment, and management of exercise intolerance

Exercise intolerance is a clinical hallmark of heart failure with preserved ejection fraction (HFpEF) that confers high morbidity and predicts mortality. The mechanisms underlying exercise intolerance in HFpEF are diverse and often include compound deficits in multi-organ reserve capacity that culminate in marked functional limitations. This review describes aetiologies of exercise intolerance in HFpEF, tools to quantify relative physiologic deficits unmasked during exercise, and insights gained from interventional trials that have aimed to augment exercise capacity in HFpEF. The domain-based phenotyping approach described highlights the value of comprehensive phenotyping of both cardiac and extra-cardiac reserve capacity to advance understanding of how to deploy individualized interventions to bolster exercise tolerance in HFpEF.