Causes of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Searching for Consensus

• We review the mechanistic basis of exercise intolerance in HFpEF from 15 exercise studies.
• We organize the pathophysiology with the use of a scheme motivated by the Fick equation.
• We examine the detailed choices that each study made regarding the diagnosis of HFpEF and how it may influence study findings.
• We suggest a taxonomy of HFpEF based on the results of exercise testing that may be useful for identifying subgroups of patients with uniform mechanisms of exercise intolerance.

Exercise intolerance is one of the cardinal symptoms of heart failure with preserved ejection fraction (HFpEF). We review its mechanistic basis using evidence from exercise studies. One barrier to a consensus understanding of the pathophysiology is heterogeneity of the patient population. Therefore, we pay special attention to varying study definitions of the disease and their possible impact on the causal factors that are implicated. We then discuss the role of exercise testing and its potential to subtype HFpEF in to more homogeneous mechanism-based subclasses.