A “Periodic Table” approach to understand the pathophysiology of heart failure with preserved ejection fraction

•There are no unifying pathophysiologic mechanism that explains HFpEF and various phenotypes.•We suggest a periodic table of pathophysiologic elements to understand the pathogenetic basis of HFpEF.•Pathophysiologic domains and hemodynamic derangements were located in X and Y axes, respectively.•We hypothesize that combinations of pathophysiologic elements lead to various HFpEF phenotypes.•Emerging evidence linking pathobiologic mechanisms with phenotypes would support the hypothesis. Heart failure with preserved ejection fraction is a complex syndrome that is characterized by symptoms and signs of heart failure without an apparent reduction in left ventricular ejection fraction. Although the main pathophysiologic pathways related to HFpEF are grossly understood, whether all or a specific number of mechanisms are related to the genesis of HFpEF for a given patient remains elusive. Moreover, it has been recently understood that HFpEF is a diverse disease with many phenotypes that have overlapping features, suggesting that a “one-way-fits-all” approach to understand the pathophysiology of this complex syndrome might not be appropriate. In this manuscript, we introduce a “periodic table” approach that incorporates both individual pathophysiologic pathways with consequent hemodynamic alterations, in which combinations of such pathophysiologic “elements” may explain the pathogenetic basis of HFpEF in each phenotype. This approach may held promise for understanding the basis of HFpEF syndrome and may contribute to the personalization of treatment approaches for each individual patient, but further evidence is needed to ascertain whether HFpEF patients have diverse pathogenetic mechanisms as suggested in the periodic table approach.