Unveiling the role of exercise training in targeting the inflammatory paradigm of heart failure with preserved ejection fraction: a narrative review

Heart failure with preserved ejection fraction (HFpEF) is currently lacking an effective pharmacological treatment with impact on major outcomes such as hospitalization and mortality. Exercise training (EXT) is recognized as an important nonpharmacological tool, capable of improving exercise capacity and quality of life, and has even been associated with a reduction in hospitalization and cardiovascular mortality risk. However, this positive impact largely lacks a physiological explanation. The aim of this narrative review was to provide an overview of the available data supporting the hypothesis that the beneficial role of EXT in HFpEF might be due to its effects on targeting the inflammatory paradigm described for this disease. A comprehensive literature search was conducted using the PubMed-NCBI database. We reviewed the effects of EXT throughout each step of the pathophysiological pathway leading to HFpEF and found clinical and/or preclinical evidence supporting the reduction of systemic inflammation, endothelial dysfunction, microvascular rarefaction, and myocardial stiffness. We also highlighted some gaps in the knowledge or topics that deserve further clarification in future studies. In conclusion, despite the scarcity of clinical studies in this population, there is compelling evidence suggesting that EXT modulates crucial aspects of the inflammatory pathway described for HFpEF and future investigation on cellular and molecular mechanisms are encouraged.