Abstract
Heart failure is a prevalent global health issue. Heart failure with preserved ejection fraction (HFpEF), which already represents half of all heart cases worldwide, is projected to further increase, driven by aging populations and rising cardiovascular risk factors. Effective therapies for HFpEF remain limited, particularly due to its pathophysiological heterogeneity and incomplete understanding of underlying pathomechanisms and implications. Coronary microvascular dysfunction (CMD), characterized by structural and functional changes in the coronary microcirculation, is increasingly recognized as a significant factor in HFpEF even though the exact nature of their causal relationship is still unclear. This review explores prevalence, prognostic implications, and potential therapeutic targets for CMD in HFpEF. CMD's role in HFpEF might involve impaired coronary blood flow regulation, leading to myocardial ischemia, impaired relaxation, and/or adverse remodeling. Vice versa, increased wall stress in patients with HFpEF might elevate coronary resistances, further worsening microvascular perfusion. Finally, abnormalities in substrate metabolism might cause both CMD and HFpEF. Current treatments, including pharmacotherapy and device-based therapies, show limited success, highlighting the need for more targeted approaches. New possible therapies, such as the coronary sinus reducer device, may show promise in improving myocardial perfusion and function. However, further large-scale studies are required to elucidate the mechanistic links between CMD and HFpEF and to develop specialized treatments for distinct heart failure phenotypes.