Role of coronary microvascular dysfunction in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFEF) is one of the greatest unmet needs in modern medicine. The lack of an appropriate therapy may reflect the lack of an accurate comprehension of its pathophysiology. Coronary microvascular rarefaction in HFEF was first hypothesized in an autopsy study that showed how HFEF patients had lower microvascular density and more myocardial fibrosis than control subjects. This was later confirmed when it was noted that HFEF is associated with reduced myocardial flow reserve (MFR) at single photon emission computed tomography (SPECT) and that coronary microvascular dysfunction may play a role in HFEF disease processes. HFEF patients were found to have lower coronary flow reserve (CFR) and a higher index of microvascular resistance (IMR). What is the cause of microvascular dysfunction? In 2013, a new paradigm for the pathogenesis of HFEF has been proposed. It has been postulated that the presence of a proinflammatory state leads to coronary microvascular endothelial inflammation and reduced nitric oxide bioavailability, which ultimately results in heart failure. Recently, it has also been noted that inflammation is the main driver of HFEF, but via an increase in inducible nitric oxide synthase (iNOS) resulting in a decrease in unfolded protein response. This review summarizes the current evidence on the etiology of coronary microvascular dysfunction in HFEF, focusing on the role of inflammation and its possible prevention and therapy.