Abstract
Heart failure with preserved ejection fraction (HFpEF) 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 HFpEF was first hypothesized in an autopsy study that showed how HFpEF patients had lower microvascular density and more myocardial fibrosis than control subjects. This was later confirmed in vivo when it was noted that HFpEF 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 HFpEF disease processes. HFpEF 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 HFpEF 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 HFpEF, 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 HFpEF, focusing on the role of inflammation and its possible prevention and therapy.
Highlights
Heart failure with preserved ejection fraction (HFpEF) is one of the greatest unmet needs in modern medicine
This was later confirmed in vivo when it was noted that HFpEF is associated with reduced myocardial low reserve (MFR) at single photon emission computed tomography (SPECT) and that coronary microvascular dysfunction may play a role in HFpEF disease processes
These results suggest that inflammation causes systemic microvascular dysfunction and is consistent with the results of Zanatta et al [31], who found that patients with systemic sclerosis had lower coronary flow reserve (CFR) than controls and that CFR was correlated with abnormalities found at nailfold videocapillaroscopy
Summary
According to the latest ESC guidelines [1], Heart Failure (HF) with preserved ejection fraction (HFpEF) is defined as signs and/or symptoms of heart failure with a left ventricular ejection fraction (LVEF) ≥ 50%, elevated levels of natriuretic peptides, and relevant structural or diastolic abnormalities. The prevalence of HF in the general population is around 1-2% [2] and HFpEF is responsible for approximately 50% of HF admissions [3]. Patients with HFpEF are generally older and have a significantly higher incidence of hypertension, diabetes and obesity compared to the sum of HF patients. These characteristics are responsible for the alterations in vascular biology seen in patients with HFpEF [4]
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