Microvascular Dysfunction across the Spectrum of Heart Failure Pathology: Pathophysiology, Clinical Features and Therapeutic Implications

Abstract

Coronary microvascular dysfunction (CMD) plays a crucial role across the spectrum of heart failure (HF) pathology, contributing to disease development, progression, and outcomes. The pathophysiological mechanisms linking CMD to HF are complex and still not completely understood and include chronic inflammation, oxidative stress, and neurohormonal activation. Despite the diagnostic and prognostic relevance in patients with HF, there is no specific therapeutic strategy targeting CMD to date. Moreover, the diagnosis of this clinical condition is challenging. In this review article, we aim to discuss the different clinical pathogenetic mechanisms linking CMD to HF across the different spectra of these diseases, their prognostic relevance, and the possible therapeutic targets along with the remaining knowledge gaps in the field.

Keywords: chronic inflammation; heart failure; microvascular dysfunction.

Figure 1

This figure illustrates the pathophysiological mechanisms linking heart failure and CMD. Created with Biorender.com. Abbreviations: CMD: coronary microvascular dysfunction.

Figure 2

This figure illustrates the pathophysiological mechanisms underlying CMD and the related interventions (pharmacological or otherwise), with the expected effects. Abbreviations: ACE: Angiotensin-converting enzyme; CFR: coronary flow reserve; CMD: coronary microvascular dysfunction; NO: nitric oxide; SGLT-2: Sodium-Glucose Transport Protein 2.