Heart failure and microvascular dysfunction: an in-depth review of mechanisms, diagnostic strategies, and innovative therapies

Abstract

Microvascular dysfunction (MVD) is increasingly recognized as a critical contributor to the pathogenesis of heart failure (HF), particularly in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Coronary microvascular dysfunction (CMD) significantly impacts HFpEF by reducing coronary flow reserve and myocardial perfusion reserve, leading to adverse outcomes such as myocardial ischemia, diastolic dysfunction, and increased risk of major cardiovascular events, including atrial fibrillation. In HFrEF, microvascular impairment is linked to heightened oxidative stress, reduced nitric oxide production, and activation of the renin-angiotensin-aldosterone system, further driving disease progression and contributing to poor prognosis. Advancements in diagnostic techniques, such as positron emission tomography, cardiac magnetic resonance imaging, and biomarker analysis, improve our ability to assess CMD in heart failure patients, enabling earlier diagnosis and risk stratification. Emerging therapies, including sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, and endothelial-targeted interventions, enhance microvascular function and improve patient outcomes. The role of personalized medicine is becoming increasingly important, as individualized therapeutic approaches tailored to patient-specific microvascular abnormalities are essential for optimizing treatment effectiveness. This review underscores the pivotal role of MVD in HF. It highlights the urgent need for innovative therapeutic strategies and diagnostic tools to address this complex condition and improve clinical outcomes for HF patients.

Keywords: coronary flow reserve (CFR); coronary microvascular dysfunction (CMD); heart failure with preserved ejection fraction (hFpEF); heart failure with reduced ejection fraction (hFrEF); microvascular dysfunction.