Coronary Microvascular Disease in Heart Failure With Preserved Systolic Function: Pathogenic Mechanisms and...

Heart failure with preserved ejection fraction accounts for approximately half of all heart failure cases globally and is associated with substantial morbidity and mortality. Coronary microvascular disease has emerged as a critical and highly prevalent comorbidity in heart failure with preserved ejection fraction, affecting up to 75% of patients in the absence of obstructive epicardial coronary artery disease. Coronary microvascular disease is characterized by impaired vasodilation or enhanced vasoconstriction of the coronary microcirculation through both endothelial-dependent and endothelial-independent mechanisms. This review synthesizes contemporary evidence on the epidemiology, pathophysiology, diagnostic approaches, prognostic implications, and therapeutic strategies for coronary microvascular disease in heart failure with preserved ejection fraction. The pathophysiological overlap between these two conditions is substantial, involving shared inflammatory pathways, oxidative stress, endothelial dysfunction, microvascular rarefaction, and mitochondrial impairment. Although a direct causal relationship remains to be definitively established, coronary microvascular disease-heart failure with preserved ejection fraction is increasingly recognized as a distinct endotype with unique therapeutic implications. Emerging evidence supports the role of lifestyle interventions, guideline-directed medical therapy, sodium-glucose cotransporter 2 inhibitors, and novel investigational approaches in targeting the microvasculature to improve outcomes in this patient population.