Coronary microvascular disease in heart failure with preserved ejection fraction

The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing because of an aging population and an unhealthy, sedentary lifestyle, predisposing to diabetes, obesity, dyslipidemia, hypertension, and chronic kidney disease. A substantial proportion of patients with HFpEF exhibits coronary microvascular disease (CMD), and the combination of CMD with left ventricular diastolic dysfunction is associated with worse outcomes. Distinct patient clusters within HFpEF populations are based on clinical and biomarker profiles, each with unique prognoses and comorbidity patterns. Most patients with HFpEF present with multiple comorbidities, adding to the disease's complexity. Since risk factors directly affect the coronary microvasculature—and considering the bidirectional paracrine signaling between cardiomyocytes and the microvasculature—there is significant pathophysiological overlap between HFpEF and CMD. Therefore, in this review, we aim to summarize epidemiological evidence for the overlap in patients with CMD and HFpEF, identify shared biomarkers pathophysiological pathways underlying the co-occurrence of CMD and HFpEF, and discuss how cardiometabolic interventions may simultaneously address both CMD and HFpEF. Established and emerging treatments for HFpEF and CMD target these shared mechanisms. A deeper understanding of these interrelated pathways may pave the way for novel therapeutic strategies to alleviate the burden of HFpEF and refine patient management.