Endothelium-Dependent and Independent Coronary Microvascular Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction

BACKGROUND: Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium-dependent and independent coronary microvascular function in HFpEF. METHODS AND RESULTS: mol/L) using a Doppler flow wire with quantitative angiography. Endothelium-independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium-dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium-independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co-morbidities or other clinical characteristics. As compared to patients with normal endothelium-independent function, HFpEF patients with endothelium-independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0 ± 1.8 vs. 8.4 ± 2.9 cm/s, P = 0.002) and higher estimated filling pressures (E/e' 13.1 ± 4.1 vs. 9.6 ± 3.4, P < 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium-dependent coronary vasodilatation. Endothelium-independent microvascular dysfunction was associated with increased mortality. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium-dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co-morbidities alone. Patients with HFpEF and endothelium-independent microvascular dysfunction display worse diastolic dysfunction and outcomes.