Endothelium-dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Eur J Heart Fail. 2019 Dec 15.
Endothelium-dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.
Yang JH1,2, Obokata M1, Reddy YNV1, Redfield MM1, Lerman A1, Borlaug BA1.
Author information
1 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
2 Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Abstract
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:
Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10-6 -10-4  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.
© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.
KEYWORDS:
Coronary microvascular dysfunction; Diastolic dysfunction; Heart failure with preserved ejection fraction
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