Endothelial Cell-Derived Extracellular Vesicles Allow to Differentiate Between Various Endotypes of INOCA: A Multicentre, Prospective, Cohort Study

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Abstract Ischemia and non-obstructive coronary artery disease (INOCA) might be due to coronary microvascular dysfunction (CMD), vasospastic angina (VSA) or both. We compared plasma concentration of various extracellular vesicles (EVs) in patients with different INOCA endotypes. Patients were divided into those with INOCA (CMD, VSA, mixed CMD + VSA) and non-anginal chest pain. Plasma concentrations of EVs were measured using flow cytometry. Out of 96 patients included, 34 had CMD (35%), 15 VSA (16%), 24 mixed endotype (25%) and 23 non-anginal chest pain (24%). Patients with INOCA had lower ratio of endothelial EVs (CD144 +) to total EVs, compared to patients with non-anginal pain (p = 0.027). Patients with mixed endotype had lower ratio of endothelial EVs (CD144 +) to total EVs, compared to CMD (p = 0.008), VSA (p = 0.014) and non-anginal pain (p < 0.001). Decreased ratio of endothelial EVs (CD144 +) to total EVs might serve as a "circulating footprint" of the mixed INOCA endotype. Graphical Abstract CCS – chronic coronary syndrome, CD – cluster of differentiation, CMD – coronary microvascular dysfunction, CFR – coronary flow reserve, EVs – extracellular vesicles, FFR – fractional flow reserve, INOCA - IMR – index of microvascular resistance, VSA – vasospastic angina

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