AUTHOR=Matan Dmitri , Mobarrez Fariborz , Löfström Ulrika , Corbascio Matthias , Ekström Mattias , Hage Camilla , Lyngå Patrik , Persson Bengt , Eriksson Maria , Linde Cecilia , Persson Hans , Wallén Håkan 

TITLE=Extracellular vesicles in heart failure – A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.952974

DOI=10.3389/fcvm.2022.952974

ISSN=2297-055X

ABSTRACT=<sec><title>Aims</title><p>Extracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype.</p></sec><sec><title>Materials and methods</title><p>Patients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; <italic>n</italic> = 19) or reduced ejection fraction (HFrEF; <italic>n</italic> = 20) were studied and compared to patients with normal left ventricular function (<italic>n</italic> = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)].</p></sec><sec><title>Results</title><p>Median concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high <italic>trans</italic>-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups.</p></sec><sec><title>Conclusion</title><p>Con43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated <italic>trans</italic>-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.</p></sec>