Key result
Concentrations of extracellular vesicles exposing Connexin-43 + Troponin T and Connexin-43 + Caveolin-3 were approximately five to six times higher in the coronary sinus compared to the radial artery, indicating cardiac release that correlates with heart failure severity.
Why the study?
Extracellular vesicles were investigated as potential biomarkers associated with heart failure pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by heart failure phenotype.
Do extracellular vesicle profiles differ between patients with HFpEF, HFrEF, and normal LV function undergoing CABG?
Cross-Sectional (n=81)
No
Do extracellular vesicle profiles differ between patients with HFpEF, HFrEF, and normal LV function undergoing CABG?
Absolute Event Rate: 1258% vs 251%
p-value: p=<0.001
Extracellular vesicle profiles from the coronary sinus suggest distinct patterns of myocardial injury and stress in HFrEF versus HFpEF.
Aims 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. Materials and methods Patients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function ( n = 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)]. Results 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 trans -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. Conclusion 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 trans -coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.
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Matan et al. (2022) conducted a cross-sectional in Heart Failure and Stable Coronary Artery Disease (n=81). Heart failure phenotype (HFrEF vs HFpEF vs Normal) vs. Normal left ventricular function was evaluated on Trans-coronary concentration gradients of extracellular vesicles (EVs) exposing Connexin-43 + Troponin T (Con43 + TnT) and Connexin-43 + Caveolin-3 (Con43 + Cav3) (p=<0.001). Concentrations of extracellular vesicles exposing Connexin-43 + Troponin T and Connexin-43 + Caveolin-3 were approximately five to six times higher in the coronary sinus compared to the radial artery, indicating cardiac release that correlates with heart failure severity.
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