TY - JOUR
T1 - Association of Microvesicles With Graft Patency in Patients Undergoing CABG Surgery
AU - Camera, Marina
AU - Brambilla, Marta
AU - Canzano, Paola
AU - Cavallotti, Laura
AU - Parolari, Alessandro
AU - Tedesco, Calogero C.
AU - Zara, Chiara
AU - Rossetti, Laura
AU - Tremoli, Elena
N1 - Funding Information:
This work was supported by a grant from Italian Ministry of Health (Ricerca Finalizzata 2013, PE-2013-02357476, to Prof. Camera). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/9
Y1 - 2020/6/9
N2 - Background: Graft patency is one of the major determinants of long-term outcome following coronary artery bypass graft surgery (CABG). Biomarkers, if indicative of the underlying pathophysiological mechanisms, would suggest strategies to limit graft failure. The prognostic value of microvesicles (MVs) for midterm graft patency has never been tested. Objectives: The aim of this study was to evaluate whether MV pre-operative signature (number, cellular origin, procoagulant phenotype) could predict midterm graft failure and to investigate potential functional role of MVs in graft occlusion. Methods: This was a nested case-control substudy of the CAGE (CoronAry bypass grafting: factors related to late events and Graft patency) study that enrolled 330 patients undergoing elective CABG. Of these, 179 underwent coronary computed tomography angiography 18 months post-surgery showing 24% graft occlusion. Flow cytometry MV analysis was performed in 60 patients (30 per group with occluded [cases] and patent [control subjects] grafts) on plasma samples collected the day before surgery and at follow-up. Results: Before surgery, cases had 2- and 4-fold more activated platelet-derived and tissue-factor positive MVs respectively than control subjects. The MV procoagulant capacity was also significantly greater. Altogether this MV signature properly classified graft occlusion (area under the curve 0.897 [95% confidence interval: 0.81 to 0.98]; p < 0.0001). By using an MV score (0 to 6), the odds ratio for occlusion for a score above 3 was 16.3 (95% confidence interval: 4.1 to 65.3; p < 0.0001). Conclusions: The pre-operative signature of MVs is independently associated with midterm graft occlusion in CABG patients and a cumulative MV score stratifies patients’ risk. Because the MV signature mirrors platelet activation, patients with a high MV score could benefit from a personalized antiplatelet therapy.
AB - Background: Graft patency is one of the major determinants of long-term outcome following coronary artery bypass graft surgery (CABG). Biomarkers, if indicative of the underlying pathophysiological mechanisms, would suggest strategies to limit graft failure. The prognostic value of microvesicles (MVs) for midterm graft patency has never been tested. Objectives: The aim of this study was to evaluate whether MV pre-operative signature (number, cellular origin, procoagulant phenotype) could predict midterm graft failure and to investigate potential functional role of MVs in graft occlusion. Methods: This was a nested case-control substudy of the CAGE (CoronAry bypass grafting: factors related to late events and Graft patency) study that enrolled 330 patients undergoing elective CABG. Of these, 179 underwent coronary computed tomography angiography 18 months post-surgery showing 24% graft occlusion. Flow cytometry MV analysis was performed in 60 patients (30 per group with occluded [cases] and patent [control subjects] grafts) on plasma samples collected the day before surgery and at follow-up. Results: Before surgery, cases had 2- and 4-fold more activated platelet-derived and tissue-factor positive MVs respectively than control subjects. The MV procoagulant capacity was also significantly greater. Altogether this MV signature properly classified graft occlusion (area under the curve 0.897 [95% confidence interval: 0.81 to 0.98]; p < 0.0001). By using an MV score (0 to 6), the odds ratio for occlusion for a score above 3 was 16.3 (95% confidence interval: 4.1 to 65.3; p < 0.0001). Conclusions: The pre-operative signature of MVs is independently associated with midterm graft occlusion in CABG patients and a cumulative MV score stratifies patients’ risk. Because the MV signature mirrors platelet activation, patients with a high MV score could benefit from a personalized antiplatelet therapy.
KW - circulating microvesicles
KW - coronary artery bypass graft
KW - graft occlusion
KW - platelets
KW - thrombin generation
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U2 - 10.1016/j.jacc.2020.03.073
DO - 10.1016/j.jacc.2020.03.073
M3 - Article
C2 - 32498810
AN - SCOPUS:85084977622
VL - 75
SP - 2819
EP - 2832
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 22
ER -