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Association of Microvesicles With Graft Patency in Patients Undergoing CABG Surgery
Marina Camera1, Marta Brambilla2, Paola Canzano2
1Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy; Centro Cardiologico Monzino IRCCS, Milan, Italy.
Insights
Microvesicles (MVs) in blood can predict graft failure after coronary artery bypass grafting (CABG). A pre-operative MV signature, reflecting platelet activation, helps identify patients at high risk for graft occlusion.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Surgical Outcomes Research
Background:
- Graft patency is crucial for long-term success after coronary artery bypass grafting (CABG).
- Identifying biomarkers for graft failure can guide strategies to improve outcomes.
- The prognostic value of microvesicles (MVs) for midterm graft patency has not been previously assessed.
Purpose of the Study:
- To determine if pre-operative microvesicle (MV) signatures predict midterm graft failure in CABG patients.
- To investigate the cellular origin and procoagulant phenotype of MVs associated with graft occlusion.
- To explore the functional role of MVs in the process of graft occlusion.
Main Methods:
- A nested case-control substudy within the CAGE study involving 330 patients undergoing elective CABG.
- Coronary computed tomography angiography at 18 months post-surgery identified 24% graft occlusion.
- Flow cytometry analysis of plasma microvesicles (MVs) from 60 patients (30 occluded, 30 patent grafts) pre-surgery and at follow-up.
Main Results:
- Pre-operative plasma samples from patients with graft occlusion showed significantly higher levels of activated platelet-derived and tissue-factor positive MVs (2- and 4-fold increases, respectively).
- The procoagulant capacity of MVs was significantly greater in patients with graft occlusion.
- A microvesicle (MV) signature accurately classified graft occlusion (AUC 0.897), with an MV score >3 indicating a 16.3-fold increased odds of occlusion.
Conclusions:
- The pre-operative microvesicle (MV) signature is an independent predictor of midterm graft occlusion in CABG patients.
- A cumulative MV score effectively stratifies patients based on their risk of graft failure.
- The MV signature's correlation with platelet activation suggests potential benefits of personalized antiplatelet therapy for high-risk patients.
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.
