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OBJECTIVE: Surgery for ascending aneurysms in bicuspid aortic valve syndrome primarily includes Bentall root replacement, aortic valve replacement with supracoronary ascending aorta replacement (AVRSCAAR), and valve-sparing root reimplantation (VSRR). Comparative analysis of long-term clinical and functional outcomes of these procedures is detailed. METHODS: From 1997 to 2017, 635 patients with bicuspid aortic valve undergoing root complex-focused procedures electively were stratified by valvulopathy (ie, aortic stenosis vs aortic insufficiency) and substratified into ascending or root aneurysm phenotype. Inverse probability weights were calculated to adjust for baseline differences. RESULTS: Kaplan-Meier curves for all-cause mortality demonstrated no difference between Bentall versus AVRSCAAR for aortic stenosis and aortic insufficiency presentations (log-rank P > .05). In patients with aortic stenosis, multivariable Cox regression showed significantly decreased risk of stroke for biologic AVRSCAAR (hazard ratio, 0.04; P = .013). Aortic reoperation rates were similar for biologic versus mechanical valves (P = .353). In patients with aortic insufficiency, similar long-term mortality (hazard ratio, 0.95; P = .93), but lower stroke risk in biologic AVRSCAAR group by Cox regression, and lower aortic reoperation rate was noted (coefficient < 0.01; P < .001). Comparing Bentall to VSRR, mortality (hazard ratio, 0.12; P = .022) was significantly improved in patients undergoing VSRR, but recurrence of moderate or greater aortic insufficiency was higher in VSRR by multistate model (beta coefficient 2.63; P < .001). CONCLUSIONS: A tailored approach to heterogeneous ascending aneurysm pathologies in bicuspid aortic valve syndrome utilizing Bentall, AVRSCAAR, and VSRR procedures renders excellent long-term clinical and functional outcomes, with biologic conduits showing equivalent to improved clinical outcomes.
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BACKGROUND: There is a critical need for development of biomarkers to noninvasively monitor for lung transplant rejection. We investigated the potential of circulating donor lung-specific exosome profiles for time-sensitive diagnosis of acute rejection in a rat orthotopic lung transplant model. METHODS: Left lungs from Wistar transgenic rats expressing human CD63-GFP, an exosome marker, were transplanted into fully MHC-mismatched Lewis recipients or syngeneic controls. Recipient blood was collected between 4 h and 10 d after transplantation, and plasma was processed for exosome isolation by size exclusion column chromatography and ultracentrifugation. Circulating donor exosomes were profiled using antihuman CD63 antibody quantum dot on the nanoparticle detector and via GFP trigger on the nanoparticle flow cytometer. RESULTS: In syngeneic controls, steady-state levels of circulating donor exosomes were detected at all posttransplant time points. Allogeneic grafts lost perfusion by day 8, consistent with acute rejection. Levels of circulating donor exosomes peaked on day 1, decreased significantly by day 2, and then reached baseline levels by day 3. Notably, decrease in peripheral donor exosome levels occurred before grafts had histological evidence of acute rejection. CONCLUSIONS: Circulating donor lung-specific exosome profiles enable an early detection of acute rejection before histologic manifestation of injury to the pulmonary allograft. As acute rejection episodes are a major risk factor for the development of chronic lung allograft dysfunction, this biomarker may provide a novel noninvasive diagnostic platform that can translate into earlier therapeutic intervention for lung transplant patients.