Endothelial damage as a predictive and diagnostic marker in aortic valve surgery: Automated assessment of circulating endothelial cell frequency in transcatheter aortic-valve replacement and conventional surgery

Introduction: Transcatheter aortic valve replacement (TAVR) represents a well-established treatment alternative to conventional aortic valve replacement (CAVR) for high-risk patients with aortic valve stenosis (AS). Circulating endothelial cells (CEC) in the peripheral blood represent a direct and unbiased marker for endothelial injury, thus, revealing patient specific predispositions and adverse effects resulting from the surgical treatment. Here, we used a novel, automated approach to enumerate CEC.

Methods: For this pilot study, 22 consecutive patients with severe AS were stratified for either CAVR or TAVR by heart team decision. Patient demographics, pre-OP characteristics and post-OP outcome were analyzed for both groups. The assessment of CEC frequency was performed using an isotype controlled flowcytometric approach, including automated pre-enrichment of a CD34 positive blood cell subpopulation. Measurements were performed pre-OP, 1 h and 5 d post-OP.

Results: CEC frequencies were significantly higher in the TAVI group before (9.8 ± 4.1 vs 5.5 ± 2.2, p = 0.019) as well as 1 hour after surgery (13.4 ± 5.1 vs 8.2 ± 4.1, p = 0.030) compared to CAVR. Five days post-OP CEC frequency was significantly increased in the CAVR group (39.0 ± 13.0 vs 14.3 ± 4.4, p < 0.001). There was a positive correlation between pre-OP Euroscore (9.55 ± 2.98 in TAVI group vs 5.18 ± 1.78 in SAVR group, p < 0.001) and CEC (9.811 ± 4.14 in TAVI group vs 5.53 ± 2.16 in SAVR group, p = 0.019) revealing a higher pre-OP risk in TAVI patients compared to CAVR patients. Additionally, pre-OP CEC frequency >10/ml was significantly correlated to concomitant coronary heart disease, de novo post-OP atrial fibrillation and increased post-OP creatinine levels (maximum 3.92 mg/dl), elevated blood product transfusion, prolonged ICU stay (maximum 13 days), higher rate of transitory psychotic disorder and paravalvular leaks.

Conclusion: Initial results confirm CEC as a valid marker for the determintation of pre-OP risk, invasiveness of surgical procedure and clinical outcome. However, further studies are necessary to validate practical clinical usefulness and potential superiority compared to conventional markers.