Evaluation of Circulating Exosomes to Predict Emerging Valve Prosthesis-patient Mismatches after Surgical Aortic Valve Replacement

Objectives: In the last years, increasing efforts have been devoted to investigating the role of exosomes in cardiovascular diseases. These nano-sized particles (30–150 nm) are secreted by different cell types and contain signaling molecules that enable participation in intercellular communication processes. The aim of this study was to examine the potential use of exosomes as a parameter in patients with calcific aortic valve stenosis (AS) for emerging valve prosthesis-patient mismatches (PPM).

Methods: Patients undergoing biological aortic valve replacement with or without coronary artery bypass grafting (isolated AVR = G1, n = 78; AVR+CABG = G2, n = 57), and who fulfil further study criteria, were enrolled from 07/2015 - 08/2016. Peripheral blood was sampled at two time points (t1 = preoperative [pre-OP], t2=3 months post-operative [pOP]). Exosomes were isolated with Exoquick, diluted 2.5*10⁵ fold with ultrapure water and analyzed by particle tracking analysis (Zeta View).

Results: In both groups (135 patients in total, 80 males, 73.2 ± 6.8 years) the number of exosomes decreased (p < 0.01) with higher shear stress (mpg/LV-EF). Further, the exosome numbers decreased with higher pre-OP peak pressure gradients (p < 0.01) in G1, whereas no correlation could be detected in G2. Dividing both groups according to severity of stenosis, in patients with low pre-OP mean pressure gradients (mpg; < 30 mm Hg) the number of exosomes decreased from pre-OP to pOP (G1: 1.13*10⁹/ml versus 1.06*10⁹/ml; G2: 1.01*10⁹/ml versus 0.72*10⁹/ml), whereas in patients with high pre-OP mpg (> 50 mm Hg) exosome numbers increased (G1: 1.10*10⁹/ml versus 1.21*10⁹/ml; G2: 0.82*10⁹/ml versus 1.06*10⁹/ml). A total of 15 patients (G1: 8; G2: 7) with a PPM (EOAi < 0.85) were detected at t2. Thereby, patients with a PPM in G2 showed more exosomes at t2 than at t1 (t2/t1 < 1; p < 0.05) regardless of pre-OP mpg, whereas this trend could be observed merely for patients in G1 with high mpg (p < 0.001).

Conclusion: This clinical study observed a correlation between the number of exosomes and echocardiographic parameters in patients undergoing AVR, with distinct differences between isolated AVR and AVR combined with CABG. While the spectrum of exosomes biological actions is yet subject to intense investigations, our results suggest a possible link between emerging PPM and circulating exosome levels. Further confirmation of these results and a focused analysis of the differences between AVR and AVR+CABG are required.