Evaluation of Circulating Exosomes as a Potential Biomarker in the Setting of Surgical Aortic Valve Replacement

Objectives: Calcific aortic valve stenosis (AS) is the most common heart valve disease in industrialized countries. Recently, increasing efforts have been devoted to investigate the role of exosomes. These nano-sized particles are secreted by different cell types and contain signaling molecules to participate in intercellular communication processes. The aim of this study was to examine the potential use of exosomes as a parameter for emerging prosthesis-patient-mismatches (PPM).

Methods: Peripheral blood from 32 patients (18 male, age 72.7 ± 8.9 years) undergoing isolated AVR (31 biological and 1 mechanical) was sampled at five defined time points (t1 = day of admission, t2 = before surgery, t3 = 24 hours post-operative [pOP], t4 = 7 days pOP, t5 = three months pOP). Exosomes were isolated by differential centrifugation with Exoquick and measured by particle tracking analysis. Additionally, echocardiographic data were collected at t1, t4 and t5.

Results: The number of exosomes decreased significantly from t1 (3.2 × 10⁷/µL) to lowest level at t3 (2.0 × 10⁷/µL; p < 0.0001) with a marked recovery thereafter to t4 (3.3 × 10⁷/µL) p < 0.0001), equalizing to initial values and remaining at this point up to t5 (3.2 × 10⁷/µL). In sub-group analysis the numbers of exosomes were tendentially lower at t4 in obese patients (BMI > 30, n = 10) compared with patients with lower BMI (p < 0.05). Considering the echocardiographic data at t1, there was a higher amount of exosomes in patients with lower mean pressure gradients (mdp) than in patients with preoperative mdp < 40 mm Hg (3.5 × 10⁷/µL vs. 2.9 × 10⁷/µL). At t4 the number of exosomes increases in patients with lower preoperative mdp (3.8 × 10⁷/µL), whereas it decreases in patients with higher mdp (2.8 × 10⁷/µL). However, at t5 both groups display comparable numbers of exosomes (3.2 × 10⁷/µL vs. 3.1 × 10⁷/µL). A total of six patients with a PPM could be detected, who show tendentially less exosomes than patients without a PPM (2.6 × 10⁷/µL vs. 3.3 × 10⁷/µL).

Conclusion: In this clinical series, a correlation between the total number of exosomes and clinical (BMI) and echocardiographic parameters (mdp) was observed after isolated conventional AVR for AS. These results suggest a possible role of exosomes as potential biomarker for diagnostics and monitoring of patients treated with AVR. Further studies, focusing on the behavior of exosomes in relation to patients with AS are necessary.