Abstract Background Cardiac allograft vasculopathy (CAV) remains a major cause of long-term mortality after heart transplant. As current invasive diagnostic methods have limited sensitivity in the early stages of CAV, there is a need for reliable non-invasive biomarkers. Purpose This study aimed to identify circulating miRNAs as potential non-invasive biomarkers for the early detection of CAV. Methods RNA-sequencing technology-based discovery phase was performed in plasma samples (n=70) from transplant recipients. Then, a validation phase using quantitative reverse transcriptase polymerase chain reaction was performed in an extended patient cohort (n=103). Results In the discovery phase, we identified nine miRNAs altered in patients with CAV. The overexpression of six of them was confirmed in the validation phase. The combination of miR-223-3p, miR-23a-3p and miR-23b-3p levels with donor age was optimal for detecting low-grade CAV1 (area under the curve AUC=0.783; p0.05) and for detecting high-grade CAV2-3 (AUC=0.917; p0.001). Moreover, this model differentiated both grades of CAV (AUC=0.944; p0.01) and independently predicted the presence of CAV1 and CAV2-3 (odds ratio=41.5; p0.05 and odds ratio=45.2; p0.001, respectively). Conclusions We propose combining miR-223-3p, miR-23a-3p, and miR-23b-3p with donor age as a criterion for detecting CAV. This model can potentially improve the diagnostic sensitivity of CAV at an early stage and help discriminate between its different grades.
Torrent et al. (Fri,) studied this question.