Proteomics and recurrence of atrial fibrillation: a pilot study nested in the PREDIMAR trial

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III (ISCIII): Fondo de Investigación Sanitaria y Fondo Europeo de Desarrollo Regional and Proteored Regional Government of Navarra. Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide. Although catheter ablation is the most efficacious therapy to decrease AF recurrences, relapses occur in 30% of patients in the first year after ablation. Novel biomarkers of recurrence are needed for a better prediction and management of AF. Purpose In this pilot study we aimed to analyze the baseline proteome of subjects included in a case-control study nested within the PREDIMAR, a secondary prevention trial, to find differential proteins associated with AF recurrence. Methods We selected 18 cases defined as AF recurrence and 18 controls without AF recurrence matched by age. After QC process, baseline serum proteomics data (354 proteins) from 16 cases and 17 controls were obtained. Results Ten proteins were differentially represented in cases vs controls. keratin type I cytoskeletal 17 (K17) (FC=2.14; p=0.017) and endoplasmic bifunctional protein (GDH/6PGL) (FC=1.65; p=0.032). Eight proteins were underregulated among cases vs controls: c4b-binding protein alpha chain (C4bpA) (FC=0.64; p=0.006), coagulation factor XI (FXI) (FC=0.83; p=0.011), chloride intracellular channel protein 1 (CLIC1) (FC=0.62; p=0.017), haptoglobin (FC=0.37; p=0.021), immunoglobulin heavy constant alpha 2 (Ig alpha-2 chain C region) (FC=0.49; p=0.022), c4b-binding protein beta chain (C4bpB) (FC=0.73; p=0.028), N-acetylglucosamine-1-phosphotransferase subunit gamma (GlcNAc-1-phosphotransferase subunit gamma) (FC=0.61; p=0.033) and platelet glycoprotein Ib alpha chain (GP-Ib alpha) (FC=0.84; p=0.038). In multivariate logistic models, we found that even after the adjustment for age, sex, BMI, T2D and hypertension the direct association between K17 and the inverse association between C4bpA, F11, CLIC1, IGHA2, GNPTG and GP1BA with AF recurrence maintained the statistical significance. F11, C4bpA, C4bpB and CLIC1 have been previously associated with first arrhythmia or AF. This pilot study suggests that the circulating proteome may serve as a predictor of AF recurrence after catheter ablation.