Early Detection of Pacing-Induced Cardiomyopathy Using MicroRNA-208b-3p and MicroRNA-9: A Prospective Cohort Analysis

Background/Objectives: Pacing-induced cardiomyopathy (PiCM) is a recognized complication of chronic right ventricular pacing (RVP), characterized by left ventricular (LV) dysfunction, adverse remodeling, and progression to heart failure. MicroRNAs (miRs) regulate gene expression and play an important role in ventricular remodeling. This study aimed to observe whether dynamic changes in miRs according to a novel peripheral blood mononuclear cell (PBMC)-based approach could serve as early predictive biomarkers of PiCM. Methods: A prospective, single-center cohort study was conducted in adult patients undergoing pacemaker implantation. Clinical characteristics, echocardiographic parameters and expression levels of miR-208b-3p and miR-9 were assessed immediately and 3 months post-pacemaker implantation. PiCM was defined as a ≥10% reduction in LVEF at one year, with no alternative cause. Statistical analyses included correlation testing, ROC curve analysis, and multivariate regression to identify factors associated with PiCM. Results: Among 126 patients, 11.1% developed PiCM. Compared with the non-PiCM group, those who developed PiCM exhibited more pronounced 3-month changes in miR-208b-3p (median Δ3log miR: +1.3 vs. −0.4, p = 0.013) and miR-9 (median Δ3log miR: −1.7 vs. +0.21, p = 0.011). In multivariate analyses, Δ3LV-GLS, Δ3logmiR-208b-3p, and Δ3logmiR-9 were associated with a higher likelihood of PiCM. Among PiCM patients, Δ3logmiR-208b-3p correlated inversely with Δ3LV-GLS (r = −0.73, p = 0.016), while Δ3logmiR-9 correlated positively (r = 0.88, p < 0.001). ROC analyses demonstrated good predictive ability for Δ3LV-GLS (AUC = 0.924), Δ3log miR-208b-3p (AUC = 0.783), and Δ3log miR-9 (AUC = 0.835), with no significant differences between curves. Conclusions: Early LV-GLS deterioration and dynamic changes in expression of miR-208b-3p and miR-9 in PBMCs precede overt LV systolic dysfunction. These miRs may serve as early predictive biomarkers for PiCM.