MicroRNA signatures of pacing-induced dyssynchrony: a translational framework for predicting pacemaker-induced cardiomyopathy: Research Article

Ferrari Andrés Di Leoni; Lignati Bernardo Neuhaus; Leiria Tiago Luiz Luz; Dressler Laura Milena; Krug Elisa Demarchi; Grande Amanda Foerster; Marinowic Daniel Rodrigo

doi:10.58372/2835-6276.1413

Authors

Ferrari Andrés Di Leoni
Lignati Bernardo Neuhaus
Leiria Tiago Luiz Luz
Dressler Laura Milena
Krug Elisa Demarchi
Grande Amanda Foerster
Marinowic Daniel Rodrigo

DOI:

https://doi.org/10.58372/2835-6276.1413

Keywords:

Pacemaker-induced cardiomyopathy, cardiac dyssynchrony, microRNA, right ventricular pacing, ventricular remodelling

Abstract

Pacemaker-induced cardiomyopathy (PICM) is a recognized complication of chronic right ventricular pacing. It typically follows dyssynchrony-induced myocardial dysfunction – a condition characterized by aberrant electrical activation, mechanical discoordination, structural remodeling, fibrosis, and progressive ventricular failure. The significant variability in PICM incidence suggests that dyssynchrony alone does not fully determine susceptibility. This translational narrative review using a structured microRNA (miRNA) prioritization framework synthesizes current evidence on miRNA-related mechanisms potentially involved in dyssynchrony-induced cardiomyopathy, aiming to establish future biomarker and therapeutic development. Using a strategy that integrates biological annotation, human validation, and mathematical modeling, we identified candidate miRNAs associated with dilated cardiomyopathy, heart failure, cardiac dyssynchrony, and PICM. Current evidence indicates that dysregulated miRNAs may drive key pathological pathways, including fibrosis, hypertrophy, inflammation, ion channel dysfunction, and impaired calcium handling. Recurrently implicated candidates include miR-1, miR-115, miR-234, miR-186, miR-195a, miR-240, miR-7a, miR-1385, miR-21, and miR-222. These molecular signatures may explain why only a subset of chronically paced patients develop PICM despite similar pacing exposure. Distinct miRNA profiles could serve as biomarkers for risk stratification and early detection, or as potential therapeutic targets. Further multicenter prospective studies are required to validate these miRNA panels and clarify their causal contribution to disease pathogenesis.

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