5th International Conference on Heart and Cardiovascular Diseases

Andres Di Leoni Ferrari is a cardiologist and researcher from Brazil, affiliated with Instituto de Cardiologia. His clinical and research interests include cardiac electrophysiology, cardiac pacing, pacing-induced cardiomyopathy, ventricular dyssynchrony, and heart failure. He has contributed to scientific literature exploring the effects of artificial cardiac pacing on cardiac function and the mechanisms underlying pacing-induced cardiomyopathy. His research, titled “MicroRNAs in Pacing-Induced Dyssynchrony and Cardiomyopathy: A Translational Review Bridging Electrical, Mechanical, and Molecular Remodeling,” explores the potential role of microRNAs as molecular regulators and biomarkers of cardiac remodeling associated with pacing-induced dyssynchrony. His work highlights the importance of integrating electrophysiological, mechanical, and molecular perspectives to improve understanding of disease mechanisms and support the development of future diagnostic and therapeutic strategies for patients at risk of pacing-induced cardiomyopathy.

Background: Pacemaker-induced cardiomyopathy (PICM) is an increasingly recognized consequence of chronic right ventricular pacing. It is preceded by dyssynchrony-related myocardial dysfunction, a condition characterized by abnormal electrical activation, mechanical discoordination, adverse remodeling, fibrosis, perfusion abnormalities, and progressive ventricular dysfunction. Marked variability in PICM incidence and patient susceptibility suggests that the paced myocardium–dyssynchrony axis alone does not fully explain disease expression. This review aimed to synthesized current evidence regarding microRNA (miRNA)-related biomolecular mechanisms potentially involved in dyssynchrony-related cardiomyopathy and PICM, while proposing a translational framework for future biomarker identification and therapeutic development.

Methods: Half-narrative, half-translational review employing an original bioinformatic literature-based prioritization strategy integrating biological annotation through the GeneCards® database, validation in human studies indexed in PubMed/MEDLINE, Embase, and SciELO, and a mathematical prioritization model incorporating literature weight, disease attribution, and cross-descriptor consistency. Candidate miRNAs were mapped across descriptors including dilated cardiomyopathy, heart failure, cardiac dyssynchrony, ventricular pacing, pacemaker-related remodeling, and PICM.

Results: Dysregulated miRNAs may mediate key pathways involved in dyssynchrony-related cardiomyopathy and PICM, including fibrosis, hypertrophy, inflammation, ion-channel dysfunction, calcium-handling abnormalities, gap-junction disorganization, and arrhythmogenic remodeling. Our prioritization model implicated the following candidate miRNAs: miRNA-1, miRNA-21, miRNA-23a, miRNA-30, miRNA133a, miRNA-146a and miRNA146b, miRNA-155, miRNA-206, miRNA-210, miRNA-221/222/223, miRNA-17 and miRNA-328. These molecular signatures may explain why only a subset of chronically paced patients develop PICM despite comparable pacing exposure.

Conclusions: Distinct miRNA profiles may serve as mechanistic mediators, biomarkers for risk stratification and early detection, and potential therapeutic targets in dyssynchrony-related PICM. Additional multicenter studies are required to validate PICM-specific miRNA panels and clarify their causal contribution to disease pathogenesis.