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Published on: August 8, 2022
High-Risk Cardiomyopathy Genotypes and Arrhythmic Risk: LMNA, FLNC, RBM20, PLN and Desmosomal Genes in the ESC 2023
Nardi Tetaj1,2, Andrea Segreti1,2, Aurora Ferro1,2
1Cardiology Unit, Campus Bio-Medico Hospital University, Via Alvaro del Portillo 200, 00128 Roma, Italy.
Inherited cardiomyopathies increase risk of ventricular arrhythmias and sudden cardiac death. Genotype-specific risk stratification, guided by new ESC 2023 guidelines, improves personalized prevention strategies beyond traditional measures.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Inherited cardiomyopathies are a leading cause of ventricular arrhythmias (VA) and sudden cardiac death (SCD), often without significant systolic dysfunction.
- Current risk stratification relies heavily on left ventricular ejection fraction (LVEF), which inadequately addresses the heterogeneity of non-ischemic cardiomyopathies.
- Advances in cardiac genetics and imaging reveal genotypes linked to disproportionate arrhythmic risk preceding ventricular remodeling.
Purpose of the Study:
- To review cardiomyopathy-associated genotypes with high arrhythmic risk.
- To examine molecular mechanisms, phenotypic trajectories, and arrhythmogenic profiles of these genotypes.
- To discuss genotype-informed strategies for implantable cardioverter-defibrillator (ICD) decision-making in SCD prevention.
Main Methods:
- Narrative review synthesizing genetic, imaging, and clinical evidence.
- Focus on specific high-arrhythmic-risk genotypes: LMNA, FLNC, RBM20, PLN p.Arg14del, and desmosomal genes.
- Integration of findings with the 2023 European Society of Cardiology (ESC) Guidelines on cardiomyopathies.
Main Results:
- Specific genotypes (e.g., LMNA, FLNC, RBM20, PLN p.Arg14del, desmosomal genes) are consistently linked to increased VA and SCD risk.
- Genotype-specific myocardial fibrosis, conduction disease, and VA patterns influence risk.
- The 2023 ESC Guidelines integrate etiology, substrate, and electrical phenotype for improved risk stratification.
Conclusions:
- Genotype-informed strategies represent a paradigm shift in personalized SCD prevention for inherited cardiomyopathies.
- Understanding genotype-specific arrhythmogenic profiles enhances ICD decision-making beyond LVEF.
- Further research is needed to address remaining gaps in evidence and risk prediction.
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