Think SCN5A: A novel variant causing multifocal Purkinje PVCs and dilated cardiomyopathy

BACKGROUND: Multifocal ectopic Purkinje-related premature contractions (MEPPC) represent a rare SCN5A-associated channelopathy characterized by high-burden, multifocal premature ventricular contractions (PVCs) arising from the His-Purkinje system, often leading to reversible left ventricular dysfunction. CASE SUMMARY: We describe a young male with a MEPPC-like phenotype and a novel SCN5A (c.655G > A, p.Arg222Gln) variant presenting with multifocal Purkinje and papillary muscle PVCs and left ventricular systolic dysfunction. Sequential focal ablations reduced the dominant ectopic burden, while adjunctive flecainide therapy further suppressed residual Purkinje activity and improved ventricular function. CONCLUSION: In young patients with multifocal Purkinje PVCs and unexplained cardiomyopathy, consider SCN5A mutation. Combined ablation and sodium-channel blockade could be considered as a treatment option.