Current Topics of Progressive Cardiac Conduction Disease

Progressive cardiac conduction disease (PCCD) is a rare inheritable cardiac conduction system disease that may lead to complete heart block, syncope, or sudden cardiac death. The estimated incidence of PCCD is 0.0005%/year. Recent advances in genetics have revealed a wide variety of diseases associated with the development of PCCD. Ion channel genes (SCN5A, KCNK17, TRPM4, HCN4), gap junction genes (GJA5, GJC1), genes associated with myopathy (LMNA, EMD, DES, DMD, TNNI3K, DMPK, ZNF9), transcription factor genes (NKX2-5, TBX5), genes associated with metabolic disease (PRKAG2, LAMP2, GLA), and mitochondrial gene variants have all been associated with the occurrence of PCCD. Pacemaker implantation is the first-line therapy for PCCD, but implantable cardioverter defibrillator implantation should be considered in some cases. This review aims to provide a clinically relevant overview of these different forms, with emphasis on their genetic basis and phenotypic expression. We propose a practical classification distinguishing isolated and associated forms of PCCD and discuss the implications for diagnosis, risk stratification, and patient management.