Publication

Abstract :

Introduction: Antiarrhythmic selection for progressive and intractable PVCs unresponsive to first and second line regimens can prove challenging. Genetic analysis assists by targeting specific genes, such as the SCN5a gene, which encodes for the alpha subunit of cardiac sodium channel NaV1.5. Mutations are associated with autosomal dominant phenotypes of multifocal ectopic Purkinje-related premature Contractions (MEPPCs).

Case: A 38 year old female with a history of syncope and moderate left ventricular systolic dysfunction status post AICD and a family history of SCD presented for follow-up with complaints of frequent palpitations. ECG and a 72 hour Holter monitor had multifocal PVCs of purkinje origin with a burden of 31%. Despite a therapeutic trial with sotalol and amiodarone in various doses, she remained unresponsive with multifocal purkinje-related PVCs. TTE revealed global LV hypokinesia with worsening LVEF, and a cardiac MRI revealed features suggestive of a dilated cardiomyopathy (DCM) phenotype. Whole exome DNA analysis showed a heterozygous missense mutation pArg814Tryp on exon 16 of the SCN5A gene. Her specific variant, R814W, is a gain-of-function variant responsible for the hyperexcitability of the Purkinje fibers, making it amenable to sodium channel blockade with flecainide. After starting gene-directed flecainide, her PVC burden drastically reduced from 31% to 3% on repeat Holter monitor after 2 months. She has remained asymptomatic with an improved LVEF.

Discussion: This is a unique case of SCN5A channelopathy with a MEPPC phenotype demonstrating a dramatic response to genotype guided management of multifocal PVCs. Clinicians should include such phenotypes in their differentials for patients that fail first and second line treatment regimens and have significant family history. It is essential to offer genetic testing to patients with a MEPPC phenotype in a DCM setting to choose the appropriate therapy and prevent SCD.