Multifocal Ectopic Purkinje-Related Premature Contractions: A New SCN5A-Related Cardiac Channelopathy

Study Questions:

What is the genetic basis of familial multifocal ectopic Purkinje-related premature contractions (MEPPCs)?

Methods:

The subjects of this study were 21 individuals in three unrelated families with MEPPC who underwent clinical evaluation and genetic testing.

Results:

There were frequent premature ventricular complexes (PVCs) that had a right and/or left bundle branch block pattern, and electrophysiological testing demonstrated that the ectopy originated in the Purkinje system. The PVCs were multifocal and often had a frequency >25,000/day. Six patients had a dilated cardiomyopathy and nine patients had paroxysmal atrial tachycardia, flutter, or fibrillation. Five family members had sudden death (SD) at ages ranging from 4 months to 62 years. Seventeen patients had periods of junctional rhythm and eight had nonsustained ventricular tachycardia. Between amiodarone, hydroquinidine, flecainide, and propafenone, hydroquinidine appeared to provide the most effective suppression of PVCs and resulted in partial or complete resolution of the cardiomyopathy. There was an autosomal pattern of inheritance and the cause was found to be a gain-of-function mutation (R222Q) of the sodium channel.

Conclusions:

MEPPC, a newly-described syndrome, is due to a sodium channel mutation that results in hyperexcitability of the Purkinje system.

Perspective:

Patients with MEPPC typically present with very frequent multifocal PVCs, atrial arrhythmias, and a cardiomyopathy that probably is secondary to the frequent ventricular ectopy rather than being a primary cardiomyopathy. Because of the multifocality of the Purkinje-related ectopy, catheter ablation is unlikely to be helpful. The results of this study suggest that quinidine is the treatment of choice. It is unclear at this point whether an implantable cardioverter-defibrillator is necessary to prevent SD in affected individuals.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Novel Agents, Statins, Acute Heart Failure, Exercise

Keywords: Quinidine, Heart Conduction System, Exercise, Electrocardiography, Genetic Testing, Sodium Channels, Tachycardia, NAV1.5 Voltage-Gated Sodium Channel, Mutation, Heart Diseases, Death, Cardiomyopathies, Heart Failure, Bundle-Branch Block, Propafenone, Cardiac Complexes, Premature, Channelopathies, Flecainide, Genetic Counseling


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