Multifocal ectopic purkinje-related premature contractions (MEPPC): clinical and genetic findings from a Swedish cohort
E Nord, J Lundstrom, E Ljungstrom, U Chaudhry, N Larsson, I Haby, A Rydberg, P G PlatonovAbstract
Background
Different genetic variants in the Sodium Voltage Gated Channel Alpha Subunit 5 (SCN5A) have previously shown to be associated with a broad range of inherited cardiac arrhythmic conditions. Multifocal Ectopic Purkinje-Related Premature Contractions (MEPPC) is a cardiac genetic disorder caused by a mutation of the SCN5A gene altering the cardiac voltage dependency of the Na+ gated channel (Nav1.5) to a gain-of-function. The gain-of-function accounts for the hyperexcitability in the cardiac purkinje cells causing premature ventricular contractions (PVCs). The high PVC-burden may trigger a PVC-induced cardiomyopathy, however potentially reversible with successful suppression of arrythmias with antiarrhythmic drugs (AADs). Due to its rarity, MEPPC remains a poorly described genetic disorder and to our knowledge no patients in Sweden have previously been described.
Purpose
The purpose of this study was to describe the clinical characteristics, management and outcomes of MEPPC patients in Sweden.
Methods
Carriers of the pathogenetic SCN5A variant (c.665G>A; p.(Arg222Gln)) with or without clinical manifestations of MEPPC syndrome were included in a prospective multicenter nationwide registry. Clinical characteristics, family history, management and outcomes were assessed.
Results
The registry recruited a total of 10 individuals (3 probands and 7 family members, 90% genetically confirmed, 80% female, median age at diagnosis 40 years, 60% with an Implantable Cardioverter Defibrillator (ICD)). All probands reported a family history of sudden cardiac death at a young age (30, 34, 50, and 51 years). Nine individuals were symptomatic, the arrhythmic phenotype consisting of frequent PVC (n=8) or both PVC and aborted cardiac arrest (n=1). One pediatric patient remained asymptomatic at the end of follow-up at age of five. Seven patients had reduced left ventricular ejection fraction, which normalized after AAD, suppressing the PVCs in six patients. During exercise tolerance test, six of seven individuals had regression of PVCs.
Conclusion
This study underscores the severity of the disease and highlights the critical importance of cardiogenetic testing. The observed benefits of antiarrhythmic therapy in symptomatic patients highlight the importance of early recognition and diagnosis of MEPPC. Our findings emphasize the need for increased awareness of MEPPC to ensure that appropriate management and treatment strategy is offered in a timely manner.Figure1_ECGTable1_Patient_Characteristics