Unraveling the clinical conundrum of Multifocal Ectopic Premature Purkinje-related Complexes (MEPPC)

Multifocal ectopic premature Purkinje-related complexes (MEPPC) represent a particularly rare manifestation within the pleiotropic clinical spectrum of SCN5A overlap syndromes. Since its first description in 2012, only anectodical cases have been reported. Further evidence is still needed to clarify phenotypic expression and establish an evidence-based management strategy.

We aimed at investigating prevalence, genotypes, phenotypes and clinical course of MEPPC patients followed-up at our center.

We identified MEPPC patients from our cohort of carriers of a pathogenic or likely pathogenic (P/LP) SCN5A variant, followed-up at our center. We retrospectively reviewed their demographic, genetic and clinical data.

In our cohort of PLP SCN5A variant carriers, we identified 13 (50% female) MEPPC patients from 7 families, including 7 probands and 6 relatives. Table 1. Considering probands, the diagnosis was an incidental finding in the 14% and followed symptom onset in the 86%, while among relatives the diagnosis was established in the context of familial screening in the 83% (5/6) of cases. Three main missense SCN5A PLP variants were identified including p.R814W (6 patients from 4 different families), p.R222Q (4 patients from 2 different families) and p.T1179M (3 patients from the same family). The 69% (9/13) of patients developed cardiac symptoms including thoracic pain, palpitations, lipothymia, syncope or dyspnea. The mean age at first cardiac symptom was 26±12 years, with the 44% becoming symptomatic before the age of 18. The 69% (9/13) presented with high incidence polymorphic premature ventricular complexes (PVCs) from the Purkinje system, declining during effort in 44%. High incidence premature atrial complexes (PACs), atrial flutter or atrial fibrillation were similarly reported in the 62% while left ventricular (LV) dysfunction was observed in 69% (9/13). The 38% (5/13) of patients underwent ICD implantation, with evidence for appropriate treatment delivered during follow-up (FU) in the 40% (2/5). During FU, a resuscitated cardiac arrest was observed in two patients (without ICD), while a sudden cardiac death was reported in another one at the age of 37. Ablation therapy was performed in 4 (31%) patients with limited efficacy in all. Hydroquinidine was introduced with or without betablockers in 69% (9/13) with clear benefits on PVC burden and/or LV ejection fraction in all cases.

In our cohort, MEPPC penetrance was quite high, and symptom onset mainly occurred during adolescence or young adulthood. High incidence polymorphic PVCs from the Purkinje system, atrial arrhythmias and associated LV dysfunction were common features. The risk of life-threatening ventricular arrhythmias should not been underestimated, as confirmed by their occurrence in the 31% of our patients. While the benefit of ablation therapy remained questionable, Hydroquinidine seemed to represent an effective treatment option.