MEPPC Syndrome: A Systematic Review and State-of-the-Art Paper

Multifocal ectopic Purkinje-related premature contractions syndrome presents as a rare cardiac disorder characterized by frequent multifocal ectopic ventricular beats with narrow QRS complexes, originating from various ectopic foci along the fascicular-Purkinje system. It is characterized by mutations in the SCN5A gene, inducing a gain-of-function in the human cardiac voltage-gated Na+ channel (Nav1.5), which causes an alteration in the action potentials of the cardiomyocytes. The syndrome was initially delineated in 2012 by Laurent et al in 3 Dutch families, subsequently garnering recognition through several reported cases worldwide. Clinically, it often manifests with a familial predisposition to other arrhythmogenic cardiac diseases, alongside symptoms such as palpitations and syncope. A key diagnostic hallmark is the high daily burden of multifocal premature ventricular contractions observed on 24-hour dynamic ECG, with evidence of repetitive ventricular arrhythmias. This can potentially induce a reversible form of left ventricular dilation with systolic dysfunction, known as premature ventricular contraction-induced cardiomyopathy. Diagnosis may be challenging, requiring exclusion of the most frequent causes of ventricular arrhythmias first. The disappearance of arrhythmias during a stress test and the inefficacy of catheter ablation procedures may serve as additional elements to bolster the suspicion of multifocal ectopic Purkinje-related premature contractions syndrome. Genetic testing and electrophysiological studies are pivotal in confirming the diagnosis. Therapeutic management of this syndrome primarily involves medical therapy with class I antiarrhythmic drugs, such as flecainide and quinidine, which may reduce ventricular arrhythmias and associated symptoms. In this systematic review, our aim was to provide an exhaustive insight into the genetic basis, diagnosis, and treatment strategies for this intriguing yet relatively underexplored syndrome.