MEPPC (Multifocal Ectopic Premature Purkinje-Related Complexes)
Definition
A distinctive cardiac arrhythmia syndrome caused by SCN5A gain-of-function mutations (prototype: R222Q), characterised by a very high burden of polymorphic premature ventricular complexes (PVCs) originating from the Purkinje system. It is a pharmacologically treatable cause of reversible dilated cardiomyopathy.
Key Concepts
Genetics and Mechanism
- Caused by SCN5A R222Q gain-of-function mutation; also reported with R222P and I141V (different variants at the same or adjacent nucleotide in SCN5A). Multiple unrelated families identified worldwide. (sources/scn5a-jaccep-2018, rating: high)
- Mechanism: R222Q alters Nav1.5 gating → pathologically increased window current → premature action potentials arise during the repolarization phase of Purkinje cells → triggered PVC activity. (sources/scn5a-jaccep-2018)
- Purkinje cells are selectively vulnerable because their action potential morphology (prominent phase 4 depolarization, unique sodium channel expression) creates the conditions under which increased window current triggers automaticity. (sources/scn5a-jaccep-2018)
ECG Phenotype
- Characteristic ECG: Very high burden of narrow complex polymorphic ventricular ectopy — many PVCs per minute, varying QRS morphology, all narrow (Purkinje origin). (sources/scn5a-jaccep-2018)
- The narrow QRS distinguishes MEPPC from typical wide-complex PVCs from the myocardium. (sources/scn5a-jaccep-2018)
Cardiomyopathy
- A subset of patients develops dilated cardiomyopathy, likely via the tachycardia/arrhythmia-mediated pathway. (sources/scn5a-jaccep-2018)
- Reversible DCM: In reported cases, LV ejection fraction normalised after successful pharmacological suppression of the ectopy burden with hydroquinidine, flecainide, or amiodarone — supporting arrhythmia as the cause of DCM rather than the consequence. (sources/scn5a-jaccep-2018)
- This reversibility provides one of the clearest clinical proofs of the arrhythmia-mediated DCM hypothesis in SCN5A mutations. (sources/scn5a-jaccep-2018)
Management
- Pharmacological suppression of PVC burden: hydroquinidine, flecainide, or amiodarone — all reported to reduce PVC burden and, in DCM cases, normalise LVEF. (sources/scn5a-jaccep-2018)
- Note that flecainide use in SCN5A LOF mutations (Brugada syndrome) is contraindicated; MEPPC is a GOF mutation — direction of effect must be established before prescribing sodium channel blockers.
- Standard heart failure therapy if DCM is present.
Contradictions / Open Questions
- MEPPC vs. SCN5A-DCM — causal direction: In most SCN5A-linked DCM cases, arrhythmias may be a consequence of structural disease rather than its cause; MEPPC is one of the few situations where the arrhythmia-mediated hypothesis is clearly supported by reversibility data. Whether all MEPPC carriers with DCM have reversible cardiomyopathy is unknown. (sources/scn5a-jaccep-2018)
- Flecainide in GOF mutations: Flecainide is a provocateur of Brugada pattern (LOF) but may be therapeutic in MEPPC (GOF). This requires confirmation of mutation direction before use. (sources/scn5a-jaccep-2018)
Connections
- Related to entities/SCN5A
- Related to concepts/Ion-Channel-Mutations
- Related to concepts/PVC-Induced-Cardiomyopathy
- Related to entities/DCM
- Related to sources/scn5a-jaccep-2018