Objectives Patients are at high risk for potentially fatal ventricular tachycardia (VT)/ventricular fibrillation (VF) when suffering from acute myocardial infarction (AMI), due to myocardial ischaemia/reperfusion injury or scar formation. Recently, it was reported that SCN5A gene mutations may also contribute to electrical storm complicating AMI. The purpose of this study was to investigate potential SCN5A mutation in patients developing VT/VF during AMI, and reveal underlying cellular electrophysiological mechanism.
Methods DNA samples of ten unrelated AMI patients with VT/VF were collected and clinical features were available in medical records. Candidate gene SCN5A was screened by direct sequencing. In expressed mutants, whole cell patch-clamp analysis was used to define the electrophysiologic properties. Current-voltage relationships, peak current, current density, voltage dependence of steady-state activation and inactivation of mutated channels were investigated.
Results A missense mutation A1427S located at the S5-S6 extracellular linker of domain III (DIII) in SCN5A gene was identified in a 56-year-old female, which was not observed in 400 healthy control chromosomes of the same ethnic background. In addition, we identified three previously reported SNPs in our subjects, including A29A, H558R and D1818D. Electrophysiological analysis showed obvious reduction of sodium current in A1427S mutant without the shape change of I-V curve. Retrospective analysis of the A1427S carrier’s medical records indicated that lidocaine infusion exacerbated episodes of VT/VF inversely and she finally died of refractory VT/VF complicating AMI.
Conclusions We identified a novel SCN5A mutation A1427S that resulted in refractory VT/VF complicating AMI. Loss-of-function of the sodium channel indicates cautiously use of prophylactic lidocaine. Genetic screening could ideally identify the patients at high risk and aid in guiding the optimal therapy.
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