SCN5A mutation associated with acute myocardial infarction.
Ventricular tachycardia and fibrillation (VT/VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) have both been linked to phase 2 reentry. Because of these mechanistic similarities in arrhythmogenesis, we examined the contribution of SCN5A mutations to VT/VF complicating AMI. Nineteen consecutive patients developing VF during AMI were enrolled. Wild-type (WT) and mutant SCN5A genes were co-expressed with SCN1B in TSA201 cells and studied using whole-cell patch-clamp techniques. One missense mutation (G400A) in SCN5A was detected in a conserved region among the cohort of 19 patients. A H558R polymorphism was detected on the same allele. Unlike the other 18 patients who each developed 1-2 VF episodes during acute MI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. All VT/VF episodes were associated with ST segment changes and were initiated by short-coupled extrasystoles. We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia. These findings suggest that a loss of function in SCN5A may predispose to ischemia induced arrhythmic storm. These results could be very useful for forensic implications regarding genetic screening in relatives.
Institute of Forensic Medicine, Catholic University, School of Medicine, Largo Francesco Vito 1, Rome, Italy. antonio.oliva@rm.unicatt.it
Antonio
A
Oliva
Dan
D
Hu
Sami
S
Viskin
Tabitha
T
Carrier
Jonathan M
JM
Cordeiro
Hector
H
Barajas-Martinez
Yusheng
Y
Wu
Elena
E
Burashnikov
Ramon
R
Brugada
Rafael
R
Rosso
Alexandra
A
Guerchicoff
Guido
G
Pollevick
Vincenzo L
VL
Pascali
Charlie
C
Antzelevitch
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015222:Sodium Channels / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000235:genetics*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels