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Open Access Green as soon as Postprint is submitted to ZB.
Torsades de pointes following acute myocardial infarction: Evidence for a deadly link with a common genetic variant.
Heart Rhythm 9, 1104-1112 (2012)
Although QT prolongation following myocardial infarction (MI) is generally moderate, cases with marked QT prolongation leading to life-threatening torsades de pointes (TdP) have been described. OBJECTIVE: To investigate the genetic substrate of this phenomenon. METHODS: We studied 13 patients who developed TdP in the subacute phase of MI (2-11 days) and a group of 133 ethnically matched controls with uncomplicated MI. Long QT syndrome genes and the KCNH2-K897T polymorphism were screened by using denaturing high-performance liquid chromatography plus direct sequencing and a specific TaqMan assay, respectively. RESULTS: Two of the 13 patients (15%) who presented with QT prolongation and TdP were found to carry long QT syndrome mutations (KCNH2-R744X and SCN5A-E446K). Nine of the remaining 11 patients (82%) carried the KCNH2-K897T polymorphism, which was present in 35% of the controls (P = .0035). Thus, patients with an acute MI carrying the KCNH2-K897T polymorphism had an 8-fold greater risk of experiencing TdP compared with controls (95% confidence interval = 2-40). CONCLUSIONS: Our data suggest that the common K897T polymorphism is associated with an increased risk of TdP developing in the subacute phase of MI. Our findings support the concept that the electrical remodeling associated with this healing phase of MI may unmask a genetic substrate predisposing to a time-limited development of life-threatening arrhythmias. They also provide the first line of evidence in support of the hypothesis that a common polymorphism, previously described as a modifier of the severity of LQTS, may increase the risk of life-threatening arrhythmias in a much more prevalent cardiac disease such as myocardial infarction.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Long Qt Syndrome; Cardiac Arrhythmia; Sudden Cardiac Death; Molecular Genetics; Single Nucleotide Polymorphism; LONG-QT-SYNDROME; SUDDEN CARDIAC DEATH; VENTRICULAR-FIBRILLATION; INTERVAL DURATION; FAMILY-HISTORY; RISK-FACTOR; POLYMORPHISM; POPULATION; CHANNEL; NOS1AP
ISSN (print) / ISBN
1547-5271
e-ISSN
1556-3871
Journal
Heart Rhythm
Quellenangaben
Volume: 9,
Issue: 7,
Pages: 1104-1112
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Human Genetics (IHG)