Document Detail

In Silico Cardiac Risk Assessment in Patients With Long QT Syndrome: Type 1: Clinical Predictability of Cardiac Models.
MedLine Citation:
PMID:  23153844     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVES: The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1).
BACKGROUND: Although attempts have been made to correlate mutation-specific ion channel dysfunction with patient phenotype in long QT syndrome, these have been largely unsuccessful. Systems-level computational models can be used to predict consequences of complex changes in channel function to the overall heart rhythm.
METHODS: A total of 633 LQT1-genotyped subjects with 34 mutations from multinational long QT syndrome registries were studied. Cellular electrophysiology function was determined for the mutations and introduced in a 1-dimensional transmural electrocardiography computer model. The mutation effect on transmural repolarization was determined for each mutation and related to the risk for cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) among patients.
RESULTS: Multivariate analysis showed that mutation-specific transmural repolarization prolongation (TRP) was associated with an increased risk for cardiac events (35% per 10-ms increment [p < 0.0001]; ≥upper quartile hazard ratio: 2.80 [p < 0.0001]) and life-threatening events (aborted cardiac arrest/sudden cardiac death: 27% per 10-ms increment [p = 0.03]; ≥upper quartile hazard ratio: 2.24 [p = 0.002]) independently of patients' individual QT interval corrected for heart rate (QTc). Subgroup analysis showed that among patients with mild to moderate QTc duration (<500 ms), the risk associated with TRP was maintained (36% per 10 ms [p < 0.0001]), whereas the patient's individual QTc was not associated with a significant risk increase after adjustment for TRP.
CONCLUSIONS: These findings suggest that simulated repolarization can be used to predict clinical outcomes and to improve risk stratification in patients with LQT1, with a more pronounced effect among patients with a lower-range QTc, in whom a patient's individual QTc may provide less incremental prognostic information.
Ryan Hoefen; Matthias Reumann; Ilan Goldenberg; Arthur J Moss; Jin O-Uchi; Yiping Gu; Scott McNitt; Wojciech Zareba; Christian Jons; Jorgen K Kanters; Pyotr G Platonov; Wataru Shimizu; Arthur A M Wilde; John Jeremy Rice; Coeli M Lopes
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  60     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2182-91     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Division of Cardiology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
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