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Risk stratification in the long-QT syndrome
Silvia G Priori1, Peter J Schwartz, Carlo Napolitano
1Department of Molecular Cardiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione S. Maugeri, University of Pavia, Pavia, Italy. spriori@fsm.it.
The New England Journal of Medicine
|May 9, 2003
Summary
Genetic mutations causing long-QT syndrome (LQT1, LQT2, LQT3) impact cardiac event risk. Risk stratification should consider the specific genetic locus, corrected QT interval (QTc), and sex for personalized patient care.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Long-QT syndrome (LQTS) is primarily caused by mutations in potassium-channel genes KCNQ1 (LQT1) and KCNH2 (LQT2), and the sodium-channel gene SCN5A (LQT3).
- Risk stratification for LQTS often involves clinical variables like sex and QT interval length.
- Understanding genotype-specific risks is crucial for effective management of LQTS.
Purpose of the Study:
- To stratify risk in patients with long-QT syndrome based on genotype, sex, and corrected QT interval (QTc).
- To determine the cumulative probability of cardiac events (syncope, cardiac arrest, sudden death) before age 40.
- To identify independent predictors of risk within different LQTS genotypes.
Main Methods:
- Evaluated 647 patients from 193 genotyped families with LQTS.
- Determined cumulative probability of first cardiac event by genotype (LQT1, LQT2, LQT3), sex, and QTc (<500 msec or ≥500 msec).
- Utilized multivariate analysis to identify independent predictors of risk.
Main Results:
- Incidence of first cardiac event before age 40 was lower in LQT1 (30%) compared to LQT2 (46%) and LQT3 (42%) mutations (P<0.001).
- Genetic locus and QTc were independent predictors of risk; sex was not a significant independent predictor overall.
- QTc predicted risk in LQT1 and LQT2, while sex predicted events only in LQT3 patients.
Conclusions:
- The causative mutation locus significantly influences the clinical course of long-QT syndrome.
- The effects of QTc and sex on clinical manifestations are modulated by the specific genetic locus.
- A risk stratification approach incorporating genotype, QTc, and sex is proposed for improved LQTS management.