Risk of Cardiac Arrest in the Long-QT Syndrome
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Synopsis: In LQTS, the timing and frequency of syncope, QTc prolongation, and sex were predictive of risk for aborted cardiac arrest and sudden cardiac death during adolescence. Among patients with recent syncope, beta-blocker treatment was associated with reduced risk.
Source: Hobbs JB, et al. Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA. 2006;296:1249-1254.
The international Long QT Syndrome registry has collected information on patients with this condition for many years, and reports from the Registry have greatly expanded our knowledge of the natural history of this condition. In this report, Hobbs and colleagues describe the pattern of life-threatening arrhythmia occurrence during adolescence among participants in the Registry.
Members of the Registry who survived to age 10 were eligible for inclusion in the study, provided they met at least one of the following criteria: QTc 450 m/sec or longer; QTc from 420-450 m/sec with syncope before age 10; or QTc from 420-450 m/sec with a genetically confirmed LQTS mutation. This report deals with a final study group of 2772 participants. Genotype information was available for 722 patients in the study group. Risk factors for 2 major end points, aborted cardiac arrest or sudden cardiac death, were then analyzed from clinical variables. Descriptive information regarding these events was obtained from the patient, first degree relatives, or from autopsy examination, if performed. Stratified and unstratified multivariable Cox models allowing for time dependent co-variates were then fit to estimate the adjusted hazard ratios of each factor as a predictor of a first life-threatening cardiac event during adolescence.
The study population included 2772 individuals. Of these, 65% were female, and the group had a mean QTc of 494 m/sec. Sixteen percent had experienced syncope only before age 10. Before age 10, 10% of the patients received beta blockers, 1% pacemakers, 0.5% left cervical thoracic sympathetic ganglionectomy, and 0.4% ICDs. Genotyping was performed in 722 patients, with 380 having LQT1, 252 LQT2 and 80 LQT3 mutations. During the period between the ages of 10 and 20, 81 patients experienced an aborted cardiac arrest and 45 others manifest sudden cardiac death. The most predictive binary threshold for QT prolongation was 530 m/sec. Patients with a QTc greater than 530 m/sec were more than twice as likely to experience events compared with those with QTc less than 530 m/sec. QTc prolongation, however, both as a continuous variable and at other cut off points, was also significant. In a time-dependent analysis, syncope, beta blocker therapy, and gender were each significantly related to the risk of life-threatening events during adolescence. Males aged 10 to 12 years vs age-matched females had a hazard ratio of 4.0, but this increased risk disappeared between ages 13 and 20. Patients who had a history of syncope but were syncope free for more than 10 years, were not at increased risk. However, patients with even one episode of syncope within the prior 2 to 10 years were at increased risk, and an even higher risk was associated with multiple syncopal episodes or with syncopal episodes within the last 2 years. In both the entire population and in a high-risk subset, beta blockers reduced risk by about two-thirds. Among low-risk patients (eg, those who had not experienced recent syncope), beta blocker use was not associated with decreased risk. Of note, there was no predictive value from the geno-type pattern in this cohort.
Hobbs et al conclude that recent syncope, the duration of the QTc interval, and gender are predictors of life-threatening events in patients with long QT syndrome.
Commentary
Management of children and adolescents with long QT syndrome is often problematic. Until genetic testing becomes more widely available and reimbursed by insurance, physicians often have difficulty diagnosing the condition in asymptomatic patients with borderline QTc intervals, even if they are first-degree relatives of a confirmed case. The options for therapy in these asymptomatic individuals are also fairly limited. Restriction of dangerous activities such as competitive sports or swimming is often hard for an asymptomatic adolescent to accept. Therapy with beta blockers may not be well tolerated, and many patients are, as a result, poorly compliant with therapy. ICD therapy, although highly protective, creates problems in children in whom the incidence of lead fractures and inappropriate shocks can be quite high.
This paper from the International Long QT Syndrome Registry helps us identify high-risk and low-risk groups. In the highest risk groups, therapy with beta blockers, followed by, particularly after the child is fully grown, ICD therapy, seems justifiable. In lower risk individuals, either all therapy may be withheld or just beta blockers used until symptoms appear.
In LQTS, the timing and frequency of syncope, QTc prolongation, and sex were predictive of risk for aborted cardiac arrest and sudden cardiac death during adolescence. Among patients with recent syncope, beta-blocker treatment was associated with reduced risk.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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