Risk factors for recurrent syncope and subsequent fatal or near-fatal events in children and adolescents with long QT syndrome

Abstract

Objectives: We aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS).

Background: Data regarding risk assessment in LQTS after the occurrence of the first syncope episode are limited.

Methods: The Prentice-Williams-Peterson conditional gap time model was used to identify risk factors for recurrent syncope from birth through age 20 years among 1,648 patients from the International Long QT Syndrome Registry.

Results: Multivariate analysis demonstrated that corrected QT interval (QTc) duration (≥500 ms) was a significant predictor of a first syncope episode (hazard ratio: 2.16), whereas QTc effect was attenuated when the end points of the second, third, and fourth syncope episodes were evaluated (hazard ratios: 1.29, 0.99, 0.90, respectively; p < 0.001 for the null hypothesis that all 4 hazard ratios are identical). A genotype-specific subanalysis showed that during childhood (0 to 12 years), males with LQTS type 1 had the highest rate of a first syncope episode (p = 0.001) but exhibited similar rates of subsequent events as other genotype-sex subsets (p = 0.63). In contrast, in the age range of 13 to 20 years, long QT syndrome type 2 females experienced the highest rate of both first and subsequent syncope events (p < 0.001 and p = 0.01, respectively). Patients who experienced ≥1 episodes of syncope had a 6- to 12-fold (p < 0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc duration. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events.

Conclusions: Children and adolescents who present after an episode of syncope should be considered to be at a high risk of the development of subsequent syncope episodes and fatal/near-fatal events regardless of QTc duration.

Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Probability of cardiac events by QTc

Kaplan-Meier estimates of the probability of (A) a first episode of syncope (with follow-up time starting at birth); and (B) a second episode of syncope (among patients who experienced first syncope, with follow-up time starting at the time of the first syncopal event), by QTc duration (dichotomized at ≥ 500 msec).

Figure 1. Probability of cardiac events by QTc

Kaplan-Meier estimates of the probability of (A) a first episode of syncope (with follow-up time starting at birth); and (B) a second episode of syncope (among patients who experienced first syncope, with follow-up time starting at the time of the first syncopal event), by QTc duration (dichotomized at ≥ 500 msec).

Figure 2. Cumulative probability of first and second syncope by gender and genotype during childhood

Kaplan-Meier estimates of the probability of (A) first syncope; and (B) a second syncopal episode (among patients who experienced first event, with follow-up time starting at the time of the first event), in genotype-gender subsets in the age-range of 0 through 10 years.

Figure 2. Cumulative probability of first and second syncope by gender and genotype during childhood

Kaplan-Meier estimates of the probability of (A) first syncope; and (B) a second syncopal episode (among patients who experienced first event, with follow-up time starting at the time of the first event), in genotype-gender subsets in the age-range of 0 through 10 years.

Figure 3. Cumulative probability of first and second syncope by gender and genotype during adolescence

Kaplan-Meier estimates of the probability of (A) first syncope; and (B) a second syncopal episode (among patients who experienced first event, with follow-up time starting at the time of the first event), in genotype-gender subsets in the age-range of 13 through 20 years.

Figure 3. Cumulative probability of first and second syncope by gender and genotype during adolescence

Kaplan-Meier estimates of the probability of (A) first syncope; and (B) a second syncopal episode (among patients who experienced first event, with follow-up time starting at the time of the first event), in genotype-gender subsets in the age-range of 13 through 20 years.

Figure 4. 5-year cumulative probability of ACA/SCD by the number of syncope and QTc*

Kaplan-Meier estimates of the probability of ACA or SCD prior to the occurrence of a first episode of syncope, and following a 1st, 2nd, 3rd, and 4th, episodes of syncope, by QTc. *Follow-up is restarted after the occurrence of a syncopal event. ACA = aborted cardiac arrest; SCD = sudden cardiac death.