Clinical Research
Heart Rhythm Disorders
Risk for Life-Threatening Cardiac Events in Patients With Genotype-Confirmed Long-QT Syndrome and Normal-Range Corrected QT Intervals

https://doi.org/10.1016/j.jacc.2010.07.038Get rights and content
Under an Elsevier user license
open archive

Objectives

This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals.

Background

Current data regarding the outcome of patients with concealed LQTS are limited.

Methods

Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤440 ms [n = 469]), LQTS with prolonged QTc interval (>440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤440 ms [n = 1,525]).

Results

The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002).

Conclusions

Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.

Key Words

corrected QT interval
long-QT syndrome
sudden cardiac death

Abbreviations and Acronyms

ACA
aborted cardiac arrest
ECG
electrocardiographic
LQTS
long-QT syndrome
LQT1
long-QT syndrome type 1
LQT2
long-QT syndrome type 2
LQT3
long-QT syndrome type 3
QTc
corrected QT interval
SCD
sudden cardiac death

Cited by (0)

This work was supported by research grants HL-33843 and HL-51618 from the National Institutes of Health. The authors have reported that they have no relationships to disclose.