Risk of death in the long QT syndrome when a sibling has died

Abstract

Background: Sudden death of a sibling is thought to be associated with greater risk of death in long QT syndrome (LQTS). However, there is no evidence of such an association.

Objective: This study sought to test the hypothesis that sudden death of a sibling is a risk factor for death or aborted cardiac arrest (ACA) in patients with LQTS.

Methods: We examined all probands and first-degree and second-degree relatives in the International Long QT Registry from birth to age 40 years with QTc >/= 0.45 s. Covariates included sibling death, QTc, gender by age, syncope, and implantable cardioverter-defibrillator (ICD) and beta-blocker treatment. End points were (1) severe events (ACA, LQTS-related death) and (2) any cardiac event (syncope, ACA, or LQTS-related death).

Results: Of 1915 subjects, 270 had a sibling who died. There were 213 severe events and 829 total cardiac events. More subjects with history of sibling death received beta-blocker therapy. Sibling death was not significantly associated with risk of ACA or LQTS-related death, but was associated with increased risk of syncope. QTc >/= 0.53 s (hazard ratio 2.5, P <.01), history of syncope (hazard ratio 6.1, P <.01), and gender were strongly associated with risk of ACA or LQTS-related death.

Conclusion: Sudden death of a sibling prompted more aggressive treatment but did not predict risk of death or ACA, whereas QTc >/= 0.53 s, gender, and syncope predicted this risk. All subjects should receive appropriate beta-blocker therapy. The decision to implant an ICD should be based on an individual's own risk characteristics (QTc, gender, and history of syncope).

Conflict of interest statement

No conflict of interest reported by the authors

Figures

Figure 1

Mantel-Byar graphs showing time-dependent cumulative probability of ACA/LQT-Death (A) and of any cardiac event (B) in the absence of versus following the death of a sibling. This analysis accrues patients over time in the sibling death group, and thus the early events, when relatively few patients are at risk, impact the trajectory of the curve somewhat disproportionately. For this type of graph, only the total number of available subjects at birth is provided, since sibling death is a time-varying risk factor.

Figure 2

A. Cumulative probability of ACA/LQT-death by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of ACA/LQT-death at each age. B. Cumulative probability of LQT-death by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of LQT-death at each age. C. Cumulative probability of any cardiac event by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of any cardiac event at each age.

Figure 2

A. Cumulative probability of ACA/LQT-death by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of ACA/LQT-death at each age. B. Cumulative probability of LQT-death by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of LQT-death at each age. C. Cumulative probability of any cardiac event by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of any cardiac event at each age.

Figure 2

A. Cumulative probability of ACA/LQT-death by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of ACA/LQT-death at each age. B. Cumulative probability of LQT-death by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of LQT-death at each age. C. Cumulative probability of any cardiac event by QTc range. The numbers below the graph represent subjects at risk in each QTc range for each age. The numbers in parentheses show the rate of any cardiac event at each age.

Figure 3

Cumulative probability of ACA/LQT-death (A) and of any cardiac event (B) by gender. The numbers below the graph represent subjects at risk in each gender category at each age. The numbers in parentheses show the rate of ACA/LQT-death (A) and of any cardiac event (B) at each age.