Implantable cardioverter-defibrillators prevent death in patients with long QT syndrome

Use of implantable cardioverter-defibrillators (ICDs) results in a reduced risk of all-cause mortality, all-cause mortality before age 50 years, and sudden cardiac death in patients with long QT syndrome (LQTS), according to a study.

In addition, ICD therapy contributed to a decreased risk of long-term postindication all-cause mortality in each of the three studied subgroups: 1) patients with a history of nonfatal cardiac arrest (NFCA); 2) patients with a history of syncope while on beta-blockers; and 3) patients with a history of syncope while off beta blockers and a QTc ≥500 milliseconds.

“This study provides population-based evidence on the survival benefit of ICD therapy in patients with LQTS,” the researchers said.

A total of 3,035 patients (597 with ICD) from the Rochester LQTS Registry with a QTc ≥470 ms or confirmed LQTS mutation were included in the analysis. The researchers used multivariable Cox proportional hazards models to estimate the risk of all-cause mortality, all-cause mortality before age 50 years, and SCD as functions of time-dependent ICD therapy.

Overall, 389 patients died (137 before age 50 years; 116 experienced SCD) during 118,837 person-years of follow-up. [J Am Coll Cardiol 2021;78:2076-2088]

In the entire population, patients with ICDs had a reduced risk of death (hazard ratio [HR], 0.54, 95 percent confidence interval [CI], 0.34–0.86), death before age 50 years (HR, 0.29, 95 percent CI, 0.14–0.61), and SCD (HR, 0.22, 95 percent CI, 0.09–0.55) compared to those without ICDs.

Moreover, patients with ICDs showed a lower mortality risk among the three indication subgroups (HR, 0.14, 95 percent CI, 0.06–0.34; HR, 0.27, 95 percent CI, 0.10–0.72; and HR, 0.42, 95 percent CI, 0.19–0.96, respectively).

“Based on current practice guidelines, ICD implantation is recommended in patients with LQTS with a history of NFCA (class I indication) and should be considered in patients with a history of syncope and/or ventricular tachycardia while on beta-blockers (class IIa indication),” the researchers said. [Eur Heart J 2015;36:41:2793-2867; J Am Coll Cardiol 2018;72:14:e91-e220]

“However, given the lack of evidence from comparative effectiveness studies, these guideline recommendations were primarily based on expert opinions and risk-stratification studies,” they added. [Circulation 2008;117:2184-2191; J Am Coll Cardiol 2010;55:8:783-788; J Am Coll Cardiol 2007;49:3:329-337; Circulation 2000;101:6:616-623; J Am Coll Cardiol 2009;54:9:832-837]

Apart from the benefits of ICD, its risk of adverse events should also be considered during the clinical decision-making process of ICD implantation, which has not been well studied in the LQTS population, according to the researchers. [Heart Rhythm 2010;7:11:1616-1622; Europace 2019;21:2:339-346]

In patients enrolled in both the LQTS Registry and LQTS-ICD Registry, the risks of major ICD complications requiring lead- or generator-related surgical procedures were generally low, with a 10-year risk of 7 percent for lead fracture/dislodgement, 2 percent for infection, and 4 percent for generator dysfunction. Only six patients had recurrent major complications.

“On the other hand, a 23-percent 10-year risk of first inappropriate ICD shocks was not negligible,” the researchers said. “A further investigation of mechanisms for inappropriate ICD shocks showed that lead malfunction, T-wave oversensing, and supraventricular tachycardia were common mechanisms in our LQTS population.”

These findings were consistent with previous LQTS studies, but they were different from those of patients with heart failure. [JAMA Intern Med 2013;173:10:859-865; J Am Coll Cardiol 2008;51:14:1357-1365; N Engl J Med 2012;367:24:2275-2283; Heart Rhythm 2005;2:5:497-504]

The current study was limited by the quality of data collected during the retrospective period, which may not be as good as those collected during the prospective period; by the failure to conclude that ICD was protective for patients before they developed a higher-risk event; by the lack of power to examine the effect of ICDs in subgroups defined by genotype or other detailed genetic information; and by its observational design.