Background: Long QT syndrome type 3 (LQT3) represents a rare and lethal variant of long QT syndrome (LQTS) caused by gain-of-function mutations in the SCN5A gene.
Objective: 1) To describe the clinical course of LQT3 patients; 2) To identify predictors of Life-threatening Arrhythmic Events (LAE, defined as aborted cardiac arrest, sudden cardiac death); 3) To test the efficacy of beta-blockers (BB) in preventing the occurrence of LAE in LQT3 patients.
Methods: Cohort study of consecutive LQT3 patients. The clinical course was determined with the Kaplan-Meier method. Predictors of LAE were determined with Cox multivariable analysis. Efficacy of BB was assessed by comparing the rate of LAE during matched time intervals of a median of 45 months [IQR: 15-118] in 67 patients (43% males).
Results: 171 LQT3 patients (52% males, age at first visit 28±21 years, QTc 492± 56ms) were followed up for 9±7 years: 13/171 (8%) patients suffered a first arrhythmic event at follow up (1% per year). Univariable analysis showed that history of previous ACA (p<0.0001), a QTc ≥ 500ms (p=0.002) and mutations in SCN5A transmembrane domains (p=0.03) were predictors of LAE. Multivariable analysis confirmed the history of previous aborted cardiac arrest (HR 5.73; p=0.004) and a QTc ≥ 500ms (HR 3.60; p=0.002) as independent predictors of LAE. Therapy with BB failed to reduce significantly the mean number of patients with LAE (from 6 to 4, p=0,688), the mean number of LAE per patient (from 0.13 to 0.10, p= 0.763) and the rate of LAE (from 3% to 4% events per year, p=1).
Conclusions: LQT3 patients experience a severe clinical course (ACA or sudden cardiac death incidence of 1% per year). History of ACA at presentation and QTc ≥ 500ms predict a worse outcome at follow up. Patients with SCN5A transmembrane domains may have an increased risk of LAE. Therapy with BB was not effective in reducing the occurrence of LAE in our population.