Key result
SCN5A loss-of-function variants are linked to a 0.7% annual arrhythmic event rate.
Why the study?
The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown.
Cohort (n=615)
Symptoms at baseline, male sex, and prolonged QRS interval are key independent predictors of long-term arrhythmic risk in patients with an SCN5A loss-of-function variant.
May support symptom-, sex-, and QRS-based stratification in SCN5A carriers; leaves open prospective validation before guiding ICD decisions.
BACKGROUND: The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown. OBJECTIVE: This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events. METHODS: Probands and family members with (likely) pathogenic SCN5A loss-of-function variants were retrospectively included. Clinical and electrocardiographic data at baseline and last follow-up were collected. Patients with a history of cardiac arrest, sustained ventricular tachycardia, symptomatic or documented atrial tachy- or bradyarrhythmia, or arrhythmogenic syncope were categorized as symptomatic. Arrhythmic events at follow-up were defined as sudden death, aborted cardiac arrest, documented ventricular fibrillation, and/or sustained ventricular tachycardia. RESULTS: We included 615 patients (349 men, 242 probands, 157 with a spontaneous type 1 Brugada electrocardiogram, and 111 symptomatic at baseline). During a median follow-up of 9.5 (Q1,Q3 5.0-14.3) years, arrhythmic events occurred in 41 patients (6.7%), equating an overall event rate of 0.7%/y: 2.0%/y in symptomatic and 0.3%/y in asymptomatic patients. In the overall study population, symptoms at baseline, male sex, and QRS prolongation were identified as independent predictors of arrhythmic events. In asymptomatic patients, male sex and QRS prolongation were also identified as predictors. Asymptomatic women with QRS interval < 100 ms did not experience arrhythmic events at follow-up. CONCLUSION: Key predictors of arrhythmic risk in patients with an SCN5A loss-of-function variant, regardless of a Brugada syndrome diagnosis, are symptoms at baseline, male sex, and prolonged QRS interval. Our findings may enable more tailored management strategies in patients with an SCN5A loss-of-function variant based on their individual risk profiles.
No takes yet. Share an insight, caveat, or question.
Tuijnenburg et al. (2024) conducted a cohort in SCN5A loss-of-function variant (n=615). SCN5A loss-of-function variant was evaluated on Arrhythmic events (sudden death, aborted cardiac arrest, documented ventricular fibrillation, and/or sustained ventricular tachycardia). An SCN5A loss-of-function variant was associated with an overall arrhythmic event rate of 0.7%/year over 9.5 years, with baseline symptoms, male sex, and prolonged QRS predicting higher risk.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: