Prevalence of early-onset atrial fibrillation in congenital long QT syndrome

Abstract

Background: The prevalence of atrial fibrillation (AF) in the young (age <50 years) is 0.1%, or 1:1,000 persons. Mutations in KCNQ1-, KCNH2-, and KCNA5-encoded potassium channels and SCN5A-encoded sodium channels have been reported in familial AF. A mechanism of atrial torsade has been suggested to occur in patients with congenital long QT syndrome (LQTS).

Objective: The purpose of this study was to determine the prevalence of AF in patients with congenital LQTS.

Methods: History of documented AF was sought from two independent cohorts. One cohort consisted of 252 consecutive patients (146 females and 106 males, average age at diagnosis 23 +/- 16 years, QTc 465 +/- 51 ms) with genetically proven LQTS seen at Mayo's LQTS Clinic. The second cohort consisted of 205 consecutive patients (133 females and 72 males, average age at testing 23 +/- 16 years, QTc 479 +/- 51 ms) with a positive FAMILION genetic test (PGxHealth) for LQTS.

Results: Early-onset AF was documented in 8 (1.7%) of 457 patients, including 6 (2.4%) of 252 patients seen at Mayo and 2 (1%) of 205 patients with a positive FAMILION test. Five (2.4%) of 211 patients with LQT1-susceptibility mutations had documented AF, compared to 0 of 174 patients with LQT2, 1 of 59 patients with LQT3, 1 of 1 patient with Andersen-Tawil syndrome, and 1 of 34 patients with multiple mutations. The average age at diagnosis of AF of the six patients evaluated at Mayo was 24.3 years (range 4-46 years). Early-onset AF (age <50 years) was significantly more common in patients with LQTS compared to population-based prevalence statistics (P <.001, relative risk 17.5).

Conclusion: Compared to the background prevalence of 0.1%, early-onset AF was observed in almost 2% of patients with genetically proven LQTS and should be viewed as an uncommon but possible LQT-related dysrhythmia. Clinical complaints of palpitations warrant thorough assessment in patients with LQTS.

Figure 1

Summary of KCNQ1 (LQT1) mutations in the patient cohort. Localization of mutations identified in the KCNQ1 gene in patients with both atrial fibrillation and long QT syndrome.

Figure 2

Summary of KCNJ2 (Andersen-Tawil syndrome [ATS1]) mutations in the patient cohort. Shown is the localization of a mutation identified in the KCNJ2 gene in one patient with both atrial fibrillation and Andersen-Tawil syndrome.

Figure 3

SCN5A (LQT3) mutation found in patient 7. Shown is localization of a single mutation identified in the SCN5A gene in one patient with both atrial fibrillation and Long QT Syndrome.

Figure 4

KCNH2 and SCN5A mutations found in patient 6. Shown is localization of the mutations identified in the KCNH2 and SCN5A genes in one patient with both long QT syndrome (diagnosed at birth) and atrial fibrillation (diagnosed at age 4 years). * = uncommon polymorphism; ^ = pathogenic mutation.

Figure 5

ECG recorded from patient 6, a young boy who presented at birth with long QT syndrome and at age 4 years with atrial fibrillation.