Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome.

Objectives: The aim of this study was to elucidate the genetic basis for long QT syndrome (LQTS) in patients with a personal or family history of postpartum cardiac events.

Background: The postpartum period is a time of increased arrhythmogenic susceptibility in women with LQTS.

Methods: Between August 1997 and May 2003, 388 unrelated patients (260 females, average age at diagnosis, 23 years, and average QTc, 482 ms) were referred to Mayo Clinic's Sudden Death Genomics Laboratory for LQTS genetic testing. Comprehensive mutational analysis of the 5 LQTS-causing channel genes was performed. The postpartum period was defined as the 20 weeks after delivery. Cardiac events included sudden cardiac death, aborted cardiac arrest, and syncope. The presence of a personal and/or family history of cardiac events during postpartum period was determined by review of the medical records and/or phone interviews and was blinded to the status of genetic testing.

Results: Fourteen patients (3.6% of cohort) had personal (n = 4) and/or family history (n = 11) of cardiac events during the defined postpartum period. Thirteen of 14 patients (93%) possessed an LQT2 mutation and 1 had an LQT1 mutation. Postpartum cardiac events were found more commonly in patients with LQT2 (13 of 80, 16%) than in patients with LQT1 (1 of 103, <1%, P = .0001).

Conclusions: There is a relatively gene-specific molecular basis underlying cardiac events during the postpartum period in LQTS. Along with previous gene-specific associations involving swimming and LQT1 as well as auditory triggers and LQT2, this association between postpartum cardiac events and LQT2 can facilitate strategic genotyping.