Prevalence, spectrum, and outcomes in patients with nonpenetrant long QT syndrome

Congenital long QT syndrome (LQTS) is characterized by prolongation of the QT interval and risk of syncope/seizures, sudden cardiac arrest, and sudden cardiac death. Despite being genotype positive, some patients have nonpenetrant LQTS, defined as the absence of any objective electrocardiographic (ECG)/cardiac evidence for abnormal cardiac repolarization.

This study aimed to determine the prevalence of nonpenetrant LQTS type 1 (LQT1) and LQTS type 2 (LQT2), assess penetrance over time, and evaluate clinical management and outcomes at a single specialty center.

A retrospective review was performed on patients with LQT1 or LQT2 to identify those with "nonpenetrant LQTS," defined as asymptomatic status plus nondiagnostic heart rate-corrected QT interval at baseline ECG and absence of maladaptive exercise stress test. Demographics, ECG phenotype, symptomatic status, and therapy over at least 12 months of follow-up were abstracted for each patient.

Between July 1, 2000, and May 1, 2024, 57 of 719 asymptomatic patients (8%; 37% female; mean age at first evaluation 17 ± 15 years) with either LQT1 (37%) or LQT2 (63%) met the inclusion criteria for nonpenetrant LQTS. Mean heart rate-corrected QT interval at first evaluation was 434 ± 18 ms. Over 7 ± 6 years of follow-up, all patients remained asymptomatic; 37 (65%) remained ECG nonpenetrant. Most recently, 32 (56%) were on beta-blocker therapy and 25 (44%) were monitored with intentional nontherapy.

The estimated prevalence of nonpenetrant LQT1 and LQT2 is approximately 8%. Two-thirds of patients remained ECG nonpenetrant, and all remained phenotypically nonexpressive during follow-up. Patients with nonpenetrant LQT1 or LQT2 may be treated with an intentional nontherapy strategy devoid of drugs, denervation, or devices.