Background-Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Methods and Results-Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers.QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers).Mean age was 35Ϯ18 years, and resting corrected QT interval (QTc) was 466Ϯ39 ms. Abnormal resting QTc (females Ն480 ms; males Ն470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc Ն445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (nϭ152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTcϭ443Ϯ47 ms), sensitivity was 0.92 and specificity was 0.82. Conclusions-A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives. (Circulation. 2011;124:2187-2194.)

No abstract

Reduced repolarization reserve in LQTS is genotype and heart rate specific.

Beta-blockers have heart-rate-dependent effects on the QT and QTc intervals in LQTS. They appear to increase the QT and QTc intervals at slower heart rates and shorten them at faster heart rates during exercise.

Genetic testing in this LQTS population suggests a common KCNQ1 Leu266Pro founder effect, with the descendants clustering in our geographical region even though no common relative has been identified. The observations highlight the utility of genotypic and phenotypic correlation and a specialized clinic.

CaseA 42-year-old woman was referred for assessment of asymptomatic QT prolongation. Her resting ECG demonstrated a corrected QT interval (QTc) of 480 ms (Fig. 1). During gradual bicycle exercise testing macrovolt T-wave