Derivation and Validation of a Simple Exercise-Based Algorithm for Prediction of Genetic Testing in Relatives of LQTS Probands

Article

关键词: LONG-QT-SYNDROME;    T-WAVE MORPHOLOGY;    BETA-ADRENERGIC AGONISTS;    HEART-RATE;    VENTRICULAR REPOLARIZATION;    SYMPATHETIC-STIMULATION;    RISK STRATIFICATION;    STRESS TEST;    INTERVAL;    FORMS;   

DOI  :  10.1161/CIRCULATIONAHA.111.028258

来源: SCIE

【 摘 要 】

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 35 +/- 18 years, and resting corrected QT interval (QTc) was 466 +/- 39 ms. Abnormal resting QTc (females >= 480 ms; males >= 470 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 >= 445 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 (n = 152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc = 443 +/- 47 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.)

【 授权许可】

Free