Derivation and Validation of a Simple Exercise-Based Algorithm for Prediction of Genetic Testing in Relatives of LQTS Probands
Open Access
- 15 November 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 124 (20), 2187-2194
- https://doi.org/10.1161/circulationaha.111.028258
Abstract
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.This publication has 38 references indexed in Scilit:
- Risk for Life-Threatening Cardiac Events in Patients With Genotype-Confirmed Long-QT Syndrome and Normal-Range Corrected QT IntervalsJournal of the American College of Cardiology, 2011
- Challenges of Diagnosing Long QT Syndrome in Patients With Nondiagnostic Resting QTcJournal of the American College of Cardiology, 2010
- The Response of the QT Interval to the Brief Tachycardia Provoked by Standing: A Bedside Test for Diagnosing Long QT SyndromeJournal of the American College of Cardiology, 2010
- Therapeutic Strategies for Long-QT SyndromeCirculation: Arrhythmia and Electrophysiology, 2008
- Corrected QT Variability in Serial Electrocardiograms in Long QT Syndrome: The Importance of the Maximum Corrected QT for Risk StratificationJournal of the American College of Cardiology, 2006
- Burst bicycle exercise facilitates diagnosis of latent long QT syndromeAmerican Heart Journal, 2005
- Is exercise testing useful in identifying congenital long QT syndrome?The American Journal of Cardiology, 2002
- Measurement of the QT interval and the risk associated with QTc interval prolongation: A reviewThe American Journal of Cardiology, 1993
- The Spectrum of Symptoms and QT Intervals in Carriers of the Gene for the Long-QT SyndromeThe New England Journal of Medicine, 1992
- Effects of exercise on heart rate, QT, QTc and QQS2 in the Romano-Ward inherited long QT syndromeThe American Journal of Cardiology, 1991