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Day to Day Variability of the QT Interval In Patients Referred to a Long QT Syndrome Clinic: Implications for Diagnosis and Screening

Friday, October 19, 2012: 9:15 AM
Room 275-277 (Morial Convention Center)
Vwaire Orhurhu, B.A., Mayo Medical School, Mayo Clinic, Rochester, MN, Justin M. Horner, M.D., MPH, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN, Bryan C. Cannon, M.D., Department of Pediatric and Adolescent Cardiology, Mayo Clinic, Rochester, MN and Michael J. Ackerman, M.D., PhD, Department of Medicine/Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN

Purpose: The 12-lead electrocardiogram (ECG) is one of the primary diagnostic tests for long QT syndrome (LQTS).  However, the intrinsic day-to-day variability of the QTc has not been examined.  Here, we sought to determine the magnitude of this day-to-day variability and its diagnostic significance for patients with LQTS compared to patients who were genotype negative and dismissed as normal (so-called “hyper-controls”).

Methods: An IRB-approved, retrospective analysis of 200 patients (116 females, average age 21 ± 15 years) who were referred to our LQTS Clinic and who had an ECG performed on two consecutive days.  These patients either i) had genetically proven LQT1 (N = 74), LQT2 (N = 50), or LQT3 (N = 24) or ii) were dismissed as genotype negative normal (N = 52).  Blinded to their genotype, both the computer-derived and manually calculated QTc, using Bazett’s formula, were recorded. 

Results: Expectantly, the QTc was far greater among patients with LQTS (479 + 44 ms) than those patients dismissed as otherwise normal, i.e. “hyper-controls” (432 + 27 ms, p < 0.0001).  The day-to-day QTc change was 21 ± 22 ms (LQT1), 25 ± 19 ms (LQT2), 33 ± 53 ms (LQT3), and 16 ± 16 ms for those dismissed as normal (p = NS at all levels except between LQT3 vs normal with p = 0.01).  The QTc variability was not influenced by age, gender, genotype, or the time of day the ECG was obtained.  Importantly, however, 37/148 LQTS patients (25%) and 6/52 hyper-controls (11.5%, p < 0.04) had a QTc > 460 ms on one day but < 460 ms on the other day.  In addition, 5 LQTS patients (2 LQT1, 1 LQT2, and 2 LQT3) had a QTc > 480 ms on one day but < 440 ms on the other day with the greatest difference being a 16-year-old LQT1 female with a QTc of 420 ms on day 1 and 492 ms on the next day.

Conclusions: For patients referred for an evaluation for LQTS, serial ECGs on consecutive days is an inexpensive and potentially invaluable tool to catch LQTS.  As shown here, a single 12-lead ECG may be insufficient to diagnose LQTS as 25% of patients with LQTS might have been missed had their ECG been performed on the wrong day.