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(Circulation. 2001;103:1095.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Notched T Waves on Holter Recordings Enhance Detection of Patients With LQT2 (HERG) Mutations

J. M. Lupoglazoff, MD; I. Denjoy, MD; M. Berthet; N. Neyroud, PhD; L. Demay; P. Richard, PhD; B. Hainque, PhD; G. Vaksmann, MD; D. Klug, MD; A. Leenhardt, MD; G. Maillard, MD; P. Coumel, MD; P. Guicheney, PhD

From Cardiologie, Hôpital Robert Debré (J.M.L., I.D., G.M.); Cardiologie, Hôpital Lariboisière (I.D., A.L., P.C.); INSERM U523, Institut de Myologie, IFR "Coeur, Muscle et Vaisseaux" n°14, Hôpital Pitié-Salpêtrière (M.B., N.N., P.G.); and Biochimie, Hôpital Pitié-Salpêtrière (L.D., P.R., B.H.), Paris; and Cardiologie, Hôpital Cardiologique, Lille (G.V., D.K.), France.

Correspondence to J.M. Lupoglazoff, Cardiologie, Hôpital Robert Debré, 48, Boulevard Sérurier, 75019 Paris, France. E-mail jean-marc.lupoglazof{at}rdb.ap-hop-paris.fr

Background—The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T waves have been proposed as a phenotypic marker of LQTS patients.

Methods and Results—The T-wave morphology of carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P<0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4% [control], P<0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG.

Conclusions—This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations.

Key Words: long-QT syndrome • genetics • electrocardiography

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