Notched T waves on Holter recordings enhance detection of patients with LQT2 (HERG) mutations

Background-The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potas sium channels, are the most common cause of the dominant long-QT syndrome ( LQTS). In addition to QT-interval prolongation, notched T waves have been p roposed 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 Holt er ECG recordings. Averaged T-wave templates were obtained at different cyc le lengths, and potential notched T waves were classified as grade 1 (G1) i n case of a bulge at or below the horizontal, whatever the amplitude, and a s 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 co mpared with LQT2 (92%, 96%, and 19%, respectively, P<0.001). G1 notches wer e 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 analys is is superior to the 12-lead ECG in detecting GI and G2 T-wave notches. Th ese repolarization abnormalities are more indicative of LQT2 versus LQT1, w ith G2 notches being most specific and often reflecting HERG core domain mi ssense mutations.