Abstract 12621: The Acquired and the Inherited Form of the LQT2 Syndrome are associated with different Abnormal T-wave Morphology
A similar mechanism is present in the congenital LQT2 patients and in individuals exposed to non-cardiac arrhythmogenic drugs associated with Ikr blockade. We investigated specific T-wave morphology changes complementary to QTc prolongation in both the acquired and the inherited forms of the hERG-related LQTS. We analyzed two retrospective datasets: ECGs from 7 drug studies consisting of healthy individuals on and off moxifloxacin (inhibition of hERG current), and ECGs from genotyped LQT2 patients and unaffected relatives. We measured T peak to T end interval, early (ERD) and late repolarization duration, repolarization complexity, T-amplitude, left (LT) and right slopes of the T-wave in addition to QT, and RR intervals. The study populations were divided equally into learning and validation sets. We used multivariable logistic regression models to predict the presence of hERG mutations and moxifloxacin while adjusting for the level of QT prolongation and the level of RR interval in LQT2 patients. The drug study data consisted of 4,874 ECGs from 411 healthy individuals (age 40±14 yrs, 267 females), while the ECGs from the congenital LQTS dataset was comprised of 213 LQT2 carriers (age 36±15 yrs, 133 females) and 177 non-carrier family members (age 40±15 yrs, 106 females). In the moxifloxacin model, increased ERD was associated with the presence of the drug (OR=1.14 per ms increase, p=0.005) after adjustment for QTc. The model for the congenital LQT2 revealed that LT was associated with the presence of the hERG mutation (OR=1.62 per 1.5 microV/10ms decrease, p=0.0002) after QTc and RR adjustment. These results were from the validation datasets. The work confirms that both drug-induced and inherited Ikr inhibitions are associated with significant changes in T-wave morphology complementary to QTc interval prolongation. The morphological abnormalities are both related to the early part of the T-wave but are different. These observations demonstrate that the phenotypic expression of hERG/KCNH2 mutations and the effect of IKr inhibitory drug on the ECG are specific. Future research should investigate if this phenomenon is linked to different level/form of loss functions of Ikr channels, and if they could result in different arrhythmogenic mechanisms.
- © 2010 by American Heart Association, Inc.