T-Wave Morphology Analysis in Congenital Long QT Syndrome Discriminates Patients From Healthy Individuals

Objectives: This study aims to assess the capability of T-wave analysis to: 1) identify genotype-positive long QT syndrome (LQTS) patients; 2) identify LQTS patients with borderline or normal QTc interval (≤460 ms); and 3) classify LQTS subtype.

Background: LQTS often presents with a nondiagnostic electrocardiogram (ECG). T-wave abnormalities may be the only marker of this potentially lethal arrhythmia syndrome.

Methods: ECGs taken at rest in 108 patients (43 with LQTS1, 20 with LQTS2, and 45 control subjects) were evaluated for T-wave flatness, asymmetry, and notching, which produces a morphology combination score (MCS) of the 3 features (MCS = 1.6 × flatness + asymmetry + notch) using QT Guard Plus Software (GE Healthcare, Milwaukee, Wisconsin). To assess for heterogeneity of repolarization, the principal component analysis ratio 2 (PCA-2) was calculated.

Results: Mean QTc intervals were 486 ± 50 ms (LQTS1), 479 ± 36 ms (LQTS2), and 418 ± 24 ms (control subjects) (p < 0.05). MCS and PCA-2 differed between LQTS patients and control subjects (MCS: 117.8 ± 57.4 vs. 71.9 ± 16.2; p < 0.001; PCA-2: 20.2 ± 10.4% vs. 14.6 ± 5.5%; p < 0.001), LQTS1 and LQTS2 patients (MCS: 96.3 ± 28.7 vs. 164 ± 75.2; p < 0.001; PCA-2: 17.8 ± 8.3% vs. 25 ± 12.6%; p < 0.001), and between LQTS patients with borderline or normal QTc intervals (n = 17) and control subjects (MCS: 105.7 ± 49.9 vs. 71.9 ± 16.2; p < 0.001; PCA-2: 18.1 ± 7.2% vs. 14.6 ± 5.5%; p < 0.001). T-wave metrics were consistent across multiple ECGs from individual patients based on the average intraclass correlation coefficient (MCS: 0.96; PCA-2: 0.86).

Conclusions: Automated T-wave morphology analysis accurately discriminates patients with pathogenic LQTS mutations from control subjects and between the 2 most common LQTS subtypes. Mutation carriers without baseline QTc prolongation were also identified. This may be a useful tool for screening families of LQTS patients, particularly when the QTc interval is subthreshold and genetic testing is unavailable.