Is myocardial repolarization duration associated with repolarization heterogeneity?

BACKGROUND: Dispersion of repolarization is theorized as one mechanism by which myocardial repolarization prolongation causes lethal torsades de pointes, (TdP). Our primary purpose was to determine whether prolongation of myocardial repolarization as measured by the heart rate-corrected J-to-T peak interval (JTpkc), is associated with repolarization heterogeneity as measured by transmural dispersion, defined as the median duration from the peak to the end of the T wave (TpTe). METHODS: A retrospective cohort study was performed at a single urban tertiary ED from July 2011-September 2012. Inclusion criteria included all consecutive ED patients with ECG based on QTc and QRS intervals. Automated measurements of all intervals were performed. The association of JTpkc with the dependent variable TpTe was assessed after adjustment for QRS and RR interval durations with a multiple linear regression model. A secondary analysis included a similar adjusted assessment of the association of JTpkc with QT dispersion, QTd. Finally, we constructed two multiple regression models to assess the association of clinical causative factors of TdP with TpTe and JTpkc. RESULTS: Eight hundred seventy-four cases were included: 186 with QTc <500 ms, 118 with QTc ≥500 and QRS ≥120 ms, and 570 with QTc ≥500 and QRS <120 ms. The coefficient for association of JTpkc with TpTe was -0.10 (95%CI -0.15 to -0.05), and for JTpkc with QTd was 0.03 (95% CI -0.01 to 0.06). Clinical causative TdP factors were associated more with JTpkc than TpTe. CONCLUSION: Repolarization duration as measured by JTpkc is not positively associated with dispersion of repolarization as measured by TpTe or QTd. Dispersion of repolarization may not be a critical mechanistic link between QTc prolongation and TdP.

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.