Risk Stratification of Patients With Type 2 Long-QT Syndrome Through Analysis of T-Wave Morphology

Risk stratification in type 2 long-QT syndrome remains challenging, as QT duration may not fully reflect all underlying arrhythmic vulnerability. We assessed whether an index derived from the T-wave morphology is associated with cardiac events in a cohort with type 2 long-QT syndrome.

We retrospectively and prospectively analyzed 54 genotype-confirmed patients with type 2 long-QT syndrome. T-wave morphology in 8 independent leads was assessed using a warping-based index, the T-wave morphology variation (TMV) index, quantifying T-wave morphologic changes from a general population-based reference T-wave. Association with the first lifetime occurrence of a cardiac event, including either syncope or the combined ventricular arrhythmia end point, was tested using univariate and multivariable Cox regression models.

Using the 25th-percentile threshold (TMV≤-18.41 ms), more negative TMV values indicating greater morphologic changes and a broader or delayed repolarization phase in the T-wave signal relative to the control, as observed in lead I, were significantly associated with increased risk of cardiac event (hazard ratio [HR], 3.505 [95% CI, 1.673-7.341]; P<0.001). The association remained significant after adjustment for corrected QT (HR, 2.92 [95% CI, 1.111-7.676]; P=0.03) and after additional adjustment for sex (HR, 3.375 [95% CI, 1.256-9.067]; P=0.016), and the T-wave morphology combination score (HR, 4.061 [95% CI, 1.369-12.046]; P=0.012).

T-wave morphology abnormalities, quantified using TMV, are associated with a higher risk of cardiac events after adjustment for corrected QT prolongation, sex, and morphology combination score. TMV could complement current risk stratification strategies, although confirmatory validation in larger, independent, prospective cohorts is pending.