Weighted Time Warping Improves T-Wave Morphology Markers Clinical Significance

Background: T-wave (TW) morphology indices based on time-warping ( <tex-math notation="LaTeX">dw</tex-math> ) have shown significant cardiovascular risk stratification value. However, errors in the location of TW boundaries may impact their prognostic power. Our aim was to test the hypothesis that a weighted time-warping function (WF) would reduce the sensitivity of <tex-math notation="LaTeX">dw</tex-math> to these errors and improve their clinical significance. Methods: The WFs were proportional to (i) the reference TW ( <tex-math notation="LaTeX">T</tex-math> ), and (ii) the absolute value of its derivative ( <tex-math notation="LaTeX">D</tex-math> ). The index <tex-math notation="LaTeX">dw</tex-math> was recalculated using these WFs, and its performance was compared to the unweighted control case ( <tex-math notation="LaTeX">C</tex-math> ) in four different scenarios: 1) robustness against simulated TW boundaries location errors; 2) ability to retain physiological information in an electrophysiological cardiac model; 3) ability to monitor blood potassium concentration changes ( <tex-math notation="LaTeX">Δ [K⁺]</tex-math> ) in 29 hemodialysis (HD) patients; 4) and the sudden cardiac death (SCD) risk stratification value of the TW morphology restitution (TMR) index, derived from <tex-math notation="LaTeX">dw</tex-math> , in 651 chronic heart failure (CHF) patients. Results and Discussion: The WFs led to a reduced sensitivity ( <tex-math notation="LaTeX">R</tex-math> ) of <tex-math notation="LaTeX">dw</tex-math> to TW boundary location errors as compared to <tex-math notation="LaTeX">C</tex-math> (median <tex-math notation="LaTeX">R</tex-math> =0.19 and 0.22 and 0.35 for <tex-math notation="LaTeX">T</tex-math> , <tex-math notation="LaTeX">D</tex-math> and <tex-math notation="LaTeX">C</tex-math> , respectively). They also preserved the physiological relationship between <tex-math notation="LaTeX">dw</tex-math> and repolarization dispersion changes at ventricular level. No improvements in <tex-math notation="LaTeX">Δ [K⁺]</tex-math> tracking were observed for the HD patients (Pearson’s median correlation [ <tex-math notation="LaTeX">r</tex-math> ] between <tex-math notation="LaTeX">Δ [K⁺]</tex-math> and <tex-math notation="LaTeX">dw</tex-math> was <tex-math notation="LaTeX">0.86≤ r ≤ 0.90</tex-math> for <tex-math notation="LaTeX">T</tex-math> , <tex-math notation="LaTeX">D</tex-math> and <tex-math notation="LaTeX">C</tex-math> ). In CHF patients, the SCD risk stratification value of TMR was improved by applying <tex-math notation="LaTeX">T</tex-math> (hazard ratio, HAR, of 2.80), followed by <tex-math notation="LaTeX">D</tex-math> (HAR=2.32) and <tex-math notation="LaTeX">C</tex-math> (HAR=2.23). Conclusions and Significance: The proposed WFs, with <tex-math notation="LaTeX">T</tex-math> showing the best performance, increased the robustness of time-warping based markers against TW location errors preserving their physiological information content and boosting their SCD risk stratification value. Results from this work support the use of <tex-math notation="LaTeX">T</tex-math> when deriving <tex-math notation="LaTeX">dw</tex-math> for future clinical applications.