Weighted Time Warping Improves T-Wave Morphology Markers Clinical Significance

<italic>Background:</italic> T-wave (TW) morphology indices based on time-warping (<inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula>) 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 <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula> to these errors and improve their clinical significance. <italic>Methods:</italic> The WFs were proportional to (i) the reference TW (<inline-formula><tex-math notation="LaTeX">$\mathcal {T}$</tex-math></inline-formula>), and (ii) the absolute value of its derivative (<inline-formula><tex-math notation="LaTeX">$\mathcal {D}$</tex-math></inline-formula>). The index <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula> was recalculated using these WFs, and its performance was compared to the unweighted control case (<inline-formula><tex-math notation="LaTeX">$\mathcal {C}$</tex-math></inline-formula>) 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 (<inline-formula><tex-math notation="LaTeX">$\Delta [K^+]$</tex-math></inline-formula>) in 29 hemodialysis (HD) patients; 4) and the sudden cardiac death (SCD) risk stratification value of the TW morphology restitution (TMR) index, derived from <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula>, in 651 chronic heart failure (CHF) patients. <italic>Results and Discussion:</italic> The WFs led to a reduced sensitivity (<inline-formula><tex-math notation="LaTeX">$\mathcal {R}$</tex-math></inline-formula>) of <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula> to TW boundary location errors as compared to <inline-formula><tex-math notation="LaTeX">$\mathcal {C}$</tex-math></inline-formula> (median <inline-formula><tex-math notation="LaTeX">$\mathcal {R}$</tex-math></inline-formula>=0.19 and 0.22 and 0.35 for <inline-formula><tex-math notation="LaTeX">$\mathcal {T}$</tex-math></inline-formula>, <inline-formula><tex-math notation="LaTeX">$\mathcal {D}$</tex-math></inline-formula> and <inline-formula><tex-math notation="LaTeX">$\mathcal {C}$</tex-math></inline-formula>, respectively). They also preserved the physiological relationship between <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula> and repolarization dispersion changes at ventricular level. No improvements in <inline-formula><tex-math notation="LaTeX">$\Delta [K^+]$</tex-math></inline-formula> tracking were observed for the HD patients (Pearson’s median correlation [<inline-formula><tex-math notation="LaTeX">$r$</tex-math></inline-formula>] between <inline-formula><tex-math notation="LaTeX">$\Delta [K^+]$</tex-math></inline-formula> and <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula> was <inline-formula><tex-math notation="LaTeX">$0.86\leq r \leq 0.90$</tex-math></inline-formula> for <inline-formula><tex-math notation="LaTeX">$\mathcal {T}$</tex-math></inline-formula>, <inline-formula><tex-math notation="LaTeX">$\mathcal {D}$</tex-math></inline-formula> and <inline-formula><tex-math notation="LaTeX">$\mathcal {C}$</tex-math></inline-formula>). In CHF patients, the SCD risk stratification value of TMR was improved by applying <inline-formula><tex-math notation="LaTeX">$\mathcal {T}$</tex-math></inline-formula> (hazard ratio, HAR, of 2.80), followed by <inline-formula><tex-math notation="LaTeX">$\mathcal {D}$</tex-math></inline-formula> (HAR=2.32) and <inline-formula><tex-math notation="LaTeX">$\mathcal {C}$</tex-math></inline-formula> (HAR=2.23). <italic>Conclusions and Significance:</italic> The proposed WFs, with <inline-formula><tex-math notation="LaTeX">$\mathcal {T}$</tex-math></inline-formula> 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 <inline-formula><tex-math notation="LaTeX">$\mathcal {T}$</tex-math></inline-formula> when deriving <inline-formula><tex-math notation="LaTeX">$d_{w}$</tex-math></inline-formula> for future clinical applications.