T-wave Peak-to-End Changes, Quantified by Time-Warping, Surrogates Ventricular Repolarization Dispersion for...

Ventricular fibrillation (VF) during acute ischemia is linked to increased dispersion of ventricular repolarization (DOR), which is considered a robust marker of arrhythmic susceptibility. In previous works, we showed that a time-warping-based index quantifying morphological changes from the T-wave peak to the T-wave end over a PCA transform lead, $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$, outperformed the T-peak-to-T-end interval ($\mathrm{T}_{pe}$) in arrhythmic risk prediction in a closed-chest porcine infarction model. In this study, we compare $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ with the DOR measured in an open-chest porcine infarction model, to test the hypothesis that $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ is a noninvasive surrogate for DOR, investigating its predictive value for VF occurrence.

Myocardial ischemia was induced by coronary ligation in 55 domestic pigs. Surface ECG and intramyocardial electrograms were recorded simultaneously. DOR was computed as the range of the end-of-repolarization times across intramyocardial electrograms, while $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ was extracted from $\mathrm{T}_{pe}$ morphology, measured in a spatially transformed PCA lead and using a warping-based approach. Additionally, the classical $\mathrm{T}_{pe}$ interval was computed as a reference. Indices were compared between pigs developing delayed VF (Delayed-VF group) and those who did not (Non-VF group).

$d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$, DOR and $\mathrm{T}_{pe}$ remained stable at baseline but showed progressive changes during ischemia, with larger changes in animals that developed VF. At 5, 10, and 15 minutes after occlusion, ROC analysis showed significant discriminatory capacity, with AUC values consistently $\geq$0.79 for all indexes and an early predictive value with AUC of 0.870 for $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ at 5 minutes, accompanied by balanced sensitivity and specificity values. Cox regression for VF risk prediction resulted in hazard ratios ranging from 5.86 to 11.95 across time points. Kaplan-Meier survival curves stratified by ROC-derived thresholds showed significant separation between groups at all three time points. Linear regression analyses between $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ and DOR showed consistent correlation in VF-susceptible animals (median ${R^{2}=0.33}$). This association was stronger than that observed between $\mathrm{T}_{pe}$ and DOR (median ${R^{2}=0.16}$).

The time-warping-based index, $d^{{\kern0.28436pt}\rm{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$, is a reliable non-invasive surrogate of DOR, with comparable predictive value for delayed VF risk under ischemic conditions, providing earlier and more robust prediction than the $\mathrm{T}_{pe}$ index. These findings highlight their translational potential and require validation in human cohort studies.