Weighted Time Warping Improves T-Wave Morphology Markers Clinical Significance

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