Inter-individual Differences in Cell Composition across the Ventricular Wall May Explain Variability in ECG Response to Serum Potassium and Calcium Variations

Non-invasive monitoring of serum potassium
$([\mathrm{K}^{+}])$
and calcium
$[\text{Ca}^{2+}]$
concentration can help to prevent arrhythmia in kidney patients. Current electrocardiogram (ECG) markers, including the T wave width
$(T_{\mathrm{w}})$
and its time-warped temporal morphological variability
$(d_{\mathrm{w}}^{\mathrm{U}})$
, correlate significantly with
$[\mathrm{K}^{+}]$
and
$[\text{Ca}^{2+}]$
but these relations vary strongly between patients. We hypothesized that inter-individual differences in cell type distribution across the ventricular wall can explain this variability. We computed
$T_{\mathrm{w}}$
and
$d_{\mathrm{w}}^{\mathrm{U}}$
in simulated ECGs from a human heart-torso model at different proportions of endo-, mid-, and epicardial cells, while varying
$[\mathrm{K}^{+}]$
(3 to 6.2 mM) and
$[\text{Ca}^{2+}]\ (1.4$
to 3.2 mM). Electrical activity was simulated with a reaction-diffusion model with modified Ten Tusscher-Panfilov dynamics. Results were compared to data from 29 patients.
$T_{\mathrm{w}}$
and
$d_{\mathrm{w}}^{\mathrm{U}}$
correlated strongly with
$[\mathrm{K}^{+}]$
(absolute median Pearson coefficient
$r=0.70$
to 0.93) and
$[\text{Ca}^{2+}] (r=0.69$
to 0.86) in simulations and in patients. Different cell type distributions reproduced inter-patient variability, with the same sign and magnitude of
$r$
. In conclusion, the inter-patient variability in the relation between serum electrolytes and their ECG markers can indeed be explained by inter-individual differences in cell type distribution across the ventricular wall.