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.