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

Abstract:

Non-invasive monitoring of serum potassium ([K+]) and calcium [Ca2+] concentration can help to prevent arrhythmia in kidney patients. Current electrocardiogram (ECG) markers, including the T wave width (Tw) and its time-warped temporal morphological variability (dwU), correlate significantly with [K+] and [Ca2+] 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 Tw and dwU in simulated ECGs from a human heart-torso model at different proportions of endo-, mid-, and epicardial cells, while varying [K+] (3 to 6.2 mM) and [Ca2+] (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. Tw and dwU correlated strongly with [K+] (absolute median Pearson coefficient r=0.70 to 0.93) and [Ca2+] (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.