Inter-individual differences in cell composition across the ventricular wall may explain variability in ECG response to serum potassium and calcium variations

Syed Hassaan Ahmed Bukhari1, Carlos Sánchez2, Pablo Laguna3, Mark Potse4, Esther Pueyo1
1University of Zaragoza, 2Centro Universitario de la Defensa de Zaragoza, 3Zaragoza University, 4Université de Bordeaux


Background and Aim: 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.

Methods: 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.

Results: 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.

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.