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 and calcium concentration ([K+] and [Ca2+]) can help to prevent arrhythmia in kidney patients. Current electrocardiogram (ECG) markers, including the width Tw and the time-warped temporal morphological variability dwu of the T wave, correlate significantly with [K+] and [Ca2+] but these relations are highly variable 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 ECGs simulated with human heart-torso models with different proportions of endocardial, midmyocardial, and epicardial cells, while varying [K+] (3-6.2mM) and [Ca2+] (1.4-3.2mM). Electrical activity was simulated with a reaction-diffusion model with modified Ten Tusscher-Panfilov dynamics. Results were compared to measurements from 29 end-stage renal disease patients undergoing hemodialysis.

Results: Tw and dwu correlated strongly with [K+] (absolute median Pearson correlation coefficient r ranging from 0.70 to 0.93) and [Ca2+] (r ranging from 0.69 to 0.86) in the simulated cases and patients. Different cell type distributions reproduced inter-patient variability, with the same sign and magnitude of r in simulations as in patients.

Conclusion: Variations in the morphology and duration of the T wave were related to [K+] and [Ca2+] variations in our models and in the patients, with the observed high inter-individual variability in patients well reproduced by variations in cell type distribution across the ventricular wall.