Transmural Ventricular Heterogeneities Play a Major Role in Determining T-Wave Morphology at Different Extracellular Potassium Levels

End-stage renal disease (ESRD) affects more than 10% of the world population. ESRD patients present impaired potassium homeostasis, which increases the risk for ventricular arrhythmias and sudden cardiac death. Noninvasive estimation of serum potassium, [K], before the patient experiences serious consequences is of major importance. In this study, we investigated the relationship of [K] with three T-wave morphological descriptors: the T-wave width (Tw), slope-to-amplitude ratio (TSA) and temporal morphological variability (dw) from ECGs of 12 ESRD patients undergoing hemodialysis and from simulated ECGs. Spearman’s correlation coefficients between the descriptors Tw, TSA and dw and [K] were −0.5, 0.8 and 0.65, respectively. These associations were, however, highly patient-dependent. The high inter-individual variability in T-wave morphology, particularly observed at high [K], was reproduced in the simulations and could be explained by differences in transmural heterogeneities, with 10% variations in the proportion of midmyocardial cells leading to changes larger than 15% in T-wave morphology. In conclusion, T-wave morphological descriptors have the potential to be used as predictors of [K] in ESRD patients, but their associated inter-individual variability should be taken into account, especially under hyperkalemic conditions.