Uncertainty quantification of conduction velocity in models of cardiac spread of activation.

This study quantified the effect of conduction velocity (CV) variability on cardiac electrical activation patterns, a key factor for cardiac digital twins. We examined how myocardial and endocardial longitudinal, transverse, and sheet CVs influence ventricular activation across multiple pacing sites. Three porcine biventricular heart models, each including a fast-conducting endocardial layer, were used to simulate electrical activation with an eikonal approach. Uncertainty quantification with polynomial chaos expansion systematically varied six CV parameters within physiological ranges. In total, 1,868 simulations from eight ventricular pacing sites were analyzed for activation time, variability, and global sensitivities. Myocardial longitudinal CV showed the greatest influence on activation timing (global sensitivity up to 0.98). Endocardial-layer longitudinal CV was similarly important for endocardial stimuli, while transverse and sheet CVs had minimal effects. Activation-time variability reached 15 ms, increasing with distance from the pacing origin. Longitudinal CVs, particularly myocardial and endocardial-layer, dominate ventricular activation dynamics and should be prioritized when personalizing cardiac digital twins. Accounting for CV uncertainty is essential for accurate prediction and therapy optimization.