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AIMS: To investigate how variability in activation sequence and passive conduction properties translates into clinical variability in QRS biomarkers, and gain novel physiological knowledge on the information contained in the human QRS complex. METHODS AND RESULTS: Multiscale bidomain simulations using a detailed heart-torso human anatomical model are performed to investigate the impact of activation sequence characteristics on clinical QRS biomarkers. Activation sequences are built and validated against experimentally-derived ex vivo and in vivo human activation data. R-peak amplitude exhibits the largest variability in terms of QRS morphology, due to its simultaneous modulation by activation sequence speed, myocardial intracellular and extracellular conductivities, and propagation through the human torso. QRS width, however, is regulated by endocardial activation speed and intracellular myocardial conductivities, whereas QR intervals are only affected by the endocardial activation profile. Variability in the apico-basal location of activation sites on the anterior and posterior left ventricular wall is associated with S-wave progression in limb and precordial leads, respectively, and occasional notched QRS complexes in precordial derivations. Variability in the number of early activation sites successfully reproduces pathological abnormalities of the human conduction system in the QRS complex. CONCLUSION: Variability in activation sequence and passive conduction properties captures and explains a large part of the clinical variability observed in the human QRS complex. Our physiological insights allow for a deeper interpretation of human QRS biomarkers in terms of QRS morphology and location of early endocardial activation sites. This might be used to attain a better patient-specific knowledge of activation sequence from routine body-surface electrocardiograms.

Original publication




Journal article



Publication Date





iv4 - iv15


Activation sequence, Computer modelling and simulation, Electrocardiogram, QRS complex, Variability, Action Potentials, Body Surface Potential Mapping, Case-Control Studies, Electrocardiography, Female, Heart Block, Heart Conduction System, Heart Rate, Heart Ventricles, Humans, Male, Models, Anatomic, Models, Cardiovascular, Patient-Specific Modeling, Predictive Value of Tests, Reproducibility of Results, Signal Processing, Computer-Assisted, Time Factors, Torso, Ventricular Function, Left, Ventricular Function, Right