Fig 1.
Cohort creation and pipeline overview.
Starting from clinical CT scans, the workflow performs multi-label segmentation and mesh generation to create simulation-ready models with assigned fibre orientations. A new dataset of 50 patients (26 controls, 24 with heart failure subtypes: narrow QRS and wide QRS) balanced by sex is processed. Resulting models are used in simulations of cardiac electrophysiology and mechanics to extract clinically relevant measurements. Heart icons in this figure were derived from a CC0 image obtained from openclipart.org (https://openclipart.org/246884) and modified to fit the figure design.
Table 1.
Summary of the 50-patient cohort demographics, grouped by sex and condition. See text for full description of the cohort and the conditions. Abbreviations: M = Male, F = Female, HF = Heart Failure, HFN=HF with Narrow QRS duration, HFW=HF with Wide QRS duration.
Fig 2.
Multi-stage segmentation process.
CemrgApp uses the deep learning model developed by [29] to segment the heart. (a) The output of the U-Net model, which identifies 10 regions, or “labels”, as described in the text. (b) The output of the intermediate stage, where the user manually splits the pulmonary veins into superior and inferior (marked by contrasting colours). (c) The final output of the post-processing stage, where the myocardium of the different structures is extracted, increasing the number of labels to 37. The final segmented images are then upsampled to an isotropic resolution of 0.1mm and smoothed.
Fig 3.
Output of the meshing process from the smooth segmentation to the final working mesh.
(a) The upsampled and smooth segmentation. (b) The mesh extracted from the segmentation using the CGAL meshing tool. It contains all the blood pool and myocardium of the different structures. (c) The final mesh after the relabelling, cleaning, smoothing, and extracting only the myocardia and valve planes. Other outputs are created from this final process, such as specific endocardial and epicardial surface meshes for the atria, which will be used later in the process.
Fig 4.
Universal Ventricular coordinates (a) are calculated from the mesh, then used to assign the fibre direction (b) using a rule-based algorithm [33]. Universal Atrial coordinates (c) are calculated from the mesh, then used to assign the fibre direction (d) using a projection from an atlas [34]. The atrial fibres, which originally are produced on surfaces, are then projected onto the 3D mesh. The fibres from the ventricles and atria are then assigned to the model (e). The final mesh is tagged with the different labels needed for the simulations (f). The fast endocardial conduction layer (FEC) is also created at this stage (f - bottom), which is a thin layer of fast conducting tissue at the endocardium of the ventricles. Finally, UVCs and UACs are used to create the sino atrial node (SAN, f.1), the left ventricle fascicles (f.2) and right ventricle fascicles (f.3).
Table 2.
Model outputs obtained from the simulations. The subscript x refers to the chamber, which can be left ventricle (LV), right ventricle (RV), left atrium (LA), or right atrium (RA).
Fig 5.
Comparison of measured ventricle volumes from the virtual cohort with clinical literature values and ranges from UKBB.
The UKBB normal ranges are defined as measurements within the 95% prediction interval of the study by [54]. Two graphs, corresponding to the LV and RV metrics and reference volumes. Each plot is separated by sex and coloured by condition, with Controls in blue and Heart Failure in orange. Normal ranges are shown as greyed areas, and exceeding the upper limit of the reference range may indicate pathological ventricular dilation. Percentages of each group within the UKBB normal range are displayed in the legend.
Fig 6.
Cohen’s d effect sizes from post-hoc comparisons following two-way ANOVA.
Metrics and group comparisons are displayed on the y-axis. This graph only shows effects with a high effect size and a corrected p-value p < 0.05. (a) Effect sizes for group comparisons performed when the Sex × Condition interaction was statistically significant, justifying 4 simple-effect post-hoc tests. (b) Effect sizes for marginal comparisons, when no significant interaction was found. Error bars line styles represent the comparison made: solid for sex, dotted for condition. Abbreviations: M = Male, F = Female; C = Control, HF = Heart Failure; TAT = Total Activation time, L/R = Left/Right, V = Ventricle.