Vascular smooth muscle cell (VSMC) plasticity is implicated in extracellular matrix (ECM) turnover and arterial failure. The osteochondrocytic phenotypes of synthetic VSMCs are thought to drive glycosaminoglycan (GAG) accumulation and swelling typically seen in connective tissue disease and hypertension. A central question is whether this phenotype switching under non-homeostatic conditions is a cause or effect of those conditions. We implement a cause–effect association between ECM damage, lost cell mechanosensitivity, and cell phenotype modulation using the Constrained Mixture Model, to simulate the evolution of VSMC population over time. We modelled a cylindrical bi-layer of media and adventitia of a mouse common carotid artery and simulated remodelling in response to initially compromised ECM, concurrent with varying degrees of hypertension. In normo- and moderately hypertensive ECM disruption, physiological remodelling restores mechanical homeostasis to cells with slightly altered mechanical properties. Alternatively, severe hypertension yields complete medial degeneration. Complete loss of stored elastic energy is observed, with stiffened arteries yielding characteristically high pulse wave velocities (PWVs). Early intervention recovering hypertensive to normotensive pressure, as well as enhanced adventitial collagen turnover, are shown to prevent medial degeneration. Our model thus offers a tool to better understand the relationship between ECM damage, arterial failure, and hypertension.

Cardiac deformation is a crucial biomarker for the evaluation of cardiac function. Current methods for estimating cardiac strain might underestimate local deformation due to through-plane motion and segmental averaging. Mesh-based mapping methods are gaining interest for localized analysis of cardiac motion and strain, yet they often do not consider important properties of cardiac tissue. In this work, we propose an extension of the large deformation diffeomorphic metric mapping framework to incorporate near incompressibility into the loss function that guides the mapping. As such, our mechanically regularized mLDDMM allows for accurate and mechanically coherent estimation of volume displacement and strain tensors from time-resolved three-dimensional meshes. We benchmark our method against the results of a finite element simulation of cardiac contraction and find a very good agreement between our estimation and the simulated ground truth. Our method forms a promising technique to extract volume displacement and strain tensors from time-resolved meshes while accounting for the incompressibility of cardiac tissue.

Abstract: Sex-based differences in cardiovascular disease are well documented, yet the precise nature and extent of these discrepancies in cardiac anatomy remain incompletely understood. Traditional scaling models often fail to capture the interplay of age, blood pressure and body size, prompting a more nuanced investigation. Here we use statistical shape modelling in a healthy subset (n = 456) of the UK Biobank to explore sex-specific variations in biventricular anatomy. We reconstruct 3D meshes and perform multivariate analyses of shape coefficients, controlling for age, blood pressure and various body size metrics. Our findings reveal that sex alone explains at least 25% of morphological variability, with strong discrimination between men and women (AUC = 0.96–0.71) persisting even after correction for confounders. Notably, the most discriminative modes highlight pronounced differences in cardiac chamber volumes, the anterior–posterior width of the right ventricle and the relative positioning of the cardiac chambers. These results underscore that sex has a fundamental influence on cardiac morphology, which may have important clinical implications for differing cardiac structural assessments in men and women. Future work should investigate how these anatomical differences manifest in various cardiovascular conditions, ultimately paving the way for more precise risk stratification and personalised therapeutic strategies for both men and women. (Figure presented.). Key points: Men's and women's hearts differ significantly in overall shape and size, but an in-depth quantification of these sex differences in healthy cardiac anatomy is lacking. We used a three-dimensional statistical shape modelling approach that goes beyond standard clinical measurements to capture subtle anatomical features. Our findings show that sex alone accounts for at least 25% of the natural variation in heart structure, even after correcting for age, blood pressure and various body size metric confounders. Female hearts consistently present smaller chambers and different inter-chamber positioning compared with male hearts. Our findings highlight the importance of sex-specific anatomical insights for better diagnosis, treatment and research on heart disease.

Personalized treatment informed by computational models has the potential to markedly improve the outcome for patients with a type B aortic dissection. However, existing computational models of dissected walls significantly simplify the characteristic false lumen, tears and/or material behavior. Moreover, the patient-specific wall thickness and stiffness cannot be accurately captured non-invasively in clinical practice, which inevitably leads to assumptions in these wall models. It is important to evaluate the impact of the corresponding uncertainty on the predicted wall deformations and stress, which are both key outcome indicators for treatment optimization. Therefore, a physiology-inspired finite element framework was proposed to model the wall deformation and stress of a type B aortic dissection at diastolic and systolic pressure. Based on this framework, 300 finite element analyses, sampled with a Latin hypercube, were performed to assess the global uncertainty, introduced by 4 uncertain wall thickness and stiffness input parameters, on 4 displacement and stress output parameters. The specific impact of each input parameter was estimated using Gaussian process regression, as surrogate model of the finite element framework, and a δ moment-independent analysis. The global uncertainty analysis indicated minor differences between the uncertainty at diastolic and systolic pressure. For all output parameters, the 4^th quartile contained the major fraction of the uncertainty. The parameter-specific uncertainty analysis elucidated that the material stiffness and relative thickness of the dissected membrane were the respective main determinants of the wall deformation and stress. The uncertainty analysis provides insight into the effect of uncertain wall thickness and stiffness parameters on the predicted deformation and stress. Moreover, it emphasizes the need for probabilistic rather than deterministic predictions for clinical decision making in aortic dissections.

Left ventricular flow is intrinsically complex, three-dimensional and unsteady. Its features are susceptible to cardiovascular pathology and treatment, in particular to surgical interventions involving the valves (mitral valve replacement). To improve our understanding of intraventricular fluid mechanics and the impact of various types of prosthetic valves thereon, we have developed a custom-designed versatile left ventricular phantom with anatomically realistic moving left ventricular membrane. A biological, a tilting disc and a bileaflet valve (in two different orientations) were mounted in the mitral position and tested under the same settings. To investigate 3D flow within the phantom, a four-view tomographic particle image velocimetry setup has been implemented. The results compare side-by-side the evolution of the 3D flow topology, vortical structures and kinetic energy in the left ventricle domain during the cardiac cycle. Except for the tilting disc valve, all tested prosthetic valves induced a crossed flow path, where the outflow crosses the inflow path, passing under the mitral valve. The biological valve shows a strong jet with a peak velocity about twice as high compared to all mechanical heart valves, which makes it easier to penetrate deeply into the cavity. Accordingly, the peak kinetic energy in the left ventricle in case of the biological valve is about four times higher than the mechanical heart valves. We conclude that the tomographic particle imaging velocimetry setup provides a useful ground truth measurement of flow features and allows a comparison of the effects of different valve types on left ventricular flow patterns.