The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a vestige of embryonic development. 1,2 The function of these trabeculae in adults and their genetic architecture are unknown. To investigate this we performed a genome-wide association study using fractal analysis of trabecular morphology as an image-derived phenotype in 18,096 UK Biobank participants. We identified 16 significant loci containing genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborisation. 3,4 Using biomechanical simulations and human observational data, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomisation, we find a causal relationship between trabecular morphology and cardiovascular disease risk. These findings suggest an unexpected role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity, and reveal their influence on susceptibility to disease. MainThe chambers of the mature human heart have a complex inner surface whose function is unknown. Unlike the smooth endothelium of the great vessels, the endocardial surfaces of both ventricles are lined by a fenestrated network of muscular trabeculae which extend into the cavity. Their embryological development is driven by highly-conserved signalling pathways involving the endocardium-myocardium and extra-cellular matrix that regulate myocardial proliferation during cardiac morphogenesis. 2,[5][6][7][8][9] 1 Cell lineage tracing suggests that trabeculae have a molecular and developmental identity which is distinct from the compact myocardium. 10 The high surface area of trabeculae enables nutrient and oxygen diffusion from blood pool to myocardium before the coronary circulation is established. 1 Trabeculae are also vital to formation of the conduction system. 11 Theoretical analyses have proposed that their complex structure may contribute to efficient intra-ventricular flow patterns. 12-14 While hypertrabeculation is observed as a feature of some genetically-characterised cardiomyopathies, 15 the physiological function of trabeculae in adult hearts, their genetic architecture, and potential role in common disease have not been determined.The distinguishing trait of trabeculae is their branching morphology and the degree of such biological complexity in the heart can be quantified by fractal dimension (FD) analysis of cardiac magnetic resonance (CMR) imaging. 8 In a replicated genomewide association study (GWAS), using FD as an image-derived phenotype, we identify loci linked with trabecular morphology. Knockout models of loci-associated genes showed a marked decrease in trabecular complexity. Using biomechanical modelling and human observational data, we find a causal relationship between myocardial trabeculation and ventricular performance, with Mendelian randomisation showing that reduced trabecula...

Bio-inspired polymeric heart valves (PHVs) are excellent candidates to mimic the structural and the fluid dynamic features of the native valve. PHVs can be implanted as prosthetic alternative to currently clinically used mechanical and biological valves or as potential candidate for a minimally invasive treatment, like the transcatheter aortic valve implantation. Nevertheless, PHVs are not currently used for clinical applications due to their lack of reliability. In order to investigate the main features of this new class of prostheses, pulsatile tests in an in-house pulse duplicator were carried out and reproduced in silico with both structural Finite-Element (FE) and Fluid-Structure interaction (FSI) analyses. Valve kinematics and geometric orifice area (GOA) were evaluated to compare the in vitro and the in silico tests. Numerical results showed better similarity with experiments for the FSI than for the FE simulations. The maximum difference between experimental and FSI GOA at maximum opening time was only 5%, as compared to the 46.5% between experimental and structural FE GOA. The stress distribution on the valve leaflets clearly reflected the difference in valve kinematics. Higher stress values were found in the FSI simulations with respect to those obtained in the FE simulation. This study demonstrates that FSI simulations are more appropriate than FE simulations to describe the actual behaviour of PHVs as they can replicate the valve-fluid interaction while providing realistic fluid dynamic results.

CH-EUS allowed differentiation between pseudocysts and other pancreatic cysts but not mucinous versus serous cysts. Malignant vegetations inside pancreatic cystic lesions were clearly shown by CH-EUS as solid components with features of hyperenhancement, directing EUS-fine needle aspiration of potential neoplastic areas and avoiding puncture of debris and mucus plugs.

In our population, standard EUS features of PM were unremarkable. At CH-EUS, most of the PM appeared hypoenhancing suggesting a possible malignant origin. However, a subset of PM showed hyperenhancing pattern. In the appropriate context, particularly when cancer history is present, CH-EUS may add to the differential diagnosis and potentially spare endoscopic ultrasonography with fine-needle aspiration.