Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.This paper has been partially funded by CompBioMed project, under H2020-EU.1.4.1.3 European Union’s Horizon 2020 research and innovation programme, grant agreement n◦ 675451. FS is supported by a grant from Severo Ochoa (n◦ SEV-2015-0493-16-4), Spain. CB is supported by a grant from the Fundació LaMarató de TV3 (n◦ 20154031), Spain. TI and PI are supported by the Institute of Engineering in Medicine, USA, and the Lillehei Heart Institute, USA.Peer ReviewedPostprint (published version

Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease

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Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia

Morphogenesis of myocardial trabeculae in the mouse embryo

Formation of trabeculae in the embryonic heart and the remodelling that occurs prior to birth is a conspicuous, but poorly understood, feature of vertebrate cardiogenesis. Mutations disrupting trabecular development in the mouse are frequently embryonic lethal, testifying to the importance of the trabeculae, and aberrant trabecular structure is associated with several human cardiac pathologies. Here, trabecular architecture in the developing mouse embryo has been analysed using high-resolution episcopic microscopy (HREM) and three-dimensional (3D) modelling. This study shows that at all stages from mid-gestation to birth, the ventricular trabeculae comprise a complex meshwork of myocardial strands. Such an arrangement defies conventional methods of measurement, and an approach based upon fractal algorithms has been used to provide an objective measure of trabecular complexity. The extent of trabeculation as it changes along the length of left and right ventricles has been quantified, and the changes that occur from formation of the four-chambered heart until shortly before birth have been mapped. This approach not only measures qualitative features evident from visual inspection of 3D models, but also detects subtle, consistent and regionally localised differences that distinguish each ventricle and its developmental stage. Finally, the combination of HREM imaging and fractal analysis has been applied to analyse changes in embryonic heart structure in a genetic mouse model in which trabeculation is deranged. It is shown that myocardial deletion of the Notch pathway component Mib1 (Mib1(flox/flox); cTnT-cre) results in a complex array of abnormalities affecting trabeculae and other parts of the heart.This work was supported by funding to TJM from the Medical Research Council (U117562103); to JCM by the Higher Education Funding Council for England; to JLdlP and GL by grants SAF2010-17555 and SAF2013-45543-R from the Spanish Ministry of Economy and Competitiveness (MINECO); and to GC by a research fellowship at the University College London Biomedical Research Centre from the UK National Institutes of Health Research Cardiometabolic Programme.S

Septomarginal trabecula and anterior papillary muscle in primate hearts: developmental issues

The septomarginal trabecula is present in all human hearts as well as in thehearts of other primates. It usually connects the interventricular septum withthe anterior papillary muscle, although there are many variations in how this isachieved. The object of the analyses was to estimate the bilateral topography ofthe septomarginal trabecula and the anterior papillary muscle in the context ofthe ontogeny and phylogeny of primates. A total of 138 hearts were examinedfrom number of different non-human primates. The presence of the septomarginaltrabecula was confirmed in 94.9% of cases, although not in the hearts ofLemur varius. Four configurations could be distinguished by defining the locationof the septomarginal trabecula and its relation to the anterior papillary muscle.For the hearts of the Strepsirrhini and the majority of Platyrrhini neither structurewas related, whereas in all examined representatives of Hominoidea they hadfused and created morphologically varying forms. On the basis of these results,a concept was developed for the sequence of changes which the topography ofthe septomarginal trabecula and the anterior papillary muscle undergo duringontogeny and phylogeny

Mechanical and morphometric study of mitral valve chordae tendineae and related papillary muscle

The mitral valve (MV) apparatus is a complex mechanical structure including annulus, valve leaflets, papillary muscles (PMs) and connected chordae tendineae. Chordae anchor to the papillary muscles to help the valve open and close properly during one cardiac cycle. It is of paramount importance to understand the functional, mechanical, and microstructural properties of mitral valve chordae and connecting PMs. In particular, little is known about the biomechanical properties of the anterior and posterior papillary muscle and corresponding chords. In this work, we performed uniaxial and biaxial tensile tests on the anterolateral (APM) and posteromedial papillary muscle (PPM), and their respective corresponding chordae tendineae, chordaeAPM and chordaePPM, in porcine hearts. Histology was carried out to link the microstructure and macro-mechanical behavior of the chordae and PMs. Our results demonstrate that chordaePPM are less in number, but significantly longer and stiffer than chordaeAPM. These different biomechanical properties may be partially explained by the higher collagen core ratio and larger collagen fibril density of chordaePPM. No significant mechanical or microstructural differences were observed along the circumferential and longitudinal directions of APM and PPM samples. Data measured on chordae and PMs were further fitted with the Ogden and reduced Holzapfel - Ogden strain energy functions, respectively. This study presents the first comparative anatomical, mechanical, and structural dataset of porcine mitral valve chordae and related PMs. Results indicate that a PM based classification of chordae will need to be considered in the analysis of the MV function or planning a surgical treatment, which will also help developing more precise computational models of MV

Reference ranges ("normal values") for cardiovascular magnetic resonance (CMR) in adults and children: 2020 update

Cardiovascular magnetic resonance (CMR) enables assessment and quantification of morphological and functional parameters of the heart, including chamber size and function, diameters of the aorta and pulmonary arteries, flow and myocardial relaxation times. Knowledge of reference ranges ("normal values") for quantitative CMR is crucial to interpretation of results and to distinguish normal from disease. Compared to the previous version of this review published in 2015, we present updated and expanded reference values for morphological and functional CMR parameters of the cardiovascular system based on the peer-reviewed literature and current CMR techniques. Further, databases and references for deep learning methods are included