Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis. © 2013 Lee et al

The living aortic valve: From molecules to function.

The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70-90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve

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

Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity?

Non-compaction of the left ventricular myocardium (LVNC) has gained increasing recognition during the last 25 years. There is a morphological trait of the myocardial structure with a spectrum from normal variants to the pathological phenotype of LVNC, which reflects the embryogenic structure of the human heart due to an arrest in the compaction process during the first trimester. It must be cautioned not to overdiagnose LVNC: the morphological spectrum of trabeculations, from normal variants to pathological trabeculations with the morphological feature of LVNC must be carefully considered. The classical triad of complications are heart failure, arrhythmias, including sudden cardiac death, and systemic embolic events. Non-compaction of the left ventricular myocardium can occur in isolation or in association with congenital heart defects (CHDs), genetic syndromes, and neuromuscular disorders among others. The clinical spectrum is wide and the outcome is more favourable than in previously described populations with a negative selection bias. Familial occurrence is frequent with autosomal dominant and X-linked transmissions. Different mutations in sarcomere protein genes were identified and there seems to be a shared molecular aetiology of different cardiomyopathic phenotypes, including LVNC, hypertrophic and dilated cardiomyopathies. Thus, genetic heterogeneity, with an overlap of different phenotypes, and the variability of hereditary patterns, raise the questions whether there is a morphological trait from dilated/hypertrophic cardiomyopathy to LVNC and what are the triggers and modifiers to develop either dilated, hypertrophic cardiomyopathy, or LVNC in patients with the same mutation. The variety in clinical presentation, the genetic heterogeneity, and the phenotype of the first transgenetic animal model of an LVNC-associated mutation question the hypothesis that LVNC be a distinct cardiomyopathy: it seems to be rather a distinct phenotype or phenotypic, morphological expression of different underlying diseases than a distinct cardiomyopath

Effects of Endocardial Microwave Energy Ablation

Until recently the treatment of atrial fibrillation (AF) consisted primarily of palliation, mostly in the form of pharmacological intervention. However because of recent advances in nonpharmacologic therapies, the current expectation of patients and referring physicians is that AF will be cured, rather than palliated. In recent years there has been a rapid expansion in the availability and variety of energy sources and devices for ablation. One of these energies, microwave, has been applied clinically only in the last few years, and may be a promising technique that is potentially capable of treating a wide range of ventricular and supraventricular arrhythmias. The purpose of this study was to review microwave energy ablation in surgical treatment of AF with special interest in histology and ultrastructure of lesions produced by this endocardial ablation procedure

MRI-Based Computational Torso/Biventricular Multiscale Models to Investigate the Impact of Anatomical Variability on the ECG QRS Complex

Aims:Patient-to-patient anatomical differences are an important source of variability in the electrocardiogram, and they may compromise the identification of pathological electrophysiological abnormalities. This study aims at quantifying the contribution of variability in ventricular and torso anatomies to differences in QRS complexes of the 12-lead ECG using computer simulations. Methods:A computational pipeline is presented that enables computer simulations using human torso/biventricular anatomically based electrophysiological models from clinically standard magnetic resonance imaging (MRI). The ventricular model includes membrane kinetics represented by the biophysically detailed O’Hara Rudy model modified for tissue heterogeneity and includes fiber orientation based on the Streeter rule. A population of 265 torso/biventricular models was generated by combining ventricular and torso anatomies obtained from clinically standard MRIs, augmented with a statistical shape model of the body. 12-lead ECGs were simulated on the 265 human torso/biventricular electrophysiology models, and QRS morphology,duration and amplitude were quantified in each ECG lead for each of the human torso-biventricular models. Results:QRS morphologies in limb leads are mainly determined by ventricular anatomy,while in the precordial leads, and especially V1 to V4, they are determined by heart position within the torso. Differences in ventricular orientation within the torso can explain morphological variability from monophasic to biphasic QRS complexes. QRS duration ismainly influenced by myocardial volume, while it is hardly affected by the torso anatomyor position. An average increase of 0.12±0.05 ms in QRS duration is obtained for eachcm3of myocardial volume across all the leads while it hardly changed due to changes in torso volume. Conclusion:Computer simulations using populations of human torso/biventricular models based on clinical MRI enable quantification of anatomical causes of variability in the QRS complex of the 12-lead ECG. The human models presented also pave theway toward their use as testbeds in silico clinical trial

A highly-detailed anatomical study of left atrial auricle as revealed by in-vivo computed tomography

The left atrial auricle (LAA) is the main source of intracardiac thrombi, which contribute significantly to the total number of stroke cases. It is also considered a major site of origin for atrial fibrillation in patients undergoing ablation procedures. The LAA is known to have a high degree of morphological variability, with shape and structure identified as important contributors to thrombus formation. A detailed understanding of LAA form, dimension, and function is crucial for radiologists, cardiologists, and cardiac surgeons.This review describes the normal anatomy of the LAA as visualized through multiple imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and echocardi-ography. Special emphasis is devoted to a discussion on how the morphological characteristics of the LAA are closely related to the likelihood of developing LAA thrombi, including insights into LAA embryology

High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees