Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Additional transcriptomics and in vitro analyses were performed to better understand how arterio-ventricular connections are originated in the embryonic heart. Our results suggest myocardial discontinuities in the developing heart promote the formation of endocardial pouch-like structures resembling human CAF. The structure of these CAF-like anomalies was compared with histopathological data from a paediatric heart CAF, showing histomorphological and immunochemical similarities, including an accumulation of smooth muscle positive cells in the pouch-like structure wall. In vitro experiments showed the abnormal contact between the epicardium and the endocardium may promote the precocious differentiation of epicardial cells to smooth muscle. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. Our results may provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.

Impact of carbon monoxide on early cardiac development in an avian model

Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association. Here, we exposed chick embryos in ovo to CO at three different concentrations (1ppm, 8ppm, 25ppm) plus air control (4 protocols in total) for the first nine days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight and ventricular wall thickness. We found that heart weight was reduced for the low and moderate exposures compared to air, and that ventricular wall thickness was increased for the moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols. This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.

Comparison of cardiac morphology and function in small for gestational age fetuses and fetuses with late-onset fetal growth retardation

Objectives To compare cardiac structural and functional findings of fetuses with fetal growth restriction (FGR) and small for gestational age (SGA). Methods In this prospective cohort study, patients were classified into three groups using Delphi procedure according to fetal weight, umbilical, uterine artery Doppler and cerebroplacental ratio. Fetal cardiac ultrasonographic morphology and Doppler examination was performed to all pregnant women at 36 weeks of gestation. Results Seventy three patients were included in the study. There were one (6.7%) patient in the control group, 2 (13.3%) in the SGA group and 12 (80%) in the FGR group who needed neonatal intensive care unit (NICU) and NICU requirement was significantly higher in FGR fetuses (p<0.001). Left spherical index was found to be lower only among FGR fetuses (p=0.046). Left ventricular wall thickness was decreased and the right/left ventricular wall ratio was increased in FGR fetuses (p=0.006, p<0.001). Tricuspid/mitral valve ratio and mitral annular plane systolic excursion value was lower in FGR fetuses (p=0.034, p=0.024 respectively). Also, myocardial performance index was remarkably higher in FGR group (p=0.002). Conclusions We detected cardiac morphological changes in cases of both SGA and FGR—more pronounced in the FGR cases. Findings related to morphological changes on the left side in FGR cases were considered secondary to volume increase in FGR cases as an indicator of a brain-protective effect. In the FGR group, both systolic and diastolic dysfunctions were detected in the left heart.

The Myosin Myocardial Mesh Interpreted as a Biological Analogous of Nematic Chiral Liquid Crystals

There are still grey areas in the understanding of the myoarchitecture of the ventricular mass. This is despite the progress of investigation methods since the beginning of the 21st century (diffusion tensor magnetic resonance imaging, microcomputed tomography, and polarised light imaging). The objective of this article is to highlight the specificities and the limitations of polarised light imaging (PLI) of the unstained myocardium embedded in methyl methacrylate (MMA). Thus, to better differentiate our method from other PLI modes, we will refer to it by the acronym PLI-MMA. PLI-MMA shows that the myosin mesh of the compact left ventricular wall behaves like a biological analogous of a nematic chiral liquid crystal. Results obtained by PLI-MMA are: the main direction of the myosin molecules contained in an imaged voxel, the crystal liquid director n, and a regional isotropy index RI that is an orientation tensor, the equivalent of the crystal liquid order parameter. The vector n is collinear with the first eigenvector of diffusion tensor imaging (DTI-MRI). The RI has not been confounded with the diffusion tensor of DTI that gives information about the three eigenvectors of the ellipsoid of diffusion. PLI-MMA gives no information about the collagen network. The physics of soft matter has allowed the revisiting of Streeter’s conjecture on the myoarchitecture of the compact left ventricular wall: “geodesics on a nested set of toroidal surfaces”. Once the torus topology is understood, this characterisation of the myoarchitecture is more accurate and parsimonious than former descriptions. Finally, this article aims to be an enthusiastic invitation to a transdisciplinary approach between physicists of liquid crystals, anatomists, and specialists of imaging.

Computational Modeling and Simulation of Stenosis of Aqueduct of Sylvius Due to Brain Tumor

Background: Stenosis of cerebral aqueduct (CA) is featured in many studies related to elevated intracranial cerebral pressures (ICP). It also presents a challenging situation to clinicians. Compressive forces play a lead role in pathological situations like tumor presence and hence can cause obstruction to the flow of cerebrospinal fluid (CSF). Due to this barrier, excessive retention of CSF in ventricles can occur. This in turn could contribute to increased pressure gradients inside the cranium. In literature, most of the numerical models are restricted to modeling the CSF flow by considering ventricle walls as rigid material unlike its behavior a deformable character. This paper, therefore, addresses the same from a holistic perspective by taking into consideration the dynamics of the flexible character of the ventricular wall. This adds to the novelty of this work by reconstructing an anatomically realistic ventricular wall behavior. To do this, the authors aim to develop a computational model of stenosis of CA due to brain tumor by invoking a fluid-structure interaction (FSI) method. The proposed 3D FSI model is simulated under two cases. First, simulation of pre-stenosis case with no interaction of tumor forces and secondly, a stenosis condition together-with dynamic interaction of tumor forces. Results: Comparing the forces with and without tumor reveals a marked obstruction of CSF outflow post third ventricle and the cerebral aqueduct. Not only this but a drastic rise of CSF velocity from 21.2 mm/s in pre-stenosis case to 54.1 mm/s stenosis case is also observed along with a net deformation increase of 0.144 mm on walls of ventricle. Conclusions: This is a significant contribution to brain simulation studies for pressure calculations, wherein the presence of tumors is a major concern.

Safety evaluation of high-risk myocardial micro-biopsy in a swine model

The objective of the study was to investigate the safety profile of high-risk micro-endomyocardial biopsy (micro-EMB) compared to conventional EMB in a large animal model. Twenty pigs were subjected to a maximum of 30 consecutive biopsies, including sampling from the free ventricular wall, with either micro-EMB (n = 10) or conventional EMB (n = 10). There were no major complications in the micro-EMB group (0/10), compared to six major complications in the EMB group (6/10; p = 0.003). Survival analysis further highlighted these differences (p = 0.004). There were significantly higher volumes of pericardial effusion in the EMB group (p = 0.01). The study shows a safety advantage of micro-EMB compared to standard EMB in the experimental high-risk circumstances investigated in this animal study. These results indicate enhanced possibilities to collect samples from sensitive areas by using the micro-EMB technique instead of standard EMB.

Postinfarction ventricular septal defect closure

After a median full sternotomy, cardiopulmonary bypass is installed in the usual manner. Apical ventriculotomy is performed through the infarcted myocardium. Polypropylene pledgeted mattress sutures are passed from the right to the left ventricular side through the ventricular septal defect, with the pledgets remaining on the right ventricle. Great care must be taken to place the suture on healthy myocardium and away from the edge of the ventricular septal defect; otherwise the chances of a recurrent postoperative ventricular septal defect would increase. The sutures are subsequently positioned through a heterologous patch, previously prepared to be appropriate for the ventricular septal defect closure. A collar of 3 to 4 cm is left on the external side of the patch. A 4-0 polypropylene running suture is placed through this collar and the left ventricle to further reinforce the ventricular septal defect closure. The left ventricular incision is closed with polypropylene 3-0 continuous sutures. For each ventricular edge, the running suture is passed through 2 polytetrafluoroethylene felts: one on the endoventricular side and the other on the epicardial side. Finally, the suture line is reinforced with a continuous 2-0 polypropylene suture, which is passed through the polytetrafluoroethylene felts, the ventricular wall, and the heterologous patch used to close the ventricular septal defect.

Early post-septal myectomy outcomes for hypertrophic obstructive cardiomyopathy

Background We aimed to evaluate early outcomes of septal myectomy in patients with hypertrophic cardiomyopathy. Methods We retrospectively analyzed data collected over a 9-year period from 583 patients who underwent septal myectomy for hypertrophic cardiomyopathy at our institution. Results The mean age was 55.7 ± 13.1 years, and 338 (58%) patients were in New York Heart Association class III or IV. There were 11 (1.9%) early deaths, including 3 (0.5%) intraoperative deaths. Early mortality was lowest after isolated septal myectomy (0.8%) and highest after concomitant mitral valve replacement (6.1%). There were 4 (0.7%) and 9 (1.5%) patients with left ventricular wall rupture and ventricular septal defect, respectively, after myectomy. New pacemaker implantation caused by atrioventricular disturbances was required in 29 (5.0%) patients, and was associated with previous alcohol septal ablation (odds ratio 3.34, 95% confidence interval 1.02–11.0, P = 0.047). Left ventricular wall rupture, intraoperative residual (15.5% moderate, 0.3% severe) mitral regurgitation, and pre-discharge residual outflow tract gradient >30 mm Hg (4.6%) occurrences were surgeon-dependent. Conclusions The early results are consistent with example targets reported in the 2020 American College of Cardiology/American Heart Association guidelines for septal reduction therapy outcomes. Septal myectomy safety and efficacy are surgeon-dependent. Previous alcohol septal ablation increases the risk of permanent pacemaker implantation due to postoperative complete atrioventricular block. Therefore, continuous education, mentoring, and learning by doing may play an important role in achieving reasonable septal myectomy safety and efficacy.

Peak ependymal cell stretch overlaps with the onset locations of periventricular white matter lesions

Deep and periventricular white matter hyperintensities (dWMH/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be stretched thin. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.