Revisiting the anatomy of the left ventricle in the light of knowledge of its development.

Despite centuries of investigation, certain aspects of left ventricular anatomy remain either controversial or uncertain. We make no claims to have resolved these issues, but our review, based on our current knowledge of development, hopefully identifies the issues requiring further investigation. When first formed, the left ventricle had only inlet and apical components. With the expansion of the atrioventricular canal, the developing ventricle cedes part of its inlet to the right ventricle whilst retaining the larger parts of the cushions dividing the atrioventricular canal. Further remodelling of the interventricular communication provides the ventricle with its outlet, with the aortic root being transferred to the left ventricle along with the newly formed myocardium supporting its leaflets. The definitive ventricle possesses inlet, apical and outlet parts. The inlet component is guarded by the mitral valve, with its leaflets, in the normal heart, supported by papillary muscles located infero-septally and supero-laterally. There is but a solitary zone of apposition between the leaflets, which we suggest are best described as being aortic and mural. The trabeculated component extends beyond the inlet to the apex and is confluent with the outlet part, which supports the aortic root. The leaflets of the aortic valve are supported in semilunar fashion within the root, with the ventricular cavity extending to the sinutubular junction. The myocardial-arterial junction, however, stops well short of the sinutubular junction, with myocardium found only at the bases of the sinuses, giving rise to the coronary arteries. We argue that the relationships between the various components should now be described using attitudinally appropriate terms rather than describing them as if the heart is removed from the body and positioned on its apex.

Feasibility and safety of synchrotron-based X-ray phase contrast imaging as a technique complementary to histopathology analysis.

X-ray phase contrast imaging (X-PCI) is a powerful technique for high-resolution, three-dimensional imaging of soft tissue samples in a non-destructive manner. In this technical report, we assess the quality of standard histopathological techniques performed on formalin-fixed, paraffin-embedded (FFPE) human tissue samples that have been irradiated with different doses of X-rays in the context of an X-PCI experiment. The data from this study demonstrate that routine histochemical and immunohistochemical staining quality as well as DNA and RNA analyses are not affected by previous X-PCI on human FFPE samples. From these data we conclude it is feasible and acceptable to perform X-PCI on FFPE human biopsies.

PKN2 deficiency leads both to prenatal 'congenital' cardiomyopathy and defective angiotensin II stress responses.

The protein kinase PKN2 is required for embryonic development and PKN2 knockout mice die as a result of failure in the expansion of mesoderm, cardiac development and neural tube closure. In the adult, cardiomyocyte PKN2 and PKN1 (in combination) are required for cardiac adaptation to pressure-overload. The specific role of PKN2 in contractile cardiomyocytes during development and its role in the adult heart remain to be fully established. We used mice with cardiomyocyte-directed knockout of PKN2 or global PKN2 haploinsufficiency to assess cardiac development and function using high resolution episcopic microscopy, MRI, micro-CT and echocardiography. Biochemical and histological changes were also assessed. Cardiomyocyte-directed PKN2 knockout embryos displayed striking abnormalities in the compact myocardium, with frequent myocardial clefts and diverticula, ventricular septal defects and abnormal heart shape. The sub-Mendelian homozygous knockout survivors developed cardiac failure. RNASeq data showed up-regulation of PKN2 in patients with dilated cardiomyopathy, suggesting an involvement in adult heart disease. Given the rarity of homozygous survivors with cardiomyocyte-specific deletion of PKN2, the requirement for PKN2 in adult mice was explored using the constitutive heterozygous PKN2 knockout. Cardiac hypertrophy resulting from hypertension induced by angiotensin II was reduced in these haploinsufficient PKN2 mice relative to wild-type littermates, with suppression of cardiomyocyte hypertrophy and cardiac fibrosis. It is concluded that cardiomyocyte PKN2 is essential for heart development and the formation of compact myocardium and is also required for cardiac hypertrophy in hypertension. Thus, PKN signalling may offer therapeutic options for managing congenital and adult heart diseases.

Expert Consensus Statement: Anatomy, Imaging, and Nomenclature of Congenital Aortic Root Malformations.

Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnormal morphogenesis and anatomy, with emphasis placed on the features of clinical and surgical relevance. We contend that the description of the congenitally malformed aortic root is simplified when approached in a fashion that recognizes the normal root to be made up of 3 leaflets, supported by their own sinuses, with the sinuses themselves separated by the interleaflet triangles. The malformed root, usually found in the setting of 3 sinuses, can also be found with 2 sinuses, and very rarely with 4 sinuses. This permits description of trisinuate, bisinuate, and quadrisinuate variants, respectively. This feature then provides the basis for classification of the anatomical and functional number of leaflets present. By offering standardized terms and definitions, we submit that our classification will be suitable for those working in all cardiac specialties, whether pediatric or adult. It is of equal value in the settings of acquired or congenital cardiac disease. Our recommendations will serve to amend and/or add to the existing International Paediatric and Congenital Cardiac Code, along with the Eleventh iteration of the International Classification of Diseases provided by the World Health Organization.

High sensitivity X-ray phase contrast imaging by laboratory grating-based interferometry at high Talbot order geometry.

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.

Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11).

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Micro-computed tomography of isolated fetal hearts following termination of pregnancy: A feasibility study at 8 to 12 weeks' gestation.

OBJECTIVES: To assess the feasibility of retrieval of intact human fetal hearts after first trimester surgical termination of pregnancy (TOP) and subsequent anatomical assessment by postmortem micro-computed tomography (micro-CT). METHODS: In a cohort of consenting women undergoing surgical TOP between 8 and 13 weeks' gestation, we attempted the retrieval of the fetal heart from the suction material. Specimens were immersion fixed in 10% formaldehyde, scanned by iodine-enhanced micro-CT and cardiac anatomy assessed by a multidisciplinary team using 3D-multiplanar analysis. RESULTS: The median gestational age at TOP was 10.7 weeks (range 8.3-12.9). In 57 (95.0%) out of 60 suction specimens, the heart could be retrieved. The median cardiac length was 5 mm (range 2-8 mm), in three (5.3%), the heart was too damaged to assess cardiac anatomy and in five (8.7%) only the four chambers could be examined. In the remaining 49 (86.0%) cases, a detailed assessment of cardiac anatomy was possible, showing a major defect in two (4.1%) and a minor defect in four (8.2%). CONCLUSIONS: Fetal hearts can be retrieved after first trimester TOP being intact in the vast majority of cases. Iodine-enhanced, postmortem micro-CT can be used to assess cardiac anatomy from as early as 8 weeks and to describe heart abnormalities.

Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre-birth.

Myoarchitectural disarray - the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoarchitectural abnormalities in HCM are present in the fetal heart. We used wild-type, heterozygous and homozygous hearts (n = 56) from a Mybpc3-targeted knock-out HCM mouse model and imaged the 3D micro-structure by high-resolution episcopic microscopy. We developed a novel structure tensor approach to extract, display and quantify myocyte orientation and its local angular uniformity by helical angle, angle of intrusion and myoarchitectural disarray index, respectively, immediately before and after birth. In wild-type, we demonstrate uniformity of orientation of cardiomyocytes with smooth transitions of helical angle transmurally both before and after birth but with traces of disarray at the septal insertion points of the right ventricle. In comparison, heterozygous mice free of LVH, and homozygous mice showed not only loss of the normal linear helical angulation transmural profiles observed in wild-type but also fewer circumferentially arranged myocytes at birth. Heterozygous and homozygous showed more disarray with a wider distribution than in wild-type before birth. In heterozygous mice, disarray was seen in the anterior, septal and inferior walls irrespective of stage, whereas in homozygous mice it extended to the whole LV circumference including the lateral wall. In conclusion, myoarchitectural disarray is detectable in the fetal heart of an HCM mouse model before the development of LVH.

Sequential segmental analysis of the crocodilian heart.

Differences between hearts of crocodilians and those of mammals and birds are only partly understood because there is no standardised approach and terminology for describing cardiac structure. Whereas most reptiles have an undivided ventricle, crocodilians have a fully septated ventricle. Their hearts, therefore, are more readily comparable with the hearts of mammals and birds. Here, we describe the heart of a crocodile (Crocodylus noliticus). We use the versatile sequential segmental approach to analysis, juxtaposing several key views of the crocodilian heart to the comparable views of human hearts. In crocodiles, the atrial and ventricular septums are complete but, unlike in placental mammals, the atrial septum is without an oval fossa. The myocardial component of the crocodilian ventricular septum dominates, but the membranous septum likely makes up a greater proportion than in any mammal. In the crocodile, the aortic trunk takes its origin from the left ventricle and is not wedged between the atrioventricular junctions. Consequently, there is a common atrioventricular junction, albeit with separate right and left atrioventricular valvar orifices. As in mammals, nonetheless, the crocodilian left atrioventricular valvar orifice is cranial to the right atrioventricular valvar orifice. By applying a method of analysis and terminology usually restricted to the human heart, we build from the considerable existing literature to show neglected and overlooked shared features, such as the offset between the left and right atrioventricular valvar orifices. Such commonalities are surprising given the substantial evolutionary divergence of the archosaur and synapsid lineages, and likely reflect evolutionarily shared morphogenetic programmes.

Duplicated left pulmonary artery: an unknown disease? Three case reports and review of the literature.

We report three cases of an abnormal finding of duplicated left pulmonary artery: two of these occurring in children with Kabuki syndrome and configuring the setting of a pseudo-pulmonary sling without any clinical or cardiac cross-sectional evidence of tracheal compression. The other case instead represents duplicated left pulmonary artery with pulmonary sling caused by the retro-tracheal course of the lower left pulmonary artery associated with "Christmas Tree" arrangement of the tracheo-bronchial system. In both patients with pseudo-pulmonary sling and Kabuki syndrome, the abnormal finding was incidental during echocardiographic examination and neither of the patients required surgical repair for the condition. To the best of our knowledge, they represent the third and fourth cases in which such an anomaly of the pulmonary artery branches not forming a sling is seen in association with Kabuki syndrome. Another case represents our second experience and the second case reported in literature with duplicated left pulmonary artery in the setting of a complex tracheal anatomy. In this symptomatic patient, surgical repair of atrial septal defect and relief of the vascular ring were indicated, and the surgical repair was performed successfully at the age of 3 years.

3D morphometric analysis of the arterial switch operation using in vivo MRI data.

The arterial switch operation (ASO) is widely used nowadays as the surgical strategy of choice to repair transposition of the great arteries (TGA). Residual morphological and geometrical abnormalities of the aorta, pulmonary arteries and coronary arteries, however, have not been fully studied in a three-dimensional (3D) domain. These morphometric complications might have implications on long-term outcomes of ASO patients, hence the need to explore them in detail and study them with reference to healthy controls of comparable age and body surface area. These anatomical characteristics were examined using 3D patient-specific anatomical models reconstructed from cardiovascular magnetic resonance (CMR) images of 20 ASO patients (mean age 14.4 ± 2.4 years, 16 males and 4 females) compared with healthy controls (mean age 15.2 ± 2.0 years, 17 males and 3 females). It was found that the aorta, pulmonary arteries and re-implanted coronary arteries of ASO patients were significantly different morphologically and geometrically to those of healthy controls. In particular, the aortic root was dilated, with abnormal 3D angulation and additional acute angulation of the curvature of the aortic arch in the ASO group compared with controls. This could theoretically impinge on aortic flow profiles and physiological stresses, which can act as a primer for the development of early atherosclerotic disease in the ASO population.

Development of Upper Extremity Deep Vein Thrombosis in a Patient With Seronegative Myasthenia Gravis: A Case Report and Review of Literature.

We present the case report of a patient with seronegative myasthenia gravis (MG) who was admitted for metabolic encephalopathy and acute on chronic hypoxic respiratory failure secondary to an MG crisis three days after an intravenous immunoglobulin treatment. In the intensive care unit, her MG was managed with intravenous immunoglobulin, plasmapheresis, prednisone, and pyridostigmine. During the course of her visit, she had urosepsis along with a left chest port that had cultured positive for Pseudomonas aeruginosa and developed a right upper extremity deep vein thrombosis (UEDVT) and superficial thrombosis in the left upper extremity despite being on heparin therapy. She had a transient drop in platelets to below 150,000 that resolved within a day. We analyzed the variables of this case report and reviewed the literature of similar cases to elucidate the factors that may have led to the development of the UEDVTs. The patient had many factors in her past medical history that could have contributed to her thrombosis including morbid obesity and prior history of pulmonary embolisms. It is hypothesized that MG disturbs the endothelial cell lining through an increased inflammatory state that could also be a causative factor. There is no definitive way we could link MG as a causative factor due to a lack of testing to assess alteration in the integrity or functionality of her endothelium. A case report we reviewed showed a presentation of UEDVT in an MG patient due to a thymoma compressing the subclavian vein. However, this is not the case in this example due to the patient having a history of thymectomy. She was also at risk due to her hospital stay which led to immobility and placement of a central venous catheter. We conclude the formation of the UEDVT was likely a combination of these factors.

The Atrioventricular Conduction Axis Revisited for the 21st Century.

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections.

Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals.

Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.

Expert Consensus Statement: Anatomy, Imaging, and Nomenclature of Congenital Aortic Root Malformations.

Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnormal morphogenesis and anatomy, with emphasis placed on the features of clinical and surgical relevance. We contend that the description of the congenitally malformed aortic root is simplified when approached in a fashion that recognizes the normal root to be made up of 3 leaflets, supported by their own sinuses, with the sinuses themselves separated by the interleaflet triangles. The malformed root, usually found in the setting of 3 sinuses, can also be found with 2 sinuses, and very rarely with 4 sinuses. This permits description of trisinuate, bisinuate, and quadrisinuate variants, respectively. This feature then provides the basis for classification of the anatomical and functional number of leaflets present. By offering standardized terms and definitions, we submit that our classification will be suitable for those working in all cardiac specialties, whether pediatric or adult. It is of equal value in the settings of acquired or congenital cardiac disease. Our recommendations will serve to amend and/or add to the existing International Paediatric and Congenital Cardiac Code, along with the Eleventh iteration of the International Classification of Diseases provided by the World Health Organization.

Major Histocompatibility Complex Class I and Dengue Hemorrhagic Fever: A Meta-Analysis of Human Leukocyte Antigens A*24 and B*44.

INTRODUCTION: Dengue fever (DF) is a disease caused by dengue virus (DENV) from the family Flaviviridae. The role of human leukocyte antigens (HLAs) in dengue fever (DF) and its more severe manifestation, dengue hemorrhagic fever (DHF), has been a topic of great research interest. In addition to HLA profile, race, age, DENV serotype, infection while having certain chronic diseases, and secondary infection are risk factors for DHF susceptibility. Antibody-dependent enhancement (ADE) of dengue virus infection is a mechanism for DHF infection. Individual studies have examined the effects of HLA-A*24 and HLA-B*44 presence on DHF, but none have analyzed these in a meta-analysis. The objective of this study was to determine the effects of HLA-A*24 and HLA-B*44 presence on DHF and DF susceptibility. MATERIALS AND METHODS: A meta-analysis on DHF and DF susceptibility in patients with HLA-A*24 and HLA-B*44 was conducted. Google Scholar was used to find studies that contained patients with HLA-A*24 or HLA-B*44 that were diagnosed with DHF or DF. Studies containing patients diagnosed using the 1997 WHO guidelines and possessing HLA-A*24 or HLA-B*44 that were diagnosed with DHF or DF, including primary or secondary infection, and studies measuring odds ratios (ORs) were included. Patients diagnosed using the 2009 WHO guidelines and studies in a foreign language, using animals, or lacking odds ratios were excluded. The National Institutes of Health (NIH) quality assessment of the case-control study tool was used, and a Doi plot was generated using MetaXL to assess for risk of bias. Review Manager version 5.4 was used to generate odds ratios and forest plots with subgroup analysis from allele and phenotype frequency data. Ten studies from 2001 to 2015 met the inclusion criteria. The studies included 2837 DHF/DF patients and 4880 healthy control (HC) patients. RESULTS:  HLA-A*24 was associated with a 1.39 times susceptibility to DHF while those possessing HLA-B*44 were 0.62 times susceptible to DHF (OR=1.39 and 95% CI=1.17-1.66; OR=0.62 and 95% CI=0.39-0.99). Neither HLA-A*24 nor HLA-B*44 presence was associated with DF susceptibility (OR=1.04 and 95% CI=0.82-1.33; OR=0.88 and 95% CI=0.68-1.14). CONCLUSION: These results indicate that two different major histocompatibility complex (MHC) class I alleles, HLA-A*24 and HLA-B*44, have opposing effects on DHF susceptibility but none on DF susceptibility. The study's specificity is limited in that it examines HLA allele groups and not specific HLA proteins. The results of this study can be used clinically to identify patients that may be at a higher risk of developing DHF based on their HLA profile.

GOing Forward With the Cardiac Conduction System Using Gene Ontology.

The cardiac conduction system (CCS) comprises critical components responsible for the initiation, propagation, and coordination of the action potential. Aberrant CCS development can cause conduction abnormalities, including sick sinus syndrome, accessory pathways, and atrioventricular and bundle branch blocks. Gene Ontology (GO; http://geneontology.org/) is an invaluable global bioinformatics resource which provides structured, computable knowledge describing the functions of gene products. Many gene products are known to be involved in CCS development; however, this information is not comprehensively captured by GO. To address the needs of the heart development research community, this study aimed to describe the specific roles of proteins reported in the literature to be involved with CCS development and/or function. 14 proteins were prioritized for GO annotation which led to the curation of 15 peer-reviewed primary experimental articles using carefully selected GO terms. 152 descriptive GO annotations, including those describing sinoatrial node and atrioventricular node development were created and submitted to the GO Consortium database. A functional enrichment analysis of 35 key CCS development proteins confirmed that this work has improved the in-silico interpretation of this CCS dataset. This work may improve future investigations of the CCS with application of high-throughput methods such as genome-wide association studies analysis, proteomics, and transcriptomics.

Detailed quantification of cardiac ventricular myocardial architecture in the embryonic and fetal mouse heart by application of structure tensor analysis to high resolution episcopic microscopic data.

The mammalian heart, which is one of the first organs to form and function during embryogenesis, develops from a simple tube into a complex organ able to efficiently pump blood towards the rest of the body. The progressive growth of the compact myocardium during embryonic development is accompanied by changes in its structural complexity and organisation. However, how myocardial myoarchitecture develops during embryogenesis remain poorly understood. To date, analysis of heart development has focused mainly on qualitative descriptions using selected 2D histological sections. High resolution episcopic microscopy (HREM) is a novel microscopic imaging technique that enables to obtain high-resolution three-dimensional images of the heart and perform detailed quantitative analyses of heart development. In this work, we performed a detailed characterization of the development of myocardial architecture in wildtype mice, from E14.5 to E18.5, by means of structure tensor analysis applied to HREM images of the heart. Our results shows that even at E14.5, myocytes are already aligned, showing a gradual change in their helical angle from positive angulation in the endocardium towards negative angulation in the epicardium. Moreover, there is gradual increase in the degree of myocardial organisation concomitant with myocardial growth. However, the development of the myoarchitecture is heterogeneous showing regional differences between ventricles, ventricular walls as well as between myocardial layers, with different growth patterning between the endocardium and epicardium. We also found that the percentage of circumferentially arranged myocytes within the LV significantly increases with gestational age. Finally, we found that fractional anisotropy (FA) within the LV gradually increases with gestational age, while the FA within RV remains unchanged.

Veno-venous bridges: the forerunners of the sinus venosus defect.

BACKGROUND: Differentiation of the so-called sinus venosus defect from other defects permitting shunting between the atrial chambers remains problematic. The lesion is not a true septal defect, and current theories to explain the existence of the sinus venosus defect fall short. The presence of persistent systemic to pulmonary venous connections has been proposed to explain the existence of the sinus venosus defect. METHODS: Clinical histories and radiological findings of six patients are reviewed. Three patients have veno-venous bridges, two have partial anomalous pulmonary venous connections, and one patient has a sinus venosus defect. The clinical information is reviewed, along with current developmental and morphological considerations. DISCUSSION: We provide radiographic, developmental, and morphological evidence to support the theory that a so-called sinus venosus defect is the consequence of persistence of foetal systemic to pulmonary veno-venous bridges, rather than of deficiencies in atrial septation.