Hydrops fetalis caused by a complex congenital heart defect with concurrent hypoplasia of pulmonary blood vessels and lungs visualized by micro-CT in a French Bulldog.

BACKGROUND: Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species, including dogs. Most of cases result from a heart defect. Exact nature of this defect is rarely clarified. CASE PRESENTATION: A newborn, male French bulldog puppy with severe HF underwent a full anatomopathological examination to diagnose the primary cause of HF. Based on the anatomopathological examination, fetal ultrasound, and micro-computed tomography, transposition of the great arteries with hypoplasia of the ascending aorta, aortic arch interruption, ostium secundum atrial septal defect, severe tricuspid valve dysplasia, as well as hypoplasia of pulmonary vessels and lungs were diagnosed. CONCLUSIONS: This is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.

Defensive and offensive behaviours in a Kleefstra syndrome mouse model.

Kleefstra syndrome in humans is characterized by a general delay in development, intellectual disability and autistic features. The mouse model of this disease (Ehmt1±) expresses anxiety, autistic-like traits, and aberrant social interactions with non-cagemates. To investigate how Ehmt1± mice behave with unfamiliar conspecifics, we allowed adult, male animals to freely interact for 10 min in a neutral, novel environment within a host-visitor setting. In trials where the Ehmt1± mice were hosts, there were defensive and offensive behaviors. Our key finding was that Ehmt1± mice displayed defensive postures, attacking and biting; in contrast, wild-type (WT) interacting with other WT did not enact such behaviors. Further, if there was a fight between an Ehmt1± and a WT mouse, the Ehmt1± animal was the most aggressive and always initiated these behaviors.

Male pseudohermaphroditism in a complex malformed calf born with an acardius amorphus cotwin-a case report.

BACKGROUND: Male pseudohermaphroditism is a developmental anomaly wherein animals are genetically and gonadally male, but their internal and/or external genitalia resemble those of females. In cattle, pseudohermaphroditism is often accompanied by multiple severe malformations. To the best of our knowledge, this is the first report of male pseudohermaphroditism in a complex malformed calf born with an acardius amorphous cotwin. CASE PRESENTATION: This report describes the case of a three-day-old, male anurous Japanese Black calf born with an acardius amorphous cotwin, complete absence of the tail, agenesis of the anus, separate scrota, and umbilical hernia. Transthoracic echocardiography and computed tomography revealed serious malformations in the skeletal system and the circulatory, digestive, urinary, and genital organs. Necropsy revealed rectal atresia, immature testes, epididymis, and penis, but no male accessory gonads. Histological analyses revealed vaginal- and uterine-like tissues adjacent to or fused to the rectum. Fluorescence in situ hybridization detected X and Y chromosomes, and some cells presented two X-probe signals in the same nucleus. CONCLUSIONS: In contrast to the male genitalia, the female genitalia derived from the Müllerian ducts were difficult to detect by necropsy in the presented case. Many similar cases may be overlooked in clinical practice.

Anomalies of the aortic arch in dogs: evaluation with the use of multidetector computed tomography angiography and proposal of an extended classification scheme.

BACKGROUND: Congenital anomalies of the aortic arch are important as they may be associated with vascular ring anomalies. The most common vascular ring anomaly in dogs is a persistent right aortic arch. However, published data of the distribution of the different types of vascular ring anomalies and other aortic arch anomalies are lacking. The objective of this retrospective descriptive study was to evaluate both the prevalence and the different types of aortic arch anomalies that can be detected using thoracic computed tomography (CT) examination. Archived thoracic CT examinations acquired between 2008 and 2020 at a single institution were retrospectively evaluated by 2 evaluators for the prevalence and type of aortic arch anomaly. Breed, age, and presenting complaint were obtained from the medical record system. RESULTS: A total of 213 CT studies were evaluated; 21 dogs (21/213, 9.9%) showed a right aortic arch and a left ligamentum arteriosum with compression of the esophagus. The following incidental additional findings were detected: aberrant left subclavian artery (17/21, 76.2%), branching from the persistent ductus arteriosus (PDA) (1/21, 4.8%), left-sided brachiocephalic trunk (3/21, 14.3%), bicarotid trunk (17/21, 81.0%), double aortic arch (1/21, 4.8%). One hundred ninety two dogs (192/213, 90.1%) showed a left aortic arch without esophageal compression. The following additional abnormalities were obtained in those dogs with left aortic arch: aberrant right subclavian artery (3/192, 1.6%) without clinical signs of esophageal compression, aberrant vessel branching from the aorta into the left caudal lung lobe (2/192, 1.0%), focal dilatation of the left or right subclavian artery (2/192, 1.0%), bicarotid trunk (1/192, 0.5%). CONCLUSION: Similar to previous studies an aberrant left subclavian artery is the most common additional finding in dogs with persistent right aortic arch. Newly, a left-sided brachiocephalic trunk was identified in 14.3% of the dogs with a persistent right aortic arch; no additional compression was caused by the left sided brachiocephalic trunk. Similarly, aberrant right subclavian artery can be an incidental CT finding without causing compression of the esophagus.

Canine infantile left ventricular noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a rare form of cardiomyopathy currently described in humans and cats. It consists of a spongy myocardium characterized by prominent trabeculation and deep recesses involving more than 50% of the ventricular thickness. We describe the clinical and pathological features of LVNC combined with tricuspid valve dysplasia, double-orifice tricuspid valve and severe pulmonary stenosis in a puppy. In addition, we briefly review the LVNC causes, pathogenesis, forms and current diagnostic criteria. CASE PRESENTATION: A seven-week-old intact German Shorthaired Pointer-cross male was presented with a poor body condition, exercise intolerance and dyspnea. Clinical exam identified a bilateral systolic murmur (grade IV/VI over the right heart base and grade III/VI over the left heart base). Echocardiography identified tricuspid valve dysplasia, mild mitral regurgitation, and severe pulmonic stenosis with a trans-valvar systolic pressure gradient of 106 mmHg. Left ventricular noncompaction was diagnosed by necropsy and further confirmed histopathologically by the presence of two distinct myocardial layers: an inner noncompacted zone covering more than 50% of ventricular thickness containing prominent trabeculation and deep recesses, and an outer zone of compact myocardium. CONCLUSIONS: This is the first case describing LVNC in a canine patient, supporting the introduction of this form of heart disease as a differential diagnosis for cardiomyopathies in juvenile and adult dogs.

Equine Congenital Heart Disease.

Congenital heart disease (CHD) represents a small proportion of horses undergoing clinical evaluation; however, both simple and complex defects occur during cardiac development leading to many unique malformations. This article reviews cardiac development and the fetal circulation, describes the morphologic method and the sequential segmental approach to CHD analysis, presents a summary of CHD in horses, and offers an overview of lesions that should be considered during evaluation of horses suspected to have CHD. For many forms of equine CHD, therapies are limited because cardiac interventions and cardiac surgery are not routinely pursued in this species.

Multiple midline defects identified in a litter of golden retrievers following gestational administration of prednisone and doxycycline: a case series.

BACKGROUND: The teratogenic effects of immunomodulatory and certain antimicrobial therapies are described in small rodents and humans. While the described teratogenic effects in small rodents have been extrapolated to make conclusions about its use in the pregnant dam, teratogenic effects of prednisone and doxycycline have not yet been reported in the dog. Here we report and describe midline defects observed in a litter of golden retriever puppies exposed to mid-gestational immunosuppressive and antimicrobial therapy. CASE PRESENTATION: Twenty-one days into gestation, the dam of a litter of eight golden retriever puppies was administered prednisone, doxycycline, and tramadol as treatment for immune-mediated polyarthritis. The individuals in the litter were subsequently diagnosed with a variety of midline defects and congenital cardiac defects. This case series describes the variety of identified defects and presents a descriptive account of complex congenital abnormalities that are likely secondary to teratogenic effects of one or more drugs administered during gestation. The available puppies, dam, and grand dam underwent thorough physical examination, complete echocardiogram, and where indicated, advanced imaging with various surgical corrections when possible. Numerous midline congenital defects and congenital heart disease were identified in the puppies evaluated. Ultimately 5 of 8 puppies born to the dam were presented for thorough evaluation. The midline defects include: gastroschisis (1), peritoneopericardial diaphragmatic hernias (4, PPDH), umbilical hernia (4), unilateral cryptorchidism (1 of 4 males), cleft palate (1), renal agenesis (1), renal abnormalities (1), sternal and vertebral abnormalities (3), remnant liver lobe (1) and malformations consistent with ductal plate malformations with congenital hepatic fibrosis (1). The congenital cardiac defects include: ventricular septal defect (4, VSD) and subaortic stenosis (4, SAS). The presence of greater than one congenital defect was noted in all 5 of the dogs evaluated. Surgical correction was necessary for PPDH in 4 puppies. Medical intervention was recommended for congenital cardiac disease in 1 puppy. CONCLUSION: This case report is the first to describe midline defects in dogs that have been exposed to immunomodulatory therapy during gestation. A causative relationship between mid-gestational immunomodulatory exposure and midline defects cannot be proven, however, this case supports a clear association and provides case-based evidence to support its avoidance when possible.

Combined double chambered right ventricle, tricuspid valve dysplasia, ventricular septal defect, and subaortic stenosis in a dog.

BACKGROUND: Double chambered right ventricle (DCRV) is a congenital heart anomaly where the right ventricle is divided into two chambers. We describe, for the first time, an unusual combination of DCRV combined with some other congenital heart defects. CASE PRESENTATION: A 1.2-year-old Golden Retriever was presented with lethargy, exercise intolerance and ascites. Physical examination revealed an irregularly irregular pulse and a grade V/VI, systolic, right cranial murmur. Electrocardiography revealed widened and splintered QRS complexes with a right bundle-branch block pattern. Radiography demonstrated right-sided cardiomegaly. Two-dimensional echocardiography identified a DCRV with tricuspid valve dysplasia. The patient died despite abdominocentesis and 4 days of oral pharmacotherapy, and necropsy revealed an anomalous fibromuscular structure that divided the right ventricle into two compartments. Another finding was tricuspid valve dysplasia with hypoplasia of the posterior and septal leaflets. The anterior leaflet was prominent, being part of the anomalous structure that divided the right ventricle. Necropsy also identified a perimembranous ventricular septal defect and mild subaortic stenosis. Histopathological examination of the fibromuscular band that separated the right ventricle identified longitudinally oriented layers of dense fibrous connective tissue and myocardial cells arranged in a plexiform pattern. The muscular component was well represented at the ventral area of the fibromuscular band, and was absent in the central zone. Superficially, the endocardium presented areas of nodular hyperplasia covering mainly the fibrous part of the abnormal structure. The nodules were sharply demarcated and were composed by loosely arranged connective tissue with myxoid appearance, covered by discrete hyperplastic endocardium. CONCLUSIONS: Concomitant cardiac malformations involving DCRV, tricuspid valve dysplasia, perimembranous ventricular septal defect and mild subaortic stenosis have not been previously described in veterinary medicine, and are reported here for the first time. Moreover, this is the first report of a canine patient with tricuspid valve dysplasia (TVD) and DCRV where the anterior leaflet is part of an anomalous structure dividing the right ventricle (RV) into two separate compartments.

An unusual case of thoracic ectopia cordis in a Toggenburg Goat and its three-dimensional images constructed with X-ray computed tomography.

A two-day-old female Toggenburg goat with thoracic ectopia cordis (EC) was diagnosed via radiography and computed tomography. The goat was born with EC, defects of the sternum and a supra-umbilical abdominal wall, but without the presence of Cantrell's syndrome. Necropsy and histopathological findings indicated the affected kid had malformation of the heart with an enlarged left ventricle. The findings showed the heart (9 x 5 x 5 cm) stayed outside the thorax, and was covered by a semitransparent membrane. This report is the first to describe a case of thoracic EC in a goat whose sternum was not developed fully and was not connected to the ribs. It is also the first paper to describe three-dimensional images of this condition constructed from computed tomography scans.

Quadricuspid aortic valves in Syrian hamsters and their formation according to current knowledge on valvulogenesis.

Occurrence of quadricuspid aortic valves has been reported in humans, in nine dogs and in a greater white-toothed shrew. Moreover, two cases of developing aortic valves with four anticipated leaflets have been described in Syrian hamster embryos. Currently, however, no case of quadricuspid aortic valve in adult hamsters has been recorded. The aim here is to present four adults of this rodent species, two of them with unequivocally quadricuspid aortic valves and the other two with quadricuspid-like aortic valves. The four anomalous aortic valves were detected among 4,190 Syrian hamsters examined in our laboratory, representing an incidence of 0.09%. None of the affected hamsters showed apparent signs of disease. The present findings are considered on the light of current empirical knowledge about the morphogenesis of quadricuspid and bicuspid aortic and pulmonary valves. Quadricuspid aortic valves result from the partition of one of the normal mesenchymal cushions which normally give rise to normal (tricuspid) valves, while quadricuspid-like valves might be the product of a combined mechanism of fusion and partition of the cushions at the onset of the valvulogenesis. The presence of aortic valves with four leaflets in ancient mammalian lineages such as insectivors and rodents suggest that quadricuspid aortic valves, although showing almost certainly a low incidence, may be widespread among the different groups of mammals, including domestic animals.

Quadricuspid aortic valve and a ventricular septal defect in a horse.

BACKGROUND: Quadricuspid aortic valve (QAV) and ventricular septal defect (VSD) are congenital heart defects and have been described in both human and veterinary medical literature. CASE PRESENTATION: A 5-year-old half-bred bay stallion was referred for surgical castration. Cardiac murmurs were heard on the presurgical clinical examination and the cardiac examination revealed subcutaneous oedema, tachycardia with a precodrial thrill and a grade 5/6 pansystolic murmur, which was heard on auscultation of the right and left side of the chest. Examination of the B-mode echocardiograms revealed the presence of a QAV (one small cusp, two equal-sized cusps, and one large cusp) and VSD in the membranous portion of the intraventricular septum. These two congenital cardiac defects were accompanied by mild aortic valve regurgitation and severe tricuspid regurgitation. Despite the presence of these cardiac defects, the horse underwent surgical castration under general anesthesia. Surgery, anaesthesia and recovery from anaesthesia were uneventful. The gelding was euthanasied after 17 months because of a progressive loss of body weight, weakness and recumbency. CONCLUSION: A QAV in combination with VSD in a horse is an interesting finding, because to the best of our knowledge, this has not been previously described in equine literature.

Aplasia of the septum transversum has no effect on plasma biochemistry following an acute hypoxic event in Atlantic salmon.

Aplasia of the septum transversum (AST) is a malformation that results in alterations in ventricle morphology. The condition has been linked to increased mortality during periods of increased cardiac demand in Atlantic salmon Salmo salar. The blood plasma biochemical response to an acute hypoxic event (1 h at 31-39% O2saturation) was investigated in fish with and without a septum transversum to assess levels of anaerobic respiration (lactate) and the stress response (cortisol, glucose, osmolality, Na⁺, Cl⁻ and K⁺). AST had no effect on body size parameters or relative ventricular mass. The hypoxic event increased the levels of anaerobic respiration and induced a typical stress response. Contrary to our expectations, AST had no effect on any plasma parameter in normoxia or following severe acute hypoxia. We conclude that in the current scenario, AST does not affect the levels of anaerobic respiration or the plasma stress response in Atlantic salmon.

The effect of ploidy and incubation temperature on survival and the prevalence of aplasia of the septum transversum in Atlantic salmon, Salmo salar L.

Heart deformities are a concern in aquaculture and are linked to egg incubation temperature. Diploid and triploid Atlantic salmon, Salmo salar L., were incubated at 6, 8 and 10 °C and analysed for aplasia of the septum transversum (n = 150 ploidy⁻¹ incubation temperature⁻¹). Heart morphology (size and shape) was assessed in fish incubated at 6 °C and in fish with and without aplasia of the septum transversum (n = 9 group⁻¹) incubated at 10 °C. Egg mortality was significantly higher in triploids than in diploids at all incubation temperatures, and increased egg incubation temperatures increased mortality in both ploidy. Triploids grew quicker than diploids after egg incubation at 10 °C, but not at 6 °C. Aplasia of the septum transversum occurred only in triploid fish after incubation at 6 °C and 8 °C (0.7% and 3.3%, respectively) and was significantly greater (P ≤ 0.05) in triploids after incubation at 10 °C compared with diploids (30% and 18%, respectively). Aplasia of the septum transversum significantly increased heart mass and resulted in a long flat ventricle compared with fish displaying a septum transversum. The results suggest triploid salmon should be incubated below 8 °C.

Congenital heart defects in Arabian horses and the prospects of genetic testing: A review.

Congenital heart defects (CHDs) can have profound and potentially life-threatening consequences on horses' health and performance capability. While CHDs are rare in the general horse population, the Arabian breed is disproportionately overrepresented and thus is widely suspected to be genetically predisposed. This review discusses the most common CHDs in Arabian horses, including ventricular septal defect (VSD), tetralogy of Fallot (TOF), patent duct arteriosus (PDA), tricuspid valve atresia (TVA) and atrial septal defect (ASD). This review also explores how future research into the genetic factors that likely underpin many CHDs can revolutionise the way these disorders are managed in Arabian horses.

64-Slice ECG-gated computed tomographic angiography for assessment of coronary arteries in brachycephalic dogs with pulmonary stenosis.

BACKGROUND: Brachycephalic dogs with pulmonary stenosis are known to have a higher incidence of concurrent coronary artery abnormalities than non-brachycephalic breeds, which increases risk when performing balloon valvuloplasty. The use of ECG-gated CT angiography has been reported for the evaluation of coronary arteries in normal dogs and dogs with pulmonary stenosis. The purpose of this study was to report findings of coronary artery origination and morphology of main branches using ECG-gated CT angiography in brachycephalic dogs with pulmonary stenosis. METHODS: An ECG-gated CT angiographic protocol was used to image coronary artery anatomy in nine brachycephalic dogs with pulmonary stenosis. Images were assessed for quality as well as coronary artery morphology by one veterinary radiologist, one veterinary cardiologist and one veterinary radiology resident. RESULTS: All nine dogs had good to excellent image quality. Coronary artery anomalies were identified in three of nine dogs: one R2A anomaly, one L2A anomaly and one L2C anomaly. Two dogs were assessed to be poor balloon valvuloplasty candidates based on CT angiographic images. LIMITATION: Coronary artery morphology was not confirmed via postmortem examination in all patients. CONCLUSION: ECG-gated CT angiography is a minimally invasive imaging modality capable of diagnosing various coronary artery anomalies in brachycephalic dogs with pulmonary stenosis and aiding in the determination of patient candidacy for balloon valvuloplasty.

Congenital right atrial diverticulum in a kitten.

A four-month-old domestic shorthair cat with no clinical signs was referred for further examination of a heart murmur. An echocardiogram revealed marked right atrial dilation, extending into the left hemithorax. Computed tomography angiography was conducted to investigate further, which revealed a balloon-shaped, contrast-filled cavity on the cranial and left side of the chest that connected to the right atrium through a narrow passage. This was diagnosed as a congenital right atrial diverticulum. Treatment included clopidogrel to reduce the risk of thrombus formation. Two months after the initial diagnosis, castration surgery was successfully performed without complications. The cat died suddenly at home 10 months after diagnosis. To the authors' knowledge, this is the first right atrial diverticulum reported in a cat.

Development of bovine embryos derived from reproductive techniques.

Assisted reproduction techniques have improved agricultural breeding in the bovine. However, important development steps may differ from the situation in vivo and there is a high mortality rate during the first trimester of gestation. To better understand these events, we investigated the development of embryos and fetal membranes following fixed-time AI (FTAI), IVF and nuclear transfer (NT). The onset of yolk-sac development was not normal in cloned embryos. Later steps differed from conditions in vivo in all three groups; the yolk-sac was yellowish and juxtaposed with the amniotic membrane. Vascularisation of the chorioallantoic membrane was relatively late and low in NT gestations, but normal in the others. The overall development of the embryos was normal, as indicated by morphology and regression analysis of growth rate. However, NT conceptuses were significantly smaller, with the livers in some embryos occupying the abdominal cavity and others exhibiting heart abnormalities. In conclusion, the yolk-sac and the cardiovascular system seem to be vulnerable to morphogenetic alterations. Future studies will focus on gene expression and early vascularisation processes to investigate whether these changes may be responsible for the high incidence of intrauterine mortality, especially in clones.

Insights into the genetic architecture of congenital heart disease from animal modeling.

Congenital heart disease (CHD) is observed in up to 1% of live births and is one of the leading causes of mortality from birth defects. While hundreds of genes have been implicated in the genetic etiology of CHD, their role in CHD pathogenesis is still poorly understood. This is largely a reflection of the sporadic nature of CHD, as well as its variable expressivity and incomplete penetrance. We reviewed the monogenic causes and evidence for oligogenic etiology of CHD, as well as the role of de novo mutations, common variants, and genetic modifiers. For further mechanistic insight, we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts. Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis, thereby facilitating early intervention to improve outcomes for patients with CHD.

Cardiac Disease and Screening in Breeding Dogs.

Acquired and congenital heart diseases are relatively common in dogs, particularly in certain breeds. Modes of inheritance and genetic causes have been established for several cardiac diseases within various breeds. Breed screening is used to try and reduce the prevalence of certain canine cardiac diseases. Although breed screening seems to help reduce the prevalence of canine heart disease, the outcomes of specific breeding programs are variable and depend on multiple factors.

A retrospective study of congenital cardiac malformations in 29 goats.

Cardiac malformations are sporadically diagnosed in domestic species; however, little literature is available for this group of developmental anomalies in goats. We performed a retrospective study to catalog congenital cardiac conditions in goats submitted to the University of California-Davis, Veterinary Medical Teaching Hospital, Anatomic Pathology Autopsy Service. From 2000 to 2021, of 1,886 goat autopsies, 29 cases of cardiac malformations were identified (1.5%). Thirteen were ≤ 2-wk-old, 8 were 1-6-mo-old, and 8 were adults 2-9-y-old. The most common malformations were ventricular septal defect (VSD; 21 of 29), atrial septal defect or persistent foramen ovale (10 of 29), and double-outlet right ventricle (3 of 29). Nine cases had > 1 malformation, typically including a VSD. Conditions that had not been reported in the goat included double-outlet right ventricle (3), tetralogy of Fallot (1), cor triatriatum sinister (1), and mitral valve dysplasia (1). Two adult cases were incidental and not suspected clinically. Cardiac malformations occur not uncommonly in goats and should be considered in a wide age range.