Variants of the promoter of MYH6 gene in congenital isolated and sporadic patent ductus arteriosus: case-control study and cellular functional analyses.

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.

A histological study of the adult ligamentum arteriosum: Novel findings with application to a patent ductus arteriosus.

The ligamentum arteriosum (LA) is the vestigial fibrous remnant of the ductus arteriosus (DA), a fetal vessel arising from the left dorsal segment of the sixth aortic arch that connects the left pulmonary artery to the aortic arch. Incomplete obliteration of the DA results in a patent ductus arteriosus (PDA), causing the shunting of oxygen-rich blood to recirculate to the lungs, which can lead to pulmonary hypertension. The current study aims to further elucidate the structural characteristics of the LA via histological analysis with data gathered from adult cadaveric specimens. The LA was harvested and histologically observed with Hematoxylin and Eosin, van Gieson, and Masson's trichrome staining. Fibrous and muscle tissues were observed in all 25 specimens. The LA was categorized into three types based on the morphological features of the LA. Type I (vessel-like structure), type II (fibrotic tissue with duct-like structure), and type III (no duct-like structure) were found in 4.0%, 80.0%, and 16.0%, respectively. Finally, the remnant of a valve in the LA was also observed at the junction between the AA and LA. We suggest that this valve be called the "pulmonary-aortic valve." In the majority of the adult LAs, a duct-like structure was still present. These data could better elucidate our understanding of the pathology and etiology of a PDA.

A harmful MYH11 variant detected in a family with thoracic aortic dissection and patent ductus arteriosus.

Thoracic aortic dissection (TAD) is an important cause of sudden cardiac death and is characterized by high morbidity, mortality, and a poor prognosis. Patent ductus arteriosus (PDA) is a common congenital heart disease. The pathogenesis of both TAD and PDA has been reported to be related to genetic factors. The MYH11 gene, which encodes myosin heavy chain 11, has been reported in individuals with both TAD and PDA. Herein, we first detected a harmful MYH11 missense variant (c. T3728C, p. L1243P) in a TAD and PDA family. This missense variant co-segregated with the TAD/PDA phenotype in this family of four individuals, providing evidence of its harmfulness. Histopathological examinations revealed the presence of fragmented, broken, and lessened elastic fibers and the deposition of proteoglycans in the median of aortic dissection. Moreover, the immunofluorescence results showed that the labeled MYH11 protein in the tissue of the aortic dissection was weaker than that in the normal aorta. We present this familial case to stress the necessity of postmortem genetic testing in such cases among forensic practices. Identifying those culprit gene variants can direct effective genetic counseling and personalized health management in family members (especially first-degree relatives) with high-risk genotypes.

Clinical and neuroimaging features of a familial pathogenic ACTA2 variant as a model of a vascular neurocristopathy.

The clinical and neuroimaging findings of a family with a variant ACTA2 gene (c351C > G), presenting with smooth muscle dysfunction in structures of neural crest derivation, are discussed. The combination of aortic abnormalities, patent ductus arteriosus, congenital mydriasis and distinctive cerebrovascular and brain morphological abnormalities characterise this disorder. Two sisters, heterozygous for the variant, and their mother, a mosaic, are presented. Brain parenchymal changes are detailed for the first time in a non-Arg179His variant. Radiological features of the petrous canal and external carotid are highlighted. We explore the potential underlying biological and embryological mechanisms.

The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants.

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

Fibulin-1 Integrates Subendothelial Extracellular Matrices and Contributes to Anatomical Closure of the Ductus Arteriosus.

OBJECTIVE: The ductus arteriosus (DA) is a fetal artery connecting the aorta and pulmonary arteries. Progressive matrix remodeling, that is, intimal thickening (IT), occurs in the subendothelial region of DA to bring anatomic DA closure. IT is comprised of multiple ECMs (extracellular matrices) and migrated smooth muscle cells (SMCs). Because glycoprotein fibulin-1 binds to multiple ECMs and regulates morphogenesis during development, we investigated the role of fibulin-1 in DA closure. Approach and Results: Fibulin-1-deficient (Fbln1-/-) mice exhibited patent DA with hypoplastic IT. An unbiased transcriptome analysis revealed that EP4 (prostaglandin E receptor 4) stimulation markedly increased fibulin-1 in DA-SMCs via phospholipase C-NFκB (nuclear factor κB) signaling pathways. Fluorescence-activated cell sorting (FACS) analysis demonstrated that fibulin-1 binding protein versican was derived from DA-endothelial cells (ECs). We examined the effect of fibulin-1 on directional migration toward ECs in association with versican by using cocultured DA-SMCs and ECs. EP4 stimulation promoted directional DA-SMC migration toward ECs, which was attenuated by either silencing fibulin-1 or versican. Immunofluorescence demonstrated that fibulin-1 and versican V0/V1 were coexpressed at the IT of wild-type DA, whereas 30% of versican-deleted mice lacking a hyaluronan binding site displayed patent DA. Fibulin-1 expression was attenuated in the EP4-deficient mouse (Ptger4-/-) DA, which exhibits patent DA with hypoplastic IT, and fibulin-1 protein administration restored IT formation. In human DA, fibulin-1 and versican were abundantly expressed in SMCs and ECs, respectively. CONCLUSIONS: Fibulin-1 contributes to DA closure by forming an environment favoring directional SMC migration toward the subendothelial region, at least, in part, in combination with EC-derived versican and its binding partner hyaluronan.

The effects of ductal size on the severity of pulmonary hypertension in children with patent ductus arteriosus (PDA): a multi-center study.

INTRODUCTION: Patent ductus arteriosus (PDA) is a common acyanotic heart disease that presents with variable symptoms. OBJECTIVES: This study is therefore aimed at determining the relationship between gender, age, and size of PDA and pulmonary hypertension. This study also seeks to determine the prevalence of elevated pulmonary artery systolic pressure in children with PDA. PATIENTS AND METHODS: A descriptive study of children with patent ductus arteriosus was carried out from 2016 to 2020 in three institutions. The data were analysed with the IBM SPSS statistics for windows, version 20 (IBM Corp, Chicago) RESULT: The mean ductal size was 3.78 (2.39) mm, with a minimum of 1.0 mm and a maximum size of 10.0 mm. The mean ductal size for males, 4.02 (2.53) mm was comparable with that of the females, 3.61 (2.28) mm (Student T-test = 0.8, 0.4). The mean pulmonary artery systolic pressure (PASP) of the patients was 43.36 (24.46) mmHg. Also the mean PASP was comparable among the males and the females, 48.37 (26.69) mmHg versus 39.63 (22.16) mmHg (Student T-test = 1.81, p = 0.07). There was no correlation between age and PASP (correlation coefficient = 0.009, p = 0.92). Sixty point two percent (60.2%) (62/103) of children with PDA had pulmonary hypertension. The proportion of males with pulmonary hypertension, 48.39% (30/62) was comparable with that of the females, 51.61% (32/62) (Chi2 = 2.05, p = 0.15) and females are 1.8 times more likely to have pulmonary hypertension as males (odds ratio 1.81, 95% CI 0.8-4.1). There was a positive correlation between ductal size and PASP (Pearson correlation coefficient = 0.26, p value = 0.007). Those with moderate and large sized duct tend to have moderate and severe pulmonary hypertension respectively and this is statistically significant. Chi2 = 17.85, p = 0.007 CONCLUSION: The prevalence of pulmonary hypertension in children with PDA is 60.2%. Moderate and large size duct presents with moderate and severe pulmonary hypertension respectively. Females are 1.8 times more likely to have pulmonary hypertension than the males.

High prevalence of a linear valve-like structure on CT at the pulmonary artery terminus of patent ductus arteriosus in adult patients, mimicking endarteritis.

PURPOSE: A linear valve-like structure at the pulmonary artery terminus is identified on CT in some patients with patent ductus arteriosus (PDA) and can potentially be mistaken for endarteritis. The purpose of this study was to evaluate the differences in CT features between adult patients with PDA and a linear structure and those without. MATERIALS AND METHODS: We retrospectively evaluated ECG-gated cardiac CT of 38 patients with PDA dividing them into two groups [patients with linear symmetrical valve-like structure (group1, n = 16), and those without (group 2, n = 22)]. We analyzed CT findings of the PDA including length, minimal and maximal diameter, presence of calcification, and PDA type, comparing the two subgroups. The authors also investigated the prevalence of endarteritis. RESULTS: There was no difference in CT findings between the two groups in the prevalence of calcification and length, and minimal and maximal diameter of PDA. Notably the linear valve-like structure was only identified in type 1 PDA (cone-shaped PDA) (p = 0.04), while there were variable types of PDA in group 2. There was only one case of endarteritis as a complication of PDA in group 1. In contrast to a linear valve-like structure, asymmetrical nodular thickening was noted in the patient with endarteritis on CT overlying the pre-existing linear valve-like structure at the pulmonary end of PDA. CONCLUSION: A linear valve-like structure is frequently identified at the pulmonary end in type 1 PDA. This CT finding should not be mistaken for endarteritis in the absence of other clinical evidence.

Role of Extracellular Matrix in Pathophysiology of Patent Ductus Arteriosus: Emphasis on Vascular Remodeling.

The ductus arteriosus (DA) is a shunt vessel between the aorta and the pulmonary artery during the fetal period that is essential for the normal development of the fetus. Complete closure usually occurs after birth but the vessel might remain open in certain infants, as patent ductus arteriosus (PDA), causing morbidity or mortality. The mechanism of DA closure is a complex process involving an orchestration of cell-matrix interaction between smooth muscle cells (SMC), endothelial cells, and extracellular matrix (ECM). ECM is defined as the noncellular component secreted by cells that consists of macromolecules such as elastin, collagens, proteoglycan, hyaluronan, and noncollagenous glycoproteins. In addition to its role as a physical scaffold, ECM mediates diverse signaling that is critical in development, maintenance, and repair in the cardiovascular system. In this review, we aim to outline the current understandings of ECM and its role in the pathophysiology of PDA, with emphasis on DA remodeling and highlight future outlooks. The molecular diversity and plasticity of ECM present a rich array of potential therapeutic targets for the management of PDA.

The AP-2 Transcription Factor APTF-2 Is Required for Neuroblast and Epidermal Morphogenesis in Caenorhabditis elegans Embryogenesis.

The evolutionarily conserved family of AP-2 transcription factors (TF) regulates proliferation, differentiation, and apoptosis. Mutations in human AP-2 TF have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterized by craniofacial deformities and patent ductus arteriosus, respectively. How mutations in AP-2 TF cause the disease phenotypes is not well understood. Here, we characterize the aptf-2(qm27) allele in Caenorhabditis elegans, which carries a point mutation in the conserved DNA binding region of AP-2 TF. We show that compromised APTF-2 activity leads to defects in dorsal intercalation, aberrant ventral enclosure and elongation defects, ultimately culminating in the formation of morphologically deformed larvae or complete arrest during epidermal morphogenesis. Using cell lineaging, we demonstrate that APTF-2 regulates the timing of cell division, primarily in ABarp, D and C cell lineages to control the number of neuroblasts, muscle and epidermal cells. Live imaging revealed nuclear enrichment of APTF-2 in lineages affected by the qm27 mutation preceding the relevant morphogenetic events. Finally, we found that another AP-2 TF, APTF-4, is also essential for epidermal morphogenesis, in a similar yet independent manner. Thus, our study provides novel insight on the cellular-level functions of an AP-2 transcription factor in development.

High incidence of ductal closure or narrowing at birth in patients with right ventricular outflow tract obstruction with normal orientation of the ductus arteriosus.

BACKGROUND: Ductal patency is mandatory to manage patients with ductal-dependent pulmonary circulation. The aim of this study is to elucidate the morphological and haemodynamic features of ductus arteriosus with right ventricular outflow tract obstruction, and investigate the appropriate perinatal management.Patients and methodsPatients with prenatal diagnosis of right ventricular outflow tract obstruction at our institution between 2010 and 2015 were included in the study. Reverse orientation of the ductus arteriosus is defined as an inferior angle of 90°. We retrospectively reviewed the shape and flow pattern of ductus arteriosus and the clinical characteristics of the cases. RESULTS: A total of 39 patients were enrolled. The shape was divided into normal orientation (n=15) and reverse orientation (n=24) of the ductus arteriosus. There was no significant difference in the type of oxygen saturation at birth and age at shunt operation between both the groups. However, the median narrowest diameter of ductus arteriosus in the normal orientation group was significantly smaller than that in the reverse orientation group (2.0 [1.0-5.4] versus 3.0 [1.3-4.4] mm, p<0.05). In two patients of the normal orientation group, ductus arteriosus had closed at birth, and one of whom died because of severe cyanosis. CONCLUSIONS: Normal orientation pattern might have high incidence of an early narrowing or closure of ductus arteriosus at birth. The critical patients need careful evaluation by repeated foetal echocardiography and further maternal interventions.

A Patient-Specific Hollow Three-Dimensional Model for Simulating Percutaneous Occlusion of Patent Ductus Arteriosus.

Percutaneous catheter closure of patent ductus arteriosus (PDA) is difficult when the ductus is large and long or shows calcification. We created a patient-specific 3-dimensional (3D) model for PDA, with which we simulated device deployment, thereby selecting the device/size in a patient-by-patient manner. We assessed whether this 3D model is effective for catheter PDA closure.The 3D model was created in this institute, requiring 3 days and 90 US dollars. After its introduction, 7 consecutive patients (the study group) with severe PDA underwent closure with the aid of the 3D model. The control group consisted of 4 patients before 3D-model introduction, with all having severe PDA: the requirement of computed tomography was considered a criterion of severe or difficult-procedure-requiring PDA.In all study group patients, the devices/sizes could be pre-selected based on the simulation, whereas devices were changed during the procedure in 2 of 4 in the control group. In the study group, compared with the control group, the fluoroscopic (median 31 [interquartile range of 16-42] versus 39 [19-71] minutes, respectively) and total procedural times (median 107 [interquartile range 67-114] versus 124 [78-184] minutes, respectively) were shorter. A questionnaire confirmed the doctors' understanding of the procedure.This 3D model may be effective for percutaneous catheter closure of PDA. This may be especially true in cases of severe or difficult-procedure-requiring PDA.

Left atrium function and deformation in very preterm infants with and without volume load.

BACKGROUND: Left atrium (LA) function can be assessed by volumetric measurements, conventional and tissue Doppler, and more recently, deformation imaging using two-dimensional speckle tracking echocardiography (2DSTE). 2DSTE allows for measurement of volume and deformation and can quantify the contribution of the reservoir, conduit, and contraction phase. A common cause for LA dysfunction in very preterm infants is volume overload with a patent ductus arteriosus (PDA). The aim of this study was to explore the feasibility and reliability of LA 2DSTE in preterm infants, and describe LA function with and without PDA volume load. METHODS: We prospectively recruited preterm infants <30 weeks of gestation referred for assessment of a possible PDA. A cardiac ultrasound was performed at day 3 and in week 4 of life and analyzed using conventional techniques and 2DSTE. RESULTS: Forty-eight infants (32 with PDA) were included. LA 2DSTE analysis was feasible in 96% of measurements with good reliability of strain and volume parameters. Strain rate was less reliable. Poorer LA contraction and reservoir function was associated with larger LA volume index, higher inflow over the mitral valve at early diastole, higher EA ratio, and higher Ee' ratio. Poorer conduit function was associated with higher Ee' ratio. A larger PDA diameter was found to be an independent contributor to deteriorating LA contraction and reservoir function. CONCLUSION: LA 2DSTE analysis is feasible in preterm infants and provides detailed information on atrium mechanics. Further studies are needed to explore the clinical value of these new parameters in this population.

Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome.

De novo heterozygous mutations changing R179 to histidine, leucine, or cysteine in the ACTA2 gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). Characteristic hallmarks of this condition, caused only by these specific ACTA2 mutations, are congenital mydriasis (mid-dilated, non-reactive pupils), a large persistent ductus arteriosus (PDA), aortic aneurysms evolving during childhood, and cerebrovascular anomalies. We describe two patients, a 3-day-old newborn and a 26-year-old woman, with this unique mutation in association with a huge PDA and an aorto-pulmonary window. In addition, one showed a coarctation of the aortic arch and the other a complete interruption of the aortic arch type A; thereby expanding the spectrum of cardiac congenital heart defect of this syndrome. Each patient displayed a huge PDA and an extra-cardiovascular phenotype consistent with MSMDS. These observations exemplify that a functional alpha 2 smooth muscle actin is necessary for proper cardiovascular organ development, and demonstrate that a very exceptional congenital heart defect (aortopulmonary window) can be caused by a mutation in a gene encoding a contractile protein of vascular smooth muscle cells. © 2017 Wiley Periodicals, Inc.

CARDIAC MAGNETIC RESONANCE IMAGING OF PATENT DUCTUS ARTERIOSUS IN THREE DOGS.

Patent ductus arteriosus (PDA) is the most common congenital cardiovascular disorder in dogs and requires an accurate diagnosis for an appropriate treatment. Cardiac MRI (cMRI) has been reported as a method for characterization of canine thoracic vasculature. However, to the authors' knowledge, no published studies describe evaluation of canine PDA through cMRI. Three dogs were selected for this exploratory study. Electrocardiogram gating and breath-hold techniques were performed using a 3T MR scanner. Both black blood imaging and bright blood cine acquisitions were performed. Quantification of stroke volume (SV) and shunting volume were calculated using a stack of short-axis cine images. Additional 4D (three-spatial dimensions plus time)-TRAK (time-resolved MR angiography with keyhole) sequences were conducted in patient 2 to verify other vasculature abnormality. Black blood images clearly depicted the course of the ductus from the descending aorta to the pulmonary artery in all three dogs. Morphological evaluation of PDA classified patients 1 and 2 as Type 2a and patient 3 as Type 1. Patient 2 was confirmed to have a concurrent persistent left cranial vena cava. Left ventricular SV, right ventricular SV, and left-to-right SV ratio were 12.4 ml, 3.36 ml, and 3.704, respectively, in patient 1; 6.85 ml, 1.22 ml, and 5.60 in the patient 2; and 3.67 ml, 2.14 ml, and 1.702 in patient 3. Findings indicated that cMRI is a feasible method for characterizing the morphology of PDA and extracardiac vasculature anomalies in dogs.

[Periorbital pallor post application of mydriatic in infants with hydrocephalus associated to systemic effects]. / Palidez peri orbitaria post aplicación de midriaticos en neonatos con hidrocefalia asociado a efectos sistémicos.

Adequate pupil dilation is needed to evaluate some neonates at risk of developing illness during this stage. However, this procedure is not free of adverse effects, either local or systemic. One of these complications is the local vasoconstriction of the preterm baby’s skin following the application of mydriatic eye drops. OBJECTIVE: To describe secondary local and systemic complications of pharmacological pupil dilation in 2 newborns. Clinical case 1: Full term baby with diagnosis of low-birth weight and hydrocephalia. An ophtalmological evaluation was performed at 5 days of age due to the presence of corneal opacities. Peri ocular pallor was observed during the procedure, as well as tachycardia and hypertension 2 hours later, spontaneosly recovered. Case 2: Preterm newborn, 27 weeks of gestational age. Neonatal respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage and hydrocephalia were diagnosed at birth. At 28 days of life an ophtalmological evaluation was performed. After 10 minutes of mydriatic drops administration to evaluate preterm retinopathy, peri ocular pallor was observed, with spontaneous resolution; however, 24 hours later, the patient showed abdominal distention and feeding intolerance. Necrotizing enterocolitis was discarded, and symptoms were spontaneosly recovered. CONCLUSION: The establishment of protocols in relation to the number of drops to apply for dilation is needed to reduce deleterious effects on high risk infants, such as premature babies and those with hydrocephalus. Therefore this monitoring practice should be performed during the evaluation.

An analysis of cardiac defects and surgical interventions in 84 cases with full trisomy 18.

Trisomy 18 (Edwards syndrome) is the second most common autosomal trisomy after trisomy 21. Medical issues commonly include cardiac defects, such as ventricular septal defect (VSD) and atrial septal defect (ASD). If untreated, these conditions can contribute to the associated infant mortality. The objective of the study was review parent-reported information on 84 cases with full trisomy 18 focusing on prenatal and postnatal assessment and confirmation of cardiac defects and on subsequent treatment with cardiac surgery and post-surgery outcomes. At birth, 65 parent responses indicated the presence of VSD (77.4%), 38 ASD (45.2%), and 50 patent ductus arteriosus (PDA) (59.5%). The presence of multiple cardiac defects was also analyzed including 25 cases with VSD, ASD, and PDA at birth. The total reduced to 18 at survey completion. Twenty-four cases had one or more cardiac defects repaired for a total of 34 corrective surgeries. Age at surgery varied from 2 weeks to 41 months of age with most performed under 1 year of age. Twenty-one cases were still living at the time of survey completion (87.5%). From these date we provide recommendations and implications.

Epidemiology, presentation and population genetics of patent ductus arteriosus (PDA) in the Dutch Stabyhoun dog.

BACKGROUND: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in dogs and is considered to be a complex, polygenic threshold trait for which a female sex predisposition has been described. Histological studies in dogs suggest that smooth muscle hypoplasia and asymmetry of the ductus tissue is the major cause of PDA. The Stabyhoun population is small and a predisposition for PDA has been suggested. The aims of this study were to describe the incidence, presentation from a clinical and histopathological perspective, and the population genetics of PDA in the Dutch Stabyhoun population. RESULTS: Forty-six cases were identified between 2000 and 2013. Between 2009 and 2012 the birth incidence of PDA in the Stabyhoun breed was 1.05 %. We estimated this to be 7-13 times higher than expected in the general dog population. Twelve of the 46 cases were part of a litter in which more than one sibling was affected. There was no sex predilection in our case cohort. Dogs diagnosed in adulthood showed severe cardiomegaly. The mean inbreeding coefficient of the reference population of Stabyhoun dogs was 31.4 % and the actual and effective numbers of founders were 14 and 6.5, respectively. The heritability of PDA was 0.51 (±0.09) for the reference population and 0.41 (±0.10) for the phenotyped population. Histopathology of sections of the PDA from two dogs showed findings similar to those described in other breeds although the smooth muscle of the ductus adjacent to the pulmonary artery appeared more hypoplastic than that in the ductus adjacent to the aorta. CONCLUSIONS: The Stabyhoun breed shows a strong predisposition for PDA. Apart from the absence of a higher incidence in females, no other significant features distinguish PDA in Stabyhouns from the condition in other dog breeds. Heritability and the mean inbreeding coefficient are both very high making the Dutch Stabyhoun breed particularly suited to the study of inherited risk factors for PDA.

Optical coherence tomography imaging of the patent ductus arteriosus: first known uses in congenital heart disease.

BACKGROUND: Angiography is used to assess ductal morphology and caliber during interventional closure of the ductus arteriosus. We are evaluating the use of optical coherence tomography (OCT) to evaluate ductal anatomy given the potential benefit of superior resolution and lower radiation. METHODS: Standard angiograms were performed on two patients with patent ductus arteriosus prior to device occlusion. OCT was then used to obtain high-resolution three-dimensional vessel reconstructions. Devices were chosen based on angiographic measurements. RESULTS: OCT resulted in excellent three-dimensional anatomic definition, with elliptical narrowest lumenal measurements of 2.2 × 3.1 mm and 1.6 × 2.3 mm, respectively, compared with angiographic measurements of 2.6 and 1.4 mm. CONCLUSIONS: To our knowledge, this is the first reported use of OCT use in pediatric patients outside the coronaries, and in patients with congenital heart disease. We found OCT imaging of the PDA to be feasible, and only used a small amount of additional radiation and contrast. The three-dimensional OCT reconstructions provided additional anatomic information that could potentially improve device selection, and in both cases may have led to choosing larger devices than what was chosen based on angiography. In addition, once the technique is perfected, little or no angiography or fluoroscopy will be required to perform imaging runs, and only a small injection of contrast appears to be sufficient for vessel imaging. However, there are certain limitations to OCT imaging that are unlikely to make it the method of choice specifically for imaging the patent ductus arteriosus, but we have shown its ability to provide high resolution imaging in a relatively simple fashion which may prove useful for other purposes. © 2014 Wiley Periodicals, Inc.

Surveillance of congenital malformations in infants conceived through assisted reproductive technology or other fertility treatments.

BACKGROUND: As assisted reproductive technology (ART) becomes more common, it is important to understand the associated risks. The objective of this study was to determine if congenital malformations are associated with ART or other fertility treatments in New York. METHODS: In a retrospective cohort study of all live births in upstate New York from 1997 to 2005, exposure was defined using ART or other fertility treatments as noted on birth certificates. Outcomes were assessed from the New York State Congenital Malformations Registry. Specific malformations were examined to determine if there is elevated risk for exposed singleton infants compared with infants conceived naturally. RESULTS: The study included 7120 in the ART group, 11,890 in the other fertility treatments group and 1,118,162 in the comparison group. The relative risk for a congenital malformation was 1.43 (95% CI 1.19-1.72) for singleton infants conceived through ART compared with singleton infants conceived naturally. The specific defects associated with ART were patent ductus arteriosus, hypospadias, and obstructive defect in the renal pelvis and ureter, while spina bifida, other specific anomalies of the spinal cord, atresia or stenosis of the pulmonary valve, hypospadias, and obstructive defects of the renal pelvis and ureter were associated with other fertility treatment. CONCLUSION: Assisted reproductive technology is associated with a slight excess risk of birth defects. The specific congenital malformations with elevated risks for singleton infants vary depending on the exposure. Further research is necessary to understand the mechanism related to the increase in risk.