Search Results (228)

The development process of the heart and cardiovascular system is fundamental in human development and highly regulated by genetic factors. This process needs to be highly regulated to prevent malformations. Nevertheless, some heart defects may be identified, especially with modern imaging methodology. Atrial septal defects (ASDs) are particularly common. Understanding the mechanisms involved in ASD formation is fundamental for developing new treatment strategies. In this article, we explore cardiac development and embryology, with a focus on atrial septal defects and their clinical implications. Full article

The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. On presentation to hospital, she was cyanotic, with clubbed fingers, and hemodynamically unstable, in sinus rhythm, with Eisenmenger syndrome and respiratory failure partially responsive to oxygen. During pregnancy, owing to systemic vasodilatation, the right-to-left shunt is increased, with more severe cyanosis and low cardiac output. Echocardiography revealed the complete common atrioventricular canal defect, with a single atrioventricular valve with severe regurgitation, right ventricular hypertrophy, pulmonary artery dilatation, severe pulmonary hypertension and a hypoplastic left ventricle. The gestational age at delivery was 38 weeks. She gave birth to a healthy boy, with an Apgar score of 10. The vaginal delivery was chosen by an interdisciplinary team. The cesarean delivery and the anesthesia were considered too risky compared to vaginal delivery. Three days later, the patient died. The autopsy revealed hepatomegaly, a greatly hypertrophied right ventricle with a purplish clot ascending the dilated pulmonary arteries and a hypoplastic left ventricle with a narrowed chamber. A single valve was observed between the atria and ventricles, making all four heart chambers communicate, also insufficiently developed interventricular septum and its congenital absence in the cranial third. These morphological changes indicate the complete common atrioventricular canal defect, with right ventricular dominance, which is a rare and impressive malformation that requires mandatory treatment in early childhood in order for the condition to be solved. Full article

Hypoplastic or absent fetal nasal bone (NB) is a significant soft marker in the risk assessment for aneuploidies. This study aimed to evaluate prenatal findings and perinatal outcomes in fetuses with absent or hypoplastic NB managed at our center. This retrospective analysis was conducted at the Department of Obstetrics at the Medical University of Vienna and including all cases with an absent or hypoplastic fetal NB between 2004 and 2022. Clinical data were extracted and analyzed using descriptive statistics. A total of 149 cases were included. Of these, 51% had chromosomal abnormalities, with trisomy 21 present in 30.9%. Malformations were identified in 55% of cases, most commonly congenital heart defects (34.9%) and facial dysmorphism (28.9%). Eighteen fetuses (12.1%) had structural anomalies without genetic disorders. In 32.9% (n = 49), the NB anomaly was isolated. Our findings show that only half of the cases had chromosomal abnormalities, and over half of the pregnancies resulted in live births with generally favorable perinatal outcomes. However, the presence of additional ultrasound abnormalities significantly increased the risk of adverse outcomes. Therefore, detection of a fetal NB anomaly should prompt comprehensive ultrasound evaluation and genetic testing. Full article

Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes. Full article

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are increasingly used in patients with type 2 diabetes, chronic kidney disease, and heart failure. However, their safety and efficacy in patients with congenital or surgically altered urogenital anatomy remains underexplored. Methods: We conducted a narrative review of current evidence regarding the use of SGLT2i in patients with urinary tract malformations, urinary diversions, and functional voiding disorders. Key risks, clinical considerations, and management strategies were synthesized from the existing literature and case reports. Results: Patients with benign prostatic hyperplasia, vesicoureteral reflux, neurogenic bladder, nephrostomies, and ileal conduits may face increased risks of urinary tract infections, fungal colonization, and therapy-related complications due to persistent glycosuria and altered urinary flow. Nevertheless, these patients may still benefit from SGLT2i’s systemic renal and cardiovascular effects. Individualized risk assessment, close monitoring, and multidisciplinary management are essential. Conclusions: Patients with urological abnormalities represent a high-risk but potentially high-reward population for SGLT2i therapy. A cautious, tailored approach is necessary, and future dedicated research is urgently needed to better guide clinical practice. Full article

Congenital heart diseases (CHDs) are among the most common congenital malformations. Despite significant advancements in understanding the embryonic development of the heart, the etiology of CHDs remains largely unknown. The complexity of the processes involved in heart formation limits our ability to identify all molecular mechanisms underlying CHDs. Recently, microRNAs (miRNAs) have provided new insights into the molecular mechanisms of CHDs. This narrative review evaluates the evidence linking expression to CHDs and discusses the potential of RNA expression regulation as a promising avenue for therapeutic biomarker development. A search of the literature, focusing on the role of miRNAs in CHDs, was carried out to identify pertinent studies published over the last decade. The literature search was performed utilizing the PubMed and Scopus databases. The selection criteria included peer-reviewed original studies, clinical research, meta-analyses, and review articles written in English. Multiple investigations have highlighted the essential role of miRNAs in cardiac development and function, showing that their distinct expression patterns can broadly and specifically influence cellular signaling pathways involved in heart abnormalities. The regulation of mRNA expression emerges as a key factor in the pathogenesis of CHD, paving the way for the identification of novel molecular biomarkers. Alterations in transcriptional profiles could offer innovative and highly specific tools for risk stratification and the clinical monitoring of patients. In conclusion, although further studies are needed to validate the efficacy and clinical applicability of these biomarkers, the mRNA-based approach stands out as a promising perspective for precision medicine in the CHD context. Full article

Introduction: Tuberous sclerosis complex (TSC) is a rare multisystemic genetic disorder characterized by the formation of benign tumors in various organs, including the central nervous system, skin, kidneys, and heart. The diagnosis is based on well-defined clinical criteria, such as those from Schwartz (2007) updated in 2012 by the International Tuberous Sclerosis Complex Consensus Group. The study aims to investigate the clinical, imaging, and molecular characteristics of patients diagnosed with tuberous sclerosis and to explore the correlation between specific genetic mutations (TSC1 and TSC2 genes) and the severity of clinical manifestations. Material and Methods: This is a retrospective longitudinal study of 13 patients diagnosed with tuberous sclerosis, identified in the records of the Bihor Regional Center for Medical Genetics (BRCMG) within the Bihor County Emergency Clinical Hospital from 1984 to 2024. Clinical, imaging, and molecular features were assessed. Patients were evaluated by a multidisciplinary team, including a geneticist, pediatrician, neurologist, psychiatrist, and psychologist. Clinical and imaging data were retrospectively collected from the congenital malformations and genetic disease records of BRCMG Bihor and statistically analyzed. Results: All patients showed clinical and imaging signs consistent with the diagnosis of tuberous sclerosis. Neurological manifestations were present in 83% of patients, including epilepsy and cognitive delays. Renal lesions were detected in 46% of cases, and dermatological lesions, such as facial angiofibromas, were observed in 69% of patients. Mutational variants identified in the TSC2 gene correlated with a more severe clinical presentation, including severe intellectual disability and treatment-resistant seizures, compared to variants in the TSC1 gene. Conclusions: Our study, although involving a small number of patients, highlights the clinical heterogeneity of tuberous sclerosis and the importance of a multidisciplinary approach in patient management. Early diagnosis and ongoing monitoring are essential to improving the quality of life for patients. Further studies are needed to assess the impact of therapeutic interventions and genetic correlations within the studied population. Full article

Background and Clinical Significance: We report on an infant with Snijders Blok–Campeau syndrome (psychomotor developmental delay, CNS malformations) and a complex heart defect with pulmonary arterial hypertension. Case Presentation: A DDX3X mutation encoding for RNA helicase was detected, which may suggest an association between Snijders Blok–Campeau syndrome and the development of pulmonary vasculopathy. However, further validation is required. Conclusions: We suggest an important role for DDX3X in the development of the pulmonary vasculature. Full article

Background: Palliative surgery for the treatment of functionally univentricular heart malformations consists of a staged approach to separation of the pulmonary and systemic circulation, including the creation of a superior cavopulmonary connection. Literature on the superior cavopulmonary connection in porcine models lacks information on details of the procedure as well as data on its acute hemodynamic effects. In preliminary experiments, we were unable to reproduce an already published porcine model. Therefore, we used a conduit extension and cardiopulmonary bypass in order to achieve hemodynamic stability and still employ the commonly used straight downward pathway for the superior caval vein onto the right pulmonary artery, as in the human clinical setting. This model of a univentricular circulation utilising the superior cavopulmonary anastomosis is intended to be applied in the setting of unilateral diaphragmatic palsy. Hence, we aim to investigate the effect of unilateral diaphragmatic pacing in a reproducible model of univentricular physiology. Methods: Therefore, we constructed an anastomosis between the superior caval vein and the right pulmonary artery (RPA) in 14 pigs on cardiopulmonary bypass using a 12 mm expanded polytetrafluorethylene interposition graft. Six pigs received a bidirectional cavopulmonary connection with unrestricted atrial septal communication (BDCPC), while eight pigs received a unidirectional cavopulmonary connection (UDCPC) to the excluded RPA. Results: The BDCPC resulted in an impaired cardiopulmonary state (cardiac output dropped from 3.15 ± 0.21 to 2.17 ± 0.19 L/min; p < 0.01), mean arterial pressure plummeted (from 80.8 ± 3.7 to 49.3 ± 7.3 mmHg; p = 0.02), arterial lactate concentration rose (from 0.82 ± 0.09 to 4.36 ± 0.96 mmol/L; p = 0.01), arterial oxygen saturation dropped (from 95.8 ± 1.1 to 60.9 ± 10.4%; p < 0.01), and right ventricular function deteriorated (tricuspid annular plane systolic excursion decreased from 12 ± 0.7 to 5 ± 0.7 mm; p < 0.01). In contrast, in the UDCPC group, the cardiopulmonary parameters indicated a stable condition. Conclusions: Consequently, a UDCPC is a more suitable acute model in pigs for a univentricular circulation. The model’s reproducibility may aid in future research on partial cavopulmonary connection. Full article

This study assessed the toxicity and therapeutic potential of Angelica dahurica and Angelica pubescens using Danio rerio (zebrafish) larvae. Toxicity was evaluated through mortality, malformations, and gene expression changes related to stress and the HPA axis. A. dahurica demonstrated low toxicity (LD50 (50% lethal dose) >200 µg/mL), with no significant malformations at 15–30 µg/mL, although higher doses caused edemas and heart defects. A. pubescens exhibited higher toxicity, with 100% mortality at 200 µg/mL and severe malformations. Both species showed potential cardiotoxicity, slowing heart rates after prolonged exposure. Gene expression studies suggested A. dahurica had stress-protective effects, increasing nr3c1 expression, while A. pubescens had dose-dependent effects, with lower concentrations having anxiolytic properties and higher concentrations increasing stress. Interestingly, diazepam showed unexpected gene expression changes, highlighting the influence of environmental and dosage factors. In conclusion, both species show therapeutic potential for anxiety, with A. dahurica showing promising effects at lower concentrations. However, A. pubescens requires careful dosage management due to its higher toxicity risks. Further studies are needed to optimize therapeutic applications and fully understand mechanisms of action. Full article

Background: Craniofacial malformations lie at the heart of fetal alcohol spectrum disorders (FASDs). While there is growing evidence for a genetic component in FASDs, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. The bone morphogenetic protein (Bmp) signaling pathway-dependent endoderm pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3, may mediate the impact of ethanol on Bmp mutants. Methods: We use an ethanol exposure paradigm with nkx2.3 knockdown approaches to test if nkx2.3 loss sensitizes Bmp mutants to ethanol-induced facial defects. We combine morphometric approaches with immunofluorescence and a hybridization chain reaction to examine the cellular mechanisms underlying Bmp–ethanol interactions. Results: We show that Bmp–ethanol interactions alter the morphology of the endodermal pouches, independent of nkx2.3 gene expression. Knockdown of nkx2.3 does not sensitize wild-type or Bmp mutants to ethanol-induced facial defects. However, we did observe a significant increase in CNCC apoptosis in ethanol-treated Bmp mutants, suggesting an ethanol sensitive, Bmp-dependent signaling pathway driving tissue interactions at the heart of FASDs. Conclusions: Collectively, our work builds on the mechanistic understanding of ethanol-sensitive genes and lays the groundwork for complex multi-tissue signaling events that have yet to be explored. Ultimately, our work provides a mechanistic paradigm of ethanol-induced facial defects and connects ethanol exposure with complex tissue signaling events that drive development. Full article

Background/Objectives: It is increasingly realized that the advances in diagnosis and treatment for those born with congenitally malformed hearts have now resulted in avoidance of morbidity being equally as important as avoiding postoperative mortality. Detailed personalized diagnoses will now be key to achieve such improvements. Methods: We have reviewed our own experience in diagnosing major phenotypic variations on selected congenital cardiac malformations, showing that the ability to personalize the findings is at hand, although not always to date universally employed. Results: We have chosen four categories to illustrate how the definitions now provided by the International Nomenclature Society, and incorporated in the 11th iteration of the International Classification of Disease, make it possible to provide personalized diagnoses. The lesions chosen for review are the arrangement of the atrial appendages, the lesions permitting interatrial shunting, the options in the setting of deficient ventricular septation, and the abnormal morphology of the aortic root. We show that not all centers, as yet, are taking advances of these opportunities at hand to tailor the chosen treatments. Conclusions: Detailed phenotypic definitions have now been provided for all the major congenital cardiac malformations. Use of these definitions should now provide personalized medicine for all those born with malformed hearts. As yet, the definitions are not used to their full effect. Full article

While the heart works as an efficient pump, it also has a high level of adaptivity by changing its structure to maintain function during healthy and diseased states. In this Review, we present examples of structure–function relationships across species and throughout embryonic development in mammals and birds. We also summarize current research on avian models aiming at understanding how biophysical and biological mechanisms closely interact during heart formation. We conclude by underscoring similarities between cardiac adaptations and structural changes over developmental and evolutionary time scales and how understanding the mechanisms behind these adaptations can help prevent or alleviate the effects of cardiac malformations and contribute to cardiac regeneration efforts. Full article

Congenital heart diseases (CHDs) are structural anomalies present at birth, resulting from aberrant embryonic development. In veterinary medicine, CHDs are an important reason for disease and death in both dogs and cats. Their prevalence varies across species and breeds, with certain defects being more common in specific breeds due to genetic predisposition. In this article, we will focus specifically on cor triatriatum dexter (CTD), an uncommon congenital defect that involves the division of the right atrium into two chambers by a fibromuscular membrane. This malformation can have serious consequences, depending on the severity of the obstruction created by the membrane, and the presence of the often-associated congenital anomalies. It can range from mild, clinically silent anomalies to severe defects that result in heart failure, cyanosis, or sudden death. The present review aims to (i) explore the pathophysiology of CTD in dogs; (ii) outline the clinical scenario underlying the increased interest in CHDs by overviewing the evolution of appropriate diagnostic techniques and the treatment options available; and (iii) provide a discussion from a medical–legal and ethical point of view. Full article