Progress of biodegradable polymer application in cardiac occluders.

Cardiac septal defect is the most prevalent congenital heart disease and is typically treated with open-heart surgery under cardiopulmonary bypass. Since the 1990s, with the advancement of interventional techniques and minimally invasive transthoracic closure techniques, cardiac occluder implantation represented by the Amplazter products has been the preferred treatment option. Currently, most occlusion devices used in clinical settings are primarily composed of Nitinol as the skeleton. Nevertheless, long-term follow-up studies have revealed various complications related to metal skeletons, including hemolysis, thrombus, metal allergy, cardiac erosion, and even severe atrioventricular block. Thus, occlusion devices made of biodegradable materials have become the focus of research. Over the past two decades, several bioabsorbable cardiac occluders for ventricular septal defect and atrial septal defect have been designed and trialed on animals or humans. This review summarizes the research progress of bioabsorbable cardiac occluders, the advantages and disadvantages of different biodegradable polymers used to fabricate occluders, and discusses future research directions concerning the structures and materials of bioabsorbable cardiac occluders.

Automatic echocardiographic anomalies interpretation using a stacked residual-dense network model.

Echocardiographic interpretation during the prenatal or postnatal period is important for diagnosing cardiac septal abnormalities. However, manual interpretation can be time consuming and subject to human error. Automatic segmentation of echocardiogram can support cardiologists in making an initial interpretation. However, such a process does not always provide straightforward information to make a complete interpretation. The segmentation process only identifies the region of cardiac septal abnormality, whereas complete interpretation should determine based on the position of defect. In this study, we proposed a stacked residual-dense network model to segment the entire region of cardiac and classifying their defect positions to generate automatic echocardiographic interpretation. We proposed the generalization model with incorporated two modalities: prenatal and postnatal echocardiography. To further evaluate the effectiveness of our model, its performance was verified by five cardiologists. We develop a pipeline process using 1345 echocardiograms for training data and 181 echocardiograms for unseen data from prospective patients acquired during standard clinical practice at Muhammad Hoesin General Hospital in Indonesia. As a result, the proposed model produced of 58.17% intersection over union (IoU), 75.75% dice similarity coefficient (DSC), and 76.36% mean average precision (mAP) for the validation data. Using unseen data, we achieved 42.39% IoU, 55.72% DSC, and 51.04% mAP. Further, the classification of defect positions using unseen data had approximately 92.27% accuracy, 94.33% specificity, and 92.05% sensitivity. Finally, our proposed model is validated with human expert with varying Kappa value. On average, these results hold promise of increasing suitability in clinical practice as a supporting diagnostic tool for establishing the diagnosis.

Discovery of GJC1 (Cx45) as a New Gene Underlying Congenital Heart Disease and Arrhythmias.

As the most prevalent type of birth malformation, congenital heart disease (CHD) gives rise to substantial mortality and morbidity as well as a socioeconomic burden. Although aggregating investigations highlight the genetic basis for CHD, the genetic determinants underpinning CHD remain largely obscure. In this research, a Chinese family suffering from autosomal dominant CHD (atrial septal defect) and arrhythmias was enrolled. A genome-wide genotyping with microsatellite markers followed by linkage assay as well as sequencing analysis was conducted. The functional effects of the discovered genetic mutation were characterized by dual patch-clamp electrophysiological recordings in N2A cells and propidium iodide uptake assays in HeLa cells. As a result, a novel genetic locus for CHD and arrhythmias was located on chromosome 17q21.31-q21.33, a 4.82-cM (5.12 Mb) region between two markers of D17S1861 and D17S1795. Sequencing assays of the genes at the mapped locus unveiled a novel heterozygous mutation in the GJC1 gene coding for connexin 45 (Cx45), NM_005497.4:c.550A>G;p.R184G, which was in co-segregation with the disease in the whole family and was not observed in 516 unrelated healthy individuals or gnomAD. Electrophysiological analyses revealed that the mutation significantly diminished the coupling conductance in homomeric cell pairs (R184G/R184G) and in cell pairs expressing either R184G/Cx45 or R184G/Cx43. Propidium iodide uptake experiments demonstrated that the Cx45 R184G mutation did not increase the Cx45 hemichannel function. This investigation locates a new genetic locus linked to CHD and arrhythmias on chromosome 17q21.31-q21.33 and indicates GJC1 as a novel gene predisposing to CHD and arrhythmias, implying clinical implications for prognostic risk assessment and personalized management of patients affected with CHD and arrhythmias.

Extravascular MDCT Findings of Pulmonary Vein Stenosis in Children with Cardiac Septal Defect.

Purpose: To retrospectively investigate the extravascular thoracic MDCT angiography findings of pulmonary vein stenosis (PVS) in children with a cardiac septal defect. Materials and Methods: Pediatric patients (age ≤ 18 years) with cardiac septal defect and PVS, confirmed by echocardiogram and/or conventional angiography, who underwent thoracic MDCT angiography studies from April 2009 to April 2021 were included. Two pediatric radiologists independently evaluated thoracic MDCT angiography studies for the presence of extravascular thoracic abnormalities in: (1) lung and airway (ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, septal thickening, fibrosis, and bronchiectasis); (2) pleura (pleural thickening, pleural effusion, and pneumothorax); and (3) mediastinum (mass and lymphadenopathy). Interobserver agreement between the two independent pediatric radiology reviewers was evaluated with kappa statistics. Results: The final study group consisted of 20 thoracic MDCT angiography studies from 20 consecutive individual pediatric patients (13 males (65%) and 7 females (35%); mean age: 7.5 months; SD: 12.7; range: 2 days to 7 months) with cardiac septal defect and PVS. The characteristic extravascular thoracic MDCT angiography findings were GGO (18/20; 90%), septal thickening (9/20; 45%), pleural thickening (16/20; 80%), and ill-defined, mildly heterogeneously enhancing, non-calcified soft tissue mass (9/20; 45%) following the contours of PVS in the mediastinum. There was a high interobserver kappa agreement between two independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (k = 0.99). Conclusion: PVS in children with a cardiac septal defect has a characteristic extravascular thoracic MDCT angiography finding. In the lungs and pleura, GGO, septal thickening, and pleural thickening are frequently seen in children with cardiac septal defect and PVS. In the mediastinum, a mildly heterogeneously enhancing, non-calcified soft tissue mass in the distribution of PVS in the mediastinum is seen in close to half of the pediatric patients with cardiac septal defect and PVS.

Ankyrin repeat domain 1: A novel gene for cardiac septal defects.

INTRODUCTION: Cardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (ANKRD1) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the ANKRD1 mutation and cardiac septal defects has not been described. METHODS: We examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation. RESULTS: A heterozygous, missense variant of ANKRD1 (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co-activated with NKX2.5, ANKRD1 repressed ANF expression as assessed by a dual-luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318 ± 0.018 versus 0.564 ± 0.048, p < 0.01). A real-time polymerase chain reaction confirmed that p.S187F mutation of ANKRD1 decreased the expression of endogenous ANF (0.85 ± 0.05 versus 0.61 ± 0.04, p < 0.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of ANKRD1. CONCLUSIONS: The present study is the first to identify the p.S187F mutant of ANKRD1, which is associated with cardiac septal defects.

Endoscopic management of perforations, leaks and fistulas.

The endoscopic management armamentarium of gastrointestinal disruptions including perforations, leaks, and fistulas has slowly but steadily broadened in recent years. Previously limited to surgical or conservative medical management, innovations in advanced endoscopic techniques like natural orifice transluminal endoscopic surgery (NOTES) have paved the path towards development of endoscopic closure techniques. Early recognition of a gastrointestinal defect is the most important independent variable in determining successful endoscopic closure and patient outcome. Some devices including through the scope clips and stents have been well studied for other indications and have produced encouraging results in closure of gastrointestinal perforations, leaks and fistulas. Over the scope clips, endoscopic sutures, vacuum therapy, glue, and cardiac device occluders are other alternative techniques that can be employed for successful endoscopic closure.

Endoscopic closure of acquired oesophagorespiratory fistulas with cardiac septal defect occluders or vascular plugs.

OBJECTIVES: To report an endoscopic treatment for inoperable oesophagorespiratory fistulas (ORFs). PATIENTS AND METHODS: Six patients with inoperable acquired tracheobronchial-oesophageal fistulas (four males and two females; mean age, 70.2 ± 10.28 years) were included. Cardiac septal defect occluders or vascular plugs were implanted through a flexible bronchoscope to close the ORFs. Monthly follow-ups were done for 16 months. RESULTS: All fistulas were successfully closed immediately after the procedure. The severe aspirated pneumonia was controlled in 7-10 days. The two mechanically ventilated patients were weaned successfully from the ventilator, and the general condition of patients improved rapidly. However, the fistulas recanalised in four patients because of the cutting effect of the edge of the occluders 1-12 months after the procedure. Other reasons, such as compression of the tracheal intubation balloon and repeated inflammation of the oesophageal diverticulum, may also have contributed to the recanalisation. CONCLUSIONS: Endoscopic closure of acquired ORFs with cardiac septal defect occluders or vascular plugs improve patients' general condition immediately after the procedure, but may result in recanalisation longterm. The occlusion might be considered an abridgement to surgery.

Mesodermal expression of Moz is necessary for cardiac septum development.

Ventricular septal defects (VSDs) are the most commonly occurring congenital heart defect. They are regularly associated with complex syndromes, including DiGeorge syndrome and Holt-Oram syndrome, which are characterised by haploinsufficiency for the T-box transcription factors TBX1 and TBX5, respectively. The histone acetyltransferase monocytic leukaemia zinc finger protein, MOZ (MYST3/KAT6A), is required for the expression of the Tbx1 and Tbx5 genes. Homozygous loss of MOZ results in DiGeorge syndrome-like defects including VSD. The Moz gene is expressed in the ectodermal, mesodermal and endodermal aspects of the developing pharyngeal apparatus and heart; however it is unclear in which of these tissues MOZ is required for heart development. The role of MOZ in the activation of Tbx1 would suggest a requirement for MOZ in the mesoderm, because deletion of Tbx1 in the mesoderm causes VSDs. Here, we investigated the tissue-specific requirements for MOZ in the mesoderm. We demonstrate that Mesp1-cre-mediated deletion of Moz results in high penetrance of VSDs and overriding aorta and a significant decrease in MOZ-dependant Tbx1 and Tbx5 expression. Together, our data suggest that the molecular pathogenesis of VSDs in Moz germline mutant mice is due to loss of MOZ-dependant activation of mesodermal Tbx1 and Tbx5 expression.

New devices and techniques for handling adverse events: claw, suture, or cover?

Increasingly invasive therapeutic endoscopic procedures and laparoscopic surgeries have resulted in endoscopists being challenged more frequently with perforations, fistulas, and anastomotic leakages, for which nonsurgical closure is desired. Devices and techniques are available and in development for endoscopic closure of gastrointestinal wall defects. Currently available devices with excellent clinical success rates include the over-the-scope clip and an endoscopic suturing system. Another device, the cardiac septal defect occluder, has been adapted for use in the gastrointestinal tract. Extensive endoscopic knowledge, a highly trained endoscopy team, and the availability of devices and equipment are required to manage complications endoscopically.