Complex Cardiac Malformations Research Articles

Right juxtaposition of left atrial appendage combined with multiple cardiac malformations: A case report and review of literature.

Juxtaposition of the atrial appendages is an extremely rare congenital cardiac malformation. It is usually discovered incidentally during autopsy or surgery. This report aims to increase awareness of right juxtaposition of the left atrial appendage. We report a Chinese Han female aged 2years and 10months with recurrent lung infections after birth, who was diagnosed with congenital heart disease, corrected transposition of the great arteries, ventricular septal defect, and arterial ductus arteriosus at the local hospital and improved after the pulmonary artery banding procedure. The patient presented to our hospital with intermittent cough. During preoperative evaluation, a review of imaging data revealed a right juxtaposition of the left atrial appendage on enhanced computed tomography. Right juxtaposition of the left atrial appendage is a rare congenital heart anomaly that often occurs in conjunction with complex cardiac malformations. Diagnosis requires a combination of imaging modalities to improve detection rates. Careful identification of cardiac structures during surgery is crucial, as alterations in cardiac anatomy may increase surgical risks. For instance, the opening of juxtaposed atrial appendages could be mistaken for an atrial septal defect.

Echocardiogram Diagnosis of Complex Congenital Cardiac Malformations

Background: Complex congenital cardiac malformations rarely reported in literature Objective: Study was undertaken to define complex congenital cardiac malformations by Echocardiogram Materials and Methods: Prospective study included 101 children aged 2 to14 years, both male and female during March 2004 to February 2005 and July 2006 who attended in-patients & outpatient departments at Vyedhi Institute of Medical Sciences and Research Centre (VIMS & RC) and Sri Jayadeva Institute of Cardio-vascular Sciences and Research of Cardiology (SJICR), Bangalore, India. Clinical diagnosis was confirmed by relevant investigations and Echocardiography. Results: Complex congenital cardiac malformations presented in 16 (15.99%) of 101 children raising the total number of cardiac defects to 121. Majority 77 (76.2%) acyanotic cardiac malformations comprised of 29 (28.72%) Atrial Septal Defects (ASD) had 11 complex cardiac malformations. Three cases ASD + Partial Anomalous Pulmonary Venous Drainage (PAPVC), 2 cases ASD + Patent Ductus Arteriosus (PDA) + Mitral Valve prolapse (MVP), 2 cases ASD + Pulmonary Stenosis (PS,) 1 case ASD + PDA + PS, 1 case ASD + Ventricular Septal Defect (VSD), 1 case ASD + Coarctation of Aorta (CoA) and 1 case ASD + MVP. Next 23 (22.77%) VSD had 4 complex cardiac malformation cases, 3 cases of VSD + Aortic Stenosis (AS) of which one case had dextrocardia and 1 case VSD + PS. Followed by AS 8 (7.9%) with 1 case of AS + CoA, another case had VSD + AS. Among 24 (23.76%) cyanotic defects, TOF18 (17.8%) was the commonest, other rare variants included Double Outlet Right Ventricle (DORV) 4(3.96%) one case with dextrocardia. Pentalogy of Fallot 1 (0.99%) and Triology of Fallot 1 (0.99%). The age distribution revealed most 30(29.8%) were young children aged 2-4 years with overall male predominance Male:Female::1.3:1, observed contrasted to female predominance noted in ASD and TOF, M:F::1:2 and M:F::1:1.3 respectively Conclusion: Complex congenital cardiac malformations presented in 16(15.99%) of 101 children raising the total number of cardiac defects to 121

Clinical phenotype and genetic analysis of a fetus with Cardiac valvular dysplasia type 1

To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1). A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing. The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4). The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.

Clinical Presentation and Therapy of Anomalies of the Situs.

Situs abnormalities may occur in many and most often more complex congenital cardiac malformations. These conditions are collectively referred to as heterotaxy syndromes, derived from the Greek words "heteros" meaning different and "taxos" meaning orientation or arrangement. Clinically, heterotaxy spectrum encompasses defects in the left-right laterality and arrangement of visceral organs. "Situs" is derived from Latin and is the place where something exists or originates. In human anatomy, situs can be solitus (derived from Latin, meaning "normal"), inversus, or ambiguus. Heterotaxy syndrome represents an intermediate arrangement of internal organs between situs solitus and situs inversus, also known as "situs ambiguous." Situs ambiguus describes an abnormal distribution of major visceral organs within the chest and abdomen. The determination of situs as normal, inversus, or ambiguus is primarily based on the location of unpaired organs such as the spleen, liver, stomach, and intestines. Diagnosis is made by clinical examination, echocardiography, a chest X-ray (position of the heart, stomach, and liver), and ultrasound of the abdominal organs. Situs is considered solitus if the left atrium, spleen, stomach, and the trilobed lung are on the left side and the liver and bilobed lung are on the right side. Situs ambiguus is present if the location of unpaired structures is random or indeterminate even after detailed and appropriate imaging. Situs inversus results when the arrangement of the thoracic and abdominal organs is mirrored. Individuals with situs inversus or situs solitus do not experience fatal dysfunction of their organ systems, as general anatomy and morphology of the abdominothoracic organ-vessel systems are conserved.

Long-Term Results Following Combined Repair of Atrioventricular Septal Defect with Tetralogy of Fallot.

Atrioventricular septal defect (AVSD) in association with tetralogy of Fallot (TOF) is a rare and complex congenital cardiac malformation. We report our institutional experience and outcomes following surgical correction over a 20-year period. Patients who underwent combined surgical AVSD and TOF correction between October 2001 and February 2020 were included for analysis. All patients underwent primary repair. The study data were prospectively collected and retrospectively analyzed. Primary outcomes were in-hospital mortality and long-term freedom from reoperation. During the study period, a total of 10 consecutive patients underwent combined surgical AVSD and TOF correction. Median age at operation was 307days (IQR 228-457) and median weight was 7.7kg (IQR 6.7-9.5). Down Syndrome was present in six of the patients. In-hospital mortality was 0%. One patient required re-exploration due to bleeding. Median follow-up was 11years (IQR 11months -16years). There was one case of reoperation due to significant residual ventricular septal defect after 2 months. None of the patients died during follow-up. Combined primary AVSD and TOF repair can be performed with low early mortality and morbidity, as well as a high long-term freedom from reoperation.

Characterization of ultrasound and postnatal pathology in fetuses with heterotaxy syndrome.

To explore the diagnostic clues and abnormality spectrum of heterotaxy syndrome by prenatal ultrasonography and postnatal verification. The prenatal ultrasonic data of 88 heterotaxy syndrome fetuses were analyzed retrospectively as left isomerism (LI) and right isomerism (RI). Prenatal ultrasound compared with the anatomical casting of the fetal body after labor induction, and the confirmatory postnatal diagnosis after delivery. Fetal LI showed typical malformations of gastric vesicles on different sides from the heart, absence of hepatic segment of the inferior vena cava (IVC), abdominal aorta (AO) parallel with the azygos vein (AV), bilateral left bronchus, bilateral left atrial appendages, and polysplenia; intracardiac malformations of AV septal defects (AVSD), single atrium (SA), left ventricular outflow tract obstruction (LVOTO), and double-outlet right ventricle (DORV); and cardiac conduction abnormalities of sinus bradycardia and AV blockage. Fetal RI reported typical malformations of gastric vesicles on different sides from the heart, juxtaposition of the IVC with AO, anomalous pulmonary venous connection (APVC), asplenia, and bilateral right atrial appendages; intracardiac malformations of AVSD, SA, single ventricle, pulmonary atresia and stenosis, and DORV. The postnatal verification revealed 3 malformations misdiagnoses and 4 malformations missed diagnoses in LI fetuses and 10 misdiagnoses and 8 missed diagnoses in RI fetuses. The proposed five-step prenatal ultrasonography has an important diagnostic value for the identification and classification of heterotaxy syndrome. The different sides of gastric vesicles and cardiac apex are important diagnostic clues for heterotaxy syndrome, featuring disconnected or hypoplastic IVC, typical complex cardiac malformation, and atrioventricular block in fetal LI, and shown APVC, juxtaposition of IVC and AO, and intracardiac malformations such as AVSD, DORV, and LVOTO in fetal RI.

Congenital porto-pulmonary shunt in a dog

Congenital extra-hepatic porto-systemic shunts (CEPS) are a non-rare vascular anomaly observed in dogs, most commonly in small and toy pure breeds. Computed tomographic angiography (CTA) examination is considered the gold standard imaging modality for the diagnosis of anomalous vascular connections. An anomalous congenital porto-pulmonary shunt was incidentally diagnosed in a 5-year-old French Bulldog. The anomalous vessel originated from the ventral aspect of the portal vein and went cranially towards the esophageal hiatus, entering the lobar vein of the caudal left pulmonary lobe. The dog did not show any significant clinical or computed tomography angiography-perceived hepatic abnormalities and no signs of portal hypertension were evidenced. No case of porto-pulmonary shunt in veterinary medicine have ever been reported, while in humans it was rarely described secondarily to portal hypertension, severe hepatopathies or complex cardiac malformations. CTA must be considered the best imaging modality for the diagnosis also of unusual CEPS and in the author's opinion the congenital porto-pulmonary shunt described in the patient was of little or no clinical relevance.

3D modeling and printing for complex biventricular repair of double outlet right ventricle.

Double outlet right ventricle (DORV) describes a group of congenital heart defects where pulmonary artery and aorta originate completely or predominantly from the right ventricle. The individual anatomy of DORV patients varies widely with multiple subtypes classified. Although the majority of morphologies is suitable for biventricular repair (BVR), complex DORV anatomy can render univentricular palliation (UVP) the only option. Thus, patient-specific decision-making is critical for optimal surgical treatment planning. The evolution of image processing and rapid prototyping techniques facilitate the generation of detailed virtual and physical 3D models of the patient-specific anatomy which can support this important decision process within the Heart Team. The individual cardiovascular anatomy of nine patients with complex DORV, in whom surgical decision-making was not straightforward, was reconstructed from either computed tomography or magnetic resonance imaging data. 3D reconstructions were used to characterize the morphologic details of DORV, such as size and location of the ventricular septal defect (VSD), atrioventricular valve size, ventricular volumes, relationship between the great arteries and their spatial relation to the VSD, outflow tract obstructions, coronary artery anatomy, etc. Additionally, physical models were generated. Virtual and physical models were used in the preoperative assessment to determine surgical treatment strategy, either BVR vs. UVP. Median age at operation was 13.2 months (IQR: 9.6-24.0). The DORV transposition subtype was present in six patients, three patients had a DORV-ventricular septal defect subtype. Patient-specific reconstruction was feasible for all patients despite heterogeneous image quality. Complex BVR was feasible in 5/9 patients (55%). Reasons for unsuitability for BVR were AV valve chordae interfering with potential intraventricular baffle creation, ventricular hypoplasia and non-committed VSD morphology. Evaluation in particular of qualitative data from 3D models was considered to support comprehension of complex anatomy. Image-based 3D reconstruction of patient-specific intracardiac anatomy provides valuable additional information supporting decision-making processes and surgical planning in complex cardiac malformations. Further prospective studies are required to fully appreciate the benefits of 3D technology.

Aortopulmonary window, aortic arch interruption, and anomalous origin of the right pulmonary artery in a neonate with Goldenhar syndrome.

The combination of aortopulmonary window, interruption of the aortic arch, and anomalous origin of the right pulmonary artery from the ascending aorta is a rare and complex congenital cardiac malformation. Despite good prenatal care in our case, this cardiac anomaly was not detected prior to birth. Untreated infants who do not undergo surgical correction have a mortality rate of 70% in their first year, and 30% will die within the first 3 months of life.

Single Cell Sequencing Reveals Mechanisms of Persistent Truncus Arteriosus Formation after PDGFRα and PDGFRβ Double Knockout in Cardiac Neural Crest Cells.

Persistent truncus arteriosus (PTA) is an uncommon and complex congenital cardiac malformation accounting for about 1.2% of all congenital heart diseases (CHDs), which is caused by a deficiency in the embryonic heart outflow tract’s (OFT) septation and remodeling. PDGFRα and PDGFRβ double knockout (DKO) in cardiac neural crest cells (CNCCs) has been reported to cause PTA, but the underlying mechanisms remain unclear. Here, we constructed a PTA mouse model with PDGFRα and PDGFRβ double knockout in Pax3+ CNCCs and described the condensation failure into OFT septum of CNCC-derived cells due to disturbance of cell polarity in the DKO group. In addition, we further explored the mechanism with single-cell RNA sequencing. We found that two main cell differentiation trajectories into vascular smooth muscle cells (VSMCs) from cardiomyocytes (CMs) and mesenchymal cells (MSs), respectively, were interrupted in the DKO group. The process of CM differentiation into VSMC stagnated in a transitional CM I-like state, which contributed to the failure of OFT remodeling and muscular septum formation. On the other hand, a Penk+ transitional MS II cluster closely related to cell condensation into the OFT septum disappeared, which led to the OFT’s septation absence directly. In conclusion, the disturbance of CNCC-derived cells caused by PDGFRα and PDGFRβ knockout can lead to the OFT septation disorder and the occurrence of PTA.

De novo disruptive heterozygous MMP21 variants are potential predisposing genetic risk factors in Chinese Han heterotaxy children

BackgroundHeterotaxy syndrome (HTX) is caused by aberrant left–right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis.MethodsEighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX.ResultsThree MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX.ConclusionOur study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

Isolated hypoplastic right ventricle – a challenge in medical practice

Isolated right ventricle hypoplasia (IRVH) is a disease characterized by an underdeveloped right ventricle. It is a congenital heart disease than can associate heterogeneous structural defects and nonspecific clinical features, which can often present a challenging therapeutic management. In this article, there are presented diagnostic methods and treatment options for right ventricle hypoplasia (RVH) according to clinical features, patients age and associated structural heart defects. RVH has a different prognosis in accordance with the severity of the heart defects and the patient's age at which the diagnosis is established. Thus, isolated forms of RVH generally present mild structural and functional defects that can be associated with the onset of symptoms in adolescence or even in adulthood. In these cases, atrial septal defect closure with or without superior cavo-pulmonary anastomosis can be the only procedures needed to correct the hemodynamic abnormalities and relief the symptomatology. Patients with severe form of RVH associated with complex cardiac malformations and onset of the symptoms in the neonatal period require prompt intervention and necessitate palliative procedures. In the long term, these patients could need multiple reinterventions. The family physician should be aware of the cardiac origin of isolated symptoms or clinical signs, such as exertional dyspnea or clubbing fingers, and send the patient for pediatric cardiological evaluation.

EP17.33: Ultrasound difficulties in diagnosing a complex fetal cardiac malformation

EP17.33: Ultrasound difficulties in diagnosing a complex fetal cardiac malformation

Double root translocation: Early experience on performance of translocated aortic and pulmonary root.

Transposition of great arteries with ventricular septal defect and pulmonary stenosis is a complex congenital cardiac malformation with varied treatment options. Double root translocation is one of the described techniques with several advantages over other techniques. Our goal of this study is to report our early experiences on the performance of translocated aortic and pulmonary root. From 2016 to 2019, a total of 12 patients (seven boys and five girls) aged from one year to three years underwent double root translocation. All our patients were diagnosed with dextro-transposition of the great arteries (d-TGA)/double-outlet right ventricle (DORV), ventricular septal defect (VSD), and pulmonary stenosis (PS). One patient (8.33%) presented with (IL 2R CX), remaining 11 patients (91.66%) had (IL CX 2R) as their coronary pattern. Mean follow-up period was two years (1-3 years). At six months follow up, one patient died due to severe MR, one patient had severe TR and was taken back for surgery after two weeks post-surgery. Three patients had trivial aortic regurgitation (AR) and nine had no AR, two patients had trivial mitral regurgitation (MR) and 10 had no MR 11 patients had post-operative sinus rhythm and were in NYHA class 1. One patient with a complete heart block was supported with extracorporeal membrane oxygenator followed by tracheostomy. Redo TV repair was done in one patient. Peritoneal dialysis was accomplished in two patients. Double root translocation is a good alternative surgical treatment for TGA/DORV, VSD, and PS, where the pulmonary valve is small, but the leaflets are usable. Although the operation is technically demanding, our early follow-up on translocated root performance shows promising outcomes.

Surgical Treatment Following Stent Angioplasty for High-Risk Neonates With Critical Coarctation of the Aorta.

BackgroundNeonatal coarctation of the aorta (CoA) is primarily treated by surgical repair. However, under certain high-risk constellations, initial stent angioplasty may be considered followed by surgical repair. We report our experience with this staged approach. Methods: All patients undergoing surgical CoA repair following prior stenting at our institution between January 2011 and December 2019 were included in this retrospective analysis. The patients were classified to be at high risk because of cardiogenic shock, associated complex cardiac malformations, neonatal infection, necrotizing enterocolitis, and extracardiac conditions, respectively. Outcomes were analyzed and compared with neonates who underwent surgical CoA repair without prior stenting in the same observation period.ResultsTwenty-six neonates received stent implantation at a median age of 20 days (IQR 9-33 days). Subsequent surgical repair was conducted at an age of 4.2 months (IQR 3.2-6.1 months) with a median body weight of 5.6 kg (IQR 4.5-6.5 kg). Cardiopulmonary bypass was applied in 96% of cases. Extended end-to-end anastomosis was possible in 11 patients. Extended reconstruction with patch material was necessary in the remaining patients. One fatality (3.8%) occurred 33 days postoperatively. At a median follow-up of 5.2 years after initial stenting, all remaining patients were alive; 15/25 patients (60%) were free from re-intervention. Of note, re-intervention rates were comparable in neonates (n = 76) who were operated on with native CoA (28/74 patients; 38%; P = .67).ConclusionsNeonatal stent angioplasty for CoA results in increased complexity of the subsequent surgical repair. Nevertheless, this staged approach allows to bridge high-risk neonates to later surgical repair with reduced perioperative risk and acceptable midterm outcomes.

Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development

Cerebellar hypoplasia and dysplasia encompass a group of clinically and genetically heterogeneous disorders frequently associated with neurodevelopmental impairment. The Neuron Navigator 2 (NAV2) gene (MIM: 607,026) encodes a member of the Neuron Navigator protein family, widely expressed within the central nervous system (CNS), and particularly abundant in the developing cerebellum. Evidence across different species supports a pivotal function of NAV2 in cytoskeletal dynamics and neurite outgrowth. Specifically, deficiency of Nav2 in mice leads to cerebellar hypoplasia with abnormal foliation due to impaired axonal outgrowth. However, little is known about the involvement of the NAV2 gene in human disease phenotypes. In this study, we identified a female affected with neurodevelopmental impairment and a complex brain and cardiac malformations in which clinical exome sequencing led to the identification of NAV2 biallelic truncating variants. Through protein expression analysis and cell migration assay in patient-derived fibroblasts, we provide evidence linking NAV2 deficiency to cellular migration deficits. In model organisms, the overall CNS histopathology of the Nav2 hypomorphic mouse revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs. Lastly, we show that the NAV2 ortholog in Drosophila, sickie (sick) is widely expressed in the fly brain, and sick mutants are mostly lethal with surviving escapers showing neurobehavioral phenotypes. In summary, our results unveil a novel human neurodevelopmental disorder due to genetic loss of NAV2, highlighting a critical conserved role of the NAV2 gene in brain and cerebellar development across species.

Dextroversion and D-Transposition of the Great Arteries, Left-Handed Ventricular Topology Related to Multiple Ventricular Septal Defects, and Left Juxtaposition of Atrial Appendage in a 1-Year-Old Child

We present a 1-year-old female infant case in natural history, affected by D-transposition of the great arteries with multiple ventricular septal defects in dextroversion, left juxtaposition of atrial appendages, and persistent left superior caval vein draining into coronary sinus. This is an uncommon case, and its particularity is due to clinical and anatomical findings diagnosed late in a setting of a complex cardiac malformation. After the diagnosis, the patient underwent palliative arterial switch operation without complications.

Integrative Bioinformatics Analysis Revealed Mitochondrial Defects Underlying Hypoplastic Left Heart Syndrome.

BackgroundHypoplastic left heart syndrome (HLHS) is one of the most complex congenital cardiac malformations, and the molecular mechanism of heart failure (HF) in HLHS is still elusive.MethodsIntegrative bioinformatics analysis was performed to unravel the underlying genes and mechanisms involved in HF in HLHS. Microarray dataset GSE23959 was screened out for the differentially expressed genes (DEGs), after which the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out using the Metascape. The protein–protein interaction (PPI) network was generated, and the modules and hub genes were identified with the Cytoscape-plugin. And the integrated network of transcription factor (TF)-DEGs and miRNA-DEGs was constructed, respectively.ResultsA total of 210 DEGs were identified, including 135 up-regulated and 75 down-regulated genes. The functional enrichment analysis of DEGs pointed towards the mitochondrial-related biological processes, cellular components, molecular functions and signaling pathways. A PPI network was constructed including 155 nodes as well as 363 edges. And 15 hub genes, such as NDUFB6, UQCRQ, SDHD, ATP5H, were identified based on three topological analysis methods and mitochondrial components and functions were the most relevant. Furthermore, by integrating network interaction construction, 23 TFs (NFKB1, RELA, HIF1A, VHL, GATA1, PPAR-γ, etc.) as well as several miRNAs (hsa-miR-155-5p, hsa-miR-191-5p, hsa-mir-124-3p, hsa-miR-1-3p, etc.) were detected and indicated the possible involvement of NF-κB signaling pathways in mitochondrial dysfunction in HLHS.ConclusionThe present study applied the integrative bioinformatics analysis and revealed the mitochondrial-related key genes, regulatory pathways, TFs and miRNAs underlying the HF in HLHS, which improved the understanding of disease mechanisms and the development of novel therapeutic targets.

Noninvasive diagnosis of liver fibrosis in the complex cardiac malformation survivors - a review of the literature.

The aim of this review is to summarize the information on the pathogenesis and diagnosis of congestive liver disease sec-ondary to the Fontan and Glenn surgery for complex cardiac malformations, focusing on non-invasive diagnostic modalities. We performed an electronic database search (Pubmed, Web of Science) with the data range from 2001 to 2020. We selected the studies that addressed the pathogenesis of congestive liver disease secondary to cardiac malformations and articles regarding noninvasive methods of determining liver fibrosis in this group. We found that conventional imaging methods do not allow the detection of the initial stages of liver fibrosis. Elastography results are altered by congestion and cut-off values are not yet validated. More studies are required in order to provide evidence-based guidelines regarding the non-invasive diagnosis of hepatic fibrosis secondary to congenital heart disease. Patients with congenital cardiac malformations require close monitoring and early diagnosis of liver complications to allow prompt therapeutic intervention.

Radiologic follow-up in Fontan-associated liver disease in Europe: European Society of Paediatric Radiology survey demonstrates the need for a consensus protocol

Fontan surgery is a life-saving procedure for newborns with complex cardiac malformations, but it originates complications in different organs. The liver is also affected, with development of fibrosis and sometimes cirrhosis and hepatocellular carcinoma. There is no general agreement on how to follow-up these children for the development of liver disease. To understand the current practice on liver follow-up, we invited members of the European Society of Paediatric Radiology (ESPR) to fill out an online questionnaire. The survey comprised seven questions about when and how liver follow-up is performed on Fontan patients. While we found some agreement on the use of US as screening tool, and of MRI for nodule characterization, the discrepancies on timing and the lack of a shared protocol make it currently impossible to compare data among centers.