Congenital Heart Disease Research Articles

Using Machine Learning and Feature Importance to Identify Risk Factors for Mortality in Pediatric Heart Surgery

Background: The objective of this IRB-approved retrospective monocentric study was to identify risk factors for mortality after surgery for congenital heart defects (CHDs) in pediatric patients using machine learning (ML). CHD belongs to the most common congenital malformations, and remains the leading mortality cause from birth defects. Methods: The most recent available hospital encounter for each patient with an age <18 years hospitalized for CHD-related cardiac surgery between the years 2011 and 2020 was included in this study. The cohort consisted of 1302 eligible patients (mean age [SD]: 402.92 [±562.31] days), who were categorized into four disease groups. A random survival forest (RSF) and the ‘eXtreme Gradient Boosting’ algorithm (XGB) were applied to model mortality (incidence: 5.6% [n = 73 events]). All models were then applied to predict the outcome in an independent holdout test dataset (40% of the cohort). Results: RSF and XGB achieved average C-indices of 0.85 (±0.01) and 0.79 (±0.03), respectively. Feature importance was assessed with ‘SHapley Additive exPlanations’ (SHAP) and ‘Time-dependent explanations of machine learning survival models’ (SurvSHAP(t)), both of which revealed high importance of the maximum values of serum creatinine observed within 72 h post-surgery for both ML methods. Conclusions: ML methods, along with model explainability tools, can reveal interesting insights into mortality risk after surgery for CHD. The proposed analytical workflow can serve as a blueprint for translating the analysis into a federated setting that builds upon the infrastructure of the German Medical Informatics Initiative.

NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.

Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism. Targeting NICD1 to mitochondria induces more EndMT compared with wild-type NICD1, and small molecule activation of PDH during pregnancy improves the phenotype in a mouse model of congenital heart defect. A NOTCH1 mutation observed in non-syndromic tetralogy of Fallot patients decreases NICD1 mitochondrial localization and subsequent PDH activity in heart tissues. Altogether, our findings demonstrate NICD1 enrichment in mitochondria of the developing mouse heart, which induces EndMT by activating PDH and subsequently improving mitochondrial metabolism.

Outcome of single-ventricle patients supported with extracorporeal membrane oxygenation

Background: Single ventricle heart disease can be left or right ventricle dominant congenital heart disease mostly associated with other risk factors like low birth weight, Preterm, chromosomal abnormality and all these risk factor associated with increase mortality. Methods: A retrospective chart review of paediatric patients from neonatal age to 14 years since 2012 to 2021, with supported by extracorporeal membrane oxygenation (ECMO) including both single ventricle heart physiology and biventricular heart, admitted in paediatric cardiac surgical intensive care unit in our hospital was conducted. All data were compared between single ventricle heart physiology and biventricular heart. Data was performed using commercially available software (SPSS), with statistical significance set p<0.05. Results: We enrolled total 124 patients who underwent ECMO cannulation. 68 children had single ventricle, while 56 being biventricular heart. Most children acquired ECMO cannulation in CICU 63 (50.8%). Male to female ratio was 74:50. 70.2% children got the ECMO cannulation when they had already been operated for surgical repair. Conclusions: Paediatric ECMO utilization in SV is valuable and recently its utilization has been increased in it with improve survival.

Clinical characteristics and long-term outcomes of Venoarterial extracorporeal membrane oxygenation in children with congenital heart disease.

To analyze the clinical outcomes of extracorporeal membrane oxygenation (ECMO) support in children with congenital heart disease (CHD) after surgery and explore the risk factors associated with mortality during long-term follow-up for 3-5 years. We conducted a retrospective observational study at Shanghai Children Medical Center (SCMC) from 2017 to 2021 and reviewed the clinical results and laboratory findings of 188 CHD patients who received ECMO support during this period. The 5-year overall survival rate was 56.38% (106/188) among CHD patients who received ECMO support. Kaplan-Meier curve showed residual anatomical malformation (RAM) (p < 0.0001), gastrointestinal bleeding (p = 0.019), single ventricular (SV) (p = 0.028), and pre-ECMO lactate level >10 mmol/L (p < 0.0001) were significantly associated with higher mortality in follow-up. Cox analysis identified RAM (p = 0.039) and pre-ECMO lactate level >10 mmol/L (p < 0.001) as independent risk factors for overall survival. Conversely, a minimum platelet count ≥50 × 109/L (p < 0.001) was found to be a protective factor. Moreover, a competing risk model showed that a CPR time ≥60 min (p < 0.001) was identified as a risk factor for death in patients who failed to be discharged from the hospital. Our study showed characteristics of long-term follow-up patients and revealed several risk factors associated with mortality in children with CHD who received ECMO support. These findings can provide valuable insights for clinical decision-making and contribute to improving patient outcomes.

Case Ascertainment in Pediatric Heart Failure Using International Classification of Disease Clinical Modification (ICD-CM) Codes.

Most epidemiological studies in pediatric heart failure (HF) use administrative database sources, defining patient cohorts by presence of a single HF ICD code. However, the ability of ICD codes to identify true HF patients is unknown in pediatrics.Here we describe the accuracy of HF ICD-10-CM code search algorithms, in identifying pediatric patients with HF from electronic data sources. Based on the adult HF literature, search algorithms were designed to incorporate HF ICD codes, imaging, and medications. Sensitivity, specificity, positive and negative predictive value and accuracy of the algorithms were tested among children in an advanced HF clinic ("Clinic cohort"). Top-performing algorithms were then tested in a large-scale regional electronic data warehouse (EDW), 01/2017 to 01/2020, generating the "EDW Cohort". False positive cases were identified and characterized by chart review. Within the Clinic Cohort, 78/378 patients (21%) had gold standard HF diagnoses. A search algorithm with one HF ICD coded visit was more sensitive but less specific than > 1 HF ICD coded visit, (sensitivity 94% and specificity 89% versus 69% and 97%, respectively). Correspondingly, > 1 ICD coded visit had a higher PPV than one ICD coded visit; 84% vs. 69%. Accuracy was similar (90% vs 91%). Presence of 1 HF ICD code combined with HF medication had high sensitivity, specificity, PPV, NPV and accuracy, all higher than the single ICD code algorithm. The "1 HF coded visit + any medication" algorithm resulted in highest accuracy (93%). Top-performing algorithms were tested in the EDW: the algorithm with > 1 HF ICD coded visit, and the algorithm with one HF ICD coded visit combined with HF medication. In the EDW Cohort, 133/248 (53.6%) patients had gold standard HF diagnoses though 115/248 (46.3%) were false positive cases; 41% of those had pulmonary over-circulation from congenital heart disease. Excluding children < 30days old and those with a history of an isolated VSD repair, complete AVSD repair, or PDA closure further reduced the proportion of false positives to 50/248 (20%). A search algorithm using a single HF ICD code can have acceptable sensitivity, specificity, PPV, NPV and accuracy in identifying children with HF from within electronic medical records. Similar to adult HF literature, specificity improves by including HF medication. When applied to large data sources, however, the search algorithms result in a high proportion of patients with pulmonary overcirculation related to congenital heart disease. To narrow the population to those with myocardial dysfunction, case identification may require use of ICD codes with linked of administrative, surgical, and/or imaging databases.

Knowledge, attitude and practice of pediatric healthcare staff towards the therapy for patients with congenital heart disease.

This study aimed to investigate the knowledge, attitude and practice (KAP) of pediatric healthcare staff towards the therapy for patients with congenital heart disease (CHD). CHD is a major global health concern, posing significant risks to health and life despite advancements in early detection and treatment. This web-based cross-sectional study was conducted from May 04, 2023 to August 12, 2023 in the Bengbu area (three counties and one city) for pediatric healthcare staff. Correlations between knowledge, attitude and practice scores were evaluated by Pearson correlation analysis. Factors associated with knowledge, attitude and practice scores were identified by multivariate logistic regression. A total of 332 valid questionnaires were enrolled, including 258 (77.7%) females, and 161 (48.5%) were pediatrician. The median (25% quartile, 75% quintile) of knowledge, attitude, and practice scores were 38 (36, 40) (possible range: 10-49), 28 (27, 31) (possible range: 7-35), and 35 (32, 39) (possible range: 9-45), respectively. Correlation analysis showed that significant positive correlations were found between knowledge and attitude (r = 0.528, P < 0.001), as well as practice (r = 0.399, P < 0.001). Meanwhile, there were also correlations between attitudes and practice (r = 0.528, P < 0.001). Univariate logistic regression showed that treated more than 100 children with congenital heart disease annually (OR = 2.976, 95% CI: 1.405, 6.303, P = 0.004) was independently associated with knowledge. Female (OR = 0.470, 95% CI: 0.277, 0.797, P = 0.005) and with more than 5years of work experience (OR = 0.507, 95% CI: 0.262, 0.982, P = 0.044) were independently associated with attitude. Female (OR = 0.584, 95% CI: 0.343, 0.994, P = 0.048) and treated more than 100 children with congenital heart disease annually (OR = 3.743, 95% CI: 1.702, 8.232, P = 0.001) were independently associated with practice. Pediatric healthcare staff had sufficient knowledge, positive attitude and proactive practice towards the therapy for patients with congenital heart disease. To improve clinical practice, prioritize training programs to build knowledge and positive attitudes among healthcare staff, encourage hands-on experience with CHD cases, and promote mentorship by experienced professionals for a collaborative work environment and better care.

Effects of Preoperative Nutritional Conditions on Postoperative Recovery in Neonates with Congenital Heart Disease

Objective: The effects of preoperative nutritional conditions on postoperative recovery in neonates with congenital heart disease (CHD) were evaluated in this study. Methods: A retrospective analysis of data from neonates with CHD who underwent surgery at our hospital from January 2020 to December 2022 was conducted. The relationships between preoperative nutritional conditions and neonatal postoperative recovery were analyzed. Results: Eighty neonates were included in this study. The average gestational age was 38.4 (37, 39.2) weeks, the average birth weight was 3.1 (2.7, 3.4) kg, the average age at surgery was 23 (21, 26) days, and the average preoperative weight was 3.5 (3.0, 3.9) kg. The postoperative mechanical ventilation duration, length of intensive care unit stay, and length of hospital stay of preterm neonates were much longer than those of full-term neonates (p &lt; 0.05). In addition, these values were notably greater for neonates with birth weights ≤3 kg than for neonates with birth weights &gt;3 kg (p &lt; 0.05). The correlation analysis suggested that gestational age, birth weight, preoperative weight-for-age z-score (WAZ) and preoperative height-for-age z-score (HAZ) were negatively correlated with postoperative mechanical ventilation duration, length of intensive care unit stay, and length of hospital stay. Conclusions: Preterm birth and low birth weight significantly prolong the duration of mechanical ventilation and postoperative intensive care unit and hospital length of stay. More attention should be given to nutritional management during the perioperative period for premature or low-birth-weight neonates with CHD. For neonates with CHD requiring surgery, the time available for nutritional support before surgery is very limited; thus, more attention and guidance are needed for prenatal nutritional strategies.

The Unique Challenge of Coronary Artery Disease in Adult Patients with Congenital Heart Disease

Advances in medical and surgical interventions have resulted in a steady increase in the number of patients with congenital heart disease (CHD) reaching adult age. Unfortunately, this ever-growing population faces an added challenge: an increased risk of acquiring coronary artery disease. This review provides insight into the complex interactions between coronary artery disease and CHD in adults. We describe the peculiar features of cardiac anatomy in these patients, the possible role cardiac sequelae may play in an increased risk of myocardial ischemia, and the diagnostic challenges in this patient group. Furthermore, this review outlines the risk factors and potential mechanisms of accelerated atherosclerosis in adults with CHD by pointing out areas where current knowledge is incomplete and highlighting areas for further research. The review concludes by examining potential management strategies for this particular population, emphasizing the necessity for a multidisciplinary approach. Understanding the unique coronary risks that adults with CHD experience can enhance patient care and improve long-term results.

Congenital heart defects during COVID-19 pandemic.

Congenital heart defects during COVID-19 pandemic.

Surgical Outcomes of Patients With Heterotaxy Syndrome - The Japanese Congenital Cardiovascular Surgery Database.

Cardiac malformations are a major component of heterotaxy syndrome and result in significant mortality and morbidity. This multicenter nationwide Japanese study evaluated mortality and morbidity after initial surgical palliation for patients with heterotaxy syndrome and determined predictors for mortality and morbidity among patients enrolled in the study. The Japanese Congenital Cardiovascular Surgery Database (JCCVSD) collects clinical data from 119 domestic institutions specializing in congenital heart disease, covering almost all major congenital heart surgery programs in Japan. Clinical data on preoperative, operative, and postoperative characteristics and survival data within 30 and 90 days were available from the JCCVSD database. Of the 561 patients with heterotaxy syndrome who underwent any of 8 specific initial cardiovascular surgeries, 45 (8.2%) and 75 (13.4%) had died at 30 and 90 days, respectively. Preoperative emergency transport, type of heterotaxy syndrome, low hospital volume, the repair of total anomalous pulmonary vein connection, and the repair of a common atrioventricular valve were identified as significant predictive factors for operative mortality. Improvements in some medical circumstances, such as fetal diagnosis and the patient transport system, will be needed to improve outcomes for severely ill patients with heterotaxy syndrome. This study describes early outcomes for the largest number of main cardiovascular surgeries to date in infants with heterotaxy syndrome.

Epicardial Lead Performance Trends in Pediatric and Congenital Heart Disease.

Background: Epicardial pacing systems, rather than transvenous systems, are utilized in pediatric patients who are too small to undergo transvenous access and/or have complex congenital heart disease (CHD) anatomically precluding a transvenous system. Longitudinal performance studies indicate that epicardial leads have higher failure rates when compared with transvenous leads but there are limited data on lead measurement changes in the acute phase after implantation. The objective of this study was to assess epicardial lead performance in the acute postimplant period and at one-year follow-up. Methods: This is a retrospective single center study of children and adult patients with CHD undergoing epicardial bipolar pacing lead and generator implantation between January 2012 and June 2022. We empirically selected 2 V as a critical lead threshold. Results: There were 256 leads implanted in 127 patients (mean age 6.1 ± 9.8 years), including 201/256 (79%) leads in patients with CHD. At the time of implant, 47/256 leads (18%) had a lead threshold of ≥2 V. Of those, 42 of 47 (89%) had recorded threshold values on postoperative day 1 (POD1) and 37 of 42 (88%) had decreased to a more acceptable threshold that was <2 V. For patients with an implant threshold of ≥2 V; impedance >1000 ohms, presence of CHD, perioperative or acute postop status, and location of the lead (atrial vs ventricular) did not significantly impact the odds of having a persistently high threshold (≥2 V) on POD1. Conclusion: Epicardial pacing lead thresholds generally improve in the immediate postop period and in our experience most leads with a high implant threshold improved to <2 V by POD1.

Preoperative Challenges for Pediatric Ambulatory Surgery

The demand for ambulatory anesthesia in pediatric surgery has been increasing, reflecting a significant shift over recent decades toward performing a growing number of procedures in an outpatient setting.1 The growing shortage of pediatric anesthesiologists, coupled with an increase in pediatric ambulatory surgery volumes, will require general anesthesiologists to deliver anesthesia care to children. Children with prematurity, hypotonia, upper respiratory tract infections (URTI), obesity, and congenital heart disease (CHD) are frequently encountered in the ambulatory setting and present significant challenges for ambulatory anesthesiologists. In addition, the management of preoperative fasting, pregnancy testing, and perioperative anxiety further complicates the care of a pediatric patient. This review will examine the existing evidence and provide guidance for ambulatory anesthesiologists on preoperative considerations for pediatric patients undergoing ambulatory surgical procedures.

Relative Factor Analysis of Postoperative Complications in Infants Below 1 Year Undergoing Repair of Ventricular Septal Defect Combined with Other Procedures through a Right Axillary Incision

Background: Compared to the traditional surgical repair of isolated ventricular septal defects, the proportion of complex congenital heart diseases has been increasing due to advancements in diagnostic capabilities and surgical techniques. Concomitant surgeries to correct multiple congenital heart diseases have become the preferred choice. Therefore, the evaluation of the safety of the combined correction of ventricular septal defects with other cardiac anomalies in young children through a right axillary incision and the analysis of related factors of perioperative complications needs to be investigated. Methods: A retrospective study was conducted on a single-center patient sample from January 2018 to December 2022 to compare outcomes between infants undergoing isolated ventricular septal defect (VSD) repair via a right axillary thoracotomy (control group) and those undergoing VSD repair combined with other cardiac procedures (experimental group). Results: A total of 397 eligible infants were included. After baseline data were matched using propensity score matching, the experimental group (n = 181) and the control group (n = 107) showed no significant differences in intraoperative blood loss, postoperative total drainage, length of hospital stay, duration of ICU monitoring, Vasoactive-Inotropic Score (VIS), pre-discharge left ventricular ejection fraction, fractional shortening (FS), postoperative severe pulmonary infection, reoperation, mortality, postoperative atrioventricular block, chylothorax, cardiac arrest, pericardial effusion, pneumothorax, pulmonary atelectasis, tricuspid regurgitation, myocardial injury, abdominal effusion, and metabolic acidosis. However, the control group had shorter surgical time [28.00 (90.00, 196.00) vs. 140.00 (95.00, 658.00) min, p &lt; 0.05], shorter cardiopulmonary bypass time [58.00 (24.00, 114.00) vs. 66.00 (33.00, 422.00) min, p &lt; 0.05], shorter aortic cross-clamp time [32.00 (17.00, 62.00) vs. 37.00 (15.00, 142.00) min, p &lt; 0.05], and shorter postoperative mechanical ventilation time [22.00 (0, 99.00) vs. 23.00 (3.00, 193.00) h, p &lt; 0.05]. The rate of abdominal effusion was lower in the experimental group than in the control group (p = 0.044). In the analysis of postoperative complication-related factors, the preoperative grade of tricuspid regurgitation, postoperative mechanical ventilation time, and VIS were positively correlated with abdominal effusion and satisfied the variable (p &lt; 0.05) in each of three established models. In the single-factor analysis, both VIS and preoperative lymphocyte count were (p &lt; 0.1) related to pericardial effusion; however, in the multi-factor analysis, only VIS met the threshold (p &lt; 0.05). Gender, height, and VIS were each associated with pleural effusion (p &lt; 0.05). Conclusion: The combination of ventricular septal defect repair with other cardiac procedures via a right axillary thoracotomy did not significantly differ from isolated VSD repair in terms of postoperative complications, monitoring, and length of hospital stay. However, increased surgical complexity was associated with longer surgical and mechanical ventilation times. Factors such as tricuspid regurgitation severity, duration of postoperative mechanical ventilation, and VIS were identified as relative factors for postoperative effusion. Additionally, the risk of postoperative pericardial effusion increased with higher VIS, while gender, height, and VIS were identified as relative factors for postoperative chylothorax.

Observation of patients after cardiac surgery, surgical aspects for pediatricians

The article discusses the practical aspects of caring for children after heart surgery. It provides information on the timing of follow-ups, the frequency of pediatrician visits, and describes the most important aspects of patient management for different groups. The article identifies several groups of patients based on their postoperative risks and follow-up needs. Purpose of the article is to present the observation features of patients who have undergone surgery for congenital heart defects, from the perspectives of surgeons and pediatricians.

Fetal Presentation of MYRF-Related Cardiac Urogenital Syndrome: An Emerging and Challenging Prenatal Diagnosis.

MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant. Detailed radiographic, pathological, clinical, and molecular data from 12 prenatal cases were collected through an international collaborative study. Adding the five fetuses previously published, we were able to study a cohort of 17 cases. Main ultrasound-accessible manifestations of MYRF-CUGS include congenital heart defects (13/17, 76%), congenital diaphragmatic hernia (10/17, 59%) and disorders of sexual differentiation in 46, XY fetuses (7/14; 50%). Postnatal examination and/or autopsy data highlighted additional birth defects and neurological findings with a large spectrum of severity. Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants). We report the first prenatal cohort of MYRF-CUGS, allowing us to further characterize the variable expressivity of this rare disorder in fetuses. Severe congenital anomalies with a poor prognosis are more frequent than previously described in postnatal cases. Our data suggest that MYRF-CUGS is characterized by a recurrent recognizable malformative association, accessible to prenatal diagnosis, with a significant intrafamilial phenotypic variability making genetic counseling challenging.

A Low-Cost Workflow to Generate Virtual and Physical Three-Dimensional Models of Cardiac Structures.

Three-dimensional modeling and printing (3DMP) of anatomical structures from cross-sectional imaging data can enhance the understanding of spatial relationships in complex congenital heart defects. Partially due to the substantial financial, material and personnel resources required, 3DMP is not yet universally used. Here, we describe a workflow that addresses and eliminates these drawbacks. The workflow utilizes the open-source software "3D Slicer" (The Slicer Community) and "Blender" (Blender Foundation) for segmentation and post-editing of datasets. This approach enables the generation of virtual or physical 3D models. The physical models are printed using a standard fused deposition modeling printer. The financial challenges that likely constrain the wider use of 3DMP are largely addressed by this approach. However, the workflow still requires a considerable amount of time to manually segment the imaging data. Three-dimensional modeling and printing might improve planning and safety of congenital cardiac surgical treatment. Furthermore, it is a useful tool for education of parents and medical professionals. This workflow increases its suitability for routine use also in regions with low economic resources.

Early-life thymectomy leads to an increase of granzyme-producing γδ T cells in children with congenital heart disease.

Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring cardiac surgery with concomitant thymectomy that is known to increase disease susceptibility later in life. Studies of γδ T cells, which are one of the dominant T cells in the early fetal human thymus, are rare. Here, we provide a comprehensive analysis of the γδ T cell compartment via flow cytometry and next-generation sequencing in children and infants with CHD, who underwent cardiac surgery shortly after birth. A perturbation of the γδ T cell repertoire is evident, and Vδ1 T cell numbers are reduced. However, those cells that are present, do retain cytotoxicity. In contrast, GZMA+CD28+CD161hi innate effector Vγ9Vδ2 T cells are found in higher proportions. TCR-seq identifies an increase in TRDJ3+ γδ T cell clones in children with CHD, but not in a confirmatory group of neonates prior to CHD surgery, which overall points to a persistence of fetal-derived effector γδ T cells in children with CHD.

Cell-based therapies reverse the heart failure-altered right ventricular proteome towards a pre-disease state.

Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy. We utilized a juvenile rat model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics. Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints. Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state in our animal model. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome.

Clinical Characteristics and Mortality Risk Factors of Hospitalized COVID-19 in Children: An Experience of Two Years Pandemic in Regional Referral Hospital

Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. COVID-19 in children is relatively mild compared to adults. However, several studies showed high mortality rates in children with underlying diseases. This study aimed to describe the clinical characteristics and outcomes of pediatric COVID-19 cases in regional referral hospital. This study was retrospective observational study using data from Medical Record Dr. Moewardi General Hospital between October 1st, 2020 and October 30th, 2022. The epidemiological and clinical data were extracted from the database and were compared with outcomes of patients. All statistical analyses were performed by SPSS software version 27. This study enrolled 371 (19,9%) children with confirmed RT-PCR SARS CoV-2 from 1856 hospitalized suspected children whereas 55% were males, and 63% aged under 5 years old. Moderate-severe patients accounted for 18% of the cases. Cough (74,4%), fever (66,6%) and shortness of breath (22,6) are the most common symptoms while 99 (26,7%) patients who had chronic diseases with the most common diseases being congenital heart disease, hematological malignancy and neurological disorders. Patient outcomes were significantly related to age, degree of severity and chronic disease with p=0.004, p&lt; 0.001, and p&lt; 0.001 respectively. After performing multivariate regression analysis, degree of severity [p&lt;0.001; adjusted OR = 28.03, 95% CI (10.73–73.21)] was found to be significant predictors for mortality. The clinical and epidemiological data revealed that the majority symptom were cough, fever and shortness of breath. Mortality rate during hospitalization was higher in children with moderate-to-severe COVID-19.

Paraganglioma and phaeochromocytoma in adult Fontan patients.

The purpose of this study was to address the gap in knowledge in the incidence, presentation and imaging features of PPGL in Fontan patients. It has been hypothesised in the literature that Fontan circulation patients have an increased incidence of these tumours. This study is the largest cohort of adult Fontan patients in North America. The Fontan procedure is a palliative procedure for single ventricle congenital heart disease where the systemic venous return is directed into the pulmonary circulation. Fontan patients are at increased risk of developing several extracardiac complications including phaeochromocytoma and paraganglioma (PPGL). This retrospective single-centre study includes all adult patients who were treated between 1 September 2015 and 1 September 2022 in a tertiary referral centre for adult congenital heart disease. Imaging and electronic medical records were retrospectively searched for the presence of PPGL. Five hundred and forty-seven Fontan patients were included in the study. Three patients had PPGL with an incidence of 0.5%. Two patients were diagnosed with paraganglioma and one with phaeochromocytoma. All patients were female. Median age of Fontan procedure was 1.8 years (range: 1.75-27 years). Median age of PPGL diagnosis was 19 years (range: 12-39 years). Median time from Fontan operation to diagnosis of PPGL was 12 years (range: 10.3-17.2 years). Fontan patients are at increased risk of PPGL. Clinically, the diagnosis of PPGL is challenging as symptoms and serum markers can be confounding in this population; however, the imaging features of PPGL remain typical making the role of the radiologist crucial.