Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: beyond neurodevelopmental disorders and epilepsy.

Neurodevelopmental disorders have been linked to numerous genes, particularly pathogenic variants in genes encoding postsynaptic scaffolding proteins, like SHANK3. This study aims to provide insights into the cardiovascular profile of patients with pathogenic SHANK3 variants, expanding beyond the well-established associations with neurodevelopmental disorders and epilepsy. We conducted a prospective study involving patients affected by neurodevelopmental disorders with pathogenic SHANK3 variants. Comprehensive cardiovascular assessments were performed and molecular genetic testing included chromosomal microarray followed by clinical exome sequencing. We identified five patients with de novo SHANK3 variants, all of whom exhibited cardiac involvement, including myocardial dysfunction, congenital heart disease (patent ductus arteriosus), and a case of postictal atrial fibrillation. Our findings emphasize an elevated risk of cardiovascular abnormalities in patients with SHANK3 pathogenic variants compared to prior reports. Despite their young age, these patients displayed significant cardiac abnormalities. The study highlights the necessity of integrating cardiac evaluation and ongoing cardiovascular monitoring into multidisciplinary care, facilitating early detection of heart failure and assessment of the risk of sudden unexpected death in epilepsy (SUDEP). Further research is needed to elucidate the underlying mechanisms of cardiac manifestations in SHANK3 mutation carriers.

Spectrum of Heart Diseases in Children in a National Cardiac Referral Center Tanzania, Eastern Africa: A Six-Year Overview.

Background: While communicable diseases have long been the primary focus of healthcare in Africa, the rising impact of paediatric and congenital heart disease (CHD) cannot be overlooked. This research aimed to estimate the frequency and pattern of heart diseases in children who underwent their first echocardiography at a national cardiac referral hospital in Tanzania. Methods: A retrospective observational study was conducted on children aged 0 to 18 years referred for first-time cardiological evaluation from January 2017 to December 2022. Retrieval of social and echocardiogram data and descriptive analysis were performed. Results: There were 6,058 children with complete reports. Of these, 52.8% (3,198) had heart disease, of whom 2,559 (80%) had CHD, while (340/639; 53.2%) with acquired heart disease (AHD) had rheumatic heart disease (RHD). Children with CHD had a median age 1.0 years (IQR: 0.3-3.5) and were predominantly 51.2% male. Children with RHD had a median age 9.7 years (IQR: 3.2-13.8) with equal gender distribution. Shunt lesions were common in 1,487 (58.1%), mainly VSD 19.3%, PDA 19.1%, ASD 15.1%, and atrioventricular septal defect (AVSD) 4.6%. Pulmonary valve stenosis was in 97 (3.8%). Around 35% (718) had cyanotic CHD, with TOF being most common (13.3%), followed by double outlet right ventricle (DORV) (3.6%). Compared to global average truncus arteriosus was higher in 69 (2.3%) children. In contrast, TGA and hypoplastic left heart syndrome (HLHS) were lower than the estimated global average seen in 2.3% and 0.5% of the cases, respectively. Atresia of the right-side valves was more common (174 vs. 24), and approximately 40% of the patients referred for first-time echocardiographic evaluation required hospitalization. Conclusion: Congenital heart disease is the primary cause of heart disease in children presenting at a national referral hospital, surpassing RHD. With its distinct distribution pattern, acyanotic lesions are more frequent than cyanotic heart diseases. The observed late referral tendencies suggest improving the referral system, enhancing CHD awareness among healthcare professionals, and instituting nationwide screening programs.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

INTRODUCTION: The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. MATERIAL AND METHODS: Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. RESULTS: A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). CONCLUSIONS: The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

Assisted reproductive technology and the risk of fetal congenital heart disease: insights from a tertiary-care referral center.

PURPOSE: To investigate whether congenital heart diseases exhibit higher rates in pregnancies achieved through assisted reproductive technology (ART) compared to natural conception. METHODS: In this retrospective cohort study, multinomial logistic regression was employed to analyze the relationship between categories of congenital heart diseases and three conception groups (IVF, ICSI, and natural pregnancies). The main outcome measures are risks of congenital heart disease categories in IVF and ICSI groups using the natural group as reference. We selected fetuses referred for fetal echocardiography to IRCCS Policlinico Sant'Orsola, Bologna, between January 2005 and November 2023, diagnosed with congenital heart diseases. RESULTS: We categorized the congenital heart diseases into six groups based on anatomical and embryological criteria. The estimated risk of left ventricular outflow tract, valvular, conotruncal, and atrioventricular septal defects was lower in the IVF group compared to natural conception. The estimated risk of valvular and atrioventricular septal defects was lower in the ICSI group vs natural. Conversely, the risk for right heart anomalies was higher both in the IVF and ICSI groups compared to natural conception. Heart rhythm diseases were more frequent in IVF pregnancies. When comparing ART methods, valvular defects, conotruncal defects, and right heart anomalies were more frequently observed in the ICSI group, while atrioventricular septal defects were more common in the IVF group. CONCLUSION: Significant differences were found in the occurrence of congenital heart diseases in pregnancies conceived through IVF and ICSI, versus those conceived naturally, underscoring the importance of further studying the underlying mechanisms of these associations.

DNA methylation of the Lamin A/C gene is associated with congenital heart disease.

BACKGROUND: Prior studies report associations of maternal serum Lamin A, encoded by the LMNA gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites in LMNA impacts the CHD susceptibility. METHODS: We investigated the associations of LMNA DNAm with CHD using publicly available data of CHD cases (n = 197) and controls (n = 134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850 K BeadChip for cases and 450 K BeadChip for controls. We tested 31 LMNA CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case-only analysis, we tested the variations in LMNA DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (n = 197) and heart tissue DNAm (n = 20) in CHD cases. RESULTS: After adjusting for age, sex, and cell types there were significant differences in 17 of the 31 LMNA CpGs between CHD cases and controls (FDR p ≤ .05). We identified lower DNAm of cg09820673 at 3' UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls. CONCLUSION: We identify statistically significant differences in LMNA DNAm between CHD cases and controls. Future studies should investigate the role of maternal LMNA DNAm in CHD development.

Advanced Echocardiography Assessment in the Management of Alcapa Syndrome: Case Report.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare and potentially life-threatening condition affecting infants that requires immediate corrective surgery to restore blood flow to the myocardium. We present a case of an infant with ALCAPA and severe heart failure. What sets this case apart is the utilization of speckle-tracking echocardiography as a non-invasive method for assessing global and regional myocardial function before and after surgical intervention. Our preoperative analysis revealed compromised contraction in specific areas of the left ventricle (LV), in the regions that were supplied by both the left coronary artery (LCA) and the right coronary artery (RCA). Interestingly, despite an increase in ejection fraction (EF) measured by conventional echocardiography, the postoperative speckle-tracking analysis revealed persistent impairment in the anterior territories supplied by LCA, highlighting the potential of this technique in identifying myocardial abnormalities during postoperative follow-up. In conclusion, speckle-tracking echocardiography may be a valuable tool for identifying subtle myocardial changes in ALCAPA patients with a higher sensitivity in detecting regional left ventricular (LV) dysfunction compared to conventional echocardiography.

Effects of an Online Health Management Program for South Korean Adolescents with Complex Congenital Heart Disease during Their Transition to Adulthood: A Randomized Controlled Trial.

Adolescents with complex congenital heart disease (CHD) are at risk of experiencing complications later in life. The purpose of this study was to develop an online health management program for adolescents with complex CHD and to evaluate its effects on self-efficacy, health behavior, and health-related quality of life. A randomized controlled trial design was used. A total of 29 adolescents with complex CHD were divided into an experimental group of 15 and a control group of 14. Participants in the intervention group took part in the 4-week online health management program (weekly online group sessions, 1:1 phone coaching, dietary diary feedback, and provision of health information) developed based on self-efficacy theory, while those in the control group received standard medical follow-up. Data were collected from August 2021 to March 2022 using a questionnaire-including the Korean Self-Rated Abilities for Health Practices: Health Self-Efficacy Measure (K-SRAHP) and Pediatric Cardiac Quality of Life Inventory (PCQLI)-and an ActiGraph accelerometer to track physical activity and sleep. The intervention group showed significant improvements in health self-efficacy (p = 0.003), psychosocial impact (p = 0.013), daily step counts (p = 0.011), and moderate to vigorous-intensity physical activity (p = 0.027). Additionally, a decrease in weekend leisure time sedentary behavior (p = 0.035) was observed. However, there were no significant differences in sleep behavior between two groups. The online health management program significantly enhanced self-efficacy, health behavior, and psychosocial impact in adolescents with complex CHD. These findings will inform the development of policies for transitional medical care tailored to adolescents with complex CHD.

Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I.

The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.

Intraoperative characterization of cardiac tissue: the potential of light scattering spectroscopy.

Significance: Damage to the cardiac conduction system remains one of the most significant risks associated with surgical interventions to correct congenital heart disease. This work demonstrates how light-scattering spectroscopy (LSS) can be used to non-destructively characterize cardiac tissue regions. Aim: To present an approach for associating tissue composition information with location-specific LSS data and further evaluate an LSS and machine learning system as a method for non-destructive tissue characterization. Approach: A custom LSS probe was used to gather spectral data from locations across 14 excised human pediatric nodal tissue samples (8 sinus nodes, 6 atrioventricular nodes). The LSS spectra were used to train linear and neural-network-based regressor models to predict tissue composition characteristics derived from the 3D models. Results: Nodal tissue region nuclear densities were reported. A linear model trained to regress nuclear density from spectra achieved a prediction r-squared of 0.64 and a concordance correlation coefficient of 0.78. Conclusions: These methods build on previous studies suggesting that LSS measurements combined with machine learning signal processing can provide clinically relevant cardiac tissue composition.

Research gaps in the neurodevelopmental assessment of children with complex congenital heart defects: a scoping review.

Background: Children with congenital heart defects (CHD) are at risk for a range of developmental disabilities that challenge cognition, executive functioning, self-regulation, communication, social-emotional functioning, and motor skills. Ongoing developmental surveillance is therefore key to maximizing neurodevelopmental outcome opportunities. It is crucial that the measures used cover the spectrum of neurodevelopmental domains relevant to capturing possible predictors and malleable factors of child development. Objectives: This work aimed to synthesize the literature on neurodevelopmental measures and the corresponding developmental domains assessed in children aged 1-8 years with complex CHD. Methods: PubMed was searched for terms relating to psycho-social, cognitive and linguistic-communicative outcomes in children with CHD. 1,380 papers with a focus on complex CHD that reported neurodevelopmental assessments were identified; ultimately, data from 78 articles that used standardized neurodevelopmental assessment tools were extracted. Results: Thirty-nine (50%) of these excluded children with syndromes, and 9 (12%) excluded children with disorders of intellectual development. 10% of the studies were longitudinal. The neurodevelopmental domains addressed by the methods used were: 53% cognition, 16% psychosocial functioning, 18% language/communication/speech production, and 13% motor development-associated constructs. Conclusions: Data on social communication, expressive and receptive language, speech motor, and motor function are underrepresented. There is a lack of research into everyday use of language and into measures assessing language and communication early in life. Overall, longitudinal studies are required that include communication measures and their interrelations with other developmental domains.

Zebrafish Congenital Heart Disease Models: Opportunities and Challenges.

Congenital heart defects (CHDs) are common human birth defects. Genetic mutations potentially cause the exhibition of various pathological phenotypes associated with CHDs, occurring alone or as part of certain syndromes. Zebrafish, a model organism with a strong molecular conservation similar to humans, is commonly used in studies on cardiovascular diseases owing to its advantageous features, such as a similarity to human electrophysiology, transparent embryos and larvae for observation, and suitability for forward and reverse genetics technology, to create various economical and easily controlled zebrafish CHD models. In this review, we outline the pros and cons of zebrafish CHD models created by genetic mutations associated with single defects and syndromes and the underlying pathogenic mechanism of CHDs discovered in these models. The challenges of zebrafish CHD models generated through gene editing are also discussed, since the cardiac phenotypes resulting from a single-candidate pathological gene mutation in zebrafish might not mirror the corresponding human phenotypes. The comprehensive review of these zebrafish CHD models will facilitate the understanding of the pathogenic mechanisms of CHDs and offer new opportunities for their treatments and intervention strategies.

Congenital Heart Defects in Patients with Anorectal Malformations: A Retrospective Cohort Study of 281 Patients.

In patients born with anorectal malformations (ARM), additional congenital heart defects (CHD) can occur. We aimed to provide an overview on disease and treatment details of CHD identified in patients born with ARM, from a unique large cohort of a very rare disease. We performed a retrospective single-center cohort study between January 2000 and July 2023. All consecutive patients with ARM were included. Outcomes were the number of patients with CHD, and screening percentage and percentage of patients diagnosed with CHD over 3 time periods (2000-2006, 2007-2014, 2015-2023). We used uni- and multi-variable logistic regression analyses to search for associations between CHD present and baseline characteristics. In total, 281 patients were included. Some 241 (85.8%) underwent echocardiography, of whom 80 (33.2%) had CHD. Screening percentage with echocardiography increased (74.1% vs. 85.7% vs. 95.9%, p < 0.001) and percentage of patients diagnosed with CHD remained similar over time (30.2% vs. 34.5% vs. 34.0%, p = 0.836). Atrial and ventricular septal defects (n = 36, n = 29), and persistent left superior vena cava (n = 17) were most identified. The presence of VACTERL-association or a genetic syndrome was independently associated with the presence of CHD. CHD were present in 33% of patients with ARM that underwent echocardiography. Over time, the number of CHD identified through screening remained similar. Patients with the presence of VACTERL-association or a genetic syndrome had a higher risk of having CHD. Therefore, acknowledging the potential presence of CHD in patients with ARM remains important.

The Effect of Physiotherapy Intervention on an Infant With Congenital Heart Defect Associated With Developmental Delay: A Case Report.

Congenital heart defects (CHDs) are one of the most prevalent anomalies present at birth globally. Children with CHD often face developmental challenges, including motor, language, and cognitive impairments. This case report presents the clinical profile of a 1.2-year-old female child with CHD and developmental delay (DD) post-CHD surgery. The child exhibited delayed gross motor, fine motor, language, and personal-social milestones, along with significant cardiac anomalies observed on CT angiograms. Physiotherapy interventions were initiated to address these DDs, encompassing manual techniques, neurodevelopmental treatment, and multimodal stimulation. The objective of this study was to assess the impact of physiotherapy interventions on improving developmental outcomes in infants with CHD-associated DD. The New Ballard Score and Hammersmith Infant Neurological Examination were utilized to evaluate improvements post-intervention. Significant enhancements in developmental outcomes were observed. This case underscores the significance of holistic care approaches in mitigating the impact of CHD on developmental trajectories and improving the quality of life for affected children.

Human Genetics of Congenital Heart Defects.

Congenital heart diseases (or congenital heart defects/disorders; CHDs) are structural abnormalities of the heart and/or great vessels that are present at birth. CHDs include an extensive range of defects that may be minor and require no intervention or may be life-limiting and require complex surgery shortly after birth. This chapter reviews the current knowledge on the genetic causes of CHD.

Molecular Pathways and Animal Models of d-Transposition of the Great Arteries.

During normal cardiovascular development, the outflow tract becomes septated and rotates so that the separate aorta and pulmonary trunk are correctly aligned with the left and right ventricles, respectively. However, when this process goes wrong, the aorta and pulmonary trunk are incorrectly positioned, resulting in oxygenated blood being directly returned to the lungs, with deoxygenated blood being delivered to the systemic circulation. This is termed transposition of the great arteries (TGA). The precise etiology of TGA is not known, but the use of animal models has elucidated that genes involved in determination of the left- embryonic body axis play key roles. Other factors such as retinoic acid levels are also crucial. This chapter reviews the animal models presenting with TGA that have been generated by genetic manipulation or with exogenous agents.

Comparison of Ductal Stent Versus Surgical Shunt as Initial Intervention for Neonates with Pulmonary Atresia with Intact Ventricular Septum.

Data comparing surgical systemic-to-pulmonary artery shunt and patent ductus arteriosus (PDA) stent as the initial palliation procedure for patients with pulmonary atresia with intact ventricular septum (PA-IVS) are limited. We sought to compare characteristics and outcomes in a multicenter cohort of patients with PA-IVS undergoing surgical shunts versus PDA stents. We retrospectively reviewed neonates with PA-IVS from 2009 to 2019 in 19 United States centers. Bivariate comparisons and multivariable logistic regression analysis were performed to determine the relationship between initial palliation strategy and outcomes including major adverse cardiovascular events (MACE): stroke, mechanical circulatory support, cardiac arrest, or death. 187 patients were included: 38 PDA stents and 149 surgical shunts. Baseline characteristics did not differ statistically between groups. Post-procedural MACE occurred in 4 patients (11%) with PDA stents versus 38 (26%) with surgical shunts, p = 0.079. Overall, the initial palliation strategy was not significantly associated with MACE (aOR:0.37; 95% CI,0.13-1.02). In patients with moderate-to-severe right ventricle hypoplasia, PDA stents were significantly associated with decreased odds of MACE (aOR:0.36; 95% CI,0.13-0.99). PDA stents were associated with lower vasoactive inotrope scores (median 0 versus 5, p < 0.001), greater likelihood to be extubated at the end of their procedure (37% versus 4%, p < 0.001), and shorter duration of mechanical ventilation (median 24 versus 96 h, p < 0.001). PDA stents were associated with significantly more unplanned reinterventions for hypoxemia compared to surgical shunts (42% vs. 20%, p = 0.009). In this multicenter study, neonates with PA-IVS who underwent PDA stenting received less vasoactive and ventilatory support postoperatively compared to those who had surgical shunts. Furthermore, patients with the most severe morphology had decreased odds of MACE.

Identifying Key Biomarkers in Pediatric Pulmonary Hypertension: An Investigative Approach.

This study assesses the utility of early biomarkers-5-hydroxyindoleacetic acid (5-HIAA) and insulin-like growth factor 1 (IGF-1)-for diagnosing and monitoring pulmonary hypertension (PH) in children with congenital heart defects (CHD). Due to the risks associated with invasive diagnostics, such as right heart catheterization, non-invasive biomarkers provide a safer alternative for early PH detection. This cohort-based study utilized blood and urine samples to measure 5-HIAA and IGF-1 levels via enzyme immunoassays. Our findings revealed significant changes in 5-HIAA concentrations across various biological matrices, supporting its potential as a diagnostic tool. Specifically, altered levels in urine and plasma reflect its role in serotonin metabolism and vascular remodeling in PH. IGF-1 levels were notably reduced in plasma, suggesting its involvement in PH pathophysiology. ROC analysis confirmed the diagnostic efficacy of these biomarkers, particularly 5-HIAA's high specificity and sensitivity. In conclusion, 5-HIAA and IGF-1 levels correlate well with PH, underscoring their diagnostic value for early PH detection in children with CHD.

Maternal Oxidative Balance Score during Pregnancy and Congenital Heart Defects.

The relationship between maternal oxidative balance score (OBS) in pregnancy, representing overall oxidative balance status by integrating dietary and lifestyle factors, and congenital heart defects (CHD) remains unclear; therefore, this study attempted to explore their associations among the Chinese population. We conducted a case-control study including 474 cases and 948 controls in Northwest China. Pregnant women were interviewed to report diets and lifestyles in pregnancy by structured questionnaires. Logistic regression models were used to estimate the adjusted ORs (95%CIs). Maternal OBS ranged from 6 to 34 among cases, and 5 to 37 among controls. Comparing the highest with the lowest tertile group, the adjusted OR for CHD was 0.31 (0.19-0.50). The CHD risk was reduced by 7% (OR = 0.93, 95%CI = 0.90-0.95) in association with per 1 higher score of OBS during pregnancy. The inverse relationship between maternal OBS and CHD risk appeared to be more pronounced among participants in urban areas (OR = 0.89, 95%CI = 0.86-0.93). Maternal OBS during pregnancy showed good predictive values for fetal CHD, with the areas under the receiver operating characteristic curve 0.78 (0.76-0.81). These findings highlighted the importance of reducing oxidative stress through antioxidant-rich diets and healthy lifestyles among pregnant women to prevent fetal CHD.

Incidence and predictive factors of mortality of infective endocarditis in adults with congenital heart disease: A systematic review and meta-analysis.

INTRODUCTION: Congenital heart diseases (CHD) with abnormal turbulent blood flow are associated with the highest risk of infective endocarditis (IE). Despite advancement in diagnostics and treatment, the mortality rate of IE remains high due the life-threatening complications. Our study aims to assess the incidence and mortality rates of IE and predictive factors for mortality among adults CHD (ACHD). METHODS: A systematic literature search was conducted on PubMed, SCOPUS, and Ovid SP to retrieve relevant studies. The pooled estimates and predictors of mortality were calculated using the random-effects generic inverse variance method using R programming. RESULTS: 12 studies involving 3738 ACHD patients were included in this meta-analysis. The overall incidence of IE in ACHD was 1.26 per 1000 patient-years (95% CI 0.55-1.96). 60% (95% CI 46-72%) of patients had surgical management for IE. The mortality rate of IE was 9% (95% CI 7-12%). The predictors of mortality were conservative management (OR: 5.07, 95% CI: 4.63-5.57), renal dysfunction (OR: 4.15, 95% CI: 2.92-5.88), cerebral complications (OR: 3.59, 95% CI: 1.78-7.23), abscesses/valve complications (OR: 2.67, 95% CI: 1.71-4.16), Staphylococcus aureus infection (OR: 2.32, 95% CI: 1.33-4.06), emboli (OR: 2.03, 95% CI: 1.47-2.79), body mass index (OR: 1.10, 95% CI: 1.01-1.21), age (OR: 1.02, 95% CI: 1.00-1.04), and previous IE (OR: 1.02, 95% CI: 1.00-1.04). CONCLUSION: The mortality rate of IE in ACHD is low. However, conservative management is associated with the highest risk of mortality.