Severe Congenital Heart Disease Research Articles

Remote magnetic navigation for catheter ablation of complex arrhythmias in congenital heart disease: an initial experience using a transnational telerobotic approach

Abstract Background The field of congenital electrophysiology (EP) is still in its relative infacncy with a limited number of electrophysiologists capable of performing catheter ablation in patients with congenital heart disease (CHD). As a result, patients or physicians are often required to travel great distances to performed specialised ablation procedures, something made near impossible during the COVID-19 pandemic. Objective We aimed to explore the feasibility and safety of a telerobotic approach to catheter ablation where the remote operator was situated approximately 1200km away from the patient and local team. Methods A 3D-printed 'phantom' heart was used in a pilot experiment in which no significant difference was seen between the local and remote operators in electroanatomic (EAM) mapping of the phantom heart using remote magnetic navigation (RMN). Catheter ablation was subsequently performed in patients with severe CHD using a transnational telerobotic approach to catheter ablation where the remote operator was able to view the dedicated console with live fluoroscopy, EAM and EP signals, as well as control the mapping and ablation catheters from 1200km away. As a safety precaution, radiofrequency (RF) could only be delivered by the local team. Results In total, 10 procedures were performed in 9 patients with severe CHD (mean age 38) between April and December 2021. All patients underwent an atrial ablation and one additional non-CHD patient underwent denervation of the pulmonary arteries. Median procedure duration was 335 (minutes) (IWR 230-349) with 11.5 minutes (QRS 3-15.4) of fluoroscopy exposure and 752 (IQR 674-905) seconds of RF delivery. There were no acute procedural complications. At one-year follow-up, one patient died as a result of heart failure and there were two arrhythmia recurrences. Conclusions Telerobotic catheter ablation is feasible and effective and creates the possibility of exciting new approaches to remote ablation and its use in the tele-proctoring of international fellows.

A “twelve-section ultrasonic screening and diagnosis method” and management system for screening and treating neonatal congenital heart disease at the grassroots level in Tang County, Hebei Province, China

BackgroundTo explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level.MethodsA total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the “twelve-section ultrasonic screening and diagnosis method” (referred to as the “twelve-section method”). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children’s Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system.ResultsThe centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children.ConclusionsThe “twelve-section method” is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

Health Service Use and Costs During Pregnancy Among Privately Insured Individuals With Congenital Heart Disease

Individuals with congenital heart disease (CHD) are increasingly reaching childbearing age, are more prone to adverse pregnancy events, and uncommonly undergo recommended cardiac evaluations. Data to better understand resource allocation and financial planning are lacking. To examine health care use and costs for patients with CHD during pregnancy. This retrospective cohort study was performed from January 1, 2010, to December 31, 2016, using Merative MarketScan commercial insurance data. Participants included patients with CHD and those without CHD matched 1:1 by age, sex, and insurance enrollment year. Pregnancy claims were identified for all participants. Data were analyzed from September 2022 to March 2024. Baseline characteristics (age, US region, delivery year, insurance type) and pregnancy-related events (obstetric, cardiac, and noncardiac conditions; birth outcomes; and cesarean delivery). Health service use (outpatient physician, nonphysician, emergency department, prescription drugs, and admissions) and costs (total and out-of-pocket costs adjusted for inflation to represent 2024 US dollars). A total of 11 703 pregnancies (mean [SD] maternal age, 31.5 [5.4] years) were studied, with 2267 pregnancies in 1785 patients with CHD (492 pregnancies in patients with severe CHD and 1775 in patients with nonsevere CHD) and 9436 pregnancies in 7720 patients without CHD. Compared with patients without CHD, pregnancies in patients with CHD were associated with significantly higher health care use (standardized mean difference [SMD] range, 0.16-1.46) and cost (SMD range, 0.14-0.55) except for out-of-pocket inpatient and ED costs. After adjustment for covariates, having CHD was independently associated with higher total (adjusted cost ratio, 1.70; 95% CI, 1.57-1.84) and out-of-pocket (adjusted cost ratio, 1.40; 95% CI, 1.22-1.58) costs. The adjusted mean total costs per pregnancy were $15 971 (95% CI, $15 480-$16 461) for patients without CHD, $24 290 (95% CI, $22 773-$25 806) for patients with any CHD, $26 308 (95% CI, $22 788-$29 828) for patients with severe CHD, and $23 750 (95% CI, $22 110-$25 390) for patients with nonsevere CHD. Patients with vs without CHD incurred $8319 and $700 higher total and out-of-pocket costs per pregnancy, respectively. This study provides novel, clinically relevant estimates for the cardio-obstetric team, patients with CHD, payers, and policymakers regarding health care and financial planning. These estimates can be used to carefully plan for and advocate for the comprehensive resources needed to care for patients with CHD.

Fluid Dynamic Study of the Penn State Pediatric Total Artificial Heart.

Penn State University is developing a pediatric total artificial heart (TAH) as a bridge-to-transplant device that supports infants and small children with single ventricle anomalies or biventricular heart failure to address high waitlist mortality rates for pediatric patients with severe congenital heart disease (CHD). Two issues with mechanical circulatory support devices are thrombus formation and thromboembolic events. This in vitro study characterizes flow within Penn State's pediatric total artificial heart under physiological operating conditions. Particle image velocimetry (PIV) is used to quantify flow within the pump and to calculate wall shear rates (WSRs) along the internal pump surface to identify potential thrombogenic regions. Results show that the diastolic inflow jets produce sufficient wall shear rates to reduce thrombus deposition potential along the inlet side of the left and right pumps. The inlet jet transitions to rotational flow, which promotes wall washing along the apex of the pumps, prevents flow stasis, and aligns flow with the outlet valve prior to systolic ejection. However, inconsistent high wall shear rates near the pump apex cause increased thrombogenic potential. Strong systolic outflow jets produce high wall shear rates near the outlet valve to reduce thrombus deposition risk. The right pump, which has a modified outlet port angle to improve anatomical fit, produces lower wall shear rates and higher thrombus susceptibility potential (TSP) compared to the left pump. In summary, this study provides a fluid dynamic understanding of a new pediatric total artificial heart and indicates thrombus susceptibility is primarily confined to the apex, consistent with similar pulsatile heart pumps.

Machine Learning to Predict Outcomes of Fetal Cardiac Disease: A Pilot Study.

Prediction of outcomes following a prenatal diagnosis of congenital heart disease (CHD) is challenging. Machine learning (ML) algorithms may be used to reduce clinical uncertainty and improve prognostic accuracy. We performed a pilot study to train ML algorithms to predict postnatal outcomes based on clinical data. Specific objectives were to predict (1) in utero or neonatal death, (2) high-acuity neonatal care and (3) favorable outcomes. We included all fetuses with cardiac disease at Sunnybrook Health Sciences Centre, Toronto, Canada, from 2012 to 2021. Prediction models were created using the XgBoost algorithm (tree-based) with fivefold cross-validation. Among 211 cases of fetal cardiac disease, 61 were excluded (39 terminations, 21 lost to follow-up, 1 isolated arrhythmia), leaving a cohort of 150 fetuses. Fifteen (10%) demised (10 neonates) and 65 (48%) of live births required high acuity neonatal care. Of those with clinical follow-up, 60/87 (69%) had a favorable outcome. Prediction models for fetal or neonatal death, high acuity neonatal care and favorable outcome had AUCs of 0.76, 0.84 and 0.73, respectively. The most important predictors for death were the presence of non-cardiac abnormalities combined with more severe CHD. High acuity of postnatal care was predicted by anti Ro antibody and more severe CHD. Favorable outcome was most predicted by no right heart disease combined with genetic abnormalities, and maternal medications. Prediction models using ML provide good discrimination of key prenatal and postnatal outcomes among fetuses with congenital heart disease.

Neonatal outcomes in preterm infants with severe congenital heart disease: a national cohort analysis.

Prematurity and congenital heart disease (CHD) are the leading causes of neonatal mortality and morbidity. Limited data are available about the outcomes of premature infants with severe CHD. We queried The National Inpatient Database using ICD-10 codes for premature patients (<37 weeks) with severe CHD from 2016 to 2020. Severe CHDs were grouped into three categories: A. left-sided lesions with impaired systemic output, B. Cyanotic CHD, and C. Shunt lesions with pulmonary overcirculation. Patients with isolated atrial or ventricular septal defects and patent ductus arteriosus were excluded. We also excluded patients with chromosomal abnormalities and major congenital anomalies. Patients' demographics, clinical characteristics, and outcomes were evaluated by comparing premature infants with vs. without CHD adjusting for gestational age (GA), birth weight, and gender. A total of 27710 (1.5%) out of 1,798,245 premature infants had severe CHD. This included 27%, 58%, and 15% in groups A, B, and C respectively. The incidence of severe CHD was highest between 25 and 28 weeks of gestation and decreased significantly with increasing GA up to 36 weeks (p < 0.001). Premature infants with severe CHD had a significantly higher incidence of neonatal morbidities including necrotizing enterocolitis (NEC) [OR = 4.88 (4.51-5.27)], interventricular hemorrhage [OR = 6.22 (5.57-6.95)], periventricular leukomalacia [OR = 3.21 (2.84-3.64)] and bronchopulmonary dysplasia [OR = 8.26 (7.50-10.06) compared to preterm infants of similar GA without CHD. Shunt lesions had the highest incidence of NEC (8.5%) compared to 5.3% in cyanotic CHD and 3.7% in left-sided lesions (p < 0.001). Mortality was significantly higher in premature infants with CHD compared to control [11.6% vs. 2.5%, p < 0.001]. Shunt lesions had significantly higher mortality (11.0%) compared to those with left-sided lesions (8.3%) and cyanotic CHD (6.4%), p < 0.001. Premature infants with severe CHD are at high risk of neonatal morbidity and mortality. Morbidity remains increased across all GA groups and in all CHD categories. This significant risk of adverse outcomes is important to acknowledge when managing this patient population and when counseling their families. Future research is needed to examine the impact of specific rather than categorized congenital heart defects on neonatal outcomes.

Morbidity and mortality in premature or low birth weight patients with congenital heart disease in three European pediatric heart centers between 2016 and 2020.

The treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group. A retrospective cohort study was conducted of preterm [<37 weeks gestational age (GA)] and/or LBW neonates (<2,500 g) born with a diagnosis of CHD, which requires invasive cardiac intervention (surgery or catheter) within their first year of life. Patients born between 2016 and 2020 and treated in three European pediatric heart centers were included. A total of 308 neonates (51% male) with CHD were included. Of those, 237 (77%) were born preterm, 259 (84%) were LBW, and 188 (61%) were both. The median GA was 35.4 weeks (interquartile range 33.3-36.9) and the mean birth weight was 2,016 ± 580 g. CHD was categorized as simple (12%), moderate (64%), or severe (24%). The overall complication rate was 45% and was highest in patients with severe CHD (p = 0.002). One-year mortality (19%) was associated with severe CHD, low relative birth weight in patients with genetic diagnoses, and low GA at birth, whereas GA at birth significantly impacted survival only after 3 months of life. The high morbidity and mortality in preterm and LBW neonates with CHD reflect their complexity and consequent limited treatment feasibility.

Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease

BackgroundHeart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking. ObjectivesThis study aims to evaluate the safety, tolerability, and short-term HF-related effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a real-world ACHD population. MethodsAll patients with ACHD treated with SGLT2i in 4 European ACHD centers were included in this retrospective study. Data were collected from 1 year before starting SGLT2i to the most recent follow-up. Data on side effects, discontinuation, mortality, and hospitalizations were collected. ResultsIn total, 174 patients with ACHD were treated with SGLT2i from April 2016 to July 2023. The mean age was 48.7 ± 15.3 years, 72 (41.4%) were female, and 29 (16.7%) had type 2 diabetes mellitus. Ten (5.7%) patients had mild, 75 (43.1%) moderate, and 89 (51.1%) severe congenital heart disease. HF was the most frequent starting indication (n = 162, 93.1%), followed by type 2 diabetes (n = 11, 6.3%) and chronic kidney disease (n = 1, 0.6%). At median follow-up of 7.7 months (Q1-Q3: 3.9–13.2 months), 18 patients (10.3%) reported side effects, 12 (6.9%) permanently discontinued SGLT2i, and 4 (2.3%) died of SGLT2i-unrelated causes. A significant reduction in the HF hospitalization rate was observed from 6 months before to 6 months after starting SGLT2i (relative rate = 0.30; 95% CI: 0.14-0.62; P = 0.001). ConclusionsSGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF hospitalization rate. These results warrant prospective randomized investigation of the potential benefits of SGLT2i for patients with ACHD.

Effects of hemodynamic alterations and oxygen saturation on cerebral perfusion in congenital heart disease.

Patients with severe congenital heart disease (CHD) are at risk for neurodevelopmental impairment. An abnormal cerebral blood supply caused by the altered cardiac physiology may limit optimal brain development. The aim of this study was to evaluate the effect of a systemic-to-pulmonary shunt, aortic arch obstruction and arterial oxygen saturation on cerebral perfusion in patients with severe CHD. Patients with severe CHD requiring cardiac surgery within the first six weeks of life, who underwent pre- and/or postoperative brain magnetic resonance imaging (MRI), and healthy controls with one postnatal scan were included. Cerebral perfusion in deep and cortical gray matter was assessed by pseudocontinuous arterial spin labeling MRI. We included 59 CHD and 23 healthy control scans. The presence of a systemic-to-pulmonary shunt was associated with decreased perfusion in cortical (p = 0.003), but not in deep gray matter (p = 0.031). No evidence for an effect of aortic arch obstruction and arterial oxygen saturation on cerebral perfusion was found. After adjusting for hemodynamic and oxygen saturation parameters, deep (p = 0.018) and cortical (p = 0.012) gray matter perfusion was increased in patients with CHD compared to controls. We detected regional differences in compensation to the cerebral steal effect in patients with severe CHD. Patients with severe congenital heart disease (CHD) have altered postnatal brain hemodynamics. A systemic-to-pulmonary shunt was associated with decreased perfusion in cortical gray matter but preserved perfusion in deep gray matter, pointing towards regional differences in compensation to the cerebral steal effect. No effects of aortic arch obstruction and arterial oxygenation on cerebral perfusion were seen. Cerebral perfusion was increased in patients with CHD compared to healthy controls after adjusting for hemodynamic alterations and oxygen saturation. To improve neuroprotection and neurodevelopmental outcomes, it is important to increase our understanding of the factors influencing cerebral perfusion in neonates with severe CHD.

Maternal and neonatal outcomes in women with congenital heart disease: A nationwide population-based study

BackgroundWe evaluated the outcomes of pregnancy in women with congenital heart disease (CHD) and their offspring in Taiwan. We also investigated how different severity levels may influence the outcomes. MethodsWe used data (2009–2017) from the Birth Certificate Application database in Taiwan, which is linked to the National Health Insurance Research Database and Taiwan Maternal and Child Health Database. We identified 2990 women with CHD who had 4227 births. Based on the CHD subtypes, patients were further divided into “severe CHD” and “simple CHD” groups. ResultsWomen with CHD have a significant risk of stillbirth. In maternal cardiac events, they had the highest risk of heart failure, followed by arrhythmia. The severity of CHD had a significant effect on the outcomes as well. The neonatal birth event that mothers with CHD have the highest risk of is preterm birth at < 32 weeks of gestation. The prominent difference in neonatal morbidities between mothers with severe and simple CHD is recurrent CHD in the offspring. The offspring of the severe CHD group had a higher risk of severe CHD, whereas those of the simple CHD group had a higher risk of simple CHD. ConclusionsDuring pregnancy, the monitoring of heart function and cardiac rhythm could be more intensive in mothers with CHD. In addition to accurately assessing fetal growth and development during antenatal care, mothers with severe CHD should be provided with careful fetal heart structure assessment and genetic testing along with counseling.

Frailty and Cognitive Function in Middle-Aged and Older Adults With Congenital Heart Disease

BackgroundLife expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential. ObjectivesThe authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits. MethodsUsing a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment. ResultsIn this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income. ConclusionsApproximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

HART: Deep learning-informed lifespan heart failure risk trajectories

BackgroundHeart failure (HF) results in persistent risk and long-term comorbidities. This is particularly true for patients with lifelong HF sequelae of cardiovascular disease such as patients with congenital heart disease (CHD). PurposeWe developed hART (heart failure Attentive Risk Trajectory), a deep-learning model to predict HF trajectories in CHD patients. MethodshART is designed to capture the contextual relationships between medical events within a patient’s history. It is trained to predict future HF risk by using the masked self-attention mechanism that forces it to focus only on the most relevant segments of the past medical events. ResultsTo demonstrate the utility of hART, we used a large cohort containing healthcare administrative data from the Quebec CHD database (137,493 patients, 35-year follow-up). hART achieves an area under the precision-recall of 28% for HF risk prediction, which is 33% improvement over existing methods. Patients with severe CHD lesion showed a consistently elevated predicted HF risks throughout their lifespan, and patients with genetic syndromes exhibited elevated HF risks until the age of 50. The impact of the birth condition decreases on long-term HF risk. The timing of interventions such as arrhythmia surgery had varying impacts on the lifespan HF risk among the individuals. Arrhythmic surgery performed at a younger age had minimal long-term effects on HF risk, while surgeries during adulthood had a significant lasting impact. ConclusionTogether, we show that hART can detect meaningful lifelong HF risk in CHD patients by capturing both long and short-range dependencies in their past medical events.

Social Determinants of Health Including Child Opportunity Index Leading to Gaps in Care for Patients With Significant Congenital Heart Disease.

Gaps in care (GIC) are common for patients with congenital heart disease (CHD) and can lead to worsening clinical status, unplanned hospitalization, and mortality. Understanding of how social determinants of health (SDOH) contribute to GIC in CHD is incomplete. We hypothesize that SDOH, including Child Opportunity Index (COI), are associated with GIC in patients with significant CHD. A total of 8554 patients followed at a regional specialty pediatric hospital with moderate to severe CHD seen in cardiology clinic between January 2013 and December 2015 were retrospectively reviewed. SDOH factors including race, ethnicity, language, and COI calculated based on home address and zip code were analyzed. GIC of >3.25 years were identified in 32% (2709) of patients. GIC were associated with ages 14 to 29 years (P<0.001), Black race or Hispanic ethnicity (P<0.001), living ≥150 miles from the hospital (P=0.017), public health insurance (P<0.001), a maternal education level of high school or less (P<0.001), and a low COI (P<0.001). Multivariable analysis showed that GIC were associated with age ≥14 years, Black race or Hispanic ethnicity, documenting <3 caregivers as contacts, mother's education level being high school or less, a very low/low COI, and insurance status (C statistic 0.66). One-third of patients followed in a regional referral center with significant CHD experienced a substantial GIC (>3.25 years). Several SDOH, including a low COI, were associated with GIC. Hospitals should adopt formal GIC improvement programs focusing on SDOH to improve continuity of care and ultimately overall outcomes for patients with CHD.

Prenatal Diagnosis of Congenital Heart Disease and Voluntary Termination of Pregnancy: A Population-Based Study in Qingdao, China.

The outcomes of fetuses with isolated congenital heart disease (CHD) diagnosed prenatally have not been investigated in a population-based study in China. This population-based study aimed to evaluate the rate of voluntary termination of pregnancy after the prenatal diagnosis of isolated CHD in Qingdao, China. This was a population-based retrospective study in which data were collected from all pregnant women in Qingdao (eastern China) from August 2018 to July 2020; fetal data, maternal data and data on pregnancy outcomes were extracted from medical records regarding prenatal diagnosis of CHD. The inclusion criteria were as follows: pregnant women or their husbands who had a household registration in Qingdao and who underwent regular prenatal screening in Qingdao. The exclusion criterion was the failure to sign an informed consent form. Counseling for all parents of fetuses with CHD was provided by a multidisciplinary team of experienced pediatric cardiologists, obstetricians, geneticists, etc. According to the type and severity of CHD, the pregnancy termination rate was analyzed. Among the 126,843 pregnant women, 1299 fetuses with a prenatal diagnosis of CHD were included in the study. Among the included fetuses, 1075 were diagnosed with isolated CHD, and the overall pregnancy termination rate was 22.8%. Termination rates varied according to the complexity of CHD (low complexity vs moderate complexity, P=0.000; low complexity vs high complexity, P=0.000; moderate complexity vs high complexity, P=0.000), with rates of 6.0% for low complexity, 54.2% for moderate complexity, and 99.1% for high complexity. The decision to terminate the pregnancy in cases of isolated CHD was unrelated to maternal age (P=0.091) but was related to gestational age (p=0.000). In Qingdao, 99.1% of parents whose fetuses were diagnosed with isolated high-complexity CHD chose to voluntarily terminate the pregnancy. The pregnancy termination rate increased with increasing complexity of prenatally diagnosed CHD.

Hypoxia-Induced Piglet Model of Cardiac Arrest with Assisted Resuscitation by Extracorporeal Membrane Oxygenation.

The mortality rate of newborns with severe congenital heart disease (CHD) has significantly decreased over the past few decades. However, many of these children experience neurological impairments, particularly following a hypoxic cardiac arrest. The use of extracorporeal membrane oxygenation (ECMO) has been considered an effective treatment for severe hypoxia in CHD cases. Various clinical studies have examined the use of ECMO for resuscitation after hypoxic cardiac arrest, but the results have been contradictory, showing a significant incidence of both mortality and morbidity in some studies while others report good outcome. In order to investigate the mechanisms behind brain injury associated with extracorporeal circulation, we have developed a neonatal porcine model of hypoxia-induced cardiac arrest followed by veno-arterial ECMO therapy.

SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability.

Up to 50% of patients with severe congenital heart disease (CHD) develop life-altering neurodevelopmental disability (NDD). It has been presumed that NDD arises in CHD cases because of hypoxia before, during, or after cardiac surgery. Recent studies detected an enrichment in de novo mutations in CHD and NDD, as well as significant overlap between CHD and NDD candidate genes. However, there is limited evidence demonstrating that genes causing CHD can produce NDD independent of hypoxia. A patient with hypoplastic left heart syndrome and gross motor delay presented with a de novo mutation in SMC5. Modeling mutation of smc5 in Xenopus tropicalis embryos resulted in reduced heart size, decreased brain length, and disrupted pax6 patterning. To evaluate the cardiac development, we induced the conditional knockout (cKO) of Smc5 in mouse cardiomyocytes, which led to the depletion of mature cardiomyocytes and abnormal contractility. To test a role for Smc5 specifically in the brain, we induced cKO in the mouse central nervous system, which resulted in decreased brain volume, and diminished connectivity between areas related to motor function but did not affect vascular or brain ventricular volume. We propose that genetic factors, rather than hypoxia alone, can contribute when NDD and CHD cases occur concurrently.

Comorbidities in congenital heart disease: different patterns in childhood and adulthood

BackgroundExisting studies were no exploration of the association between congenital heart disease (CHD) in children and comorbidities. This study was to assess the prevalence and number of comorbidities in CHD among children and adults, and to compare the comorbidity patterns by children and adults using association rule analysis.MethodsPatients identified by the International Classification of Diseases, Ninth Revision (ICD‐9) code in the Medical Information Mart for Intensive Care III (MIMIC-III) 2001–2012 and MIMIC-IV 2008–2018 were included in this cross-sectional study. Association rule analysis was used to explore associations between CHD and comorbidities in children and adults using values of support (%), confidence (%), and lift.ResultsAmong 60,400 eligible patients, 1.54% of adults had CHD and 0.83% of adults had CHD with at least one comorbidity, 13.79% had CHD and 12.37% had CHD with at least one comorbidity in children. The most common comorbidities were circulatory system diseases (53.78%), endocrine diseases (35.76%), and respiratory system diseases (23.46%) in adults with CHD, and the most common comorbidities were perinatal diseases (87.50%) in children with CHD. The comorbidity rate was 90.19% and 56.68% in children and adults, respectively. In children, perinatal diseases, circulatory system diseases, and endocrine diseases had the highest prevalence. The incidence of circulatory system diseases, perinatal diseases and endocrine diseases in CHD adults was confidence = 31.56%, 36.11%, and 23.23%, respectively. Perinatal diseases were common comorbidities among all CHD severity groups in children and adults.ConclusionThe prevalence of comorbidities in children with CHD was higher than that in adults with CHD. The most common comorbidities were perinatal diseases and endocrine diseases among children and adults with CHD, respectively. Our study provided insights into comorbidity patterns in children and adults with CHD.

Anorectal malformations (ARM) and VACTERL association and severity of congenital heart diseases (CHD): Experience of 396 consecutive patients in a tertiary center

ObjectiveCongenital heart diseases (CHD) are the most frequently associated anomalies with anorectal malformations (ARM). Nevertheless, many specific aspects of CHD in ARM patients have yet to be studied. The aims of this study were to evaluate the prevalence and distribution of CHD in neonates-infants with ARM, and to explore whether the severity of ARM, and the presence of VACTERL association, had an impact on CHD rate, severity, and timing at first cardiac surgery. Study designAll consecutive newborn-infants with ARM managed in our tertiary center (January-1999; December-2021) were collected from a prospective database and retrospectively analyzed. Prevalence and distribution of CHD in ARM patients were assessed. Patients were divided into groups depending on ARM severity and presence of VACTERL association. Pairwise comparison for CHD prevalence, severity, and timing at first cardiac surgery was performed between groups. ResultsOf 396 ARM patients identified, those with severe ARM showed a higher number of overall CHD compared to patients with non-severe ARM (36.7 % vs. 25.2 %, p = 0.032). VACTERL + patients had a significantly higher prevalence of CHD (73.4 % vs. 16.4 %; p <0.001) and major CHD (51.7 % vs. 26.9 %; p = 0.008) when compared with VACTERL-patients. Furthermore, VACTERL + patients underwent first cardiac surgery at a significantly younger age than VACTERL-patients (5.2 ± 15.2 months vs. 11.9 ± 6.3, p = 0.039). ConclusionsPatients with severe ARM had a higher number of CHD compared to patients with non-severe ARM. VATERL + patients had significantly more CHD and more severe CHD than VACTERL-patients. Early screening for CHD is strongly recommended in all newborns diagnosed with ARM before surgery. Level of evidenceIII retrospective comparative study.

Clinical risk associated with COVID-19 among 86000 patients with congenital heart disease

ObjectiveTo determine the magnitude of any excess risk of mortality and hospitalisation due to COVID-19 infection in patients with congenital heart disease (CHD) in the UK healthcare system.MethodsMatched case–control study...