Cyanotic Cyanotic Congenital Heart Disease Research Articles

Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease

BackgroundFetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. ObjectivesThis study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. MethodsIn this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. ResultsA total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). ConclusionsAmong fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

SAT631 EPAS1 Mutations In Three Adjacent Nucleotides Resulting In Different Phenotypes

Abstract Disclosure: M. Alswailem: None. B. Alghamdi: None. L.A. Alobaid: None. H. Al-Hindi: None. M. Aldawish: None. O. Alsagheir: None. A.S. Alzahrani: None. EPAS1 (HIF2a) mutations have been described in patients (pts) with paragangliomas (PGL) in association with cyanotic congenital heart disease (CHD), polycythemia and some additional tumors. Here, we present 3 cases of PGL with closely located EPAS1 mutations. Despite the common gene location, their manifestations are different. 1. A 14-year-old girl found at age 9 years (yrs) to have polycythemia (Hb 177-195 g/l) and hypertension. At age 14 years, she was diagnosed to have multiple mid abdomenal and the urinary bladder PGLs. U. noremetanephrine was 35.8 umol/day (0-3.43). No evidence of somatostatinoma so far. Family hx is negative for PGL and WES revealed no germline mutations in PGL-associated genes. Tumor testing revealed a novel heterozygous EPAS1 variant (c.1589C&amp;gt;T, p.A530V). 2. A 32-yr-old woman has a complex cyanotic CHD diagnosed since birth. She underwent five cardiac surgeries between 1993 and 2015. In 2011, she was diagnosed with two abdominal PGLs. She underwent surgery and remained free of disease until 2019 when she developed recurrence with metastases (mets) to the liver and spine. She received external beam radiotherapy to the spine. Currently PGL mets remained stable. WES was negative for any germline mutation but tumor testing revealed a heterozygous EPAS1 mutation (c.1591C&amp;gt;T, p.P531S). 3. A 55-yr-old man diagnosed to have an upper abdominal PGL with lung and bone metastases at the age of 9 yrs. Biopsy from a right femoral met confirmed the diagnosis of bone mets. He underwent four abdominal surgeries between 1978-2008 and received MIBG Tx 6 times with a cumulative dose is 586 mCi. His last surgery in 2008 revealed PGLs but also a non-functioning Pancreatic neuroendocrine tumor (pNET). PGL mets remained stable over the last 15 yrs. WES revealed no germline mutation in any of the known PGL genes but tumor testing revealed an EPAS1 mutation (c.1592C&amp;gt;A, p.P531H). Discussion:EPAS1 mutations are very rare. In this series, we present 3 pts with EPAS1 mutations in 3 adjacent nucleotides (c.1589, 1591, 1592) in 2 adjacent codons (p.530-531). These mutations are located in a domain that is important for recognition by propyl hydroxylases that normally lead to inactivation and proteasomal degradation of HIF2a (EPAS1). Despite the common location, the manifestations are quite different. Although all of them developed PGL at a young age, Pt # 1 had severe polycythemia, Pt#2 had complex CHD, and pt#3 had pNET. The first two patients had extensive mets but these mets have a smoldering course, especially in pt#3 who has been living with these mets for 44 yrs! Since EPAS1 mutations are usually postzygotic, as suggested by its involvement of more than one organ, it is possible that the variable presentations of these same domain adjacently located mutations is related to the timing of their post zygotic development. Another possibility is that the variable expression of the mutated EPAS1 in different tissues Presentation: Saturday, June 17, 2023

Comparison of Patent Ductus Arteriosus Stenting and Blalock-Taussig Shunt in Ductal Dependent Blood Flow Congenital Heart Disease and Decreased Pulmonary Blood Flow.

Congenital ductal-dependent cyanotic congenital heart disease (CHD) is a group of diseases that require early intervention during early infancy or the neonatal period. In this study, we compared the effectiveness, safety, and side effects of stenting patent ductus arteriosus versus a modified Blalock-Taussig (BT) shunt. Thirty-six neonates and infants with cyanotic CHD who were <6 months old and were not suitable for complete surgery were admitted to Chamran Hospital in Isfahan and enrolled in this prospective longitudinal cross-sectional study. Ductal stenting (DS) was performed in 18 patients and BT shunt in 18 patients. Data were collected and compared in these patients. Age, height, and weight were lower in the DS group compared to the shunt group (1.28 ± 0.46 vs. 2.50 ± 0.51 months, 53.22 ± 1.80 vs. 56.11 ± 1.67 cm, 3.38 ± 0.45 vs. 4.98 ± 0.57 kg, respectively P < 0.001). The duration of the intensive care unit stay as well as hospital stay in patients in the DS group was much shorter than the shunt group (1.33 ± 0.68 vs. 2.83 ± 0.70 days, 3.33 ± 0.68 vs. 9.55 ± 0.51, P < 0.001, respectively). In both groups, the diameter of the pulmonary branches increased after the procedure compared to before the procedure (P < 0.001). Furthermore, the patient's hemoglobin was significantly decreased compared to before the procedure (P < 0.001). In both groups, one patient died in the postprocedure period. In ductal stent group one patient died in catheterization lab and in shunt group died 48 hours after surgery. There was no significant difference in postprocedural complications between the two groups. Duct stents can be used as an effective and safe method in duct-dependent cyanotic CHD patients who are not suitable candidates for complete surgery. As operators become proficient, this method can be a good alternative to BT shunts with fewer complications.

Neurodevelopmental Outcomes among Brazilian Children with Cyanotic Congenital Heart Disease and Its Associated Factors.

Objectives: The aim of this study was to evaluate neurodevelopmental outcomes (motor development, nonverbal intelligence, and attention) in children with cyanotic congenital heart disease (CHD) compared with healthy children from a public hospital in southern Brazil. Materials and Methods: This was a cross-sectional study with pediatric patients of both sexes: 37 children with cyanotic CHD and a control group with 38 healthy children. Parents/guardians undertook a questionnaire and the SNAP IV scale (to evaluate attention) was applied. Two instruments were applied to each child: the R-2 Non-Verbal Intelligence test and the motor development scale. To assess the factors associated with insufficient performance in the three fields of neurodevelopment, a Poisson regression analysis was performed with a robust estimate. Results: There were no significant differences between children with cyanotic CHD and the control group for any of the neurodevelopmental outcomes studied. Low socioeconomic class was a factor associated with worse performance on the intelligence test and inattention. Furthermore, age was a factor for performance on the intelligence test, while a greater number of siblings was a factor associated with worse performance on the attention test. Conclusions: Public policies regarding child health must involve prioritizing the improvement of families' social conditions.

Correlation between Mean Arterial Pressure and Regional Cerebral Oxygen Saturation on Cardiopulmonary Bypass in Pediatric Cardiac Surgery.

Some pediatric cardiac patients might experience low regional cerebral oxygen saturation (rSO2) during surgery. We investigated whether a pediatric patient's mean arterial pressure (MAP) can affect the rSO2 value during cardiopulmonary bypass (CPB). We retrospectively analyzed the cases of the pediatric patients who underwentcardiac surgery at our hospital (Jan. -Dec. 2019; n=141). At each MAP stage, we constructed line charts through the mean of the rSO2 values corresponding to each MAP and then calculated the correlation coefficients. We next divided the patients into age subgroups (neonates, infants, children) and into cyanotic congenital heart disease (CHD) and acyanotic CHD groups and analyzed these groups in the same way. The analyses of all 141 patients revealed that during CPB the rSO2 value increased with an increase in MAP (r=0.1626). There was a correlation between rSO2 and MAP in the children (r=0.2720) but not in the neonates (r=0.06626) or infants (r=0.05260). Cyanotic CHD or acyanotic CHD did not have a significant effect on the rSO2/MAP correlation. Our analysis demonstrated different patterns of a correlation between MAP and rSO2 in pediatric cardiac surgery patients, depending on age. MAP was positively correlated with rSO2 typically in children but not in neonate or infant patients.

Risk factors for mortality in children with cyanotic congenital heart disease associated with brain abscess

Brain abscess is a local infection within the brain parenchyma. Predisposing factors include cyanotic congenital heart disease (CHD). Identification of risk factors for mortality is important to determine the prognosis. A case-control study of children with cyanotic CHD associated with brain abscess was conducted in the pediatric ward of a hospital from January 2016 to December 2020. Data were collected from medical records with the case to controls ratio of 1:3.07. A total of 61 children were evaluated, 46 children survived and 15 children non-survived. From 11 risk factors evaluated, 6 risk factors had a significant different of mortality risk included the level of hemoglobin (p=0.07), leukocyte (p=0.063), Neutrophil-to-lymphocyte ratio (NLR) (p&lt;0.001), peripheral oxygen saturation (SpO2) (p=0.00), multiple abscesses (p=0.008), brain abscess diameter (p&lt;0.001). Multivariate logistic regression analyses revealed significant risk factors for mortality in cyanotic CHD children with brain abscesses were NLR (OR 13.62, 95%CI 2.123-87.319, p=0.006); SpO2 (OR 1.5, 95% CI 1.25-2, p=0.04); brain abscess diameter (OR 7.61, 95%CI 1.064-54.434, p=0.043). NLR, brain abscess diameter, and SpO2 were the risk factors in increasing mortality in cyanotic CHD children with brain abscess. The prevention of abscess cerebral development and cyanotic CHD management are needed to reduce the mortality.

Characteristics of Cyanotic Congenital Heart Disease at Dr. Soetomo General Hospital Surabaya

Introduction. Cyanotic congenital heart disease (CHD) is an abnormality of the heart that causes blood with low oxygen content to circulate directly to the body.Objective. To evaluate the profile of cyanotic congenital heart disease at Dr. Soetomo General Hospital Surabaya.Methods. This is a descriptive study using medical records of cyanotic CHD patients aged ≤18 years old from June 2018 – May 2020. Gender, age, nutritional status, sign and symptom, type of cyanotic CHD, complication and treatment were taken as the variables.Result. Out of 116 patients in this study, the majority were male (58.62%). Most patients first diagnosed at the age of 0 – &lt;1 year (76.72%) with normal nutritional status (51.72%). Tetralogy of Fallot (TOF) is the most common type (42.24%). Murmur was the most common sign and symptom (92.24%). Frequently observed complications were pneumonia (37.07%).Conclusion. Patients with cyanotic CHD are mostly male, diagnosed at the age of 0 – &lt;1 year with normal nutritional status. TOF is the most common type. Most patients present with murmurs. Predominant complication is pneumonia.

Abstract 45: Trends In Ductal Arteriosus Stent Versus Blalock-Thomas-Taussig Shunt Utilization In Neonates With Ductal-dependent Pulmonary Blood Flow

Background: Neonates with cyanotic congenital heart disease (CHD) and ductal-dependent pulmonary blood flow require a life-saving intervention soon after birth. The modified Blalock-Thomas-Taussig shunt (BTTS) is a well-established palliative intervention for securing pulmonary blood flow. More recently, development of the ductus arteriosus stent (DAS) has presented an alternative option. There is no consensus regarding the optimal strategy. Observational studies have not demonstrated clear differences in mortality or unplanned reintervention for cyanosis between DAS and BTTS, with DAS associated with shorter length of stay but greater likelihood of other reinterventions. Objective: To examine trends in DAS versus BTTS utilization in a cohort of US neonates with cyanotic CHD. Methods: An observational study of neonates undergoing DAS or BTTS within 30 days of birth discharged 1/2017-12/2020 was performed using the Pediatric Health Information Systems database. Mixed-effects multivariate regression was used to adjust for patient characteristics and center-level covariance. Results: A total of 2143 subjects from 39 centers were studied (29% DAS). The proportion of DAS increased over the study period (PANEL A). Prematurity (OR 2.0, p&lt;0.001), genetic anomalies (OR 1.2, p=0.02), and pulmonary atresia (OR 2.1, p&lt;0.001) were associated with increased odds of performing DAS over of BTTS. Adjusting for measurable confounders, the odds of DAS increased significantly over time (OR 1.3 per year, p&lt;0.001, PANEL B). However, there was significant intra-hospital practice variation not explained by differences in case-mix (MOR 3.48, 95% CI 2.58-5.15). Conclusion: Utilization of DAS is increasing overall. However, there remains significant variability in practice across US pediatric hospitals. Studies guiding optimal patient selection for DAS and BTTS are warranted.

Preoperative Hemoglobin Level, Oxygen Saturation and Postoperative Outcomes in Children With Cyanotic Congenital Heart Disease: A Propensity-Score Matching Analysis.

BackgroundThe optimal preoperative hemoglobin (Hb) level is difficult to define in children with cyanotic congenital heart disease (CHD) due to hypoxemia-induced secondary erythrocytosis. This retrospective study integrated preoperative Hb and pulse oxygen saturation (SpO2) using the product of Hb × SpO2 to predict postoperative outcomes in children with cyanotic CHD.Patients and MethodsChildren aged <18 years undergoing cardiac surgery with cyanotic CHD were included. The cutoff value of Hb × SpO2 was the age-adjusted lower limit of normal Hb (aaHb) in healthy children. The main outcomes were in-hospital death and the composite outcome of severe postoperative events. Multivariate logistic regression analysis and propensity score matching analysis were used to adjust for important confounders.ResultsThe presence of preoperative Hb × SpO2 < aaHb was observed in 21.6% of cyanotic children (n = 777). Children with Hb × SpO2 < aaHb had higher in-hospital mortality (12.5% vs. 4.6%, P < 0.001) and composite outcome incidence (69.6% vs. 32.3%, P < 0.001) than those with Hb × SpO2 ≥ aaHb. After propensity score matching, 141 pairs of children were successfully matched. Multivariate analysis showed that preoperative Hb × SpO2 < aaHb was significantly associated with the composite outcome in the entire population (odds ratio = 4.092, 95% confidence interval = 2.748–6.095, P < 0.001) and the matched cohorts (odds ratio = 2.277, 95% confidence interval = 1.366–3.795, P = 0.002).ConclusionOur results suggest that a preoperative Hb × SpO2 value below the lower limit of normal hemoglobin is a prognostic factor in cyanotic children undergoing cardiac surgery and is a potential criterion to evaluate preoperative anemia in this population.

Effect of oxygen therapy on exercise performance in patients with cyanotic congenital heart disease: Randomized-controlled trial

BackgroundPatients with unrepaired cyanotic congenital heart disease (CHD) suffer from aggravated hypoxemia during exercise. We tested the hypothesis that supplemental oxygen improves exercise performance in these patients. MethodsIn this randomized, sham-controlled, single-blind, cross-over trial cyanotic CHD-patients underwent four cycle exercise tests to exhaustion, while breathing either oxygen-enriched (FiO2 0.50, oxygen) or ambient air (FiO2 0.21, air) using incremental (IET) or constant work-rate (CWRET) exercise test protocols (75% of maximal work rate achieved under FiO2 0.21). Pulmonary gas-exchange, electrocardiogram, arterial blood gases, oxygen saturation (SpO2), cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. ResultsWe included seven patients with cyanotic CHD (4 Eisenmenger syndrome, 3 unrepaired cyanotic defects, 4 women) median (quartiles) age 36 (32;50) years, BMI 23 (20;26) kg/m2 and SpO2 at rest 87 (83;89) %. When comparing supplemental oxygen with air during exercise, maximal work-rate in IET increased from 76 (58;114) Watts to 83 (67;136) Watts, median difference 9 (0;22) W (p = 0.046) and CWRET-time increased from 412 s (325;490) to 468 s (415;553), median increase 56 (39;126) s (p = 0.018). In both IET and CWRET SpO2 was significantly higher and ventilatory equivalent for carbon dioxide significantly lower at end-exercise with oxygen compared to air, whereas CTO and QMTO did not significantly differ. ConclusionsPatients with cyanotic CHD significantly improved their exercise performance, in terms of maximal work-rate and endurance time along with an improved arterial oxygenation and ventilatory efficiency with supplemental oxygen compared to air.

Abstract 10383: Patent Ductus Arteriosus Stent versus Blalock-Thomas-Taussig Shunt for Initial Palliation of Cyanotic Congenital Heart Disease with Ductal Dependent Pulmonary Blood Flow: Results of a Meta-Analysis

Introduction: In patients with cyanotic congenital heart disease (CHD) and ductal-dependent pulmonary blood flow (DDPBF), initial palliation may include patent ductus arteriosus (PDA) stent or Blalock-Thomas-Taussig shunt (BTTS). This meta-analysis aimed to compare outcomes after PDA stent and BTTS. Methods: A comprehensive search of PubMed and Embase databases was performed. Newcastle-Ottawa tool assessed risk of bias in observational studies. Odds ratios and hazard ratios were pooled. Adjusted hazard ratios controlled for covariates and assessed time to event in survival analysis. Meta-analysis was performed using DerSimonian-Laird random-effects models. Results: Six retrospective observational studies were included, all low risk of bias. Of 757 patients, 243 (32.1%) had PDA stent and 514 (67.9%) had BTTS. There was no significant difference in mortality between PDA stent (HR 0.71; 95% CI: 0.26-1.93, p=0.50; I 2 =54%) and BTTS. PDA stent was associated with lower risk of complications (OR 0.45; 95% CI: 0.25-0.81, p=0.008; I 2 =0%) and post-procedural mechanical circulatory support (OR 0.27; 95% CI: 0.09-0.79, p=0.02; I 2 =0%). PDA stent was associated with shorter intensive care unit (-4.03 days; 95% CI: -5.99 to -2.07, p&lt;0.001; I 2 =66%) length of stay (LOS), hospital LOS (-5.54 days; 95% CI: -9.20 to -1.88, p=0.003; I 2 =78%) and duration of mechanical ventilation (-3.41 days; 95% CI -5.29 to -1.52, p&lt;0.001; I 2 =88%). There were no differences in pulmonary artery growth or hazard of unplanned reinterventions to treat cyanosis between groups. Conclusions: In this large meta-analysis of cyanotic CHD and DDPBF, initial palliation with PDA stent or BTTS demonstrated similar risks of mortality and unplanned reintervention to treat cyanosis. PDA stent was associated with fewer complications and shorter hospital LOS. Given limitations inherent to observational study, this analysis supports the development of a randomized clinical trial in this population.

Cardiopulmonary exercise testing in adults with congenital heart disease: Prognostic role in cyanotic patients

IntroductionThere are few and conflicting data concerning cardiopulmonary exercise testing (CPET) in cyanotic congenital heart disease (CHD) in whom the ventilation patterns could be affected. Aim was to assess the functional capacity and stratifying power of CPET in cyanotic CHD. MethodsRetrospective evaluation of CHD adults submitted to CPET in a tertiary centre and followed for at least one year. Patients were divided according to presence of cyanosis (rest oxygen saturation<90%). CPET parameters were analysed as potential predictors of the primary endpoint of cardiac death and hospitalization. Results286 patients, median age 34 years and 3.6 years of follow-up, sixty (21%) cyanotic. Primary endpoint was reached by 49.1% and 22.9% in cyanotic and non-cyanotic patients, respectively. There were significant differences in CPET parameters: cyanotic patients had lowest values for peak oxygen consumption, partial pressure end-tidal carbon dioxide stages, chronotropic index and higher minute ventilation/carbon dioxide production slope and optimal point of ventilation. In cyanotic population the predictors of primary endpoint were: chronotropic index (HR 0.985) in non-Eisenmenger patients; optimal point of ventilation (HR 1.269), rest oxygen saturation (HR 0.621), partial pressure end-tidal carbon dioxide at anaerobic threshold (HR 0.952) and chronotropic index (HR 0.973) after Fontan circulation; partial pressure end-tidal carbon dioxide at rest (HR 1.129) and rest oxygen saturation (HR 1.129) after biventricular repair. ConclusionCyanotic patients had worst exercise capacity and prognosis. Non-traditional CPET parameters as chronotropic index, optimal point of ventilation and partial pressure end-tidal carbon dioxide stages can predict major cardiac events in cyanotic subgroups.

Age Differences in the Mediating Effects of Parenting Stress on the Relationship Between Cyanotic Congenital Heart Disease and Externalizing Problems in Children and Adolescents.

Cyanotic congenital heart disease (CHD) has detrimental effects on behavioral function in children and adolescents. However, few study authors have examined the underlying mechanisms of these effects. The aims of this study were to investigate the mediating effects of parenting stress in the association between cyanotic CHD and externalizing problems and to explore whether age moderated these mediating effects. A total of 697 children and adolescents (aged 2-17 years) with CHD (252 with cyanotic CHD and 445 with acyanotic CHD) in Taiwan were enrolled. The Child Behavior Checklist and the Parenting Stress Index were used to assess externalizing problems and parenting stress, respectively. Mediation analysis was performed to determine the mediating effects of parenting stress in the association between cyanotic CHD and externalizing problems. A moderated mediation model was used to investigate the moderating effect of age on the observed mediating effects. Parenting stress significantly mediated the relationship between cyanotic CHD and externalizing problems (unstandardized coefficient B = 0.98; 95% bootstrap confidence interval, 0.23-1.78). Children's age further moderated the mediating effects, with greater effects in older children. Age also moderated the association between cyanotic CHD and parenting stress, such that the effects were only significant in children older than 5.7 years. Our study revealed that age affected the mediating effects of parenting stress in the relationship between cyanotic CHD and externalizing problems. Efforts to reduce externalizing problems in children and adolescents with cyanotic CHD by targeting parenting stress may be more effective when age differences are considered.

Effect of Hemodilution on Fluctuation of Cerebral Oxygen Saturation during Cardiopulmonary Bypass in Children with Cyanotic Congenital Heart Disease

Background: In patients with cyanotic congenital heart disease (CHD), cerebral oxygenation may be maintained by elevations in hematocrit (Hct). Hemodilution accompanying cardiopulmonary bypass (CPB), however, can disrupt cerebral oxygen balance, leading to fluctuations in cerebral oxygen saturation (ScO2). The present study investigated the effects of Hct changes on the fluctuation of ScO2 during CPB in cyanotic CHD using performance measurement (PM). Methods: Children with CHD (51 acyanotic and 46 cyanotic) who had undergone cardiac surgery using CPB were enrolled. Median performance error (MDPE), median absolute performance error (MDAPE), and wobble parameters of ScO2 were calculated before (reference value), during, and after CPB. Correlations of PM parameters with Hct and reductions in Hct (ΔHct) were also evaluated. Results: Before CPB, patients with cyanotic CHD had lower MDPE and larger wobble than those with acyanotic CHD, although mean ScO2 did not differ significantly between the two groups. During CPB, ScO2 of acyanotic CHD increased as ΔHct increased, but PM variables were not associated with ΔHct. In cyanotic CHD, MDPE (r = −0.324, p = 0.032) and MDAPE (r = 0.339, p = 0.024) correlated significantly with ΔHct during CPB. After CPB, MDPE (r = 0.574, p = 0.025) and MDAPE (r = −0.543, p = 0.036) were significantly correlated with Hct in children with cyanotic CHD who underwent palliative surgery. Conclusion: Therefore, ScO2 fluctuation during CPB in children with cyanotic CHD may be affected by the decrease in Hct, suggesting that excessive hemodilution can negatively influence the maintenance of cerebral oxygenation in these patients.

Effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease: a propective randomized controlled study

OBJECTIVE To study the effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease (CHD). METHODS A total of 100 infants with cyanotic CHD who underwent surgical operation from January to December, 2017, were randomly divided into a high-calorie group (receiving calorie-enriched formula after surgery) and a conventional group (receiving standard formula after surgery), with 50 infants in each group. All infants were followed up for 6 months. The observation indices included body height, body weight, prealbumin, and N-terminal pro-brain natriuretic peptide before surgery, at the time of ventilator weaning and extubation after surgery, and at 1, 3, and 6 months after surgery. Height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height Z-score (WHZ) were also assessed. Adverse reactions were recorded for both groups. RESULTS There were 25 cases (50%) and 21 cases (42%) of malnutrition in the high-calorie group and the conventional group respectively before surgery (P > 0.05). The nutritional status of the two groups improved 6 months after surgery (P < 0.05). At 6 months after surgery, compared with the conventional group, the high-calorie group had a lower proportion of infants with malnutrition (18% vs 36%, P < 0.05) and also a lower proportation of infants with a WAZ score of < -2 (P < 0.05). The infants with malnutrion in the high-calorie group had higher HAZ, WAZ, and WHZ than those in the conventional group (P < 0.05). No gastrointestinal intolerance was observed in both groups during hospitalization. CONCLUSIONS Compared with the standard formula, calorie-enriched formula can better help with postoperative catch-up growth in infants with cyanotic CHD.

Abstract TMP110: Antithrombotic Therapy and Risk of Stroke Recurrence in Children With Congenital and Acquired Cardiac Disease

Background: Antithrombotic therapy (ATT) is currently recommended for stroke prevention in pediatric cardioembolic arterial ischemic stroke (CE-AIS) where the risk of recurrence is high. Methods: We conducted a retrospective study of a prospectively enrolled cohort of neonates and children with radiologically-confirmed cardioembolic arterial ischemic stroke (CE-AIS) from January 2003 - December 2017. We evaluated the clinical and radiographic predictors of hemorrhagic transformation (HT) and stroke recurrence to assess the safety and efficacy of ATT. Results: Eighty-two children met inclusion criteria [53.7% males and 28% neonates; median age 0.43 (IQR: 0.08 - 4.23) years]. Stroke recurred in 11 children at a median of 32 days (IQR: 5.5 - 93) from the index event. Most recurrent infarcts were silent (n=6; 54.5%) and found on follow-up neuroimaging with an average follow-up interval of 4.1 ±3 .5 years. Procedure-related recurrence took place in 1 (9.1%) child. Ten (90.9%) children were receiving antithrombotic therapy at the time of recurrence: 8 (72.7%) were on anticoagulant therapy (ACT) and 2 (18.2%) were on a combination of antiplatelet (ATP) and ACT. HT occurred in 20 of 82 children (24.4%), all of whom were receiving ACT, 5 (6.1%) of whom were symptomatic. Four (4.9%) had systemic hemorrhage. There was no difference in the frequency of stroke recurrence between those with and without HT [3 (15.0%) vs. 8 (12.9%); p=1.00]. Children with univentricular physiology were less likely to have HT [15% vs. 43.5%; p=0.03] and had higher rates of recurrent stroke, prior to definitive cardiac repair, despite receiving ATT. Stroke recurrence was highest in those with cyanotic congenital heart disease (CHD) pre-surgery (3/11), cyanotic CHD post-palliative surgery with residual right-to-left-shunt (3/11) and in those with cardiomyopathy (4/11). HT was not associated with ATP vs. ACT use nor combination therapy. Conclusion: ATT appears to be relatively safe in children with CE-AIS. However, ATT warrants further optimization to prevent stroke recurrence, particularly in those with single ventricle physiology and reduced left ventricular function.

Effect of sodium acetate Ringer injection on perioperative fluid therapy in children with cyanotic congenital heart disease

To evaluate the efficacy of volume therapy with sodium acetate Ringer solution during the perioperative period in children with cyanotic congenital heart disease (CHD). The children who underwent elective surgery for cyanotic CHD admitted to Shanghai Children's Medical Center Affiliated to the Medical School of Shanghai Jiaotong University from September to December 2018 were divided into three groups according to random number table with the informed consent of their legal representatives. All of the children received volume therapy with infusion of sodium acetate Ringer solution intravenously upon anesthesia induction. The volume of infusion was calculated according to the "4-2-1" formula (group A, the rehydration volume was 4 mL×kg-1×h-1 for the first 10 kg body weight, 2 mL×kg-1×h-1 for the second 10 kg, and 1 mL×kg-1×h-1 for the third 10 kg and above), and the volume was increased by 50% or 100% in groups B and C, respectively. The intravenous infusion lasted for 30 minutes in all the three groups. Arterial blood gas analysis was performed before and 30 minutes after infusion to observe the acid-base status and electrolyte level. Pulse oxygen saturation (SpO2), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) before and 10, 20, 30 minutes after infusion, central venous pressure (CVP) at 30 minutes after infusion were recorded, as well as adverse events occurred after infusion. Twenty-six children with cyanotic CHD, 17 male and 9 female, aged from 1 to 36 months, body weight 3.6 to 16.0 kg, and America Society of Anesthesiologists (ASA) level of III or IV, were enrolled in the study. The pH value in group B at 30 minutes after infusion was significantly higher than that before infusion (7.35±0.05 vs. 7.32±0.06, P < 0.05), while no significant changes were found before and after infusion in the other two groups. The hematocrits (Hct) after infusion in three groups were significantly lower than those before infusion (0.433±0.141 vs. 0.473±0.146 in group A, 0.324±0.054 vs. 0.372±0.063 in group B, 0.363±0.097 vs. 0.418±0.111 in group C, all P < 0.01), indicating that all the children in the three groups achieved effective hemodilution. However, there was no significant difference in blood gas analysis before and after infusion among the three groups. The level of blood lactic acid (Lac) in all CHD children was decreased from (1.33±0.63) mmol/L to (0.98±0.36) mmol/L after infusion of sodium acetate Ringer solution, the serum Ca2+ concentration was decreased from (1.22±0.06) mmol/L to (1.19±0.06) mmol/L, and the serum Cl- concentration was increased from (108.74±2.70) mmol/L to (109.77±2.54) mmol/L with the statistically significant differences (all P < 0.01). However, no significant difference was found in Lac or electrolyte levels before and after infusion among the three groups. There was no significant difference in vital signs before and after infusion among the three groups, but the period of infusion had an effect on SpO2 (F = 5.998, P < 0.01), HR (F = 34.279, P < 0.01) and SBP (F = 4.345, P < 0.05). HR in groups A and C were significantly lower than those before infusion, and SBP in group A was decreased gradually with the prolongation of infusion time. The CVP value at 30 minutes after infusion in group B was higher than that in group A. No adverse reactions such as rash or anaphylactic shock occurred after infusion of sodium acetate Ringer solution in all children. The perioperative volume therapy with sodium acetate Ringer solution in children with cyanotic CHD can effectively prevent the increase in Lac level and does not aggravate metabolic acidosis. The volume of infusion was well tolerated by all the children without disturbing the hemodynamic parameters.

MiR-182 alleviates the development of cyanotic congenital heart disease by suppressing HES1

miRNAs have been pointed to play critical roles in the protection and development of cyanotic congenital heart disease (CHD). MiR-182 is found to be associated with multiple heart diseases. However, little is known about the function and underlying mechanisms of miR-182 on cyanotic CHD. Here, H9c2 cells were exposed to hypoxia to construct the model of cyanotic CHD in vitro. qRT-PCR assay revealed that miR-182 expression was downregulated in serum samples from patients with cyanotic CHD and hypoxia-induced cardiomyocytes. Gain- and loss-of-function demonstrated that miR-182 overexpression promoted cell proliferation and suppressed apoptosis in hypoxia-induced H9c2 cells, while miR-182 knockdown repressed cell proliferation and promoted apoptosis. Dual-luciferase reporter assay verified that HES1 was a direct target of miR-182, and miR-182 repressed HES1 expression by binding to its 3′-UTR. Moreover, miR-182-mediated regulatory effect on cell proliferation and apoptosis was reversed by the restoration of HES1 expression. In conclusion, our study demonstrated that miR-182 exerted protection effect through suppressing HES1 in hypoxia-induced cardiomyocytes, highlighting its role as a potential therapeutic strategy for cyanotic CHD.

Long-term Management of the Arterial Switch Patient.

This review paper describes the management of patients with dextro-transposition of the great arteries (D-TGA) with a focus on the complications seen and the appropriate care required to identify and prevent adverse events. D-TGA is a form of cyanotic congenital heart disease (CHD) representing ~ 3% of all CHD and almost 20% of all cyanotic CHD. Since the late 1980s, standard of care is to repair these patients with an arterial switch operation (ASO) as opposed to a Mustard/Senning operation. The long-term survival and complication rates are superior in the ASO. Long-term follow-up is recommended for all D-TGA patients and includes management with adult congenital heart disease specialists and the use of echocardiography and advanced imaging with CT or MRI. The most common complications seen are pulmonary stenosis, coronary artery stenosis, and neo-aortic regurgitation. Careful evaluation of new symptoms or declining function is essential in preventing and treating these long-term sequelae.

Changes in Near-Infrared Spectroscopy After Congenital Cyanotic Heart Surgery.

Since oxygen saturation from pulse oximetry (SpO2) and partial pressure of arterial oxygen (PaO2) are observed to improve immediately after surgical correction of cyanotic congenital heart disease (CHD), we postulate that cerebral (CrO2) and somatic (SrO2) oximetry also improves immediately post-correction. We aim to prospectively examine CrO2 and SrO2, before, during, and after surgical correction as well as on hospital discharge in children with cyanotic CHD to determine if and when these variables increase. This is a prospective observational trial. Eligibility criteria included children below 18 years of age with cyanotic CHD who required any cardiac surgical procedure. CrO2 and SrO2 measurements were summarized at six time-points for comparison: (1) pre-cardiopulmonary bypass (CPB); (2) during CPB; (3) post-CPB; (4) Day 1 in the pediatric intensive care unit (PICU); (5) Day 2 PICU; and (6) discharge. Categorical and continuous variables are presented as counts (percentages) and median (interquartile range), respectively. Twenty-one patients were analyzed. 15 (71.4%) and 6 (28.6%) patients underwent corrective and palliative surgeries, respectively. In the corrective surgery group, SpO2 increased immediately post-CPB compared to pre-CPB [99 (98, 100) vs. 86% (79, 90); p < 0.001] and remained in the normal range through to hospital discharge. Post-CPB CrO2 did not change from pre-CPB [72.8 (58.8, 79.0) vs. 72.1% (63.0, 78.3); p = 0.761] and even decreased on hospital discharge [60.5 (53.6, 62.9) vs. 72.1% (63.0, 78.3); p = 0.005]. Post-CPB SrO2 increased compared to pre-CPB [87.3 (77.2, 89.5) vs. 72.7% (65.6, 77.3); p = 0.001] but progressively decreased during PICU stay to a value lower than baseline at hospital discharge [66.9 (57.3, 76.9) vs. 72.7% (65.6, 77.3); p = 0.048]. CrO2 and SrO2 did not increase after corrective surgery of cyanotic CHD even up to hospital discharge. Future larger studies are required to validate these findings. (This study is registered with ClinicalTrials.gov ID: NCT02417259.).