Cyanotic Congenital Heart Disease Patients Research Articles

E-selectin and asymmetric dimethylarginine plasma levels in adult cyanotic congenital heart disease patients: relation to biochemical parameters, vascular function, and clinical status.

Abstract Background and Aim Patients with cyanosis secondary to congenital heart disease (CHD) are characterized by erythrocytosis and increased blood viscosity, which contributes to endothelial dysfunction, increased arterial stiffness, and impaired vascular function, which may affect the final clinical presentation. Asymmetric dimethylarginine (ADMA) and e-selectin (e-sel) are valuable biomarkers for prognosis of endocardial dysfunction and vascular damage. Their concentration levels in blood serum have the potential to be a rapid and easily accessible tool that reflects the severity of the disease. We aimed to assess e-sel and ADMA levels, their relationship with clinical status, as well as endothelial and vascular function. Methods A cross-sectional study including 36 adult CHD cyanotic patients [(17 males)(42.3 +/- 16.3 years)] with arterial blood oxygen saturation less than 92% and 20 healthy controls [(10 males)( 38.2 +/- 8.5 years)] was performed. All patients underwent clinical examination, blood testing, and cardiopulmonary tests. Endothelial function was assessed using intima-media thickness and flow-mediated dilatation (FMD). Vascular function using applanation tonometry methods was completed while considering aortic systolic pressure, aortic pulse pressure (AoPP), augmentation pressure (AP), augmentation index (AI), pulse pressure amplification (PPampl), and pulse wave velocity (PWV). Results Concentrations of e-sel and ADMA were significantly higher in patients with CHD than in controls (56.3 ± 13.6 ng/mL vs. 15.5 +/- 8.6 ng/mL, p<0.001) and (1.48 ± 0.48 ng/mL vs. 0.46 ± 0.1 ng/mL, p<0.001) respectively. E-sel levels correlated with gender, blood oxygen saturation, red blood cell, hemoglobin concentration, hematocrit, augmentation pressure, forced expiratory one second volume, forced vital capacity, and oxygen uptake. ADMA levels were found to correlate with age only. Conclusions E-sel level, unlike ADMA concentration, reflects the degree of severity of erythrocytosis and hypoxia and, thus, the physical status of patients with cyanotic CHD. E-selectin predicts increased augmentation pressure.Figure 1.A) ROC analysis for e-selectin

7068 Paraganglioma in Cyanotic Congenital Heart Disease

Abstract Disclosure: R. Lis: None. V. Hamidi: None. Paragangliomas arise from the non-chromaffin cells of the parasympathetic nervous system, which are composed of glomus cells. These function as chemoreceptors in response to hypoxia. Carotid body paragangliomas have been linked to conditions with chronic hypoxia. This was first seen in residents of high altitude locations in a case report presented by Saldana et. al and regression of a paraganglioma with resolution of hypoxia was reported by Gruber et. al. There have been few additional case reports of Paraganglioma in other hypoxic states. We present a rare case of a functional Paraganglioma in a patient with Cyanotic Congenital Heart Disease (CCHD).This is a 19 year old female with a history of CCHD due to double inlet left ventricle and transposition of the great arteries. Soon after birth, she had a fontan procedure. She subsequently developed fontan associated liver disease as well as chronic kidney disease, hypertension, sinus node dysfunction, and complete heart block. Her baseline oxygen saturation was 78-85%. Her heart rate was 40-49 beats per minute with upcoming plans for pacemaker placement. Her blood pressure ranged 90/50 to 150/80 mmHg on Amlodipine 5 mg and Lisinopril 2.5 mg. She routinely received abdominal imaging to monitor her liver disease. A liver MRI incidentally revealed a retroperitoneal mass concerning for a paraganglioma. Serum Normetanephrines were found to be 26.60 nmol/L (reference range less than 0.89). 24 hr Urine Norepinephrine was 1,187 ug/d (reference range 14-20). Further imaging was negative for additional sites of disease. Given her complete heart block, she was started on alpha blockade only prior to pacemaker placement. After the pacemaker was placed, she was started on beta blockade and underwent surgical resection of her paraganglioma. The pathology confirmed paraganglioma and mutation testing was negative for germline mutations including SDH, VHL, RET, NF1 mutations. Paragangliomas in patients with CCHD have been scarcely described in the literature given the rarity of both of these conditions. However, there is a relatively increased incidence of paragangliomas in the CCHD population due to chronic hypoxia triggering the hypoxia pathway. EPAS1 mutated HIF2alpha is often found to be the culprit in these patients. In addition, case reports have often described these patients to either be asymptomatic or have potential symptoms masked by their cardiac disease. Therefore, CCHD patients are at increased risk for paragangliomas and warrant additional awareness and regular screening. Screening has been proposed to start after 10 years of hypoxia in a case review by Agarwal et. al. as paraganglioma incidence in CCHD populations has not been seen before age 11. Incidence of recurrence is not yet widely studied, but significant concern for recurrence is warranted if the etiology of hypoxia is not reversed. Presentation: 6/3/2024

A new strategy for monitoring of direct oral anticoagulants in patients with cyanotic and complex congenital heart disease

BackgroundPatients with congenital heart disease (CHD) often require an oral anticoagulation. Vitamin K antagonists (VKA) are the standard treatment, however, an increased hematocrit in patients with secondary erythrocytosis due to cyanosis complicates the correct measurement of the international normalized ratio. Direct oral anticoagulants (DOAC) could be an alternative, but data on their efficacy and safety in complex and cyanotic CHD patients are scarce. This study proposes a new strategy of DOAC monitoring in these patients using D-dimers and DOAC trough levels. MethodsThis is a retrospective study including cyanotic and complex CHD patients requiring oral anticoagulation. Clinical, cardiac imaging and laboratory data were collected before and after start of DOAC. The new monitoring strategy consists of determination of D-dimers and DOAC trough levels at 1–4 weeks, 1–6 months, 6–12 months, >1 year after start of DOAC. ResultsEleven patients were included. For 10 patients D-dimers and DOAC trough levels were in target range. In one patient, D-dimers increased continuously after start of DOAC despite dose escalation, suggesting insufficient DOAC efficacy and finally requiring a switch to VKA. D-dimers subsequently decreased under VKA to the therapeutic range. In three patients, one thromboembolic and two minor bleeding complications occurred. No major complications were observed. ConclusionsWe propose a new strategy of monitoring of oral anticoagulation with DOAC and report its implementation in clinical routine. Highlighting the importance of pharmacokinetic and -dynamic monitoring, this strategy could improve safety and efficacy of DOAC in cyanotic and complex CHD which, however, requires a prospective validation.

Current follow-up results of Cyanotic Congenital Heart Diseases detected during Pregnancy in a specific Region

Background/Aims: Congenital heart disease (CHD) is the main cause of death in infants among congenital anomalies. Fetal echocardiography is important for the diagnosis and treatment plan of congenital heart diseases in the prenatal period. This study aimed to retrospectively screen the follow-up and treatment results of cyanotic CHD patients detected on fetal echocardiography. Methods: Fetal echocardiography results were scanned from the hospital record system. Data of fetuses with major cardiac anomalies and cyanotic CHD were examined retrospectively. Results: Fetal echocardiography was performed on 420 pregnant women between July 2020 and April 2023. Major cardiac anomalies and cyanotic heart disease were detected in the fetuses of 40 pregnant women (9.5%) out of 420. The median age of the pregnant women was 29 (19-41 years). The median gestational age at check-up was 23 weeks (22-28 weeks). 9/40 pregnant women (22.5%) had risk factors. The most common cyanotic congenital heart diseases were hypoplastic left heart syndrome (HLHS) and unbalanced complete atrioventricular septal defects (AVSDs) with obstructive lesions of the right or left ventricle. Three fetuses (7.5%) with heart failure findings died intrauterine. Two fetuses with HLHS and critical aortic stenosis (AS) died before being operated on. A patient with complete AVSD, hypoplasia of the left heart chambers, AS, and severe aortic coarctation died due to sepsis during the post-operative follow-up period. Chromosome analysis was performed in 8 patients. Down syndrome was detected in 3 of the patients with complete AVSD. 22q11 deletion and DiGeorge Syndrome were detected in 2 patients with tetralogy of Fallot. Conclusions: Congenital heart diseases and rhythm problems can be safely detected with fetal echocardiography. It is beneficial to perform a fetal echo scan at the appropriate gestational week, especially in fetuses with risk factors and in whom the four chambers view cannot be seen.

Investigation of flow-mediated vasodilatation (FMD) and comparison with carotid intima-media thickness (CIMT) in children with cyanotic congenital heart disease.

There is a high mortality rate in cyanotic patients with congenital heart disease (CHD) due to cardiovascular complications. The cardiovascular prognosis is negatively affected by endothelium dysfunction, increased arterial stiffness, and impaired vascular system. This study aimed to determine carotid intimal mean thickness (CIMT) and flow-mediated dilatation (FMD) in a group of children with cyanotic CHD (CCHD). FMD and CIMT were evaluated for 45 children with CHKD and 38 patients who did not have CHKD over the period 2021 to 2022, as part of this case-control study. In terms of age and gender, the case group has been compared to controls. Men accounted for 61.3% of the participants, with a mean standard deviation age of 7.8 5.39 years. In subjects with CCHD, CIMT increased non-significantly and FMD decreased significantly, but systolic blood pressure was significantly higher in patients than in the healthy group. (P=0.003). FMD was reduced in children with CCHD, but in controls, systolic blood pressure and CIMT were lower. The risk of developing atherosclerosis in CCHD patients may be increased by an increase in CIMT and systolic blood pressure.

Effects of trimetazidine on cardiac function in adult cyanotic congenital heart disease patients: Protocol for a 3-month multicenter, randomized, double-blind controlled trial

Nearly 20% Patients with cyanotic congenital heart disease (CCHD) are not able to receive surgery. These patients experience a decline in cardiac function as they age, which has been demonstrated to be associated with changes in energy metabolism in cardiomyocytes. Trimetazidine (TMZ), a metabolic regulator, is supposed to alleviate such maladaptation and reserve cardiac function in CCHD patients. This is a randomized, double-blind, placebo-controlled clinical trial. Eighty adult CCHD patients will be recruited and randomized to the TMZ (20 mg TMZ 3 times a day for 3 months) or placebo group (placebo 3 times a day for 3 months). The primary outcome is the difference in cardiac ejection fractions (EF) measured by cardiac magnetic resonance (MRI) between baseline and after 3 months of TMZ treatment. The secondary outcomes include TMZ serum concentration, rate of cardiac events, NYHA grading, fingertip SpO2, NT-proBNP levels, 6-minute walking test (6MWT), KCCQ-CSS questionnaire score, echocardiography, ECG, routine blood examination, liver and kidney function test, blood pressure and heart rate. This trial is designed to explore whether the application of TMZ in adult CCHD patients can improve cardiac function, reduce cardiac events, and improve exercise performance and quality of life. The results will provide targeted drug therapy for CCHD patients with hypoxia and support the application of TMZ in children with CCHD.

Incidence, clinical profile and short term outcome of cerebral abscess in cyanotic congenital heart diseases

BackgroundBrain abscess is a serious infection of brain parenchyma in patients with cyanotic congenital heart disease (CCHD) and around 25–46 % of unrepaired CCHD patients develop brain abscess. Aim of this study was to determine the incidence, clinical features, microbiology and factors associated with early and short term outcome of cerebral abscess in CCHD. Methodology: This is a retrospective study, conducted at Pediatric cardiology department, National Institute of Cardiovascular Diseases (NICVD) Karachi. The data was collected from January 2019 to December 2021. All CCHD patients between 1 and 25 years of age were included. Data of patients with cerebral abscess was reviewed. ResultsAmong the 544 pediatric patients hospitalized in the last two years, brain abscesses were identified in 51 (9.3 %). Polycythemia (31.4 %) was the most significant contributing factor, especially in patients aged above 10 years. The most frequently seen CCHD was tetralogy of fallot (TOF) 60.8 %. Majority of the patients (84.3 %) had a single abscess while 15.7 % had multiple abscesses. E coli (9.7 %) was the most common isolated pathogen. Immediate complication identified was cerebral edema in 22 (43.1 %). Four patients (7.8 %) died, 47 (92.2 %) patients completed treatment course. 45.1 % had complete recovery however, 17 (33.3 %) had neurological deficits, 8 (15.7 %) had seizures and 2 (3.9 %) patients had residual abscess. Prolonged hospitalization was observed in patients of age group <10 years. ConclusionIn patients with underlying CCHD,early referrals and intervention are key to mitigating the severe consequences of cerebral abscesses and can drastically improve patient outcomes.

Efficacy of intravenous iron therapy compared to usual treatment in iron deficient adult cyanotic congenital heart disease patients for improvement in clinical outcomes at three months

Abstract Background Iron deficiency is frequent in CCHD patients and is associated with poorer outcomes. Patients with iron deficiency anaemia are treated with oral iron which results in improved clinical outcomes. The use of intravenous iron in CCHD patients is not well studied. Purpose We aimed to compare effectiveness of intravenous iron with usual care (i.e., no therapy for CCHD patients with iron deficiency without anemia, and oral iron therapy for CCHD patients with iron deficiency anemia) on 6-minute walk distance(6MWD) after 3 months of treatment, improvement in arterial Haemoglobin saturation, Quality of life, WHO functional class and safety of intravenous Iron. Methods We enrolled 27 patients of which 13 were randomized to IV iron arm and 14 to usual treatment arm. The mean age (±SD) of enrolled patient was 23.3 (±5.55) years. 24 out of 27 patients (88.9%) were Eisenmenger Syndrome patients, while the other three patients were TOF with pulmonary atresia, DORV with pulmonary atresia and post-Fontan. 6MWD was performed to access functional capacity and WHOQOL-BREF questionnaire was used for assessment of quality of life. All the clinical findings, data and test recordings were repeated after three months. Results The mean (±SD) haemoglobin(Hb) of patients included in the study was 16.7 (±2.0) g/dl. The Hb levels improved by 0.91 (±0.85) g/dl in patients who received any form of iron therapy (IV or oral iron). Hb improvement was not significantly different between those who received IV or oral iron [IV iron: 1.15 (±0.88) g/dl, Oral iron: 0.59 (±0.79) g/dl; p= 0.12]. The baseline 6MWD was not different in both the arms (p= 0.639). The mean (±SD) 6MW distance covered in IV iron arm and usual treatment arm was 401 (±35.2) m and 408.6 (±46.5) m respectively at baseline, which improved to 425 (±28.7) m and 421.5 (±43.2) m respectively at 3 months follow up. The change in 6MWD in IV iron arm and usual treatment arm was 24 (±22.3) m and 13.1 (±16.4) m respectively. The difference of change in 6MWD between the two arms was non-significant (p= 0.157). There was a significant improvement in WHOQOL-BREF Score Domains 2,3 and 4 and there was a trend towards improvement on Domain 1 score in IV iron arm compared to usual treatment arm. WHO functional class was similar at baseline in both arms (p= 0.534). The change in WHO functional class at follow up was similar in both arms (p= 0.082) Conclusion This study demonstrated no improvement in clinical outcomes of 6MW distance, arterial hemoglobin saturation and WHO functional class. However, there was significant improvement in quality of life and iv iron was found safe and equally efficacious as oral iron for correcting iron deficiency. Further studies for determining ideal hemoglobin levels and dose of iron in CCHD patients are pertinent.

SAT310 Single Institution Retrospective Case Cohort Of Adult Cyanotic Congenital Heart Disease And Associated Pheochromocytoma And Paraganglioma

Abstract Disclosure: R.B. Jones: None. B. Bennett: None. D. Cohen: Consulting Fee; Self; Novartis Pharmaceuticals, Consultant, Medtronic, Consultant, Recor, Consultant. Grant Recipient; Self; Medtronic, Research Support, Recor, Research Support. Other; Self; Metavention, DSMB. Introduction: Improved management for patients with cyanotic congenital heart disease (CCHD) has led to prolonged lifespan and a noticeable increase in patients with CCHD presenting with pheochromocytoma and paraganglioma (PPGL). PPGL susceptibility genes including VHL, SDH(x), FH, EPAS1 have been connected to a common signaling pathway that activates hypoxia-inducible factors (HIF). 4 of 5 patients with CCHD and PPGL were reported to have a somatic gain-of-function mutation in EPAS1 encoding HIF-2α. One hypothesis is that the hypoxic environment positively selects for cells with gain-of-function mutations predisposing patients to develop PPGL even when environment is no longer hypoxic. PPGL was diagnosed 13-53 years after surgical correction of CCHD in these patients. We report a case series on 9 CCHD/PPGL patients treated at our institution. Objective: To describe a cohort of patients with CCHD who developed PPGLs. Methods: A retrospective chart review of patients with CCHD treated for PPGL at our institution was performed describing demographics, CCHD and related treatments, symptoms of PPGL and Hct/SpO2 at diagnosis, tumor size, catecholamine biochemistries, imaging and genetic analysis when available. Results: Four of 9 patients were female. Average age of diagnosis of PPGL was 30.7 years (SD 9.6 years, range 15-47 years). CCHD anomalies included Tetralogy of Fallot (2), hypoplastic right ventricle (2) and hypoplastic left ventricle (2). Most surgeries to correct CCHD were performed within days of life; the latest reported surgical procedure was at age 12, 1 patient had a subsequent heart transplant. Patients experienced hot flashes (5), arrhythmias (4), hypertension (4), abdominal pain and nausea (2), headaches (1) and asymptomatic (1). Hct and SpO2 ranged from 38%-53% and 85%-99% respectively. Three patients had multiple PPGLs; 2 had metastatic or recurrent PPGL. Metanephrines at diagnosis ranged from normal to 23x the upper limit of normal (ULN). Catecholamines ranged from normal to 16x ULN. Location of PPGL included 6 mediastinal and abdominal paraganglioma (PGLs), 5 head and neck PGLs, and 3 pheochromocytomas. Tumor size ranged from 9-65mm at maximum diameter on pathology. 7/9 patients had germline mutation testing; one SDHB mutation, one SDHA mutation of undetermined significance, and one BARD1 mutation were identified. Conclusions: The extended timeframe between onset of cyanosis and development of PPGL supports long term regular monitoring of CCHD patients to detect PPGL. We suggest screening with plasma metaneprines and catecholamines at age 15 and every 3-5 years after.

Thyroid Function in Children with Cyanotic and Non-Cyanotic Congenital Heart Disease.

Congenital heart disease (CHD) is one of the common diseases of childhood, which is classified into non-cyanotic and cyanotic types. It can affect thyroid function and lead to disruptions in thyroid hormone secretion and hypofunction. This study aimed to evaluate thyroid function in patients younger than 2 years old with cyanotic and non-cyanotic CHD. In our study, 101 patients (female/male: 50/51) were included. The thyroid-stimulating hormone and thyroid hormones such as thyroxine (T4) and triiodothyronine (T3) were measured using the electrochemiluminescence method, and thyroid peroxidase antibodies were measured by an enzyme-linked immunosorbent assay. Subclinical hypothyroidism referred to normal levels of T4, with elevated levels of thyroid-stimulating hormone in the serum. The frequency of subclinical hypothyroidism and hypothyroidism in patients with cyanotic CHD was estimated at 27.5% and 10%, respectively, and 1 patient had hyperthyroidism. The majority of cyanotic and non-cyanotic CHD cases were diagnosed with tetralogy of Fallot (30%) and patent ductus arteriosus (32.79%). There were no significant differences between cyanotic and non-cyanotic groups regarding T3, T4, free T3, free T4, and anti-thyroid peroxidase antibody levels (0.389, 0.142, 0.354, 0.248, and 0.333, respectively). Based on the present findings, subclinical hypothyroidism is a common finding in cyanotic CHD patients during childhood, which is associated with increased levels of oxygen saturation, severity of cyanosis, and age.

COVID-19 in Cyanotic Congenital Heart Disease.

Congenital heart disease (CHD) is the most prevalent congenital defect in newborn infants. Due to the various types of heart abnormalities, CHD can have a wide range of symptoms. Cardiac lesions comprise a range of different types and accordingly varying severities. It is highly helpful to classify CHD into cyanotic and acyanotic heart diseases. In this review, we are investigating the course of Coronavirus disease 2019 (COVID-19) in cyanotic CHD patients. The infection may directly or indirectly affect the heart by affecting the respiratory system and other organs. The effect on the heart that is pressure- or volume-overloaded in the context of CHD is theoretically more severe. Patients with CHD are at a higher risk of mortality from COVID-19 infection or suffering worse complications. While the anatomic complexity of CHD does not seem to predict the severity of infection, patients with worse physiological stages are more susceptible such as cyanosis and pulmonary hypertension. Patients with CHD exhibit continuous hypoxemia and have lower oxygen saturations because of a right-to-left shunt. Such individuals run the danger of rapidly deteriorating in the event of respiratory tract infections with inadequate oxygenation. Additionally, these patients have a higher risk of paradoxical embolism. Hence, critical care should be given to cyanotic heart disease patients with COVID-19 in comparison to acyanotic patients and this is through proper management, close observation, and adequate medical therapy.

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.

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.

The value of myocardial strain imaging in the evaluation of patients with repaired Tetralogy of Fallot: a review of the literature.

Tetralogy of Fallot (ToF) is considered to be the most common, complex, cyanotic congenital heart disease (CHD) representing 7-10% of all congenital heart defects, whereas the patients with ToF are the most frequently operated in their early infancy or childhood. Cardiac magnetic resonance (CMR) consists a valuable imaging technique for the diagnosis and serial follow-up of CHD patients. Furthermore, in recent years, advanced echocardiography imaging techniques have come to the fore, aiming to achieve a complete and more accurate evaluation of cardiac function using speckle tracking imaging modalities. We conducted a review of the literature in order to assess the myocardial deformation of patients with repaired ToF (rToF) using echocardiographic and CMR parameters. Patients with rToF have impaired myocardial strain parameters, that are well standardized either with the use of speckle tracking echocardiography or with the use of CMR imaging. Subclinical left ventricular dysfunction (low GLS) and myocardial dyssynchrony are commonly identified in rToF patients. Impaired left atrium (LA) and right atrium (RA) mechanics are, also, a common finding in this study population, but the studies using atrial strain are a lot fewer than those with LV and RV strain. No studies using myocardial work were identified in the literature, as far as rToF patients are concerned, which makes it an ideal field for further investigation.

Role of Balloon Pulmonary Valvuloplasty in the Management of Pulmonary Stenosis

Although there is definitive evidence for pressure gradient relief both immediately after and at follow-up after balloon pulmonary valvuloplasty (BPV) for pulmonary stenosis (PS), the progression of pulmonary insufficiency (PI) at late follow up emerged as a concern. To address the concern for development of PI during late follow-up, balloon/annuls ratio used for BPV was reduced to 1.2 to 1.25. Recurrence of stenosis was seen in nearly 10% of patients. The causes of recurrence were identified to be balloon/annulus ratio less than 1.2 and immediate post-BPV gradients in excess of 30 mmHg. Recurrent obstructions can be effectively relieved by repeat BPV. The BPV procedure is safe and effective in fetal, neonatal and adult subjects as well. The BPV is also effective in palliating cyanotic congenital heart disease patients with valvar PS. Despite the limitations, BPV is currently considered as therapeutic procedure of choice in the management of congenital PS in both the pediatric and adult populations. BPV provides an excellent alternative to surgical intervention and has become the preferred intervention for initial treatment for PS in neonates, infants, children, adolescents, and adults. Careful follow-up to detect development of significant PI and investigate methods to prevent PI are recommended.

Improved Retinal Microcirculation After Cardiac Surgery in Patients With Congenital Heart Disease

Background: Microcirculatory changes in congenital heart disease (CHD) patients undergoing cardiac surgery are not fully understood. We aimed to investigate the changes of retinal microcirculation in CHD patients after cardiac surgery by optical coherence tomography angiography (OCTA) and explore the association between retinal microcirculation and surgical outcome.Methods: This prospective observational study consisted of 71 CHD patients aged ≥6 years undergoing cardiac surgery including 19 cyanotic CHD (CCHD) and 52 acyanotic CHD (ACHD). Optical coherence tomography angiography (OCTA) was used to measure vessel density (VD) and capillary density (CD) of radial peripapillary capillary (RPC) and peripapillary, VD of superficial capillary plexus (SCP) and deep capillary plexus (DCP), thickness of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) preoperatively and 1 month postoperatively. Transthoracic echocardiography was conducted to measure macrocirculation.Results: In CCHD patients, VD and CD of RPC and peripapillary increased postoperatively (all P < 0.05). In ACHD patients, VD of peripapillary, CD of RPC and peripapillary, and RNFL thickness increased postoperatively (all P < 0.05). VD of SCP and DCP, and GCC thickness did not change significantly in CHD patients after surgery. Lower preoperative retinal microvascular density was associated with longer cardiopulmonary bypass (CPB) time and postoperative length of stay (PLOS). No correlation was found between microcirculatory and macrohemodynamic parameters (all P > 0.05).Conclusions: Improved retinal microcirculation was observed after congenital cardiac surgery and impaired preoperative retinal microvasculature was associated with prolonged CPB time and PLOS, which might provide potential information about the outcome of congenital cardiac surgery.

MiR-27b-3p Down-Regulation Prevents Hypoxia-Induced Cardiomyocyte Apoptosis Through Regulating Yes-Associated Protein 1 (YAP1) Expression

Background: Congenital heart disease (CHD) is one of the most common birth defects. MicroR-NAs (miRNAs) are a group of endogenous, non-coding small RNAs and mediate the target genes expression. An increasing evidence showed that in recent years, miRNAs have given rise to more and more attention in heart protection and development. In our research, the main purpose was to determine the effect of miR-27b-3p in CHD and analyze related mechanisms. Methods: We performed qRT-PCR analysis to examine miR-27b-3p expression in myocardial tissue from 30 patients with CHD and hypoxia-induced H9C2 cells. Then, we performed biological software TargetScan to predict the relationship of miR-27b-3p and YAP1, and dual luciferase reporter gene assay was used to verify the results. H9C2 cells were transfected with inhibitor control, miR-27b-3p inhibitor, miR-27b-3p inhibitor + control-siRNA or miR-27b-3p inhibitor + YAP1-siRNA for 6 hours and then induced by hypoxia for 72 hours. Subsequently, we performed MTT and FCM analysis to detect cell viability and apoptosis. Finally, we used western blot assay to measure the expression of apoptosis-related proteins. Results: Our study indicated that miR-27b-3p expression in myocardial samples of cyanotic CHD patients was significantly higher than that of the acyanotic CHD patients. miR-27b-3p expression was gradually up-regulated with the increase of hypoxia induction time in H9C2 cells. Besides, we confirmed that YAP1 was a target gene of miR-27b-3p. Moreover, our results showed that miR-27b-3p inhibitor improved cell viability, decreased apoptosis, and affected apoptosis-related proteins expression in hypoxia induced H9C2 cells. These changes were reversed by YAP1-siRNA. All data demonstrated that miR-27b-3p/YAP1 might be new potential bio-marker and therapeutic target for CHD treatment.

Aspirin Resistance in Children with Congenital Heart Disease and Its Relationship with Laboratory and Clinical Parameters

Background: Patients with congenital heart disease (CHD) are more prone to thromboembolism. Aspirin is the most commonly used medication around the world to prevent thrombosis in cardiovascular diseases. Objectives: This study aimed to define the frequency of aspirin resistance in pediatric patients with CHD and to evaluate the correlation of clinical and laboratory parameters with aspirin resistance. Methods: The study population consisted of 103 patients using aspirin, including 53 cases of cyanotic CHD and 50 cases of non-cyanotic CHD. Platelet aggregation was measured by the AggreGuide A-100 ADP Assay. Results: The prevalence of aspirin resistance was 36.9% in children with CHD. Although aspirin resistance in cyanotic CHD patients (41.5%) was higher than in non-cyanotic patients (32%), the difference was not statistically significant (P = 0.414). There was no significant association between aspirin responsiveness or resistance and the patient’s sex, age, duration of aspirin use, and concomitant medication use. Comparison of the laboratory data of aspirin-responsive and -resistant patients showed no significant difference between these groups, except for albumin (P = 0.032) and serum fibrinogen (P = 0.0001) levels. The fibrinogen level and thromboembolism history were independent risk factors for aspirin resistance. Also, there was a significant correlation between platelet aggregation in peripheral blood smears and aspirin resistance (P = 0.0001). Conclusions: Our findings suggest that measurement of the serum fibrinogen level and platelet aggregation in blood smears may be the first step to predict aspirin resistance.

Serum Metabolomics Profiling to Identify Novel Biomarkers for Cyanotic Heart Disease

Congenital heart disease (CHD) is one of the most important causes of the death of children and young adults. Most of the patients do not survive past their teen years. This occurs either due to delay in diagnosis or no diagnosis at all. In recent times, several studies have shown the importance of biomarkers in the prediction of such defects. These biomarkers give the real time snapshot of the on going processes inside the cells and can significantly support the diagnosis of CHD. The present experiment was designed as an observational single centre pilot study to identify and establish the diagnostic metabolic signatures associated with the congenital heart diseases. Metabolic profiles of sera collected from 35 cyanotic congenital heart disease patients and 15 controls were obtained using high-resolution 1D 1H CPMG and NMR spectra. The metabolic profiles were compared using multivariate statistical analysis to identify the disease specific metabolic disturbances associated with cyanotic heart disease. The results show perturbation in several metabolites in cyanotic CHD patients versus controls. The discriminatory metabolites were further analysedwith area under receiver operating characteristic (AUROC) curve and identified five metabolic entities (i.e.valine, glucose, glutamine, creatinineand PUFA) which could differentiate cyanotic CHDs from controls with higher specificity.In conclusion, untargeted metabolic approach proved to be helpful in identifying and differentiating disease causing metabolites in cyanotic cases from controls.

Preoperative level of neutrophil-lymphocyte ratio: Comparison between cyanotic and acyanotic congenital heart disease.

Elevated neutrophil-lymphocyte ratio (NLR) has been associated with poorer outcomes in children undergoing congenital heart surgery under cardiopulmonary bypass (CPB). To compare preoperative NLR levels between cyanotic and acyanotic children undergoing surgical repair with CPB. We performed a retrospective cohort study in 60-paired children (30 with tetralogy of Fallot [TOF] and 30 with ventricular septal defect [VSD]) between January 2018 and December 2019 matched by age, weight, and gender. Preoperative NLR was measured from the last complete blood count test before the surgery. All of them had negative viral screening. The median age in VSD children was 9.5 months (interquartile range [IQR]: 5-12), weight 7 kg (IQR: 5.5-8.7), 19 (63%) was female, and NLR was 0.45 (IQR: 0.3-0.65). The median age in TOF children was 8.5 months (IQR: 5-12), weight 7.6 kg (IQR: 5.8-8.7), 16 (53%) were female, and NLR was 0.67 (IQR: 0.41-1.1). Demographic parameters did not show any statistically significant difference between groups (p > .05). Children with TOF had higher preoperative NLR compared with VSD patients (p = .004). As lower O2 saturation as higher the NLR (p = .005). The preoperative level of NLR was higher in cyanotic congenital heart disease patients.