Does the ST2 Level in Pediatric Heart Failure Patients Correlate with Cardiovascular Events and Mortality?

INTRODUCTION: The suppression of tumorigenicity 2 (ST2) is a receptor member belonging to the interleukin-1 (IL-1) family. The ligand and soluble versions are its two isoforms. The IL-33-ST2L ligand complex's development provides protection against heart fibrosis and hypertrophy. Investigations on heart failure in adults have demonstrated that it does not change by age, body mass index (BMI), creatinine, hemoglobin, and albumin levels, in contrast to NT pro BNP. In adult heart failure patients, it has been demonstrated to be an independent predictor of mortality and cardiovascular events. The most recent guideline recommends using it as class 2b in the diagnosis of adult heart failure. Studies on ST2 in children are rare. The purpose of this study is to assess the prognostic value of ST2 for cardiovascular events in young individuals suffering from heart failure. METHOD: This study included pediatric patients (0-18 years old) with congenital heart disease or cardiomyopathy who needed medical care, as well as surgical or interventional treatment. Height, weight, gender, saturation, heart failure classification (Ross or NYHA), medications, the electrocardiogram, echocardiography, pro BNP, and sST2 values of the patients, as well as any hospitalization, lower respiratory tract infection, organ dysfunction, or need for angiography or surgery during follow-up data on arrhythmia and death were gathered during a 1-year follow-up. The SPSS software version 25 application was used to carry out the statistical analysis. RESULTS: This study included 59 patients, of whom 27 (46.6%) were male. The average age of the patients was 55.5 months (1-228 months) and the average body weight was 16 kg (2.6-90 kg). Major cardiovascular events occurred in 45 of 59 patients (76.3%). Twenty-four patients experienced one MACE, while twenty-one patients experienced multiple MACEs. Pro BNP and sST2 levels were similar in the groups that developed MACE compared to those that did not. Pro BNP was discovered to be significantly higher in patients with hospitalization, growth retardation, lower respiratory tract infection, and organ failure, however, when assessing each situation (p = 0.001, p = 0.011, p = 0.001, p = 0.007, respectively). Soluble ST2 was found to be higher in patients with growth retardation than in those without (p = 0.037). Although the soluble ST2 level failed to demonstrate a correlation with pro BNP, it did show a positive correlation (r = 0.437) with the Ross score. When compared to other groups, it was discovered to be higher in patients with valvular insufficiency type heart disease. CONCLUSIONS: In this study, higher sST2 levels were discovered, particularly in the group with valve insufficiency and children with growth retardation. It was associated with the Ross score, but not with the pro BNP level. Although it increases in correlation with clinical heart failure, its predictive value for MACE is low. Similarly, pro BNP is not proven to be predictive; nonetheless, its high levels in patients with hospitalization, growth retardation, lower respiratory tract infection, and organ failure demonstrate that pro BNP may increase for a variety of causes. Long-term studies with more patients are needed for ST2 to be suitable for clinical use in pediatric patients.

Percutaneous Closure of Hemodynamically Significant Postoperative Residual Ventricular Septal Defects.

The experience with percutaneous closure of postoperative residual ventricular septal defects (VSDs) is expanding with improved device technology and techniques. To report our experience with percutaneous closure of residual VSDs after cardiac surgeries. Retrospective clinical data review of patients who had percutaneous closure of postoperative residual VSDs at our institution between 2010 and 2022. Patients' demographics, procedural, and follow-up data were looked at. Twelve patients (50% males) with a median age of 9.2 years (range 0.9-22) were identified. Baseline surgeries were 8 tetralogy of Fallot corrections, 2 pulmonary bandings for large muscular VSD (mVSD) including 1 coarctation repair, 1 atrioventricular septal defect repair, 1 sub-aortic membrane resection-induced iatrogenic VSD, 1 isolated VSD closure, and 1 additional mVSD. Median duration between baseline surgery and percutaneous VSD closure was 2.2 years (range 0.2-8.3). Residual VSD shunting was secondary to surgical patch leakage in 8/12 patients. The median angiographic defect diameter was 6.8 mm (range 4.8-14). The defect was balloon-calibrated in 3/12 patients. Defects were tackled retrogradely in 3/9 patients. Amplatzer Membranous VSD occluder (n = 1), Lifetech Multifunctional (n = 5), Membranous (n = 1) and muscular VSD occluders (n = 2) and Occlutech Membranous (n = 1) and Muscular (n = 2) VSD occluders were used. The procedure was successful in 10/12 patients. Two devices embolized to the pulmonary artery and were snare-retrieved. Both patients were referred for surgery. The median follow-up was 1.3 years (range 0.1-12). Six-month ultrasound showed one trivial residual shunt and one mild right ventricular outflow obstruction. One patient is receiving targeted therapy for pulmonary hypertension at 2 years of follow-up. Transcatheter closure of postoperative residual VSDs is a feasible yet challenging intervention. Procedural complications can be encountered.

Proinflammatory indicators and the relevance of echocardiography in children with cystic fibrosis.

As the life expectancy improves in cystic fibrosis, cardiac dysfunction is becoming an important risk factor for morbidity and mortality. Here, the association of cardiac dysfunction with proinflammatory markers and neurohormones between cystic fibrosis patients and healthy children was investigated. Echocardiographic measurements of right and left ventricular morphology and functions together with levels of proinflammatory markers and neurohormones (renin, angiotensin-II, and aldosterone) were obtained and analysed in a study group of 21 cystic fibrosis children aged 5-18 years and compared with age- and gender-matched healthy children. It was shown that patients had significantly higher interleukin-6, C-reactive protein, renin and aldosterone levels (p < 0.05), dilated right ventricles, decreased left ventricle sizes, as well as both right and left ventricular dysfunction. These echocardiographic changes correlated with hypoxia, interleukin-1 α, interleukin-6, C-reactive protein, and aldosterone (p < 0.05) levels. The current study revealed that hypoxia, proinflammatory markers, and neurohormones are major determinants of subclinical changes in ventricular morphology and function. While the right ventricle anatomy was affected by cardiac remodeling, the left ventricle changes were induced by right ventricle dilation and hypoxia. A significant but subclinical systolic and diastolic right ventricle dysfunction in our patients was associated with hypoxia and inflammatory markers. Systolic left ventricle function was affected by hypoxia and neurohormones. Echocardiography is a reliable and non-invasive method that is used safely in cystic fibrosis children for screening and detection of cardiac anatomical and functional changes. Extensive studies are needed to determine the time and frequency of screening and treatment suggestions for such changes.

Evaluation of Arterial Stiffness and Carotid Intima-Media Thickness in Children with Primary and Renal Hypertension.

Hypertension is an increasing disease in children and the risk of endothelial damage and target organ damage increases in the presence of additional risk factors such as obesity. In our study, the effect of hypertension on early atherosclerotic changes and target organ damage in children was investigated. Twenty four-hour ambulatory pulse wave analysis was performed by oscillometric method in 71 children aged 8-18 years, 17 of whom were diagnosed with primary hypertension without obesity, 18 had both primary hypertension and obesity, and 16 had renal hypertension. Twenty healthy normotensive children were included as the control group. Carotid intima-media thickness (CIMT) and Left Ventricular Mass Index were measured. Central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in the primary hypertension group compared to controls (p = 0.001, p = 0.005, p = 0.001, p = 0.009, respectively), cSBP was higher in the renal hypertension group than the control group (p = 0.018). There was no difference between the groups in terms of pulse wave analysis parameters, CIMT, or left ventricular mass index (p > 0.05). Pulse wave velocity was positively correlated with SBP, DBP, cSBP, cDBP (p < 0.001). Augmentation index was positively correlated with DBP and cDBP (p = 0.01, p = 0.002, respectively). Our findings show that high blood pressure is associated with arterial stiffness and target organ damage beginning in childhood. The detection of early atherosclerotic vascular changes using pulse wave analysis allows to take necessary precautions such as lifestyle changes to prevent target organ damage in hypertensive children.

Evaluation of cardiovascular risk in children with solitary functioning kidney.

BACKGROUND: The present study investigates cardiovascular risk and kidney damage in patients with solitary kidneys. METHODS: Included in the study were 40 children with a unilateral functioning kidney and 60 healthy controls, all of whom were evaluated for carotid intima-media thickness, ischemia-modified albumin and oxidative stress parameters, and 24-h ambulatory blood pressure monitoring. RESULTS: Serum creatinine and urine microalbumin levels were higher and creatinine clearance was lower in the patient group than in the control group, and serum ischemia-modified albumin, carotid intima-media thickness, aldosterone, plasma renin activity and blood pressure were all higher in the patient group than in the control group. In addition, the patient group was showed a non-dipper pattern. CONCLUSION: Children with a normal functioning solitary kidney are likely at higher risk of developing cardiovascular disease and such patients should be followed closely before marked kidney impairment occurs.

Evaluation of arterial stiffness and central blood pressure by oscillometric method in normotensive offspring of hypertensive parents.

Children with a family history of hypertension have higher blood pressure and hypertensive pathophysiological changes begin before clinical findings. Here, the presence of arterial stiffness was investigated using central blood pressure measurement and pulse wave analysis in normotensive children with at least one parent with essential hypertension. Twenty-four-hour ambulatory pulse wave analysis monitoring was performed by oscillometric method in a study group of 112 normotensive children of hypertensive parents aged between 7 and 18 comparing with a control group of 101 age- and gender-matched normotensive children of normotensive parents. Pulse wave velocity, central systolic and diastolic blood pressure, systolic, diastolic and mean arterial blood pressure values were higher in the study group than the control group (p < 0.001, p = 0.002, p = 0.008, p = 0.001, p = 0.005, p = 0.001, p = 0.001, respectively). In all age groups (7-10, 11-14, and 15-18 years), pulse wave velocity was higher in the study group than the control group (p < 0.001). Pulse wave velocity was higher in children whose both parents are hypertensive compared to the children whose only mothers are hypertensive (p = 0.011). Pulse wave velocity values were positively correlated with age, weight, height, and body mass index (p < 0.05). Higher pulse wave velocity, central systolic and diastolic blood pressure values detected in the study group can be considered as early signs of hypertensive vascular changes. Pulse wave analysis can be a reliable, non-invasive, and reproducible method that can allow taking necessary precautions regarding lifestyle to prevent disease and target organ damage by detecting early hypertensive changes in genetically risky children.

Rigidez Arterial e Funções Miocárdicas do Ventrículo Esquerdo em Crianças com Válvula Aórtica Bicúspide Funcional / Arterial Stiffness and Left Ventricular Myocardial Function in Children with a Well-Functioning Bicuspid Aortic Valve

Resumo Fundamento: A rigidez arterial é um importante preditor de aortopatia e remodelamento miocárdico em pacientes com válvula aórtica bicúspide, podendo estar aumentada na infância. Objetivo: Avaliar a rigidez arterial e a função miocárdica do ventrículo esquerdo em crianças com válvula aórtica bicúspide funcional. Métodos: Quarenta e quatro crianças com válvula aórtica bicúspide e 41 pares saudáveis com válvula aórtica tricúspide foram incluídos neste estudo caso-controle. Foram obtidos os diâmetros e os escores-z relacionados da raiz aórtica e da aorta ascendente. Quanto à função miocárdica do ventrículo esquerdo, juntamente com as velocidades de fluxo mitral e parâmetros do Modo M, as velocidades miocárdicas e os intervalos de tempo foram avaliados com Doppler tecidual. A análise da onda de pulso foi realizada por aparelho oscilométrico (Mobil-o-Graph). Um valor de p<0,05 foi considerado significativo. Resultados: O índice da massa ventricular esquerda, a velocidade A do fluxo mitral, o diâmetro e o escore z da aorta ascendente e o índice de desempenho miocárdico estavam significativamente maiores nos pacientes (p = 0,04, p = 0,02, p = 0,04, p <0,001 e p <0,001 respectivamente). O índice de desempenho miocárdico correlacionou-se positivamente com o diâmetro da aorta ascendente e a velocidade A (r=0,272; p=0,01, r=356; p=0,001, respectivamente). A análise multivariada revelou que o índice de desempenho miocárdico estava relacionado ao diâmetro da aorta ascendente (p = 0,01). O índice de aumento e a velocidade da onda de pulso foram semelhantes entre os grupos (p> 0,05). Conclusão: De acordo com a análise da onda de pulso oscilométrico, as crianças com válvula aórtica bicúspide funcional apresentam rigidez arterial semelhante a seus pares saudáveis. O diâmetro da aorta ascendente foi estabelecido como preditor independente da função miocárdica do ventrículo esquerdo. A rigidez arterial pode não ser um fator de risco grave em pacientes pediátricos sem dilatação acentuada da aorta ascendente.

Abstract Background: Arterial stiffness is an important predictor factor of aortopathy and myocardial remodeling in patients with a bicuspid aortic valve and it might be increased in childhood. Objective: To assess the arterial stiffness and left ventricular myocardial function in children with a well-functioning bicuspid aortic valve. Methods: Forty-four children with a bicuspid aortic valve and 41 healthy peers with a tricuspid aortic valve were included in this case-control study. Diameters and the related z-scores of the aortic root and ascending aorta were obtained. As for the left ventricular myocardial function, along with the mitral inflow velocities and M-Mode parameters, myocardial velocities and time intervals were assessed with tissue Doppler imaging. A pulse wave analysis was performed by oscillometric device (Mobil-o-Graph). A p value <0.05 was considered significant. Results: The left ventricular mass index, mitral inflow A velocity, diameter and z-score of the ascending aorta, and myocardial performance index were significantly higher in patients (p=0.04, p=0.02,p=0.04, p<0.001,and p<0.001 respectively). The myocardial performance index was positively correlated with the diameter of the ascending aorta and A velocity (r=0.272;p=0.01, r=356;p=0.001, respectively). The multivariate analysis revealed that the myocardial performance index was related to the ascending aorta diameter (p=0.01). The augmentation index and pulse wave velocity were similar between the groups (p>0.05). Conclusion: According to the oscillometric pulse wave analysis, the children with a well-functioning bicuspid aortic valve had similar arterial stiffness to that of the healthy peers. The ascending aorta diameter was established as an independent predictor of left ventricular myocardial function. Arterial stiffness may not be a severe risk factor in pediatric patients without marked ascending aorta dilation.

Arterial Stiffness and Left Ventricular Myocardial Function in Children with a Well-Functioning Bicuspid Aortic Valve. / Rigidez Arterial e Funções Miocárdicas do Ventrículo Esquerdo em Crianças com Válvula Aórtica Bicúspide Funcional.

BACKGROUND: Arterial stiffness is an important predictor factor of aortopathy and myocardial remodeling in patients with a bicuspid aortic valve and it might be increased in childhood. OBJECTIVE: To assess the arterial stiffness and left ventricular myocardial function in children with a well-functioning bicuspid aortic valve. METHODS: Forty-four children with a bicuspid aortic valve and 41 healthy peers with a tricuspid aortic valve were included in this case-control study. Diameters and the related z-scores of the aortic root and ascending aorta were obtained. As for the left ventricular myocardial function, along with the mitral inflow velocities and M-Mode parameters, myocardial velocities and time intervals were assessed with tissue Doppler imaging. A pulse wave analysis was performed by oscillometric device (Mobil-o-Graph). A p value <0.05 was considered significant. RESULTS: The left ventricular mass index, mitral inflow A velocity, diameter and z-score of the ascending aorta, and myocardial performance index were significantly higher in patients (p=0.04, p=0.02,p=0.04, p<0.001,and p<0.001 respectively). The myocardial performance index was positively correlated with the diameter of the ascending aorta and A velocity (r=0.272;p=0.01, r=356;p=0.001, respectively). The multivariate analysis revealed that the myocardial performance index was related to the ascending aorta diameter (p=0.01). The augmentation index and pulse wave velocity were similar between the groups (p>0.05). CONCLUSION: According to the oscillometric pulse wave analysis, the children with a well-functioning bicuspid aortic valve had similar arterial stiffness to that of the healthy peers. The ascending aorta diameter was established as an independent predictor of left ventricular myocardial function. Arterial stiffness may not be a severe risk factor in pediatric patients without marked ascending aorta dilation.

FUNDAMENTO: A rigidez arterial é um importante preditor de aortopatia e remodelamento miocárdico em pacientes com válvula aórtica bicúspide, podendo estar aumentada na infância. OBJETIVO: Avaliar a rigidez arterial e a função miocárdica do ventrículo esquerdo em crianças com válvula aórtica bicúspide funcional. MÉTODOS: Quarenta e quatro crianças com válvula aórtica bicúspide e 41 pares saudáveis com válvula aórtica tricúspide foram incluídos neste estudo caso-controle. Foram obtidos os diâmetros e os escores-z relacionados da raiz aórtica e da aorta ascendente. Quanto à função miocárdica do ventrículo esquerdo, juntamente com as velocidades de fluxo mitral e parâmetros do Modo M, as velocidades miocárdicas e os intervalos de tempo foram avaliados com Doppler tecidual. A análise da onda de pulso foi realizada por aparelho oscilométrico (Mobil-o-Graph). Um valor de p<0,05 foi considerado significativo. RESULTADOS: O índice da massa ventricular esquerda, a velocidade A do fluxo mitral, o diâmetro e o escore z da aorta ascendente e o índice de desempenho miocárdico estavam significativamente maiores nos pacientes (p = 0,04, p = 0,02, p = 0,04, p <0,001 e p <0,001 respectivamente). O índice de desempenho miocárdico correlacionou-se positivamente com o diâmetro da aorta ascendente e a velocidade A (r=0,272; p=0,01, r=356; p=0,001, respectivamente). A análise multivariada revelou que o índice de desempenho miocárdico estava relacionado ao diâmetro da aorta ascendente (p = 0,01). O índice de aumento e a velocidade da onda de pulso foram semelhantes entre os grupos (p> 0,05). CONCLUSÃO: De acordo com a análise da onda de pulso oscilométrico, as crianças com válvula aórtica bicúspide funcional apresentam rigidez arterial semelhante a seus pares saudáveis. O diâmetro da aorta ascendente foi estabelecido como preditor independente da função miocárdica do ventrículo esquerdo. A rigidez arterial pode não ser um fator de risco grave em pacientes pediátricos sem dilatação acentuada da aorta ascendente.

Evaluation of Cardiotoxic Effects of Anthracyclines by Tissue Doppler Imaging in Survivors of Childhood Cancer.

BACKGROUND: Childhood cancer survivors (CCSs) are at risk for anthracycline-induced cardiotoxicity which tends to be more prominent long after completion of the chemotherapy. The aim of this study was to examine echocardiographic parameters of anthracycline-induced subclinical cardiotoxicity in children who had received chemotherapy. MATERIALS AND METHODS: A cross-sectional single-center study was conducted in a tertiary level university hospital in Eskisehir, Turkey. A total of 50 CCSs and 40 healthy peers were included. The CCSs were divided into 3 subgroups according to cumulative anthracycline dose (100-200 mg/m2, 201-299 mg/m2, and ≥ 300 mg/m2). Biventricular cardiac examination was performed with conventional echocardiography and tissue Doppler echocardiography imaging (TDI). RESULTS: The mean duration from termination of chemotherapy to echocardiographic assessment was 3.9 ± 2.2 years. The mean age of the CCSs was 11.6 ± 3.9 years. TDI-derived mitral annular isovolumetric relaxation time (IVRT) and myocardial performance index (MPI) were higher in the high-dose group of CCSs than in controls (P = .006, P = .007, P < .001, P = .0014, respectively). IVRT was also higher in patients with ≥ 300 mg/m2 cumulative dose than in those with < 200 mg/m2 (P = .007). TDI-derived mitral annular MPI and IVRT were significantly associated with cumulative anthracycline dose (r = 0.288, P = .006, r = 0.340, P = .001). CONCLUSION: A cumulative anthracycline dose > 300 mg/m2 may lead to subclinical cardiotoxicity, and is therefore a potential risk factor for late onset cardiac failure. TDI-derived MPI can be a sensitive tool to reveal subtle signs of myocardial damage, which may facilitate implementation of preventive therapies for patients suspected to be at risk.

Impact of the expanded examination of fetal heart to the prenatal diagnosis of congenital heart diseases.

OBJECTIVE: In the present study, for which reasons fetal cardiac evaluation was requested from our pediatric cardiology clinic, the effects of routine fetal cardiac evaluation in obstetric ultrasonography (USG) on the detection of congenital heart disease (CHD) and the distribution of intrauterine diagnosis of CHD according to pregnancy risk profiles were retrospectively analyzed. MATERIALS AND METHODS: Fetal echocardiography reports which containing the nineteen-month period were retrospectively examined. We performed a fetal echocardiography for all pregnant women who were referred to pediatric cardiology clinic after detail obstetric USG screening. The pregnancies were categorized into two groups based on the risk of CHD: Low-risk and high-risk groups. Detected congenital cardiac structural malformations were classified as complex, moderate, and mild according to perinatal mortality risk. RESULTS: Of the 736 pregnancies, 22 were twin, and fetal cardiac evaluation was performed in 758 fetuses. There were 341 (46.3%) pregnancies in the high-risk group and 395 (53.6%) pregnancies in the low-risk group. The most common reason for fetal cardiac evaluation request was inability to adequately visualize the fetal heart (36.1%), while suspected fetal cardiac abnormality was the second most common cause (21.3%). Number of fetuses detected with cardiac abnormalities was 80 (23.5%) among high-risk pregnancies, and 20 (5%) among low-risk pregnancies. The most common type of malformation was simple cardiac abnormalities (6%) followed by complex lesions (4.1%). The most common cardiac abnormality was ventricular septal defect comprised of 18 cases (2.4%) while the most common complex cardiac abnormality was pulmonary atresia (1.2%). The rate of consistency was 40.1% between obstetricians and pediatric cardiologist in terms of the diagnosis of the congenital cardiac malformations. CONCLUSION: Routine evaluation of the fetal heart by means of obstetric USG, including four chambers, outflow tracts' and three vessel views, would allow for diagnosing congenital cardiac malformations to a large extent during the intrauterine period.

Evaluation of blood pressure responses to treadmill exercise test in normotensive children of hypertensive parents.

BACKGROUND: Hypertension is a progressive disease with a prehypertensive phase. The most important feature of this period is the abnormal cardiovascular reactivity to various stressors. In our study, we focused on normotensive children of hypertensive parents, a special group that is at risk. METHODS: We evaluated the children according to age, studying whether they showed higher cardiovascular reactivity at different steps of an exercise test and during a recovery period than their counterparts with a negative history. A total of 110 normotensive children who were between the ages of 6 and 18 years were enrolled into the study. Sixty-two children whose parent(s) had a history of hypertension formed the study group while 48 without this history formed the control group. An exercise test was performed according to the Bruce protocol. Maximal systolic blood pressures and systolic blood pressures were taken while the participants were at rest; during phases 2 and 3; and also in the first, third, and sixth minutes of the recovery period. RESULTS: Measurements were significantly higher in the study group (p < 0.05). In the group of children between the ages of 6 and 10 years, cardiovascular responses were similar. Children older than 10 years, however, had significantly higher blood pressure levels than those in the control group. The children who were at risk of hypertension showed more exaggerated cardiovascular responses during the exercise test and recovery period. This response was particularly evident for those children 10 years of age and older. CONCLUSIONS: Our study indicates that treadmill exercise is a safe and effective investigational method which can be used to identify children who are at risk for development of hypertension before this condition becomes clinically evident.

A Case of Congenital Hepatoblastoma Coexisting with Pulmonary Hypertension.

Hepatoblastoma (HBL) is the most frequently detected malignant tumor of the liver in childhood. HBLs detected antenatally or up to 3 months after birth are considered congenital HBLs. We report a five-day-old female infant in whom a hepatic mass was detected at 20 weeks' gestation. At birth (36 weeks), the hepatic mass measured 12x6 cm, and she had respiratory distress. Pulmonary hypertension (PHT) was detected on echocardiographic evaluation. Despite dual medical therapy, her PHT did not improve. Histologically, the biopsy demonstrated a mixed epithelial-mesenchymal HBL with predominance of fetal morphology in the epithelial component. Chemotherapy was initiated on postnatal day 15; however, the baby died of respiratory failure on postnatal day 23. Conclusion: HBL is an embryonal tumor which can develop early in the intrauterine period. Although the mechanism is not known, it may cause PHT which would affect the prognosis negatively.

Maternal and fetal tuberous sclerosis complex: a case report questioning clinical approach.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease with multisystem involvement. CASE: Here, a mother and infant couple was presented with maternal and fetal TSC including demonstrative clinical findings and genetic analysis. The interesting point of this case report is that maternal and fetal TSC was identified after the mother gave birth to a child with a cardiac rhabdomyoma. The genetic analysis revealed a novel mutation which was the same in both the mother and her infant. CONCLUSION: We would like to bring to the attention of clinicians this entity and to emphasize that maternal and fetal TSC can adversely affect maternal and fetal health, and deserves close follow up. Our recommendation is that if cardiac rhabdomyoma/cortical tuber/renal angiomyolipoma are present in prenatal ultrasonography, the parents should be evaluated for TSC.

Myocardial functions, blood pressure changes, and arterial stiffness in children with severe hemophilia A.

INTRODUCTION: Prolonging the life span of patients with hemophilia has led to the emergence of comorbidities. Cardiovascular diseases are one of the important causes of mortality in patients with hemophilia. This study investigated the myocardial functions, blood pressure changes, arterial stiffness, and risk factors associated with cardiovascular diseases in children with hemophilia. MATERIAL AND METHODS: In total, 17 children with severe hemophilia A and 23 healthy children were included in the study. Myocardial functions were evaluated using standard and tissue Doppler echocardiography. Peripheral and central blood pressure measurements were performed, and arterial stiffness was evaluated. Carotid intima-media thicknesses (CIMT) serum glucose, insulin, insulin resistance index, and lipoprotein levels were measured. RESULTS: There were no differences between the two groups in terms of age, and biochemical parameters (P > 0.05). The HDL-C levels in the hemophilia group were lower than those in the control group (P < 0.05). Five of the patients had insulin resistance (29.4%), whereas four had low HDL-C levels (23.5%). There were no differences between the groups in terms of the CIMT, peripheral blood pressure, and central systolic blood pressure (P > 0.05). In the hemophilia group, central diastolic blood pressure (cDBP), arterial stiffness, and myocardial performance index were higher (P < 0.05, P = 0.01, P < 0.01), whereas the ejection time was shorter than in the control group (P < 0.05). CONCLUSIONS: Compared with the control group, there is an onset of arterial stiffness, cDBP values tend to increase, and serum HDL-C levels are lower in the hemophilia group. Moreover, myocardial systolic functions demonstrate a deterioration that becomes more prominent with the increase in arterial stiffness.

Alterations in cerebral blood flow in children with congestive heart failure due to ventricular septal defect.

OBJECTIVE: We aimed to investigate the effect of ventricular septal defect (VSD) and heart failure on cerebral blood flow (CBF) in children, whether heart failure treatment improves CBF, and if there is any relationship between CBF and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. METHOD: Forty children with VSD (13 with heart failure) aged between 1 and 36 months were studied. The control group comprised 25 healthy children in the same age group. Maximum, minimum, and mean blood flow velocities and pulsatility indices of the right and left middle cerebral arteries were assessed using transcranial Doppler ultrasonography. Measurements of CBF and serum NT-proBNP levels were repeated in patients with heart failure a month post-heart failure treatment initiation. The groups were also compared in terms of defect diameters, cardiac structural changes, left ventricular systolic function, and findings related to pulmonary hypertension determined by echocardiography. Correlations between echocardiographic measurements and CBF parameters were analyzed. RESULTS: Although no significant difference was found between patient and control groups for CBF, right and left maximum CBF velocities significantly increased posttreatment in patients with heart failure (P = .04 and P = .01, respectively). Serum NT-proBNP levels in children with VSD associated with heart failure were significantly higher than those in children with VSD alone (P = .04) or in healthy children (P < .001). NT-proBNP levels were negatively correlated with right and left maximum CBF velocities (r = -0.39, P = .013 and r = -0.32, P = .043, respectively). CONCLUSION: Although no significant difference was found in CBF velocity among the study groups, increase in the CBF velocity post heart failure treatment and negative correlations between CBF velocity and both the VSD diameter and NT-proBNP levels indicate that the hemodynamic status due to VSD associated with heart failure has an effect on CBF.

Early myocardial changes in normotensive children of hypertensive parents: a tissue Doppler study.

The aim of this study was to examine early left ventricular systolic and diastolic changes using tissue Doppler imaging (TDI) in normotensive children of hypertensive parents (NCHP), a risk group for cardiovascular diseases. Ninety-two children characterized as NCHP (age range: 6-18 years) and 90 age-, gender-, height-, weight-, and body mass index-matched children characterized as normotensive children of normotensive parents (NCNP) were included in the study. Left ventricular diastolic parameters were assessed using transmitral flow pulse wave Doppler echocardiography and mitral septal and lateral annular TDI. Left ventricular systolic and diastolic function was evaluated globally using the TDI-derived myocardial performance index (MPI'). Mean systolic, diastolic, and average blood pressure values were found to be higher in the NCHP group than in the NCNP group. Echocardiographic parameters in the NCHP group showed statistically significant differences, including increased interventricular septum end-diastolic wall thickness (p = 0.039), left ventricular end-diastolic posterior wall thickness (p = 0.011), relative wall thickness (p = 0.013), and transmitral flow A velocity (p = 0.003); parameters determined by TDI included a prolonged isovolumetric relaxation time (p < 0.001) and isovolumetric contraction time (p = 0.002), shortened ejection time (p = 0.001), and increased MPI' (p < 0.001) in the NCHP group. Early alterations in myocardial function, indicated by increased MPI' values, had a positive correlation with systolic blood pressure and myocardial thickness. Conversely, they were negatively correlated with the ejection fraction and E/A ratio, which decreases with diastolic dysfunction. The MPI' is considered a repeatable, non-invasive, and low-cost assessment method that can surpass conventional methods in the detection of early left ventricular systolic and diastolic functional changes in the subclinical period of hypertension in children with familial risk.

Evaluation of cardiac autonomic function using heart rate variability in children with acute carbon monoxide poisoning.

Introduction Carbon monoxide poisoning may cause myocardial toxicity and cardiac autonomic dysfunction, which may contribute to the development of life-threatening arrhythmias. We investigated the potential association between acute carbon monoxide exposure and cardiac autonomic function measured by heart rate variability. METHOD: The present study included 40 children aged 1-17 years who were admitted to the Pediatric Intensive Care Unit with acute carbon monoxide poisoning and 40 healthy age- and sex-matched controls. Carboxyhaemoglobin and cardiac enzymes were measured at admission. Electrocardiography was performed on admission and discharge, and 24-hour Holter electrocardiography was digitally recorded. Heart rate variability was analysed at both time points - 24-hour recordings - and frequency domains - from the first 5 minutes of intensive care unit admission. RESULTS: Time domain and frequency indices such as high-frequency spectral power and low-frequency spectral power were similar between patient and control groups (p>0.05). The ratio of low-frequency spectral power to high-frequency spectral power was significantly lower in the carbon monoxide poisoning group (p<0.001) and was negatively correlated with carboxyhaemoglobin levels (r=-0.351, p<0.05). The mean heart rate, QT dispersion, corrected QT dispersion, and P dispersion values were higher in the carbon monoxide poisoning group (p<0.05) on admission. The QT dispersion and corrected QT dispersion remained longer in the carbon monoxide poisoning group compared with controls on discharge (p<0.05). CONCLUSION: The frequency domain indices, especially the ratio of low-frequency spectral power to high-frequency spectral power, are useful for the evaluation of the cardiac autonomic function. The decreased low-frequency spectral power-to-high-frequency spectral power ratio reflects a balance of the autonomic nervous system, which shifted to parasympathetic components.

A case of Donohue syndrome "Leprechaunism" with a novel mutation in the insulin receptor gene.

Donohue syndrome (Leprechaunism) is characterized by severe insulin resistance, hyperinsulinemia, postprandial hyperglycemia, preprandial hypoglycemia, intrauterine and postnatal growth retardation, dysmorphic findings, and clinical and laboratory findings of hyperandrogenemia due to homozygous or compound heterozygous inactivating mutations in the insulin receptor gene. A female newborn presented with lack of subcutaneous fat tissue, bilateral simian creases, hypertrichosis, especially on her face, gingival hypertrophy, cliteromegaly, and prominent nipples. Her laboratory tests revealed hyperandrogenism, postprandial hyperglycemia and preprandial hypoglycemia, and very high concurrent insulin levels. She was diagnosed as having Donohue syndrome. Metformin and continuous nasogastric feeding were administrated. During follow-up, relatively good glycemic control was obtained. However, severe hypertrophic obstructive cardiomyopathy and severe malnutrition developed. She died aged 75 days of severe heart failure and pneumonia. Her insulin receptors gene analysis revealed a compound heterozygous mutation. One of these mutations was a p.R813 (c.2437C>T) mutation, which was defined previously and shown also in her father, the other mutation was a novel p.777-790delVAAFPNTSSTSVPT mutation, also shown in her mother. The parents were heterozygous for these mutations.