Soluble urokinase plasminogen activator receptor in type 1 diabetic children, relation to vascular complications.

BACKGROUND: Endothelial dysfunction caused by chronic inflammation is the cornerstone of vascular complications in type 1 Diabetes-Mellitus (T1DM). Soluble Urokinase Plasminogen Activator Receptor (SuPAR) is a novel marker of inflammation and endothelial dysfunction. AIM: To evaluate SuPAR in T1DM children and correlate it to diabetic vascular complications. METHODS: Seventy T1DM children and 40 matched healthy controls were studied focusing on disease duration, insulin therapy and symptoms of diabetic complications. Blood-pressure, fundus and screening for peripheral-neuropathy were done. Fasting lipid profile, fraction-C of glycosylated hemoglobin (HbA1c%), Urinary albumin excretion (UAE), estimated-glomerular filtration rate (eGFR) and SuPAR were measured. Internal aortic diameter was measured with calculation of aortic distensibility and stiffness index. RESULTS: Sixteen T1DM patients(22.9%) had peripheral neuropathy, 12(17%) had nephropathy and none had retinopathy. SuPAR was significantly elevated in diabetic nephropathy (p < 0.01) and neuropathy (p < 0.01). Aortic stiffness index was significantly higher (p < 0.01) whereas, aortic strain and distensibility were significantly lower (p < 0.01) in T1DM than controls. SuPAR was significantly correlated to disease duration (p < 0.01), systolic blood pressure (p < 0.01), total cholesterol (p < 0.01), triglycerides (p < 0.01), UAER (p < 0.01) and aortic strain (0.013). CONCLUSION: Increased SuPAR early in diabetes might become a useful indicator of developing vascular complications. Further prospective studies are needed to determine the cut-off level of SuPAR for detection of T1DM and its complications.

Left Ventricular Structural and Functional Changes in Children With ß-Thalassemia and Sickle Cell Disease: Relationship to Sleep-disordered Breathing.

Cardiovascular complications are well recognized in ß-thalassemia and sickle cell disease (SCD). The objective of this study was to evaluate left ventricular (LV) structural and functional changes and their relationship to sleep-disordered breathing (SDB) in children with ß-thalassemia and SCD. One hundred patients recruited from the hematology clinic were subjected to Pittsburgh Sleep Quality Index score; 26 patients had positive score (Pittsburgh Sleep Quality Index ≥5) (15 ß-thalassemia major and 11 SCD) and were compared with 25 age-matched and sex-matched controls. All underwent polysomnography and tissue Doppler echocardiography. SDB was detected in 73% of thalassemia patients (all had increased LV mass index [LVMI], diastolic dysfunction [increased E/Em], and 53% had pulmonary hypertension [tricuspid valve resurgence (TR) velocity ≥2.5 m/s]) and in 46% of SCD patients ( all had increased LVMI, 81.8% had pulmonary hypertension, and 76% had diastolic dysfunction). Sleep O2 saturation of ß-thalassemia patients negatively correlated with TR velocity and LVMI (P=0.027, 0.015), and lower asleep O2 saturation was associated with increased E/Em. In SCD patients, sleep and awake O2 saturation negatively correlated with TR velocity and E/Em (P=0.024 and 0.041), and lower sleep O2 saturation was associated with increased LV diameter (P=0.021). SDB is common and associated with LV structural and functional changes in ß-thalassemia and SCD.

Three Dimensional (3D) Echocardiography as a Tool of Left Ventricular Assessment in Children with Dilated Cardiomyopathy: Comparison to Cardiac MRI.

BACKGROUND: Left ventricular (LV) volumes and ejection fraction (EF) is Strong prognostic indicators for DCM. Cardiac MRI (CMRI) is a preferred technique for LV volumes and EF assessment due to high spatial resolution and complete volumetric datasets. Three-dimensional echocardiography is a promising new technique under investigations. AIM: Evaluate 3D echocardiography as a tool in LV assessment in DCM children about CMRI. PATIENTS AND METHODS: A group of 20 DCM children (LVdiastolic diameter < 2 Z score, LVEF < 35%) at Children s Hospital, Ain-Shams University (gp1) (mean age 6.6 years) were compared to 20 age and sex-matched children as controls (gp2). Patients were subjected to: clinical examination, conventional echocardiography, automated 3D LV quantification, 3D speckle tracking echocardiography (3D-STE) (VIVID E9 Vingmed, Norway) and CMRI (Philips Achieva Nova, 1.5 Tesla scanner) for LV end systolic volume (LVESV), LVend diastolic volume (LVEDV) that were indexed to body surface area, EF% and wall motion abnormalities assessment. RESUTS: No statistically significant difference was found between automated 3D LV quantification echocardiography, 3D-STE, and CMRI in ESV/BSA and EDV/BSA assessment (p = 1, 0.99 respectively), between automated LV quantification echocardiography and CMRI in EF% assessment (p = 0.99) and between CMRI and 3D-STE in LV Global hypokinesia detection (P = 0.255). As for segmental hypokinesia CMRI was more sensitive [45% of patients vs. 40%, (P = 0,036), basal septal hypokinesia 85% vs. 75%, (p = 0.045), mid septal hypokinesia 80% vs. 65%, (p = 0.012) and lateral wall hypokinesia 75% vs. 65%, (p = 0.028)]. CONCLUSION: Automated 3D LV quantification echocardiography and 3D-STE are reliable tools in LV volumetric and systolic function assessment about CMRIas a standard method. 3D speckle echocardiography is comparable to CMRI in global wall hypokinesia detection but less sensitive in segmental wall hypokinesia which mandates further studies.

Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With ß-Thalassemia Intermedia.

Endothelial damage has been implicated in the pathogenesis of vascular complications in ß-thalassemia intermedia (ß-TI). Soluble fms-like tyrosine kinase 1 (sFLT-1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. Soluble fms-like tyrosine kinase 1 is an antiangiogenic protein that induces endothelial dysfunction by adhering to and inhibiting VEGF and placenta growth factor. The aim of this study was to assess the level of sFLT-1 in 35 children and adolescents with ß-TI, correlating it with markers of hemolysis and iron overload as well as cardiopulmonary complications. Patients were studied focusing on the history of cardiac disease, splenectomy, transfusion, chelation/hydroxyurea therapy, serum ferritin, and sFLT-1 levels. Echocardiography and measurement of carotid intima-media thickness (CIMT) were done for all participants. Soluble fms-like tyrosine kinase 1 was significantly higher in TI patients compared to the control group (median [interquartile range], 110 [80-155] pg/mL versus 70 [60-90] pg/mL; P < .001). Splenectomized patients and those who had pulmonary hypertension risk or heart disease had higher sFLT-1 levels than those without ( P < .001). The sFLT-1 cutoff value that differentiates patients with and without pulmonary hypertension risk or heart disease was determined. Soluble fms-like tyrosine kinase 1 was lower among patients who received chelation therapy and/or hydroxyurea. Significant positive relations were observed between sFLT-1 and lactate dehydrogenase, serum ferritin, liver iron concentration, tricuspid regurgitant jet velocity, and CIMT. We suggest that sFLT-1 represents a link between angiogenesis, endothelial dysfunction, and subclinical atherosclerosis. Measurement of sFLT-1 as a marker of vascular dysfunction in ß-TI may provide utility for early identification of patients at increased risk of cardiopulmonary complications.

The Prevalence and Risk Factors of Early Arrhythmias Following Pediatric Open Heart Surgery in Egyptian Children.

AIM: This study aimed to assess the prevalence of early postoperative arrhythmias after cardiac operation in the pediatric population, and to analyse possible risk factors. MATERIAL AND METHODS: Cross-sectional study included 30 postoperative patients, with age range four up to 144 months. They were selected from those admitted to the Cardiology Unit in the Pediatric department of Ain Shams University hospitals, after undergoing cardiopulmonary bypass (CPB) surgery for correction of congenital cardiac defects. All patients had preoperative sinus rhythm and normal preoperative electrolytes levels. All patients' records about age, weight, type of surgery, intraoperative arrhythmias, cardiopulmonary bypass time, ischemic time and use of inotropic drugs were taken before they were admitted to the specialised pediatric post-surgery intensive care unit (ICU). RESULTS: Arrhythmia was documented in 15 out of 30 patients (50%). Statistically significant difference between the arrhythmic and non-arrhythmic group were recorded in relation to the age of operation (23 vs 33 months), weight (12 vs. 17 kg), ischemic time (74.5 vs. 54 min), cardiopulmonary bypass time (125.5 vs. 93.5min), inotrope use (1.6 vs. 1.16) and postoperative ICU stay (5.8 vs. 2.7 days), P<0.05. CONCLUSION: Early postoperative arrhythmias following surgery for congenital heart disease are relatively frequent in children (50%). Younger age, lower body weight, longer ischemic time and bypass time, and more inotrope use are all risk factors for postoperative arrhythmias and lead to increase the hospital stay.

Galectin-3 in Children with Chronic Heart Failure with Normal and Reduced Ejection Fraction: Relationship to Disease Severity.

Heart failure (HF) progression has not been studied in pediatric patients as well as HF in patients with a normal ejection fraction (HFNEF). We aimed to evaluate galactin-3 in children with HFNEF and reduced ejection fraction (HFREF) and its correlation to disease severity and progression. This cross-sectional study involved 45 chronic HF patients taking G1a (23 HFNEF children) and G1b (22 HFREF children) compared to 45 age- and sex-matched controls (G2) subjected to history taking, Ross functional HF classification, conventional and tissue Doppler echocardiographic systolic and diastolic function assessment (FS%, E/A, S m, E m/A m, E/E m) and laboratory investigations [glomerular filtration rate, serum galactin-3 level (ELISA)]. The results showed that serum galactin was increased in patients compared to controls (p > 0.001); a cutoff value of 3.5 ng/ml was estimated for HF diagnosis HFNEF patients who had higher galactin-3 levels than HFREF patients, but it did not reach statistical significance (p = 0.194). Galactin-3 levels positively correlated to the Ross HF classification (p = 0.01) and E/E m (p = 0.032) and negatively correlated to FS%, S m and E m/A m (p = 0.028, 0.022, 0.043). Galactin-3 levels were significantly reduced in patients receiving spironolactone (p = 0.049). Galactin-3 can be a tool for chronic HF diagnosis and a marker of disease severity and staging in children with HFNEF and HFREF. The role of spironolactone in reducing galactin-3 in pediatric HF requires further research.

Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy.

BACKGROUND: Heart disease is the leading cause of mortality and one of the main causes of morbidity in ß-thalassemia. Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-ß superfamily, is a marker of ineffective erythropoiesis in several anemias. AIM: To determine GDF-15 levels in children and adolescents with TI and the relation to hemolysis, iron overload and cardiovascular complications. METHODS: GDF-15 was measured in 35 TI patients without symptoms for heart disease and correlated to echocardiographic parameters and carotid intima media thickness (CIMT). RESULTS: GDF-15 levels were significantly higher in TI patients compared with controls (p < 0.001). Transfusion dependent patients had higher GDF-15 than non-transfusion dependent patients. TI patients with splenectomy, pulmonary hypertension risk, and heart disease had higher GDF-15 levels than those without. GDF-15 was lower among hydroxyurea-treated patients. Multiple linear regression analysis revealed that transfusion index (p=0.012), serum ferritin (p < 0.001), tricuspid regurgitant jet velocity (p < 0.001), ejection fraction (p=0.01) and CIMT (p=0.007) were independently related to GDF-15. According to ROC curve analysis, the cutoff value of GDF-15 at 1500 pg/mL could differentiate patients with and without heart disease. CONCLUSION: GDF-15 would identify TI patients at increased risk of pulmonary and cardiovascular complications as well as subclinical atherosclerosis.

Cardiac autonomic balance in children with epilepsy: value of antiepileptic drugs.

BACKGROUND: Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, there is still uncertainty about whether imbalance of sympathetic, vagal, or both systems occurs in epilepsy as well as the effect of anticonvulsants on the autonomic system. AIM: To evaluate cardiac autonomic status in children with epilepsy on antiepileptic drugs. PATIENTS AND METHODS: Sixty patients with epilepsy were recruited from the Outpatient Neurology Clinic at Ain Shams University and were divided into the following groups: group I, drug naive; and group II, patients with epilepsy on regular antiepileptic drugs. The second group was further subdivided into the following groups: group IIa, received monotherapy; and group IIb, received polytherapy. Forty age- and sex-matched healthy children served as controls. Included patients underwent videorecorded electroencephalograph, Holter electrocardiogram (EKG) for time and frequency domains of heart rate variability, and standard EKG recording for QTc, QTd. RESULTS: Mean values of all time domain, total power, and high-frequency power were significantly lower, whereas low-frequency and low-frequency/high-frequency power, QTc. and QTd were significantly higher in group I compared with group II and in patients compared with controls. No significant difference was found between patients on different antiepileptic drug regimens regarding heart rate variability values. A significant negative correlation was found between Chalfont severity score and 50% of difference between adjacent, normal RR intervals in patient groups. CONCLUSIONS: Children with epilepsy have cardiac autonomic dysfunction evident in their heart rate variability assessment. Patients on antiepileptic drugs had better autonomic balance than those not on antiepileptic drugs. Holter and EKG follow-up should be considered for early detection in those at high-risk cardiac complications.

Platelet-derived microparticles and platelet function profile in children with congenital heart disease.

Platelet microparticles (PMPs) and function profile in children with congenital heart disease (CHD) have not been widely explored. We investigated platelet aggregation, flow cytometric platelet surface receptors (P-selectin and glycoprotein (GP) IIb/IIIa) and PMPs in 23 children with cyanotic CHD (CCHD), 30 children with acyanotic CHD (ACHD) and 30 healthy controls correlating these variables to hematological and coagulation parameters including von Willebrand factor antigen (vWF Ag) as a marker of endothelial dysfunction. Hemoglobin, hematocrit (HCT), D-dimer, and vWF Ag were significantly higher in CCHD than ACHD group. Platelet MPs and P-selectin expression were increased in patients than controls, particularly in CCHD and positively correlated to HCT, D-dimer, and vWF Ag while platelet count, aggregation, and GP IIb/IIIa expression were decreased in CCHD compared with ACHD group and negatively correlated to HCT. The overproduction of PMPs and platelet activation with suppressed aggregation may be implicated in the pathogenesis of coagulation/hemostatic abnormalities in children with CCHD.

Adiponectin as a marker of complications in type I diabetes.

OBJECTIVE: To evaluate adiponectin levels in children and adolescents with type I diabetes, and their relationship to long term complications. DESIGN: Cross sectional. SETTING: Tertiary referral hospital, Cairo, Egypt. PARTICIPANTS: Thirty children and adolescents with type I diabetes mellitus, classified into complicated and non-complicated and compared to 10 healthy age and sex matched subjects as a control group. METHODS: All children underwent anthropometric measurements, neurological assessment, fundus examination, echocardiography and assays of HbA1c, creatinine, 24-hr urinary protein, and serum adiponectin. MAIN OUTCOME MEASURE: Relationship of serum adiponectin to complications of type I diabetes mellitus, and glucose control. RESULTS: Serum adiponectin was significantly elevated in complicated diabetes (10.3 ± 5.9 pg/dL) as compared to the controls (6.5 ± 3.7 pg/dL) (P<0.01), and correlated directly with HbA1c (P<0.05) and creatinine (P<0.001). Patients with nephropathy showed high values of adiponectin (15.7 ± 3.7 pg/dL). CONCLUSION: Elevated adiponectin level in children and adolescents with type I diabetes indicates poor glycemic control and development of complications, especially nephropathy.