Plasma mid-regional proadrenomedullin level in children with pulmonary hypertension associated with CHD.

Adrenomedullin has been shown to inhibit proliferation in pulmonary artery smooth muscle cells and to alleviate pulmonary artery collagen accumulation in pulmonary hypertension. We aimed to assess mid-regional proadrenomedullin level in children with pulmonary hypertension due to CHDs. The current study was conducted in the Pediatric Cardiology Unit, Tanta University Hospital, on 50 children with CHDs: twenty-five patients had a complication of pulmonary hypertension and the other 25 patients without pulmonary hypertension. Another 25 children without CHDs were concluded as a control group. We performed complete history taking, full clinical assessment, chest X-ray, electrocardiogram, and echocardiographic assessment. Plasma level of mid-regional proadrenomedullin was assessed using a sandwich enzyme-linked immunosorbent assay test. Our results showed that the mean plasma level of mid-regional proadrenomedullin was significantly increased in patients with pulmonary hypertension. Significant positive correlation was found between mid-regional proadrenomedullin and mean pulmonary artery pressure. The best cut-off point of mid-regional proadrenomedullin as a diagnostic biomarker to discriminate patients with CHDs complicated with pulmonary hypertension was 199.22 nmol/l. Mid-regional proadrenomedullin significantly increased in patients with pulmonary hypertension who died as compared to patients who survived, with the best cut-off point was 428,8 nmol/l. We concluded that plasma levels of mid-regional proadrenomedullin were significantly elevated in children with pulmonary hypertension complicated by the CHDs. It could be used as a cardiac biomarker in these patients, with good diagnostic and prognostic value.

Serum-soluble suppression of tumourigenicity-2 as a biomarker in children with congestive heart failure.

BACKGROUND: We aimed to evaluate serum soluble suppression of tumorigenicity-2 in children with congestive heart failure, to assess the diagnostic and prognostic values of soluble suppression of tumorigenicity-2 in these patients, and to correlate its levels with various clinical and echocardiographic data. METHODS: We included 60 children with congestive heart failure as the patient group. Sixty healthy children of matched age and sex served as the control group. Patients were evaluated clinically and by echocardiography. Serum level of suppression of tumorigenicity-2 was measured for patients at admission. All patients were followed up for death or readmission for a period of one year. RESULTS: Soluble suppression of tumorigenicity-2 was significantly higher in children with congestive heart failure as compared to the control group. Soluble suppression of tumorigenicity-2 was significantly increased in patients with higher severity of congestive heart failure. There was a significant increase in soluble suppression of tumorigenicity-2 in patients with bad prognosis compared to those with good prognosis. There was a significant positive correlation between soluble suppression of tumorigenicity-2 and respiratory rate, heart rate, and clinical stage of congenital heart failure, while there was a significant negative correlation between soluble suppression of tumorigenicity-2 and left ventricular systolic and diastolic function. The best cut-off of soluble suppression of tumorigenicity-2 to diagnose congestive heart failure was > 3.6 with 87% sensitivity and 79% specificity. The cut-off point of soluble suppression of tumorigenicity-2 to diagnose congestive heart failure in children was ≥ 31.56 ng/ml, with 95% sensitivity and 91.37% specificity. Moreover, the cut-off point of soluble suppression of tumorigenicity-2 to predict bad prognosis in children with congestive heart failure was ≥ 255.5 ng/ml, with 92% sensitivity and 89.0% specificity. CONCLUSION: Soluble suppression of tumorigenicity-2 is a good diagnostic and predictive biomarker in children with congestive heart failure.

Propionic and Methylmalonic Acidemias: Initial Clinical and Biochemical Presentation.

PA and MAA have numerous nonspecific presentations, potentially leading to delayed diagnosis or misdiagnosis. In this paper, we present the clinical and biochemical characteristics of MMA and PA patients at initial presentation. Results. This is a retrospective review of 20 patients with PA (n = 10) and MMA (n = 10). The most observed symptoms were vomiting (85%) and refusing feeding (70%). Ammonia was 108.75 ± 9.3 µmol/l, showing a negative correlation with pH and bicarbonate and positive correlation with lactate and anion gap. Peak ammonia did not correlate with age of onset (r = 0.11 and p = 0.64) or age at diagnosis (r = 0.39 and p = 0.089), nor did pH (r = 0.01, p = 0.96; r = -0.25, p = 0.28) or bicarbonate (r = 0.07, p = 0.76; r = -0.22, p = 0.34). There was no correlation between ammonia and C3 : C2 (r = 0.1 and p = 0.96) or C3 (r = 0.23 and p = 0.32). The glycine was 386 ± 167.1 µmol/l, and it was higher in PA (p = 0.003). There was a positive correlation between glycine and both pH (r = 0.56 and p = 0.01) and HCO3 (r = 0.49 and p = 0.026). There was no correlation between glycine and ammonia (r = -0.435 and p = 0.055) or lactate (r = 0.32 and p = 0.160). Conclusion. Clinical presentation of PA and MMA is nonspecific, though vomiting and refusing feeding are potential markers of decompensation. Blood gas, lactate, and ammonia levels are also good predictors of decompensation, though increasing levels of glycine may not indicate metabolic instability.

Clinical Course and Nutritional Management of Propionic and Methylmalonic Acidemias.

Propionic and methylmalonic acidemias result in multiple health problems including increased risk for neurological and intellectual disabilities. Knowledge regarding factors that correlate to poor prognosis and long-term outcomes is still limited. In this study, we aim to provide insight concerning clinical course and long-term complications by identifying possible correlating factors to complications. Results. This is a retrospective review of 20 Egyptian patients diagnosed with PA (n = 10) and MMA (n = 10) in the years 2014-2018. PA patients had lower DQ/IQ and were more liable to hypotonia and developmental delay. The DQ/IQ had a strong negative correlation with length of hospital stay, frequency of PICU admissions, time delay until diagnosis, and the mode ammonia level. However, DQ/IQ did not correlate with age of onset of symptoms or the peak ammonia level at presentation. Both the growth percentiles and albumin levels had a positive correlation with natural protein intake and did not correlate with the total protein intake. Additionally, patients on higher amounts of medical formula did not necessarily show an improvement in the frequency of decompensation episodes. Conclusion. Our findings indicate that implementation of NBS, vigilant and proactive management of decompensation episodes, and pursuing normal ammonia levels during monitoring can help patients achieve a better neurological prognosis. Furthermore, patients can have a better outcome on mainly natural protein; medical formula should only be used in cases where patients do not meet 100-120% of their DRI from natural protein.

Diagnostic and predictive values of plasma connective tissue growth factor in children with pulmonary hypertension associated with CHD.

OBJECTIVE: To evaluate the diagnostic and predictive values of plasma connective tissue growth factor in children with pulmonary hypertension (PH)-related CHD. PATIENTS AND METHODS: Forty patients with PH-related CHD were enrolled as group I, and 40 patients with CHD and no PH served as group II. Forty healthy children of matched age and sex served as a control group. Echocardiographic examinations and plasma connective tissue growth factor levels were performed for all included children. Cardiac catheterisation was performed for children with CHD only. RESULTS: Plasma connective tissue growth factor levels were significantly higher in children with PH-related CHD compared to CHD-only patients and to control group and this elevation went with the severity of PH. There was a significant positive correlation between connective tissue growth factor levels and mean pulmonary pressure, pulmonary vascular resistance, and right ventricular diameter. A significant negative correlation was noticed between connective tissue growth factor levels, oxygen saturation, and right ventricular diastolic function. The sensitivity of plasma connective tissue growth factor as a diagnostic biomarker for PH was 95%, and the specificity was 90% at a cut-off value ≥650 pg/mL. The predictive value of plasma connective tissue growth factor for adverse outcome had a sensitivity of 88% and a specificity of 83% at a cut-off value ≥1900 pg/mL. CONCLUSION: Connective tissue growth factor is a promising biomarker with good diagnostic and predictive values in children with PH-related CHD.

Comparison of transcatheter versus surgical closure of perimembranous ventricular septal defect in pediatric patients: A systematic review and meta-analysis.

OBJECTIVE: Perimembranous ventricular septal defect (pmVSD) is a common congenital heart disease (CHD) usually treated with either catheter or surgical closure. Superiority of one procedure over the other in children is still a matter of debate. We performed this meta-analysis to compare the clinical outcomes and cost of transcatheter and surgical closure of pmVSD in children. MATERIALS AND METHODS: We searched seven databases (MEDLINE, PubMed, EMBASE, Google Scholar, CENTRAL, CINHAL, and Cochrane library) and literature references for articles published in the past 10 years (between January 2008 and January 2018) comparing closure of pmVSD by both procedures in children. The outcomes of interest were success rate, residual shunt, need for blood transfusion, complications especially complete atrioventricular block, length of hospital stay, and cost. RESULTS: A total of 1750 articles were identified. However, only five studies fulfilled the inclusion criteria. As regards success rate, no significant difference was found between surgical and catheter closure. Residual shunt was significantly lower in catheter closure than surgical closure [risk ratio (RR) = 0.44; 95% confidence interval (CI), 0.23-0.83, p = 0.01). The need for blood transfusion and the length of hospital stay were significantly lower in the catheter closure compared to surgical closure (RR = 0.02; 95% CI, 0.01-0.08; p < 0.00001), (RR = -4.81; 95% CI, -7.76 to -1.86; p = 0.001), respectively. However, overall complications, complete atrioventricular block, and the cost were comparable in both procedures. CONCLUSION: Transcatheter closure of pmVSD in children was as effective as surgical closure with a lower residual shunt and need for blood transfusion, and shorter hospital stay.

Predictive value of P-wave and QT interval dispersion in children with congenital heart disease and pulmonary arterial hypertension for the occurrence of arrhythmias.

OBJECTIVES: To evaluate P-wave dispersion (PWD) and QT dispersion (QTd) in children with congenital heart disease and pulmonary arterial hypertension (PAH-CHD) and to investigate the predictive value of both PWD and QTd for prediction of arrhythmias in such children. MATERIALS AND METHODS: We included 40 children with PAH-CHD as Group I. Forty other children with CHD and no PAH were included as Group II. Forty healthy children of matched age and sex served as a Control group. Electrocardiography was performed to determine PWD and QTd. Furthermore, 24-hour Holter monitoring was performed to detect the presence of arrhythmias. Echocardiographic evaluation was also performed. RESULTS: QTd and PWD were significantly higher in Group I than in Group II and Control group. A significant positive correlation was present between both QTd and PWD and mean pulmonary artery pressure, right ventricular diameter, pulmonary vascular resistance (PVR), and PVR to systemic vascular resistance ratio. QTd showed 93% sensitivity, 80% specificity, and 85% accuracy for prediction of occurrence of arrhythmias in patients with PAH-CHD at a cutoff point of 61 ms, whereas PWD showed 87% sensitivity, 80% specificity, and 85% accuracy for prediction of arrhythmias at a cutoff point of 32.5 ms in such patients. Logistic regression analysis showed that both QTd and PWD were good predictors for the occurrence of arrhythmias in children with PAH-CHD (p = 0.003 and p = 0.01, respectively). CONCLUSIONS: PWD and QTd were good predictors for the occurrence of various arrhythmias in children with PAH-CHD.

Role of plasma asymmetric dimethyl-L-arginine levels in detection of pulmonary hypertension in children with CHD.

OBJECTIVES: The objectives of this study were to evaluate the plasma levels of asymmetric dimethyl-L-arginine in children with pulmonary hypertension due to CHD before and after treatment with sildenafil and to evaluate its diagnostic and prognostic value as a biomarker in such children. METHODS: A total of 60 children with CHD and 30 healthy control children matched for age and sex were recruited. Children with CHD were divided into two equal groups: the normal pulmonary pressure group (n=30) and the pulmonary hypertension group (n=30). Children with pulmonary hypertension were treated with sildenafil and were followed up for 6 months. Clinical data, haemodynamic parameters, echocardiographic examination, and asymmetric dimethyl-L-arginine levels were evaluated before and after treatment. RESULTS: Asymmetric dimethyl-L-arginine levels were significantly higher in patients with pulmonary hypertension than in those with CHD-only or the control group, and this increase was positively correlated with increased severity of pulmonary hypertension. Asymmetric dimethyl-L-arginine levels, mean pulmonary artery pressure, and pulmonary vascular resistance were significantly decreased after treatment with sildenafil. Moreover, asymmetric dimethyl-L-arginine level was significantly lower in patients who responded to sildenafil treatment compared with those who did not. At a cut-off point of more than 0.85 nmol/ml, asymmetric dimethyl-L-arginine has a sensitivity of 83% and a specificity of 80% to diagnose pulmonary hypertension-CHD. Asymmetric dimethyl-L-arginine has a sensitivity of 100% and a specificity of 94% to predict poor prognosis in pulmonary hypertension-CHD children at a cut-off point of 1.3 nmol/ml. CONCLUSION: Asymmetric dimethyl-L-arginine level has a good diagnostic and prognostic value as a biomarker in children with pulmonary hypertension-CHD and can be used for following up patients with pulmonary hypertension and predicting response to treatment.

Serum levels of N-terminal-pro B-type natriuretic peptide as a diagnostic marker for left ventricular dysfunction in children with end-stage renal disease on hemodialysis.

The objective of this study was to determine the diagnostic cutoff value of N-terminal-pro B-type natriuretic peptide (NT-pro BNP) as a marker of left ventricular (LV) dysfunction in children with end-stage renal disease (ESRD) on regular hemodialysis (HD). The study was carried out on thirty children with ESRD on regular HD and thirty healthy controls. Echocardiographic studies were done, including a conventional mode for ejection fraction, fractional shortening, tissue Doppler imaging, and longitudinal global strain by speckle tracking. Serum levels of NT-pro BNP were measured in venous blood samples before and about 30 min after HD by ELISA. Volume status was assessed by calculating interdialytic weight gain %. There were significant higher serum NT-pro BNP levels before HD (mean: 702.3 ± 274.3 ng/L) compared to controls (mean: 365.55 ± 76.5 ng/L) (P <0.001) and these levels decreased significantly after the HD session (mean: 625.1 ± 117.69 ng/L) (P = 0.031). Echocardiographic studies showed a significant impairment of LV function of the patients compared to controls. Patients with LV dysfunction had significant higher serum concentrations of NT-pro BNP compared to patients without dysfunction both before (P = 0.003) and after dialysis (P <0.001). Receiver operating curve demonstrated better prediction of LV dysfunction by NT-pro BNP levels after HD compared to its levels before HD (area under the curve was 0.9 and 0.73, respectively). Using a cutoff value of 630 ng/L, serum NT-pro BNP levels after dialysis were a diagnostic predictor of LV dysfunction with a sensitivity of 86.6%, specificity of 93.3%, positive predictive value of 92.8%, and negative predictive value of 87.5%. Serum NT-pro BNP levels were strongly correlated with the parameters of LV dysfunction in children with ESRD on regular HD. A postdialysis cutoff value of 630 ng/L could serve as a biochemical marker of LV dysfunction in those children regardless of chronic fluid overload.

Serum Level of Heart-Type Fatty Acid Binding Protein (H-FABP) Before and After Treatment of Congestive Heart Failure in Children.

Remodeling of the heart following injury affects the morbidity and mortality in children presented with heart failure (HF). Heart-type fatty acid binding protein (H-FABP) is a novel biomarker that could be of help to predict the prognosis and risk stratification in those children. We aimed to evaluate the diagnostic and prognostic value of H-FABP in children with heart failure before and after treatment. The study was conducted as a prospective cohort study. It included 30 children with HF as a patient group and 20 healthy children matched for age and sex as a control group. Echocardiographic assessment of the heart was done using conventional Doppler echocardiography. Serum levels of (H-FABP) were measured using enzyme-linked immunosorbent assay before and after treatment of HF. All patients were observed during follow-up period of 3 months. There was a significant difference in the serum level of H-FABP in our patients before treatment (5.278 ± 3.253 ng/ml) compared with after treatment (2.089 ± 0.160 ng/ml) with significant difference compared with the control group. There was a significant increase in the serum level of H-FABP with increase in the severity of heart failure according to Ross classification. Significant increase in the H-FABP was associated with adverse outcome. Serum levels of H-FABP strongly correlated with clinical and echocardiographic assessment of LV performance of children with HF, and its levels significantly increased in children with adverse outcome suggesting its value as a useful diagnostic and prognostic predictor (with high sensitivity and specificity).