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Background: Left ventricular dysfunction is an important co-morbidity of end-stage renal disease (ESRD) and is associated with a poor prognosis in the adult population. In pediatric ESRD, left ventricular function is generally well preserved, but limited information is available on early changes in myocardial function. The aim of this study was to investigate myocardial mechanics in pediatric patients with ESRD using speckle-tracking echocardiography (STE). Methods: Echocardiographic studies, including M-mode, tissue Doppler imaging (TDI) and STE, were performed in 19 children on dialysis, 17 transplant patients and 33 age-matched controls. Strain measurements were performed from the apical four-chamber and the short axis view, respectively. Results: The interventricular and left ventricular posterior wall thickness was significantly increased in dialysis and transplant patients compared to healthy controls. No significant differences were found in shortening fraction, ejection fraction and systolic tissue Doppler velocities. Dialysis and transplant patients had a decreased mean longitudinal strain compared to healthy controls, with a mean difference of 3.1 [95 % confidence interval (CI) 2.0-4.4] and 2.7 (95 % CI 1.2-4.2), respectively. No differences were found for radial and circumferential strain. Conclusions: Speckle-tracking echocardiography may reveal early myocardial dysfunction in the absence of systolic dysfunction measured by conventional ultrasound or TDI in children with ESRD. [ABSTRACT FROM AUTHOR]

Background: Left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac disease in pediatric chronic kidney disease (CKD), but few studies have analyzed longitudinal trends. We conducted a prospective 3-year follow-up study in pediatric CKD and kidney transplant (CKD-T) patients. Methods: The patient cohort comprised 30 CKD and 42 CKD-T patients. The results of annual clinical and echocardiographic analyses using tissue Doppler imaging (TDI) and pulse wave Doppler (PWD) were assessed, and associations to predictive risk factors were studied using multivariate modeling. Results: The mean age of CKD and CKD-T patients at inclusion was 9.8 ± 4.4 and 11.8 ± 4.3 years, respectively; the glomerular filtration rate was 35.3 ± 18.3 and 60.3 ± 18.8 mL/min/1.73 m, respectively. The prevalence of left ventricular diastolic dysfunction (LVDD), as assessed using TDI (lateral z-score e′) was 7.1 and 12.5 % in CKD and CKD-T patients, respectively; the corresponding values with PWD E were 3.3 and 2.4 %, respectively. In unadjusted analyses, both TDI and PWD markers of diastolic function worsened over the follow-up period; following adjustments, an elevated systolic ambulatory blood pressure was the most important predictor of cardiac disease. Conclusions: Children with CKD show early signs of LVDD, with TDI being more sensitive than PWD in terms of diagnostic potential. An increased ambulatory systolic blood pressure predicted progression in diastolic function, suggesting opportunities for future interventions. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate cardiac function in children with end-stage renal disease (ESRD) on regular hemodialysis using speckle tracking echocardiography (STE) and correlate results with plasma glutathione level as a marker of oxidative stress. Methods: The study involved 30 children with ESRD and 30 healthy controls. The plasma glutathione and C-reactive protein (CRP) levels were measured, and cardiac function was evaluated using conventional echocardiography and STE. Results: Plasma glutathione levels were significantly lower and CRP significantly higher in patients than in controls. Children with ESRD had significant systolic and diastolic cardiac dysfunctions detected by STE compared with controls. Conventional echocardiography failed to detect these dysfunctions. There was significant increase in left-ventricular relative wall thickness (LV-RWT) in patients, especially those with hypertension, compared with the control group. There was also significant impairment of LV and right-ventricular (RV) global longitudinal strain (GLS) and torsion; however, LV-GLS was significantly better in hypertensive than in normotensive patients. The degree of impairment in GLS and cardiac torsion negatively correlated with plasma glutathione levels. Conclusion: Significant oxidative stress was present in children with ESRD and was correlated with the degree of cardiac dysfunction detected early using the new cardiac imaging modality, STE. [ABSTRACT FROM AUTHOR]

Background: As cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD. Methods: Forty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups. Results: Initial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment. Conclusions: Our interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the association of serum intact fibroblast growth factor 23 (FGF23) concentrations with indexed left ventricular mass in children with non-dialysis stages 3-5 of chronic kidney disease (CKD). Methods: The study cohort comprised 83 children (51 boys; mean age 12.1 ± 3.2 years) with a mean estimated glomerular filtration rate (eGFR) of 32.3 ± 14.6 ml/min/1.73 m who underwent clinic and ambulatory blood pressure measurement (ABPM), echocardiography and evaluation of biochemical markers of CKD-associated mineral bone disease. Results: The mean left ventricular mass index (LVMI) was 35.9 ± 8.5 g/m (± standard deviation), with 30 (36.1 %) children showing left ventricular hypertrophy (LVH), all eccentric, as defined using age-specific criteria. For all subjects, the mean FGF23 concentration was 142.2 ± 204.4 ng/l and the normalised distribution following log transformation was 1.94 ± 0.39. There was significant univariate correlation of LVMI with GFR, body mass index (BMI) z-score and calcium intake, but not with 24-h systolic ABPM z-score, log intact parathyroid hormone or log FGF23. On multivariate analysis following adjustment for confounders, only elemental calcium content (g/kg/day) estimated from prescribed calcium-based phosphate binder dose (β = 154.9, p < 0.001) and BMI z-score (β = 2.397, p = 0.003) maintained a significant positive relationship with LVMI (model r = 0.225). Conclusions: We observed no significant relationship of FGF23 with LVMI. Larger studies in children are needed to clarify the roles of calcium-containing phosphate binders and FGF23 with LV mass and their roles in the evolution of the development of adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV) systolic dysfunction is a relatively uncommon but serious complication of pediatric chronic kidney disease, and may be related to uremia and uncontrolled hypertension. There is limited information on the strategy for managing these children. In some cases, combined heart-kidney transplant may be considered or kidney transplant delayed until cardiac function improves. It is unknown whether these patients are at increased risk for poor outcomes after kidney transplantation. Methods: We conducted a retrospective, multicenter study on the outcomes of children with severe and symptomatic cardiomyopathy who underwent kidney transplantation. Results: Eleven patients receiving maintenance dialysis with systolic dysfunction underwent kidney transplantation without simultaneous heart transplant. Nine patients had congestive heart failure in the pre-transplant period. There were no identified complications post-transplant related to the underlying cardiac dysfunction. LV systolic function normalized in all patients and the mean shortening fraction increased from 19.0 ± 4.6 % to 32.0 ± 4.4 % ( p < 0.0001). Conclusions: Kidney transplantation should be considered for children receiving maintenance dialysis with severe LV dysfunction. [ABSTRACT FROM AUTHOR]

Background: The blood pressure (BP) burden is high in pediatric hemodialysis (HD) patients and adversely affects prognosis. The aim of this study was to examine whether 44-h ambulatory BP monitoring (ABPM) provides additional relevant BP data compared with 24-h ABPM. Methods: ABPM was initiated at the end of the mid-week dialysis run in 13 stable pediatric HD patients and continued until the next run for 44 h. Day 1 was defined as the initial 24-h ABPM and Day 2 as the time period after that until the next dialysis run. All patients had an echocardiogram to calculate the left ventricular mass index (LVMI). Results: A higher percentage of patients were diagnosed with hypertension from the 44-h ABPM than from the 24-h ABPM. All BP indexes and loads (except nighttime diastolic load) were significantly higher on Day 2 than on Day 1. Patients with BP loads of ≥25 % on 44-h ABPM had significantly higher LVMI than those patients with normal BP loads. No such association was found with 24-h ABPM and LVMI. Higher interdialytic weight gain was associated with higher Day-2 nighttime systolic BP load. Conclusions: The 44-h ABPM provides more information than the 24-h ABPM in terms of diagnosing and assessing the true burden of hypertension in pediatric HD patients. Elevated BP loads from 44-h ABPM correlate with a higher LVMI on the echocardiogram. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is a common cause of morbidity and mortality in children with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and diastolic dysfunction (LVDD) are early markers. The aims of this study were to evaluate (1) LVH and LVDD, using both conventional echocardiographic evaluation and Tissue Doppler Imaging (TDI), and (2) the correlation between cardiac disease and possible risk factors, in children with CKD. Methods: The study cohort comprised 34 paediatric patients with CKD and 34 healthy children (mean ± standard deviation: age 9 ± 4.6 and 8.2 ± 4.3 years, respectively). Thirteen (38 %) patients were in CKD stage 2, 15 (44 %) in stage 3 and six (18 %) in stage 4-5. LVH was defined as a left ventricular mass index (LVMI) of >95th percentile (38 g/h). Results: Left ventricular hypertrophy was present in 13 patients (38 %). Diastolic function evaluated with TDI (E′/A′ = early/late diastolic myocardial velocity) worsened with the reduction of glomerular filtration rate ( p = 0.020). There was a positive correlation between LVMI and body mass index-standard deviation score ( p = 0.020) and a negative correlation between E′/A′ and serum phosphorus and calcium levels and their respective product ( p = 0.004, p = 0.017, p < 0.001). The relaxation index E′ was reduced in 68 % of patients. Conclusion: Based on our results, TDI is a simple procedure and would appear to be a more accurate diagnostic tool than conventional echocardiography in the early diagnosis of LVDD. [ABSTRACT FROM AUTHOR]

Background: In patients with systemic lupus erythematous (SLE) late-onset deaths are due to morbid cardiovascular changes (CVCs). Inflammatory and immune-mediated mechanisms are involved in promoting atherosclerosis development in SLE that is reflected in both functional and morphological changes in the cardiovascular system. The aim of our study was to determine the presence of these changes in pediatric SLE patients. Methods: Fifty-one consecutive patients (13 male, 38 female) with SLE and 25 healthy controls were included in the study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWVcf) and augmentation index (AIx), as measured by the Vicorder. Carotid intima-media thickness (cIMT) and the left ventricular mass index (LVMi) were also determined. Results: Patients with SLE, despite equivalent exposure to 'traditional' cardiovascular risk factors, presented a higher mean PWVcf and AIx than controls (6.56 ± 1.45 vs. 5.29 ± 0.67 m/s, P =0.01 and 14.7 ± 8.1 vs. 9.36 ± 3.59 %, P = 0.02, respectively). SLE patients had greater values of cIMT and LVMi than controls (0.54 ± 0.06 vs. 0.35 ± 0.12 mm, P = 0.00 and 32.4 ± 10.8 vs 28.8 ± 1.5, P = 0.01, respectively). Nine patients had left ventricular hypertrophy (LVMi >38 g/m). There was no significant difference in PWV, AIx, cIMT and LVMi values between presence of hypertension or nephritis within SLE patients. We found significant correlations between all parameters and activity scores. Conclusions: Our results demonstrate that functional and morphological CVCs are independent of traditional risk factors in pediatric SLE patients and correlate with SLE disease activity scores in the early disease stages. [ABSTRACT FROM AUTHOR]

Background: The relation between primary hypertension (PH), target organ damage (TOD) and oxidative stress (SOX) is not known. Methods: We assessed SOX in 86 children with PH before and after 12 months of standard non-pharmacological and pharmacological therapy based on renin-angiotensin system blockade. Results: Patients with left ventricular hypertrophy (LVH) and with carotid intima-media thickness (cIMT) >2SDS had higher thiobarbituric acid reactive substances (TBARS) concentrations in comparison to patients without LVH or with normal cIMT. Patients with metabolic syndrome (MS) had lower activity of gluthatione peroxidase, higher asymmetric dimethyloarginine (ADMA) and oxidized LDL cholesterol (oxyLDL) in comparison to patients without MS. TBARS correlated with left ventricular concentric hypertrophy, cIMT, albuminuria and SBP/24 h. ADMA and oxyLDL correlated with CRP and TG/HDL ratio. After 1 year of antihypertensive treatment blood pressure, TOD and prevalence of MS decreased. TBARS decreased and glutathione concentrations increased. The decrease of TBARS concentration correlated with the decrease of body mass index (BMI). Decrease of oxyLDL and ADMA correlated with increased insulin sensitivity, however markers of SOX did not correlate with BP decrease. Conclusion: SOX in children with PH correlates with TOD, metabolic abnormalities, changes in fat amount and improvement of insulin sensitivity, but not with BP decrease. [ABSTRACT FROM AUTHOR]

Background: Renal transplantation improves left ventricular (LV) function, but cardiovascular mortality remains elevated. The aim of this cross-sectional study was to determine whether subclinical abnormalities of LV longitudinal function also persist in patients who underwent renal transplant in childhood. Methods: Conventional and speckle tracking echocardiography was performed in 68 renal transplant recipients (34 children and 34 adults, median 9.8 years (range 2.0-28.4 years) after first transplantation and 68 age- and sex-matched healthy controls. Results: Mean age at first transplantation was 8.8 ± 4.8 years. Forty-three percent had a pre-emptive transplant. Of the remaining, 70% received haemodialysis and 30% peritoneal dialysis on average for 6.9 months. Thirty-one percent of paediatric and 35% of adult patients had hypertension. LV mass index was increased in adult patients (92 ± 24 vs 75 ± 11 g/m, P< 0.01). LV diastolic function and exercise capacity were impaired in both paediatric and adult patients. LV longitudinal peak systolic strain and strain rate were comparable in patients and controls. In multivariate analysis, systolic blood pressure and LV diastolic relaxation were the main covariates of LV peak systolic strain and strain rate (all P < 0.01). Conclusions: Patients who underwent renal transplantation in childhood have abnormal LV diastolic function and impaired exercise capacity, despite preserved LV longitudinal systolic deformation. [ABSTRACT FROM AUTHOR]

Background: Carnitine plays a key role in energy production in the myocardium. Carnitine deficiency commonly occurs in patients on chronic hemodialysis (HD) and may contribute to cardiomyopathy. Methods: Carnitine levels and cardiac function of nine children on HD were assessed before and after 6 months of intravenous levocarnitine supplementation. Standard echocardiographic (ECHO) measures of left ventricular (LV) function as well as strain and strain rate analysis using novel speckle-tracking echocardiography were performed and the results compared to those of a control group of children on chronic HD. Results: Following carnitine supplementation, total (49.0 ± 1.67 vs. 298.0 ± 31.8 μmol/L) and free carnitine (29.0 ± 1.20 vs. 180.4 ± 19.2 μmol/L) increased ( p < 0.0001), and the acyl:free (A:F) carnitine ratio improved (0.73 ± 0.04 vs. 0.65 ± 0.05; p = 0.02). There were no changes in standard ECHO measures of LV function, including end diastolic dimension, mass index, ejection fraction, and fractional shortening. There was significant ( p = 0.017) improvement in the longitudinal strain rate (−1.48 ± 0.11 vs −1.91 ± 0.12) after carnitine supplementation in the study group. No improvements in LV function, strain, or strain rate occurred in controls. Conclusions: Levocarnitine supplementation improved carnitine levels, the A:F ratio, and longitudinal strain rate in children on HD. [ABSTRACT FROM AUTHOR]

Myocardial damage and strain are common in children with chronic renal failure. The most prevalent pathologies, as defined by echocardiography, are left ventricular hypertrophy (LVH), diastolic and systolic dysfunction, and altered LV geometry. Troponin I and T, as well as B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP, are known to be good markers of myocardial damage and stress, respectively, in the general adult population and among those with chronic kidney disease (CKD). In this study we measured the levels of troponins I and T, BNP, and NT-proBNP in a group of children and young adults with CKD stages 3-5 and determined their respective correlations with echocardiographic and laboratory abnormalities. BNP and NT-proBNP levels and their log values correlated well with the following parameters: diastolic blood pressure, estimated glomerular filtration rate, time-averaged hemoglobin levels, and LV mass. Both BNP and NT-proBNP levels, but not those of either troponin, were found to be reliable surrogate markers of strained hearts, defined as having LVH or diastolic or systolic dysfunction, in the pediatric CKD stages 3-4 group. The log NT-proBNP value was also found to be a good marker of cardiac strain in the CKD stage 5 group of patients. Serum BNP and NT-proBNP threshold concentrations of 43 and 529 pg/ml, respectively, were found to have the best sensitivity and specificity in predicting strained hearts. Based on these findings, we conclude that both BNP and NT-proBNP levels, but not those of troponins I and T, can serve as inexpensive, simple, and reliable markers of stressed hearts in the pediatric CKD patient population. [ABSTRACT FROM AUTHOR]