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Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.
Shroff, R, Bayazit, A, Stefanidis, CJ, Askiti, V, Azukaitis, K, Canpolat, N, Agbas, A, Anarat, A, Aoun, B, Bakkaloglu, S, et al
BMC nephrology. 2018;(1):199
Abstract
BACKGROUND Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. METHODS 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38). DISCUSSION This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD. TRIAL REGISTRATION ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.
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Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.
Dias, KA, Coombes, JS, Green, DJ, Gomersall, SR, Keating, SE, Tjonna, AE, Hollekim-Strand, SM, Hosseini, MS, Ro, TB, Haram, M, et al
BMJ open. 2016;(4):e010929
Abstract
INTRODUCTION The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER NCT01991106.
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3.
Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.
Stirrat, CG, Alam, SR, MacGillivray, TJ, Gray, CD, Forsythe, R, Dweck, MR, Payne, JR, Prasad, SK, Petrie, MC, Gardner, RS, et al
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. 2016;(1):46
Abstract
BACKGROUND Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems. METHODS Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues. RESULTS Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T). CONCLUSION Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement. TRIAL REGISTRATION ClinicalTrials.gov Identifier - NCT02319278 . Registered 03.12.2014.
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Role of non-invasive assessment in prediction of preclinical cardiac affection in multi-transfused thalassaemia major patients.
Said Othman, KM, Elshazly, SA, Heiba, NM
Hematology (Amsterdam, Netherlands). 2014;(7):380-7
Abstract
BACKGROUND The principal cause of mortality and morbidity in β-thalassemia major (β-TM) is the iron overload as these patients receive about 20 times the normal intake of iron, which leads to iron accumulation and damage in the liver, heart, and endocrine organs. Chronically transfused patients used to die from cardiac iron overload in their teens and twenties. Monitoring of iron status through cardiac magnetic resonance imaging (CMRI) has replaced the conventional methods of assessment, yet this modality is not readily available in centers where the disease distribution is maximal. Objectives The aim of this work is to study some simple non-invasive tools and their abilities to predict preclinical cardiac affection reflecting cardiac iron deposition (CID) in multi-transfused β-TM patients taking the T2* CMRI as a gold standard reference test. METHODS One hundred consecutive multi-transfused, clinically stable β-TM patients with age ranging from 16 to 30 years (mean ± SD, 21.1 ± 3.9) were included in this study. Assessment of serum ferritin, serum hepcidin, and high-sensitivity C-reactive protein as well as cardiac assessment by echo-doppler and 24-hour Holter were used to predict CID, and consequently predict preclinical cardiac affection, in reference to CMRI results as the standard method of cardiac iron assessment. RESULTS According to CMRI results, patients were subdivided into a group of 42 patients with detectable myocardial iron (T*≤ 20 ms) and a group of 58 patients with no detectable myocardial iron (T* > 20 ms). No differences in age, gender, or distribution of splenectomized patients were observed between both groups. Patients with detectable myocardial iron received significantly higher number of transfusions per year than those with no detectable myocardial iron (mean ± SD, 14.6 ± 1.7 vs. 12.5 ± 1.7; P < 0.001) yet comparable levels of serum ferritin, serum hepcidin, and hepcidin/ferritin ratio (P > 0.05) were noted. Cardiac iron detection was associated with significantly lower heart rate (mean ± SD, 75 ± 6.1 vs. 80 ± 6.9; P < 0.001), lower left ventricular ejection fraction (LVEF) (mean ± SD 60.1 ± 3.2 vs. 70.1 ± 2.8; P < 0.001), and higher total number of premature ventricular contractions (PVCs) (median 78 vs. 14; P < 0.001). The group with CID comprised significantly more patients with left ventricular diastolic dysfunction (15/42, 35.7% vs. 3/58, 5.2%; P < 0.001); PVCs ≥10/hour (13/42, 31% vs. 2/58, 3.4%; P < 0.001); episodes of sinus pauses (6/42, 14.3% vs. 1/58, 1.7%; P < 0.05); episodes of high-grade atrio-ventricular block (5/42, 11.9% vs. 1/58, 1.7%; P < 0.05) compared to the group with no (CID). In presence of normal LVEF, detection of 10 or more PVCs per hour was the most predictive of cardiac iron loading with a positive predictive value of 86.7% and specificity of 96.6%, and the highest likelihood ratio (9.09). Detection of more than 22 PVCs/24 hours had the best sensitivity (81%) and the best negative predictive value (84%). The positive likelihood ratio of the studied parameters was highest in case of presence of PVCs ≥10/hour and lowest in case of average heart rate with a cut-off level of ≤77.5 bpm (9.09 and 1.46, respectively). CONCLUSION Our results support our hypothesis that monitoring β-TM patients with echo and Holter electrocardiogram can help in the detection of preclinical cardiac affection in centers lacking cardiac MRI; however, due to relatively low sensitivity they can not fully replace CMRI. Further work is needed to identify additional simple parameters that can form a diagnostic model with adequate sensitivity.
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Efficacy of thyroid blockade on thyroid radioiodine uptake in 123I-mIBG imaging.
Friedman, NC, Hassan, A, Grady, E, Matsuoka, DT, Jacobson, AF
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2014;(2):211-5
Abstract
UNLABELLED Although iodinated radiopharmaceuticals usually contain a small quantity of unbound iodine, it is difficult to establish the degree to which thyroid activity on scintigraphic images reflects uptake of free radioiodine. The objective of the present study was to examine the effectiveness of thyroid blockade in subjects undergoing (123)I-meta-iodobenzylguanidine (mIBG) imaging and to estimate the relative contribution of bound and unbound radioiodine to imaging findings. METHODS All subjects were participants in prospective trials of (123)I-mIBG cardiac imaging in which pretreatment with thyroid blockade was optional unless locally required. In a pilot project, 15 subjects (6 blocked) had thyroid uptake measured at 4 h using a probe system. Fifteen-minute (early) and 4-h (late) anterior planar chest images that included the thyroid region were visually scored for thyroid uptake (scale of 0-4) in another group of 152 subjects (98 blocked). Quantitative analysis based on thyroid regions of interest was performed on anterior planar images from a further sample of 669 subjects (442 blocked). For all 3 investigations, quantitative comparisons of thyroid uptake were made between the blocked and nonblocked subjects. RESULTS There was no statistical difference between probe uptake of the 6 blocked and 9 nonblocked subjects. However, in the second series, mean visual score on the late images was significantly lower for blocked than nonblocked subjects (P < 0.001). In the region-of-interest analyses, net thyroid counts were significantly higher on the late images of nonblocked subjects (P < 0.0001), and compared with early images, 87% of subjects who received blockade showed decreased or unchanged counts whereas 75% of nonblocked subjects had increased net thyroid activity. In nonblocked subjects, an estimated 79% of thyroid counts on late images could be attributed to unbound (123)I. CONCLUSION On the basis of 3 different methods for assessing thyroid uptake of (123)I, use of thyroid blockade pretreatment in (123)I-mIBG imaging prevents increase of thyroid activity over time because of uptake of unbound (123)I. In most subjects, there is a low level of (123)I-mIBG thyroid activity that probably represents specific uptake in sympathetic nerve terminals.
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6.
Antihypertensive efficacy and safety of benidipine and its effects on cardiac structure and function in elderly Chinese patients with mild to moderate hypertension: an open-label, long-term study.
Qi, W, Fan, W, ,
Arzneimittel-Forschung. 2011;(3):160-6
Abstract
Benidipine (CAS 91599-74-5) has been reported as an effective antihypertensive treatment and its cardioprotective effects have been shown in several basic and clinical studies. However, the long-term efficacy and safety of benidipine remain unknown in elderly Chinese patient with hypertension. In this prospective, multicenter, open-label clinical trial, 152 eligible patients aged 60 to 75 years with mild to moderate essential hypertension (sitting systolic blood pressure (BP) > or = 140 mmHg and/or sitting diastolic BP > or = 90 mmHg) entered a 52-week study. All patients initially received benidipine 2-4 mg once a day, followed by titration to benidipine 8 mg/day to achieve the target BP (< 140/90 mmHg in non-diabetics and <130/80 mmHg in diabetics). Add-on hydrochlorothiazide (CAS 58-93-5) and/or metoprolol tartaric acid (CAS 3750-58-6) were permitted during the study. Overall, 132 patients completed the 52-week treatment with benidipine as monotherapy or combination therapy. It showed that the regimen based on benidipine provided an obvious mean trough BP reduction of 13.8 +/- 12.4/8.3 +/- 9.2 mmHg (p < 0.001), and 62.5% of patients reached the target BP. In patients with left ventricular hypertrophy, the left ventricular mass index significantly decreased from 147.1 +/- 27.6 g/m2 at baseline to 136.0 +/- 17.5 g/m2 at 52 weeks (p = 0.036). Clinical adverse events (AEs) were found in 15.1% of all patients, and six patients discontinued the treatment due to drug-related AEs during the entire trial. Patients' compliance was an average of 98.7%. Benidipine, with a favorable tolerability profile, provides a long-term antihypertensive effect and potential benefit for the heart in elderly patients with mild to moderate hypertensive, suggesting that it is suitable for elderly patients with hypertension.
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7.
Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial.
Wood, JC, Glynos, T, Thompson, A, Giardina, P, Harmatz, P, Kang, BP, Paley, C, Coates, TD
Haematologica. 2011;(7):1055-8
Abstract
The US04 trial was a multicenter, open-label, single arm trial of deferasirox monotherapy (30-40 mg/kg/day) for 18 months. Cardiac iron response was bimodal with improvements observed in patients with mild to moderate initial somatic iron stores; relationship of cardiac response to labile plasma iron is now presented. Labile plasma iron was measured at baseline, six months, and 12 months. In patients having a favorable cardiac response at 18 months, initial labile plasma iron was elevated in only 31% of patients at baseline and no patient at six or 12 months. Cardiac non-responders had elevated labile plasma iron in 50% of patients at baseline, 50% patients at six months, and 38% of patients at 12 months. Risk of abnormal labile plasma iron and cardiac response increased with initial liver iron concentration. Persistently increased labile plasma iron predicts cardiac non-response to deferasirox but labile plasma iron suppression does not guarantee favorable cardiac outcome. Study registered at www.clinicaltrials.gov (NCT00447694).
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HEART: heart exercise and remote technologies: a randomized controlled trial study protocol.
Maddison, R, Whittaker, R, Stewart, R, Kerr, A, Jiang, Y, Kira, G, Carter, KH, Pfaeffli, L
BMC cardiovascular disorders. 2011;:26
Abstract
BACKGROUND Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) is aimed at improving health behaviors to slow or reverse the progression of CVD disease. Exercise is a central element of CR. Technologies such as mobile phones and the Internet (mHealth) offer potential to overcome many of the psychological, physical, and geographical barriers that have been associated with lack of participation in exercise-based CR. We aim to trial the effectiveness of a mobile phone delivered exercise-based CR program to increase exercise capacity and functional outcomes compared with usual CR care in adults with CVD. This paper outlines the rationale and methods of the trial. METHODS A single-blinded parallel two-arm randomized controlled trial is being conducted. A total of 170 people will be randomized at 1:1 ratio either to receive a mHealth CR program or usual care. Participants are identified by CR nurses from two metropolitan hospitals in Auckland, New Zealand through outpatient clinics and existing databases. Consenting participants are contacted to attend a baseline assessment. The intervention consists of a theory-based, personalized, automated package of text and video message components via participants' mobile phones and the Internet to increase exercise behavior, delivered over six months. The control group will continue with usual CR. Data collection occurs at baseline and 24 weeks (post-intervention). The primary outcome is change in maximal oxygen uptake from baseline to 24 weeks. Secondary outcomes include post-intervention measures on self-reported physical activity (IPAQ), cardiovascular risk factors (systolic blood pressure, weight, and waist to hip ratio), health related quality of life (SF-36), and cost-effectiveness. DISCUSSION This manuscript presents the protocol for a randomized controlled trial of a mHealth exercise-based CR program. Results of this trial will provide much needed information about physical and psychological well-being, and cost-effectiveness of an automated telecommunication intervention. If effective, this intervention has enormous potential to improve the delivery of CR and could easily be scaled up to be delivered nationally (and internationally) in a very short time, enhancing the translational aspect of this research. It also has potential to extend to comprehensive CR (nutrition advice, smoking cessation, medication adherence). TRIAL REGISTRATION ACTRN12611000117910.
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Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC).
Pop-Busui, R, Low, PA, Waberski, BH, Martin, CL, Albers, JW, Feldman, EL, Sommer, C, Cleary, PA, Lachin, JM, Herman, WH, et al
Circulation. 2009;(22):2886-93
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Abstract
BACKGROUND The Epidemiology of Diabetes Interventions and Complications (EDIC) study, a prospective observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort, reported persistent benefit of prior intensive therapy on retinopathy and nephropathy in type 1 diabetes mellitus. We evaluated the effects of prior intensive insulin therapy on the prevalence and incidence of cardiac autonomic neuropathy (CAN) in former DCCT intensive and conventional therapy subjects 13 to 14 years after DCCT closeout. METHODS AND RESULTS DCCT autonomic measures (R-R variation with paced breathing, Valsalva ratio, postural blood pressure changes, and autonomic symptoms) were repeated in 1226 EDIC subjects in EDIC year 13/14. Logistic regression models were used to calculate the odds of incident CAN by DCCT treatment group after adjustment for DCCT baseline covariates, duration in the DCCT, and quantitative autonomic measures at DCCT closeout. In EDIC year 13/14, the prevalence of CAN using the DCCT composite definition was significantly lower in the former intensive group versus the former conventional group (28.9% versus 35.2%; P=0.018). Adjusted R-R variation was significantly greater in the former DCCT intensive versus the former conventional group (29.9 versus 25.9; P<0.001). Prior DCCT intensive therapy reduced the risks of incident CAN by 31% (odds ratio, 0.69; 95% confidence interval, 0.51 to 0.93) and of incident abnormal R-R variation by 30% (odds ratio, 0.70; 95% confidence interval, 0.51 to 0.96) in EDIC year 13/14. CONCLUSIONS Although CAN prevalence increased in both groups, the incidence was significantly lower in the former intensive group compared with the former conventional group. The benefits of former intensive therapy extend to measures of CAN up to 14 years after DCCT closeout.
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123 I-mIBG scintigraphy to predict inducibility of ventricular arrhythmias on cardiac electrophysiology testing: a prospective multicenter pilot study.
Bax, JJ, Kraft, O, Buxton, AE, Fjeld, JG, Parízek, P, Agostini, D, Knuuti, J, Flotats, A, Arrighi, J, Muxi, A, et al
Circulation. Cardiovascular imaging. 2008;(2):131-40
Abstract
BACKGROUND Disturbances of autonomic function after infarction are associated with both total mortality and sudden death. Although many imaging techniques for assessing the cardiac autonomic nervous system have been studied, the clinical usefulness of these techniques remains uncertain. This exploratory pilot study examined the relationship between abnormalities of ventricular sympathetic innervation delineated by scintigraphic imaging with (123)I-mIBG and inducible ventricular tachyarrhythmias in patients with left ventricular dysfunction and previous myocardial infarction. METHODS AND RESULTS Fifty patients underwent electrophysiological (EP) testing and 15-minute and 4-hour planar and single photon emission computed tomography (SPECT) imaging with (123)I-mIBG and SPECT imaging with (99m)Tc-tetrofosmin. The primary efficacy variables were the 4-hour heart:mediastinum ratio (H/M) and the (123)I-mIBG/(99m)Tc-tetrofosmin SPECT mismatch score. EP studies were categorized as positive (EP(+)) or negative (EP(-)) for inducibility of sustained (>30 seconds) ventricular tachyarrhythmias. Thirty patients were EP(+), and 20 were EP(-). There were no significant differences in the 4-hour H/M ratios or (123)I-mIBG/(99m)Tc-tetrofosmin SPECT mismatch scores between the two groups. In a multivariable analysis using all (123)I-mIBG and (99m)Tc-tetrofosmin SPECT measurements, the only variable that showed a significant difference between EP(+) and EP(-) patients was the 4-hour (123)I-mIBG SPECT defect score. A 4-hour (123)I-mIBG SPECT defect score of > or =37 yielded a sensitivity of 77% and specificity of 75% for predicting EP results. CONCLUSIONS The standard indices of (123)I-mIBG imaging (H/M and innervation-perfusion mismatch score) are not predictive of EP test results. The association of (123)I-mIBG SPECT defect severity with EP test inducibility in this exploratory study will require confirmation in a larger cohort of patients.