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den Hoedt C.H.,Maasstad Hospital | den Hoedt C.H.,University Utrecht | Bots M.L.,University Utrecht | Grooteman M.P.C.,Medical Center | And 10 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2014

Background and objectives: Inflammation and malnutrition are important features in patients with ESRD; however, data on changes in these parameters over time are scarce. This study aimed to gain insight into changes over time in serum albumin, body mass index, high-sensitivity C-reactive protein, and IL-6 in patients with ESRD and aimed to identify clinical risk factors for deterioration of these parameters. Design, setting, participants, & measurements: Data were analyzed from the Convective Transport Study, a randomized controlled trial conducted from June 2004 to January 2011, in which 714 patients with chronic ESRD were randomized to either online hemodiafiltration or low-flux hemodialysis. Albumin and body mass index were measured up to 6 years and predialysis C-reactive protein and IL-6 were measured up to 3 years in a subset of 405 participants. Rates of change in these parameters over time were estimated across strata of predefined risk factors with linear mixed-effects models. Results: Albumin and body mass index decreased and C-reactive protein and IL-6 increased over time. For every incremental year of age at baseline, the yearly excess decline in albumin was 0.003 g/dl (-0.004 to -0.002; P<0.001) and the excess decline in body mass index was 0.02 kg/m2 per year (-0.02 to -0.01; P<0.001). In patients with diabetes mellitus, there was a yearly excess decline of 0.05 g/dl in albumin (-0.09 to -0.02; P=0.002). Compared with women, men had an excess decline of 0.03 g/dl per year in albumin (-0.06 to -0.001; P=0.05) and an excess increase of 11.6% per year in IL-6 (0.63%-23.6%; P=0.04). Conclusions: Despite guideline-based care, all inflammatory and nutritional parameters worsened over time. The deterioration of some of these parameters was more pronounced in men, older patients, and patients with diabetes mellitus. Special focus on the nutritional status of at-risk patients by individualizing medical care might improve their prognosis. © 2014 by the American Society of Nephrology.


Alders D.J.C.,VU University Amsterdam | Alders D.J.C.,Institute for Cardiovascular Research | Johan Groeneveld A.B.,VU University Amsterdam | Binsl T.W.,Center for Integrative Bioinformatics | And 2 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2011

Heterogeneity of regional coronary blood flow is caused in part by heterogeneity in O 2 demand in the normal heart. We investigated whether myocardial O 2 supply/ demand mismatching is associated with the myocardial depression of sepsis. Regional blood flow (microspheres) and O 2 uptake ([ 13C] acetate infusion and analysis of resultant NMR spectra) were measured in about nine contiguous tissue samples from the left ventricle (LV) in each heart. Endotoxemic pigs (n = 9) showed hypotension at unchanged cardiac output with a fall in LV stroke work and first derivative of LV pressure relative to controls (n = 4). Global coronary blood flow and O 2 delivery were maintained. Lactate accumulated in arterial blood, but net lactate extraction across the coronary bed was unchanged during endotoxemia. When LV O 2 uptake based on blood gas versus NMR data were compared, the correlation was 0.73 (P = 0.007). While stable over time in controls, regional blood flows were strongly redistributed during endotoxin shock, with overall flow heterogeneity unchanged. A stronger redistribution of blood flow with endotoxin was associated with a larger fall in LV function parameters. Moreover, the correlation of regional O 2 delivery to uptake fell from r = 0.73 (P<0.001) in control to r = 0.18 (P = 0.25, P = 0.009 vs. control) in endotoxemic hearts. The results suggest a redistribution of LV regional coronary blood flow during endotoxin shock in pigs, with regional O 2 delivery mismatched to O 2 demand. Mismatching may underlie, at least in part, the myocardial depression of sepsis. © 2011 the American Physiological Society.


Penne E.L.,University Utrecht | Penne E.L.,Medical Center | van der Weerd N.C.,University Utrecht | van der Weerd N.C.,Medical Center | And 10 more authors.
American Journal of Kidney Diseases | Year: 2010

Background: Hyperphosphatemia is an independent risk factor for all-cause and cardiovascular mortality in hemodialysis (HD) patients. Phosphate control often is unsuccessful using conventional dialysis therapies. Study Design: Short-term analysis of a secondary outcome of an ongoing randomized controlled trial. Setting & Participants: 493 (84%) consecutive patients from 589 patients included in the Convective Transport Study (CONTRAST) by January 2009 from 26 centers in 3 countries. Intervention: Online hemodiafiltration (HDF) versus continuation of low-flux HD. Outcomes: Differences in change from baseline to 6 months in phosphate levels and proportion of patients reaching phosphate treatment targets (phosphate ≤ 5.5 mg/dL). Measurements: Phosphate, use of phosphate-binding agents, and proportion of patients achieving treatment targets at baseline, 3 months, and 6 months. Results: Phosphate levels decreased from 5.18 ± 0.10 (SE) mg/dL at baseline to 4.87 ± 0.10 mg/dL at 6 months in HDF patients (P < 0.001) and were stable in HD patients (5.10 ± 0.10 mg/dL at baseline and 5.03 ± 0.10 mg/dL after 6 months; P = 0.5). The difference in change in phosphate levels between HD and HDF patients (B = -0.24; 95% CI, -0.52 to 0.03; P = 0.08) increased after adjustment for phosphate-binder use (B = -0.36; 95% CI, -0.65 to -0.06; P = 0.02). The proportion of patients reaching phosphate treatment targets increased from 64% to 74% in HDF patients and was stable in HD patients (66% and 66%); the difference between groups reached statistical significance (P = 0.04). Nutritional parameters and residual renal function were similar in both treatment groups. Limitations: Only predialysis serum phosphate levels were measured; phosphate clearance could therefore not be calculated. Conclusion: HDF may help improve phosphate control. Whether this contributes to improved clinical outcome remains to be established. © 2009 National Kidney Foundation, Inc.


Mostovaya I.M.,University Utrecht | Bots M.L.,University Utrecht | van den Dorpel M.A.,Maasstad Hospital | Grooteman M.P.C.,Medical Center | And 8 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2014

Background and objective Increased left ventricularmass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV. Design, setting, participants, & measurements Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models. Results Patients had a mean age of 63 years, and 61%weremale. At baseline,median LVMwas 227 g (interquartile range [IQR], 183-279 g), andmedian EFwas 65%(IQR, 55%-72%).Median PWVwas 9.8m/s (IQR, 7.5-12.0m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change,20.9 g/yr [95%confidence interval (95%CI),28.9 to 7.7 g];HD: change, 12.5 g/yr [95%CI,23.0 to 27.5 g]; P for difference=0.13), EF (HDF: change,20.3%/yr [95%CI,22.3% to 1.8%];HD: change,23.4%/yr [95% CI, 25.9% to 20.9%]; P=0.17), or PWV (HDF: change, 20.0 m/s per year [95% CI, 20.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, 20.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume. Conclusions Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD. © 2014 by the American Society of Nephrology.


Ferreira I.,Clinical Epidemiology and Medical Technology Assessment | Ferreira I.,Maastricht University | Beijers H.J.,VU University Amsterdam | Schouten F.,Maastricht University | And 9 more authors.
Hypertension | Year: 2012

Maladaptive arterial remodeling may constitute a mechanism underlying the risk of stroke in individuals with the metabolic syndrome (MetS), but evidence supporting this contention derives from cross-sectional studies only. We, therefore, investigated, in apparently healthy adults, whether changes in MetS status between the ages of 36 and 42 years (never [n=207, reference group], incident [n=31], recovery [n=23], and persistent [n=32]) were associated with changes in carotid interadventitial diameter, lumen diameter, intima-media thickness, circumferential wall tension and stress, and Young's elastic modulus. All data analyses were adjusted for sex, height, and (changes in) age, lifestyle variables, low-density lipoprotein cholesterol, and use of antihypertensive medication. At baseline and as compared with the reference group, individuals with persistent MetS had significantly higher interadventitial diameter, circumferential wall tension, circumferential wall stress, and Young's elastic modulus but not intima-media thickness. In the course of follow-up, these individuals (versus reference group) displayed significantly steeper increases in intima-media thickness (0.011 versus 0.005 mm/y), which were accompanied by significantly steeper increases in interadventitial diameter (0.077 versus 0.032 mm/y) and lumen diameter (0.055 versus 0.023 mm/y) but not circumferential wall stress, which decreased (-0.34 versus 0.12 kPa/y). These findings suggest that increases in intima-media thickness in young adults with the MetS may primarily reflect an adaptive mechanism that attempts to restore local hemodynamic conditions to an equilibrium rather than atherosclerosis, per se. However, carotid adaptations did not restore circumferential wall stress to levels comparable with those of the reference group, and, therefore, outward remodeling was maladaptive. Importantly, individuals who recovered from the MetS restored carotid properties to levels comparable to the reference group, emphasizing the potential for reversibility. © 2012 American Heart Association, Inc.


Ruiter G.,VU University Amsterdam | Ying Wong Y.,VU University Amsterdam | De Man F.S.,VU University Amsterdam | Louis Handoko M.,VU University Amsterdam | And 6 more authors.
Journal of Heart and Lung Transplantation | Year: 2013

Background: In pulmonary arterial hypertension (PAH), high right ventricular (RV) power output requires increased myocardial oxygen consumption. Oxygen supply, however, does not increase in proportion. It is unknown what cellular mechanisms underlie this lack of adaptation. We therefore determined oxygen supply parameters in RV tissue slices of deceased PAH patients and compared them with RV tissue of patients who died from left ventricular myocardial infarction (MI). Because autopsy tissue only reflects end-stage disease, rat models with stable and progressive pulmonary hypertension (PH) were studied as well. Methods: Myocardial tissue of 10 PAH and 10 MI patients was collected at autopsy. In rats, stable PH (n = 6) and progressive PH (n = 6) was induced by 40 or 60 mg/kg monocrotaline, respectively. Six rats were used as controls. Results: RV cardiomyocyte cross-sectional area was strongly increased in PAH compared with MI patients (p < 0.001), whereas capillary density decreased (p < 0.01). Rat data showed similar RV hypertrophy in stable and progressive PH, and RV capillary density was decreased in both (p < 0.01 and p < 0.0001 vs control rats, respectively). RV myoglobin protein content and functional concentration were reduced in both human and rat PH RVs. In rats, this results from a lack of increase in myoglobin mRNA transcription per cardiomyocyte nucleus. Conclusions: All measured cellular oxygen supply parameters are decreased in the failing human and rat pulmonary hypertensive RV. In contrast to stable PH rats, compensatory adaptations do not occur in end-stage PAH, despite higher myocardial oxygen consumption. © 2013 International Society for Heart and Lung Transplantation.


Wu L.,VU University Amsterdam | Wu L.,Institute for Cardiovascular Research | Germans T.,VU University Amsterdam | Guclu A.,VU University Amsterdam | And 6 more authors.
Journal of Cardiovascular Magnetic Resonance | Year: 2014

Background: Left ventricular segmental wall motion analysis is important for clinical decision making in cardiac diseases. Strain analysis with myocardial tissue tagging is the non-invasive gold standard for quantitative assessment, however, it is time-consuming. Cardiovascular magnetic resonance myocardial feature-tracking (CMR-FT) can rapidly perform strain analysis, because it can be employed with standard CMR cine-imaging. The aim is to validate segmental peak systolic circumferential strain (peak SCS) and time to peak systolic circumferential strain (T2P-SCS) analysed by CMR-FT against tissue tagging, and determine its intra and inter-observer variability. Methods. Patients in whom both cine CMR and tissue tagging has been performed were selected. CMR-FT analysis was done using endocardial (CMR-FTendo) and mid-wall contours (CMR-FTmid). The Intra Class Correlation Coefficient (ICC) and Pearson correlation were calculated. Results: 10 healthy volunteers, 10 left bundle branch block (LBBB) and 10 hypertrophic cardiomyopathy patients were selected. With CMR-FT all 480 segments were analyzable and with tissue tagging 464 segments.Significant differences in mean peak SCS values of the total study group were present between CMR-FT endo and tissue tagging (-23.8 ± 9.9% vs -13.4 ± 3.3%, p < 0.001). Differences were smaller between CMR-FTmid and tissue tagging (-16.4 ± 6.1% vs -13.4 ± 3.3%, p = 0.001). The ICC of the mean peak SCS of the total study group between CMR-FTendo and tissue tagging was low (0.19 (95%-CI-0.10-0.49), p = 0.02). Comparable results were seen between CMR-FTmid and tissue tagging. In LBBB patients, mean T2P-SCS values measured with CMR-FTendo and CMR-FTmid were 418 ± 66 ms, 454 ± 60 ms, which were longer than with tissue tagging, 376 ± 55 ms, both p < 0.05. ICC of the mean T2P-SCS between CMR-FTendo and tissue tagging was 0.64 (95%-CI-0.36-0.81), p < 0.001, this was better in the healthy volunteers and LBBB group, whereas the ICC between CMR-FTmid and tissue tagging was lower.The intra and inter-observer agreement of segmental peak SCS with CMR-FTmid was lower compared with tissue tagging; similar results were seen for segmental T2P-SCS. Conclusions: The intra and inter-observer agreement of segmental peak SCS and T2P-SCS is substantially lower with CMR-FTmid compared with tissue tagging. Therefore, current segmental CMR-FTmid techniques are not yet applicable for clinical and research purposes. © 2014 Wu et al.; licensee BioMed Central Ltd.


Schulkens I.A.,Angiogenesis Laboratory | Castricum K.C.M.,Angiogenesis Laboratory | Weijers E.M.,Institute for Cardiovascular Research | Koolwijk P.,Institute for Cardiovascular Research | And 3 more authors.
Journal of Vascular Research | Year: 2014

Metallothioneins (MTs) are small cysteine-rich proteins which are involved in e.g. metal homeostasis, metal detoxification and protection against oxidative stress. In addition, several MTs have been shown to regulate expression of proangiogenic growth factors like vascular endothelial growth factor. Detailed information about the expression and regulation of specific MT isoforms in endothelial cells (EC) is limited. We therefore performed extensive mRNA expression profiling of all known human MTs in EC. We found that the basal endothelial expression is restricted to MT1E, MT1X, MT2A, and MT3. Physiological activation of EC by exposure to serum increased the expression of MT1E and MT2A and induced the expression of MT1M. Furthermore, exposure to zinc or copper induced the expression of most MT1 isoforms, while hypoxia specifically increased the expression of MT1E, MT1M, MT1X, and MT3. Finally, knockdown of the dominant MT isoform in EC, i.e. MT2A, resulted in decreased proliferation and sprouting as well as in increased migration of human umbilical vein EC. Together, these findings provide a link between MTs and angiogenesis. © 2014 S. Karger AG, Basel.


Grooteman M.P.C.,VU University Amsterdam | Grooteman M.P.C.,Institute for Cardiovascular Research | Van Den Dorpel M.A.,Maasstad Hospital | Bots M.L.,University Utrecht | And 13 more authors.
Journal of the American Society of Nephrology | Year: 2012

In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving highvolume hemodiafiltration during the trial associated with lower all-causemortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation. Copyright © 2012 by the American Society of Nephrology.


Slagt C.,Koningin Julianaplein 58 | Slagt C.,Zaans Medical Center | Beute J.,Zaans Medical Center | Hoeksema M.,Zaans Medical Center | And 3 more authors.
European Journal of Anaesthesiology | Year: 2010

Background and objective We studied the evolution of software in the accuracy of the FloTrac/Vigileo system to measure cardiac output less invasively from arterial pressure waveform analysis without calibration, in comparison with pulmonary artery catheter-derived thermodilution measurements, in patients with septic shock and presumed alterations in vascular tone. Methods Nine patients who received a pulmonary artery catheter and were on mechanical ventilation and in sinus rhythm were monitored by the FloTrac/Vigileo. Paired cardiac output measurements by both techniques were analysed for 86 measurements in four patients using the 1.07 software version and 73 measurements in five subsequent patients using the later 1.10 version. Results For the 1.07 version, bias was -1.6 L min-1, precision 1.6 L min-1, limits of agreement -4.8-1.5 L min-1 and error 48%. Measurements correlated at partial r equal to 0.32 (P=0.003). For the 1.10 version, bias was -1.2 L min-1, precision 1.1 L min-1, limits of agreement -3.5-1.0 L min-1 and error 32%. Measurements correlated at partial r equal to 0.90 (P<0.001 vs. version 1.07). Differences were inversely related to mean cardiac output (P<0.001, generalized estimating equations), particularly for software version 1.07 vs. 1.10 (P=0.017, generalized estimating equation). Changes in thermodilution cardiac output over the course of time were also better tracked by the FloTrac/Vigileo when applying the latest software (P<0.001, generalized estimating equation). Conclusions Evolving software versions are thus better able to account for the effect of vascular tone on cardiac output measurements by less invasive waveform analyses without calibration (FloTrac/Vigileo), so that the latter may become useful in the haemodynamic monitoring of septic shock. © 2010 Copyright European Society of Anaesthesiology.

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