Interuniversity Cardiology

Utrecht, Netherlands

Interuniversity Cardiology

Utrecht, Netherlands
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Oemrawsingh R.M.,Erasmus University Rotterdam | Oemrawsingh R.M.,Interuniversity Cardiology | Lenderink T.,Atrium Medical | Akkerhuis K.M.,Erasmus University Rotterdam | And 5 more authors.
Heart | Year: 2011

Objective: To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Design and Setting: Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). Patients: 1090 patients with NSTEACS. Main outcome measure: All-cause mortality and non-fatal MI during a median follow-up of 4 years. Results: The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 μg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 μg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). Conclusion: In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.


Brouwer W.P.,VU University Amsterdam | Brouwer W.P.,Interuniversity Cardiology | Germans T.,VU University Amsterdam | Head M.C.,VU University Amsterdam | And 4 more authors.
European Heart Journal Cardiovascular Imaging | Year: 2012

Aims: Crypts can be found with cardiovascular magnetic resonance imaging (CMR) in hypertrophic cardiomyopathy (HCM) mutation carriers without hypertrophy (carriers) using a modified two-chamber view through the inferoseptum, but also in other patients and healthy individuals with standard long-axis views. Since it is currently unknown if carriers display a specific crypt morphology, we compared crypts in carriers with other cardiac pathologies (controls). Besides, we aimed to determine the optimal imaging plane for the detection of crypts by comparing modified two-chamber views with standard long-axis views. Finally, we evaluated the accuracy of crypts to identify carriers in HCM family screening. Methods and results: Standard CMR long-axis views with additional modified two-chamber views were prospectively performed in carriers (n = 43), consecutive CMR control patients (n = 252), and mutation-negative family members (n = 15). Crypts were found in 70% (30/43) of carriers and in 12% (31/252) of controls (P < 0.001). Crypts in carriers showed deeper penetrance into the myocardium compared with controls (74 ± 21% vs. 59 ± 22%, P < 0.01). Detection of two or more crypts had a sensitivity of 51% and specificity of 94% for carriership. Modified two-chamber views doubled the sensitivity to detect crypts compared with standard long-axis views. In family screening, ≥2 crypts had a 100% positive predictive value to identify carriers. Conclusions: Multiple crypts in the absence of left ventricular hypertrophy are highly specific for HCM mutation carriership and warrant clinical follow-up. A modified two-chamber view has a superior sensitivity compared with standard long-axis views for crypt detection. CMR may be of additional value to identify carriers in family screening. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012.


Jukema J.W.,Leiden University | Jukema J.W.,Durrer Center for Cardiogenetic Research | Jukema J.W.,Interuniversity Cardiology | Cannon C.P.,Brigham and Women's Hospital | And 7 more authors.
Journal of the American College of Cardiology | Year: 2012

The debate whether statins, 3-hydroxymethyl-3-methylglutaryl coenzyme A reductase inhibitors, are safe to use has been raging since their introduction in 1987. Statins are generally well tolerated and are believed to have minimal adverse effects. However, individual, specific rare adverse events have been reported, such as elevations of liver enzymes, muscle aches, and very rarely, rhabdomyolysis. Discontinuation and/or reduction in the dose of the statin usually leads to resolution of these side effects. Recently, however, debate has focused on the possible negative long-term effects of statin treatment on cognitive decline, the incidence of cancer, and the development of diabetes mellitus. Recently, the U.S. Food and Drug Administration has expanded the warning for statins with a statement that statin use may lead to cognitive impairment. In this review, we discuss all levels of evidence, from case reports to large randomized controlled clinical trials, for the possible adverse effects of statins on cognitive decline, cancer, and diabetes. After careful consideration of all discussed scientific evidence, we conclude that there is no increased risk of cognitive decline or cancer with statin use. However, statin use is related to a small increased risk of type 2 diabetes mellitus. In view of the overwhelming benefit of statins in the reduction of cardiovascular events, we believe the small absolute risk for development of diabetes is outweighed by the cardiovascular benefits in patients for whom statin therapy is recommended. We, therefore, suggest that clinical practice for statin therapy should not be changed on the basis of the most recent Food and Drug Administration informational warnings. © 2012 American College of Cardiology Foundation.


Delewi R.,University of Amsterdam | Delewi R.,Interuniversity Cardiology | Andriessen A.,University of Amsterdam | Tijssen J.G.P.,University of Amsterdam | And 3 more authors.
Heart | Year: 2013

Context Numerous randomized controlled studies assessing intracoronary bone marrow cell therapy (BMC) after acute myocardial infarction (AMI) have been performed. Objective To systematically review the effect of autologous BMC therapy on left ventricular function by performing an up to date meta-analysis of randomized controlled trials (RCTs) including long-term follow-up. Data sources Trials were indentified through a literature search from 1980 to June 2012 of the Pubmed, Embase, Cochrane database, and the Current Controlled Trials Register. Study selection Randomized clinical trials comparing intracoronary BMC infusion to control as treatment for AMI. Data extraction The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to follow-up. Secondary endpoints were changes in left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), infarct size and clinical outcomes. Results Improvement of LVEF in patients receiving intracoronary BMC was significantly better within 6 months (23 studies, 2.23% (95% confidence interval (CI) 1.00 to 3.47); p<0.001). At 12 months of follow-up, this effect sustained with 3.91% more LVEF improvement (11 studies, (95% CI 2.56 to 5.27), p<0.001). At long-term follow-up, we found a trend for better LVEF improvement in favor of cell therapy (7 studies, 1.90% (95% CI-0.43 to 4.23); p=0.11). There was no clear effect in infarct size or LVEDV. However, we found a significant reduction in LVESV at 6 months (-4.81 ml (95% CI-7.86 to-1.76); p<0.001 and at 12 months (-9.41 ml (95% CI-13.64 to-5.17); p<0.001). Moreover, there was a statistically significant decrease in recurrent AMI (Relative Risk (RR) 0.44 (95% CI 0.24 to 0.79); p=0.007), and readmission for heart failure, unstable angina or chest pain (RR 0.59 (95% CI 0.35 to 0.98); p=0.04) in favour of cell therapy. Conclusion Intracoronary BMC treatment leads to a moderate improvement of LVEF and reduction of LVESV at 6 months that sustained at 12 months follow-up, without a clear significant effect on LVEDV, or infarct size. Furthermore, we found that intracoronary cell therapy is significantly associated with a reduction in recurrent AMI and readmission for heart failure, unstable angina or chest pain.


Yetgin T.,Erasmus Medical Center | Yetgin T.,Interuniversity Cardiology | Manintveld O.C.,Erasmus Medical Center | Boersma E.,Erasmus Medical Center | And 6 more authors.
Circulation Journal | Year: 2012

Background: Although remote ischemic conditioning (RIC) by transient limb ischemia in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) has shown favorable effects on myocardial (ischemiareperfusion) injury, recent trials provide inconsistent results. The aim of the present study was to assess the effect of RIC in PCI or CABG. Methods and Results: Medline/Embase/conference reports were searched for randomized RIC trials and were included if they reported on biomarkers of myocardial injury (CK-MB/troponin T/I), after which, standardized mean differences (SMDs) were calculated (Hedges g statistic). Meta-analysis of 4 studies on PCI, involving 557 patients, indicated reduced biomarkers for myocardial injury with RIC compared to control (random effects model: SMD,-0.21; 95% confidence interval [CI]:-0.66 to 0.24). Analysis of primary PCI studies, involving 314 patients, indicated a highly significant positive effect of RIC on myocardial injury (SMD,-0.55; 95% CI:-0.77 to-0.32). The 13 CABG studies taken together, involving 891 patients, indicated a significant effect of RIC on myocardial injury (SMD,-0.34; 95% CI:-0.59 to-0.08). The statistical tests indicated moderate to high heterogeneity across the studies (Q-statistic: PCI, P=0.0006, I2=83%; CABG, P<0.0001, I2=69%). Conclusions: In patients undergoing PCI or CABG, RIC with transient episodes of limb ischemia is associated with lower biomarkers of myocardial injury compared to control, but this effect failed to reach statistical significance in the overall PCI analysis.


Boogerd C.J.J.,University of Amsterdam | Boogerd C.J.J.,University of California at San Diego | Wong L.Y.E.,University of Amsterdam | Van Den Boogaard M.,University of Amsterdam | And 8 more authors.
Cellular and Molecular Life Sciences | Year: 2011

Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to cotransfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity. © The Author(s) 2011.


Lagendijk A.K.,University Utrecht | Smith K.A.,University of Queensland | Bakkers J.,University Utrecht | Bakkers J.,Interuniversity Cardiology
Trends in Cardiovascular Medicine | Year: 2010

By using a candidate gene approach, we have identified novel single-nucleotide polymorphisms specific to patients diagnosed with atrioventricular valve and septum defects. Here we discuss how the gene products, in which these polymorphisms were found, functionally interact to regulate endocardial cushion formation during embryo development. These findings support a model in which mutations in different genes but regulating the same process can cause or make one more susceptible to developing atrioventricular valve and septum defects. © 2010 Elsevier Inc.


Luijkx T.,University Utrecht | Velthuis B.K.,University Utrecht | Prakken N.H.J.,University Utrecht | Cox M.G.P.J.,University Utrecht | And 5 more authors.
European Journal of Preventive Cardiology | Year: 2012

Background: Cardiac magnetic resonance (CMR) evaluation of athletes for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is complicated by overlapping features such as right ventricular (RV) volume increase. The revised ARVC/D diagnostic Task Force Criteria (TFC) incorporate cut-off values for RV ejection fraction (EF) and RV end-diastolic volume (EDV) on CMR.Design: To distinguish ARVC/D patients from athletes we compared CMR ventricular volumes, function, TFC cut-off values, and LV/RV ratios since athletes show proportionate, and ARVC/D patients disproportionate, changes in LV and RV.Methods: Quantitative CMR parameters of 33 ARVC/D patients (64% male, mean age 45.4 years, diagnosed by revised TFC), 66 healthy athletes and 66 healthy non-athletes (sex and age matched) were compared using revised TFC and new cut-off values representing LV/RV balance.Results and conclusions: Absolute values for ARVC/D patients/athletes/non-athletes were: in males, RV EDV 149/133/106 ml/m2, ratio EDV LV/RV 0.70/0.91/0.93, RV EF 34/52/54%, LV EF 48/57/58%, ratio EF LV/RV 1.49/1.10/1.09; and in females, RV EDV 115/115/91 ml/m2, ratio EDV LV/RV 0.86/0.94/0.97, RV EF 43/54/58%, LV EF 52/57/61%, ratio EF LV/RV 1.23/1.08/1.04 (p-values < 0.05). Areas under the ROC-curve are 0.68 (RV EDV index), 0.84 (LV/RV EDV ratio) and 0.93 (RV EF), demonstrating significantly (p < 0.001) better performance of RV EF and LV/RV EDV ratio. If a wall motion abnormality is present (observed in 30 ARVC/D patients and not in healthy subjects), RV EF can help distinguish ARVC/D from physiological cardiac adaptation in athletes on CMR whereas RV EDV index cannot. A good alternative in athletes is the LV/RV EDV ratio, representing normal proportionate adaptation of both ventricles. © 2011 The European Society of Cardiology.


Boogers M.J.,Leiden University | Boogers M.J.,Interuniversity Cardiology | Broersen A.,Leiden University | Van Velzen J.E.,Leiden University | And 14 more authors.
European Heart Journal | Year: 2012

Aims Previous studies have used semi-automated approaches for coronary plaque quantification on multi-detector row computed tomography (CT), while an automated quantitative approach using a dedicated registration algorithm is currently lacking. Accordingly, the study aimed to demonstrate the feasibility and accuracy of automated coronary plaque quantification on cardiac CT using dedicated software with a novel 3D coregistration algorithm of CT and intravascular ultrasound (IVUS) data sets.Methods and resultsPatients who had undergone CT and IVUS were enrolled. Automated lumen and vessel wall contour detection was performed for both imaging modalities. Dedicated automated quantitative software (QCT) with a unique registration algorithm was used to fuse a complete IVUS run with a CT angiography volume using true anatomical markers. At the level of the minimal lumen area (MLA), percentage lumen area stenosis, plaque burden, and degree of remodelling were obtained on CT. Additionally, mean plaque burden was assessed for the whole coronary plaque. At the identical level within the coronary artery, the same variables were derived from IVUS. Fifty-one patients (40 men, 58 ± 11 years, 103 coronary arteries) with 146 lesions were evaluated. Quantitative computed tomography and IVUS showed good correlation for MLA (n 146, r 0.75, P < 0.001). At the level of the MLA, both techniques were well-correlated for lumen area stenosis (n 146, r 0.79, P < 0.001) and plaque burden (n 146, r 0.70, P < 0.001). Mean plaque burden (n 146, r 0.64, P < 0.001) and remodelling index (n 146, r 0.56, P < 0.001) showed significant correlations between QCT and IVUS.ConclusionAutomated quantification of coronary plaque on CT is feasible using dedicated quantitative software with a novel 3D registration algorithm. © 2011 The Author.


Hardziyenka M.,University of Amsterdam | Hardziyenka M.,Interuniversity Cardiology | Campian M.E.,University of Amsterdam | Reesink H.J.,University of Amsterdam | And 9 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. Background The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. Methods We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. Results At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m2 vs. 44 ± 7 g/m2, p = 0.007) or volunteers (42 ± 6 g/m2, p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m2 to 44 ± 9 g/m2, p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. Conclusions RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass. © 2011 American College of Cardiology Foundation.

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