Jozef Bartunek

OLV Ziekenhuis Aalst, Alost, Flanders, Belgium

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Publications (247)2026.75 Total impact

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    ABSTRACT: Background: -The fractional flow reserve (FFR) value of 0.75 has been validated against ischemic testing, while the FFR value of 0.80 has been widely accepted to guide clinical decision-making. However, revascularization when FFR is 0.76-0.80, within the so-called "gray zone", is still debatable. Methods and results: -From February 1997 to June 2013, all patients with single-segment disease and an FFR value within the gray zone or within the two neighboring FFR strata (0.70-0.75 and 0.81-0.85) were included. Study endpoints consisted of major adverse cardiovascular events (MACE: death, myocardial infarction and any revascularization) up to 5 years. Out of 17380 FFR measurements, 1459 patients were included. Of them, 449 were treated with revascularization (Rev), and 1010 with medical therapy (MT). In the gray zone, MACE rate was similar (37[13.9%] vs. 21[11.2%], respectively, p=0.3) between MT and Rev, while a strong trend toward higher rate of death or myocardial infarction (25[9.4] vs. 9[4.8], p=0.06) and overall death (20[7.5] vs. 6[3.2], p=0.059) was observed in the MT group. Among MT patients, a significant step-up increase in MACE rate was observed across the 3 FFR strata, especially with proximal lesion location. In Rev patients, MACE rate was not different across the 3 FFR strata. Conclusions: -FFR in and around the "gray zone" bears a major prognostic value especially in proximal lesions. These data confirm that FFR ≤ 0.80 is valid to guide clinical decision-making.
    No preview · Article · Jan 2016 · Circulation
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    ABSTRACT: Aims: Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Methods: Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (<35%), and at high risk for recurrent HF-related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 10(6) bone marrow-derived and lineage-directed autologous cardiopoietic stem cells administered via a retention-enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months. Conclusion: The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF. Trial registration: NCT01768702.
    No preview · Article · Dec 2015 · European Journal of Heart Failure

  • No preview · Article · Dec 2015 · Vascular Pharmacology
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    ABSTRACT: Aims: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI), along with optimal medical therapy, improves clinical outcome by targeting ischemia-inducing stenosis. Yet, plaque progression or stent failure may cause recurring cardiac events. We assessed the potential prognostic role of different inflammatory biomarkers, known to be associated with plaque progression or stent failure, in patients undergoing FFR-guided PCI. Methods: We prospectively enrolled 169 stable angina patients with intermediate coronary stenosis at angiography undergoing FFR-guided PCI. PCI was performed if FFR was 0.80 or less, deferred if FFR was more than 0.80. Serum baseline levels of high-sensitivity C-reactive protein (hs-CRP), eosinophil cationic protein (ECP), cystatin-C (Cys-C), and thromboxane A2 (TXA2) were assessed. Rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, recurrent myocardial infarction, and target vessel revascularization (TVR), was evaluated. Results: PCI was performed in 78 patients (46%) (mean age 69 ± 10 years, men 73%) and deferred in 91 patients (54%) (mean age 64 ± 11 years, men 53%). Mean clinical follow-up was 31 ± 11 months. Within the PCI group, patients with MACE (n = 14 [18%]) had significantly higher ECP levels than those without (14.4 [9.3-19.5] vs. 4.9 [2.8-10.9] mg/l, P < 0.001), and ECP was a significant predictor of MACE (hazard ratio: 1.05, 95% confidence interval [1.01-1.09], P = 0.021). Within the deferred group, patients with MACE (n = 8 [9%]) had significantly higher CRP levels than those without (15 [6.5-31.9] vs. 1.6 [0.9-2.9] mg/l, P < 0.001) and CRP was a significant predictor of MACE (hazard ratio: 1.04, 95% confidence interval [1.01-1.07], P = 0.015). Cys-C and TXA2 were not significantly different between the two groups. Conclusion: Assessing inflammatory biomarkers allows the identification of patients remaining at residual higher risk of MACE after FFR-guided PCI.
    No preview · Article · Nov 2015 · Journal of Cardiovascular Medicine
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    ABSTRACT: In the past decade, novel cell-based products have been studied in patients with acute and chronic cardiac disease to assess whether these therapies are efficacious in improving heart function and preventing the development of end-stage heart failure. Cardiac indications studied include acute myocardial infarction (AMI), refractory angina, and chronic heart failure (CHF). Increased clinical activity, experience, and multiple challenges faced by developers have been recognized at the regulatory level. In May 2014, the Committee for Advanced Therapies (CAT) discussed in an expert meeting various cell-based medicinal products developed for cardiac repair, with a focus on non-manipulated bone marrow cells, sorted bone marrow or apheresis, and expanded cells, applied to patients with AMI or CHF. The intention was to share information, both scientific and regulatory, and to examine the challenges and opportunities in this field. These aspects were considered from the quality, and non-clinical and clinical perspectives, including current imaging techniques, with a focus on AMI and CHF. The scope of this overview is to present the European regulatory viewpoint on cell-based therapies for cardiac repair in the context of scientific observations.
    Full-text · Article · Oct 2015 · European Journal of Heart Failure
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    ABSTRACT: The goal of this paper is to provide an updated review for scientists and clinicians on the major areas in cardiovascular medicine published in the Journal. Leading topics in regenerative and personalized medicine are presented along with a critical overview of the field. New standards in large preclinical animal models of pulmonary hypertension and left bundle branch block are highlighted. Finally, clinical care in the areas of atherosclerosis, the aortic valve, platelet biology, and myocarditis is discussed as well as autonomic modulation therapies.
    Full-text · Article · Oct 2015 · Journal of Cardiovascular Translational Research

  • No preview · Article · Oct 2015 · Journal of the American College of Cardiology
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    Jozef Bartunek · Marc Vanderheyden · Atta Behfar
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    ABSTRACT: The traditional cardiac regenerative paradigm using non-modified adult stem cells with various routes of delivery into the myocardial target has thus far yielded unconvincing clinical outcomes. Besides factors related to heterogeneity in trial methodology, inter-patient variability and the rare incidence of adult stem cells with intrinsic repair potency underscore the importance of further optimization and standardization of regenerative platforms. Cardiac tissue engineering seizing upon the advances of cellular, molecular, and biomaterial development is shaping the next generation of the regenerative paradigm and thereby fostering disruptive curative treatments in heart failure.
    Preview · Article · Sep 2015 · Stem Cell Research & Therapy
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    Preview · Article · Sep 2015 · BMC pharmacology & toxicology
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    ABSTRACT: Despite multimodal regimens and diverse treatment options alleviating disease symptoms, morbidity and mortality associated with advanced ischemic heart failure remain high. Recently, technological innovation has led to the development of regenerative therapeutic interventions aimed at halting or reversing the vicious cycle of heart failure progression. Driven by the unmet patient need and fueled by encouraging experimental studies, stem cell-based clinical trials have been launched over the past decade. Collectively, these trials have enrolled several thousand patients and demonstrated the clinical feasibility and safety of cell-based interventions. However, the totality of evidence supporting their efficacy in ischemic heart failure remains limited. Experience from the early randomized stem cell clinical trials underscores the key points in trial design ranging from adequate hypothesis formulation to selection of the optimal patient population, cell type and delivery route. Importantly, to translate the unprecedented promise of regenerative biotherapies into clinical benefit, it is crucial to ensure the appropriate choice of endpoints along the regulatory path. Accordingly, we here provide considerations relevant to the choice of endpoints for regenerative clinical trials in the ischemic heart failure setting.
    Full-text · Article · Aug 2015 · Stem Cell Research & Therapy
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    ABSTRACT: The present study involved both human cohorts and animal experiments to explore the performance of soluble CD146 (sCD146), a marker of endothelial function, as a diagnostic marker of acutely decompensated heart failure (ADHF), to determine the influence of patients' characteristics on that performance and to explore the potential application of CD146 in the pathophysiology of ADHF. NT-proBNP and sCD146 were measured in three hundred ninety-one patients admitted to the emergency department for acute dyspnea. ROC curve analysis demonstrated that AUCs for ADHF diagnosis in dyspneic patients were 0.86 (95% CI: 0.82-0.90) for sCD146 and 0.90 (95% CI: 0.86-0.92) for NT-proBNP. Subgroup analyses demonstrated that adding sCD146 to NT-proBNP improved the diagnostic performance for patients lying in the gray zone of NT-proBNP (p=0.02) and could be especially useful for ruling-out ADHF. An experimental model of ADHF in rats using thoracic aortic constriction suggests that CD146 is expressed in the intima of large arteries and associated with both left ventricular function and organ congestion. sCD146, a marker of endothelial function, seems to be as powerful as NT-proBNP is used to detect the cardiac origin of an acute dyspnea. The combination of sCD146 and NT-proBNP may have better performance than NT-proBNP used alone in particular for patients underlying in the "gray" zone and could therefore be an improved option for ruling-out ADHF. Both experimental and human data suggest that CD146 is related to systolic left ventricular function and to organ congestion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Jul 2015 · International journal of cardiology
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    ABSTRACT: -Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the ARISTOTLE trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. -We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18,201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or prior valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR] 0.70, 95% CI 0.51-0.97 and HR 0.84, 95% CI 0.67-1.04; interaction p=0.38), causing less major bleeding (HR 0.79, 95% CI 0.61-1.04 and HR 0.65, 95% CI 0.55-0.77; interaction p=0.23), and reducing mortality (HR 1.01, 95% CI 0.84-1.22 and HR 0.84, 95% CI 0.73-0.96; interaction p=0.10). -More than a quarter of the patients in ARISTOTLE with "nonvalvular" atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. Clinical Trial Registration Information-clinicaltrials.gov. Identifier: NCT00412984.
    Full-text · Article · Jun 2015 · Circulation
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    ABSTRACT: Stem cell therapy shows promise for regeneration in heart disease, yet interpatient variability challenges implementation into practice. To establish a biomarker profile, predictive of reparative potential in patient-derived progenitors, human mesenchymal stem cells were isolated from patients undergoing coronary artery bypass grafting. Stem cell delivery postinfarction translated into divergent benefit, distinguishing reparative from nonreparative populations. While the nonreparative subtype was characterized by low expression of cardiac transcription factors, reparative human mesenchymal stem cells demonstrated high expression of cardiac transcription factors. This index of factors (cardiopoietic index) was found sensitive and specific in predicting impact of stem cell benefit on left ventricular function. The cardiopoietic index thus offers a tool to screen stem cell fitness for heart repair prior to intervention.
    No preview · Article · May 2015 · Biomarkers in Medicine
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    ABSTRACT: We investigated changes in electrocardiographic spatial QRS and T vectors as markers of electrical remodeling before and after cardiac resynchronization therapy (CRT) and their association with altered outcome. In 41 patients with LBBB, ECGpost was recorded during intrinsic rhythm after interrupting CRT pacing and compared to the pre-implant ECGpre and the ECG during CRT (ECGCRT). Mean spatial angles between QRS and T vectors were determined with the Kors matrix conversion. Left ventricular ejection fraction (LVEF) was determined with nuclear isotope ventriculography before CRT implantation (LVEFpre) and at inclusion (LVEFpost). Following CRT, LVEF improved significantly from 26±10 to 36±14% (p=0.01). Duration of QRSpre (168±15ms) was not different from QRSpost (166±15ms). A smaller angle between QRSCRT and Tpost was related to a greater angle between Tpre and Tpost (Pearson's R -0.61 - p<0.001). During follow-up (30±2months) 9 patients (22%) died. Univariate Cox regression revealed higher mortality in the patients with lower LVEFpost (HR 1.10, p=0.01), a larger angle QRSCRTTpost (HR 1.03, p=0.03), a smaller angle QRSpreQRSpost (HR 0.97, p=0.03) and smaller angle TpreTpost (HR 0.95, p<0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03). Electrical remodeling can be quantified by measuring the angles between spatial QRS and T vectors before, during and after CRT. In absence of QRS duration changes, more extensive electrical remodeling is associated with a significantly better survival. QRS and T vector changes deserve further investigation to better understand the individual response to CRT. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Feb 2015 · Journal of Electrocardiology
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    ABSTRACT: Rationale: The ACCRUE (Meta-Analysis of Cell-based CaRdiac stUdiEs) is the first prospectively declared collaborative multinational database including individual data of patients (IPD) with ischemic heart disease treated with cell therapy. Objective: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI) including IPDs from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). Methods and Results: The primary endpoint was freedom from combined major adverse cardiac and cerebrovascular events (MACCE; including all-cause death, re-AMI, stroke, and target vessel revascularization). The secondary endpoint was freedom from hard clinical endpoints (death, re-AMI, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy endpoints included changes in end-diastolic volume (ΔEDV), end-systolic volume (ΔESV), and ejection fraction (ΔEF), analyzed with random-effects meta-analyses and analysis of covariance. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on MACCE (14.0% vs. 16.3%, hazard ratio 0.86, 95%CI: 0.63;1.18) or death (1.4% vs 2.1%) or death/re-AMI/stroke (2.9% vs 4.7%) was identified in comparison to controls. No change in ΔEF (mean difference: 0.96%, 95%CI: -0.2;2.1), ΔEDV, or ΔESV was observed compared to controls. These results were not influenced by anterior AMI location, reduced baseline EF, or the use of MRI for assessing left ventricular parameters. Conclusions: This meta-analysis of IPD from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function.
    Full-text · Article · Feb 2015 · Circulation Research
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    ABSTRACT: Extended anterior myocardial infarction (MI) is frequently followed by left ventricular (LV) remodeling ensuing in heart failure and aneurysmatic transformation of the infarcted myocardial segment. Therapies that attenuate or reverse pathological LV remodeling have been shown to improve functional status and outcomes. This case reports our recent experience with a catheter based technique for ventricular restoration.
    No preview · Article · Nov 2014
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    ABSTRACT: We investigated the effect of β- and α-adrenergic blockers on fractional flow reserve (FFR) and index of microvascular resistance (IMR). In 43 patients (pts) with intermediate stenoses, we measured FFR and IMR before and after nonselective β-blocker propranolol (30 μg/kg, n = 20) and selective β1-blocker metoprolol (40 μg/kg, n = 23) IC; (b) In additional 21 pts after percutaneous coronary intervention (PCI), FFR and IMR were measured before and after α-blocker phentolamine (3 mg) IC. Neither propranolol nor metoprolol changed values of FFR and IMR. Phentolamine slightly decreased FFR (from 0.88 ± 0.05 to 0.87 ± 0.06, p = 0.025) but did not change IMR. FFR decreased from >0.80 to ≤0.80 in 3 pts (14 %), but in none, the value decreased to <0.75. β-blockers do not affect FFR and IMR in intermediate stenoses. After PCI, a mild decrease in FFR occurs after α-blockers, though of limited clinical impact.
    No preview · Article · Nov 2014 · Journal of Cardiovascular Translational Research
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    ABSTRACT: Background: This study assessed the independent significance of color Doppler 3-D vena contracta area (VCA) at rest and during exercise as a predictor of clinical outcome in mild-moderate functional mitral regurgitation (FMR). METHODS AND RESULTS: The subjects consisted of 62 patients (age, 68±11 years; 76% male) with chronic systolic heart failure and mild-moderate FMR (<2+/4) at rest. All patients underwent VCA assessment at rest and during semi-supine bicycle exercise. During median follow-up of 17 months (IQR, 13-20 months), 15 patients (24%) had composite endpoint of all-cause death (n=3), heart failure admission (n=11), and heart transplantation (n=1). At baseline, patients with vs. without endpoint had significantly larger VCA at rest (17±6 mm(2)vs. 13±7 mm(2), P=0.002) and at peak exercise (35±16 mm(2)vs. 21±12 mm(2), P<0.001). On Cox regression analysis, large (≥15-mm(2)) resting VCA (HR, 7.6; 95% CI: 1.93-13.02; P=0.004) and large (≥20-mm(2)) exercise-induced increase of VCA (HR, 5.1; 95% CI: 1.39-15.21; P=0.014) were independently associated with composite endpoint. Concomitant presence of large VCA at rest and its large increase during exercise occurred in 53% of patients with, vs. in only 8% without, endpoint (negative predictive value, 86%). Conclusions: The presence of relatively large VCA at rest and its significant increase during exercise is independently associated with adverse clinical outcome in patients with mild-moderate FMR at rest.
    No preview · Article · Oct 2014 · Circulation Journal
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    ABSTRACT: Background: The presence of ergoreflex activity and its current relationship to hyperventilation and prognosis in cardiac patients is unclear. Therefore, we evaluated ergoreflex activity in cardiac patients with and without heart failure (CHF) as well as in healthy subjects, and we examined how ergoreceptor activity was related to a mortality risk score in CHF (MAGGIC). Methods and results: Twenty-five healthy subjects and 76 patients were included, among whom were 25 with ischemic heart disease (IHD), 24 with stable CHF, and 27 with unstable CHF. Ergoreflex activity was measured with a dynamic handgrip exercise, followed by post-handgrip regional circulatory occlusion (PH-RCO). Ergoreflex activity contributed significantly to ventilation (median [interquartile range] %V) in unstable CHF (81 [73-91] %V without PH-RCO, 92 [82-107] %V with PH-RCO, and 11 [6-20] difference in %V; P < .001) and was positively correlated with the MAGGIC risk score (Spearman ρ = 0.431; P = .002). No ergoreflex activity was observed in healthy subjects (-4 [-10 to 5] difference in %V), IHD (0 [-8 to 3] Diff in %V) and stable CHF (-3 [-11 to 6] difference in %V). Conclusions: Ergoreflex activity contributes to hyperventilation, but only in CHF patients with persistent symptoms, and is closely related to the MAGGIC risk score. Ergoreflex activity was not present in patients with IHD or stable CHF, suggesting other reasons for the increased ventilatory drive in those patients.
    No preview · Article · Jul 2014 · Journal of Cardiac Failure
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    ABSTRACT: Aims: Treatment with percutaneous edge-to-edge mitral valve repair (Mitraclip) has recently been recommended as an alternative to conventional mitral valve repair for high surgical risk patients with symptomatic severe mitral regurgitation (MR). In this study, we report the first use of Mitraclip therapy in Belgium. Methods and results: This prospective registry includes 41 consecutive patients treated with the Mitraclip in two Belgian centres from October 2010 to June 2013. Acute procedural success, in-hospital safety end points and clinical status were analysed on an intention-to-treat basis up to one year after the procedure. In addition, determinants of major adverse cardiac events (MACE, death, surgical mitral valve intervention, and rehospitalization for heart failure) were analysed. Acute procedural success (successful clip placement and reduction of colour Doppler flow MR to < or = 2) was obtained in 32 patients (78%) and 18 of these patients received two clips. The primary safety end point was reached in 36 pts (88%): one patient died due to intracranial bleeding, there were three urgent surgical interventions and one severe access site bleeding. The MACE rate after one year was 41% (17 patients). There were 11 deaths (27%), six surgical interventions (15%) and 10 rehospitalizations for heart failure (24%). Additional subgroup analysis revealed that the one-year MACE rate was particularly high in patients with left ventricular ejection fraction (LVEF) < 25%: 62% vs. 36% in patients with LVEF > or = 5% (P = 0.05). At one year, MR < or = 2+ and NYHA class < or = 2 was present in 83% of the surviving patients Conclusion: In high-risk patients with functional MR, treatment with the Mitraclip-device is a feasible and safe option resulting in improvement of MR severity and clinical symptoms. However, as MACE is high in some subgroups (e.g. LVEF < 25%), careful patient selection is crucial to ensure the maximum benefit from this new technique.
    No preview · Article · Jun 2014 · Acta cardiologica

Publication Stats

9k Citations
2,026.75 Total Impact Points

Institutions

  • 1994-2015
    • OLV Ziekenhuis Aalst
      Alost, Flanders, Belgium
  • 2010
    • Technische Universiteit Eindhoven
      Eindhoven, North Brabant, Netherlands
  • 2008
    • University of San Diego
      San Diego, California, United States
  • 2007-2008
    • Cardiovascular Research Foundation
      New York, New York, United States
  • 2001-2003
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
  • 1997-2000
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1999
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States