Robert Naeije

University Hospital Brussels, Bruxelles, Brussels Capital Region, Belgium

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Publications (414)2038.62 Total impact

  • Gabor Kovacs, Robert Naeije, Horst Olschewski
    American Journal of Respiratory and Critical Care Medicine 11/2014; 190(10):1198-9. · 11.04 Impact Factor
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    ABSTRACT: Right ventricular contractile response to pharmacological stress in pulmonary arterial hypertension (PAH) has not been characterised. We evaluated right ventricular contractile reserve in adults with PAH using dobutamine stress echocardiography. 16 PAH patients and 18 age-matched controls underwent low-dose dobutamine stress echocardiography. Contractile reserve was assessed by the change (Δ; peak stress minus rest value) in tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (S'). A subgroup of 13 PAH patients underwent treadmill cardiopulmonary exercise testing for peak oxygen uptake (V'O2peak). At rest, TAPSE and S' were reduced in the PAH group compared with controls (1.7±0.4 versus 2.4±0.2 cm and 9.7±2.6 cm·s(-1) versus 12.5±1.2 cm·s(-1), respectively; p<0.05). Contractile reserve was markedly attenuated in PAH compared to controls (ΔTAPSE 0.1±0.2 versus 0.6±0.3 cm and ΔS' 4.6±2.8 versus 11.2±3.6 cm·s(-1); p<0.0001). In the sub-group of PAH patients with preserved right ventricular systolic function at rest, contractile reserve remained depressed compared to controls. V'O2peak was significantly correlated with ΔS' (r = 0.87, p = 0.0003) and change in stroke volume (r = 0.59, p = 0.03). Dobutamine stress can reveal sub-clinical reduction in right ventricular contractile reserve in patients with PAH. A correlation with exercise capacity suggests potential clinical value beyond resting measurements.
    The European respiratory journal. 10/2014;
  • Laurence Dewachter, Robert Naeije
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    ABSTRACT: Introduction: Parenteral prostacyclins are considered the gold standard treatment of severe pulmonary arterial hypertension (PAH). However, the technical and clinical burden of their continuous parenteral administration has led to the development of long-acting oral analogs.Areas covered: Following suggestive uncontrolled studies, an initial 3-month randomized placebo-controlled trial of the oral prostacyclin analog beraprost sodium (BPS) was completed, demonstrating significant improvement in the primary endpoint, which was the six-minute walk test. However, a subgroup analysis revealed that only idiopathic PAH patients benefited from the drug, secondary end points were negative and dosing was limited by side effects. A second 1-year randomized trial with a primary end point combining clinical stability and exercise capacity was negative. A secondary analysis revealed significant improvement after BPS intake at 6 months. Recent open-label studies with a modified release BPS formulation (BPS-MR) suggested long-term improvement in exercise capacity and clinical state in PAH patients. Randomized controlled trials with BPS-MR are underway but have been slowed by regulatory requirements of single optical isomer reformulation of BPS-MR (BPS-414d-MR).Expert opinion: BPS is efficacious in PAH but has failed until now in randomized controlled trials mainly because of side effects limiting dosing. Successive reformulations will hopefully produce better tolerated, purer and longer-acting preparations.
    Expert Opinion on Orphan Drugs. 09/2014;
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    ABSTRACT: Prognosis in pulmonary hypertension (PH) is largely determined by RV function. However, uncertainty remains about what metrics of RV function might be most clinically relevant. The purpose of this study was to assess the clinical relevance of metrics of RV functional adaptation to increased afterload.
    Heart (British Cardiac Society) 09/2014; · 5.01 Impact Factor
  • Echocardiography 09/2014; · 1.26 Impact Factor
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    ABSTRACT: The right ventricle (RV) can be described in terms of 3 components: the inlet, the apex, and the infundibulum. In the normal adult, the RV shows an arrangement suited for pumping blood against low resistance, with a mass about one sixth that of left ventricle (LV) mass, and a larger volume than the LV. The RV is able to manage a progressive increase in the afterload by increasing contractility and remodeling. The gold standard measurement of contractility is maximal elastance (Emax), or the ratio between end-systolic pressure (ESP) and end-systolic volume (ESV), and the best measurement of afterload is arterial elastance (Ea), or the ratio between ESP and stroke volume (SV). The ratio Emax/Ea defines RV-arterial coupling. The optimal energy transfer from the RV to the pulmonary circulation is measured at Emax/Ea ratios of 1.5–2. In the presence of pulmonary hypertension, the SV/ESV ratio may be an acceptable surrogate of Emax/Ea. The right atrium (RA) has 3 anatomical components: the appendage, the venous part, and the vestibule. It is a dynamic structure having different functions: reservoir, conduit, and booster pump function. In case of increased afterload, the RA is enlarged, denoting high RA pressure, as a consequence of elevated RV diastolic pressure. RA area is a strong predictor of adverse clinical outcome in pulmonary arterial hypertension. In patients with severe pulmonary hypertension, in several congenital heart diseases, and in Eisenmenger syndrome, symptoms and prognosis are greatly dependent on RV function and its ability to adapt to a chronic increase in afterload.
    Echocardiography 09/2014; · 1.26 Impact Factor
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    ABSTRACT: Echocardiography is a key screening tool in the diagnostic algorithm of pulmonary arterial hypertension (PAH). It provides an estimate of right ventricular function and pulmonary artery pressure, either at rest or during exercise, and is useful in ruling out secondary causes of pulmonary hypertension (PH) such as left heart disease or congenital heart disease. Several studies have showed that echocardiography is insufficiently precise as single tool for the ultimate diagnosis of PH respect to the right heart catheterization, considered the gold standard technique. Echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease. The ideal imaging modality for accurate noninvasive assessment of the right heart should be accurate and precise, not influenced by loading conditions, routinely practicable and easily repeatable. For all such reasons and considering that PAH is a rare and severe condition, a complete noninvasive assessment of right heart function requires a deep knowledge of the disease and a multimodality approach.
    Echocardiography 09/2014; · 1.26 Impact Factor
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    Robert Naeije, Michele D'Alto
    The European respiratory journal. 08/2014; 44(2):553-4.
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    ABSTRACT: The accuracy of pulmonary vascular pressure measurements is of great diagnostic and prognostic relevance. However, there is variability of zero leveling procedures, and the current recommendation of end-expiratory reading may not always be adequate. A review of physiological and anatomical data, comforted by recent imaging, leads to the practical recommendation of zero leveling at the cross-section of three trans-thoracic planes which are respectively mid-chest frontal, transverse through the fourth intercostal space, and mid-sagittal. As for the inevitable respiratory pressure swings, end-expiratory reading at functional residual capacity allows for minimal influence of elastic lung recoil on pulmonary pressure reading. However, hyperventilation is associated with changes in end-expiratory lung volume and increased intra-thoracic pressure, eventually exacerbated by expiratory muscle contraction and dynamic hyperinflation, all increasing pulmonary vascular pressures. This problem is amplified in patients with obstructed airways. With the exception of dynamic hyper-inflation states, it is reasonable to assume that negative inspiratory and positive expiratory intrathoracic pressures cancel each other out, so averaging pulmonary vascular pressures over several respiratory cycles is most often preferable. This recommendation may be generalized, for the purpose of consistency, and makes sense as pulmonary blood flow measurements are not corrected either for phasic inspiratory and expiratory changes in clinical practice.
    American Journal of Respiratory and Critical Care Medicine 05/2014; · 11.04 Impact Factor
  • Robert Naeije, Marion Delcroix
    European Respiratory Journal 05/2014; 43(5):1541-1542. · 6.36 Impact Factor
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    ABSTRACT: Stress-testing of the pulmonary circulation (via increasing pulmonary blood flow) can reveal abnormal mean pulmonary artery pressure-cardiac output (mPpa-Q) responses, which may facilitate early diagnosis of pulmonary vascular disease. We investigated the application of dobutamine stress echocardiography for the non-invasive assessment of pulmonary mPpa-Q relationships. Dobutamine stress echocardiography using an incremental dose protocol (up to 20 mcg/kg/min) was performed in 38 subjects (16 patients with pulmonary arterial hypertension (PAH) and 22 healthy controls). An additional 22 healthy controls underwent exercise stress echocardiography as a comparator group. Multipoint mPpa-Q plots were analyzed and pulmonary vascular distensibility coefficient α calculated. Dobutamine stress echocardiography was feasible and informative in 93% of subjects. The average dobutamine-induced mPpa-Q slope was 1.1 ± 0.7 mmHg/L/min in healthy controls and 5.1 ± 2.5 mmHg/L/min in PAH patients (p < 0.001). Dobutamine-induced α was markedly reduced in PAH patients (0.003 ± 0.001 vs. 0.02 ± 0.01 mmHg-1 in controls, p < 0.001). When exercise and dobutamine stress were compared in healthy controls, exercise-induced mPpa-Q slope was modestly higher (1.6 ± 0.7 mmHg/L/min, p=0.03 vs. dobutamine). In PAH patients, lower functional class status was associated with lower dobutamine-induced mPpa-Q slopes (p=0.013), but not with resting total pulmonary vascular resistance. Non-invasive assessment of pulmonary mPpa-Q relationships is feasible with dobutamine stress. Dobutamine stress echocardiography may potentially be a useful non-invasive technique for stress testing of the pulmonary vasculature.
    Chest 03/2014; · 7.13 Impact Factor
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    ABSTRACT: Systemic hypertension may be associated with an increased pulmonary vascular resistance, which we hypothesized could be, at least in part, mediated by increased leptin. Vascular reactivity to phenylephrine (1 mumol/L), endothelin-1 (10 nmol/L) and leptin (0.001-100 nmol/L) was evaluated in endothelium-intact and -denuded isolated thoracic aorta and pulmonary arteries from spontaneously hypertensive versus control Wistar rats. Arteries were sampled for pathobiological evaluation and lung tissue for morphometric evaluation. In control rats, endothelin-1 induced a higher level of contraction in the pulmonary artery than in the aorta. After phenylephrine or endothelin-1 precontraction, leptin relaxed intact pulmonary artery and aortic rings, while no response was observed in denuded arteries. Spontaneously hypertensive rats presented with increased reactivity to phenylephrine and endothelin-1 in endothelium-intact pulmonary arteries. After endothelin-1 precontraction, endothelium-dependent relaxation to leptin was impaired in pulmonary arteries from hypertensive rats. In both strains of rats, aortic segments were more responsive to leptin than pulmonary artery. In hypertensive rats, pulmonary arteries exhibited increased pulmonary artery medial thickness, associated with increased expressions of preproendothelin-1, endothelin-1 receptors type A and B, inducible nitric oxide synthase and decreased endothelial nitric oxide synthase, together with decreased leptin receptor and increased suppressor of cytokine signaling 3 expressions. Altered pulmonary vascular reactivity in hypertension may be related to a loss of endothelial buffering of vasoconstriction and decreased leptin-induced vasodilation in conditions of increased endothelin-1.
    Respiratory research 02/2014; 15(1):12. · 3.64 Impact Factor
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    ABSTRACT: If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favour redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4,350 m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (–10%, p < 0.001) and decreased similarly during incremental exercise (p < 0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (-7%, p < 0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p < 0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favour the hypothesis of blood flow redistribution.
    Respiratory Physiology & Neurobiology 01/2014; · 2.05 Impact Factor
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    ABSTRACT: Background Elevated serum uric acid is detected in pulmonary arterial hypertension (PAH) and is associated with poor patient outcomes. High serum uric acid is an independent risk factor for cardiovascular disease and renal impairment. We analyzed the effects of endothelin receptor antagonism on serum uric acid in PAH patients participating in the Sitaxentan to Relieve Impaired Exercise (STRIDE)-2/2X trial, and the impact of uric acid on 6-minute walk distance (6MWD), time to clinical worsening (TtCW), and survival. Methods In the 18-week, double-blind, placebo-controlled STRIDE-2 trial, 246 PAH patients were randomized and received matched placebo, sitaxentan 50 or 100 mg orally once daily, or open-label bosentan 125 mg twice daily. STRIDE-2X was a 1-year, open-label extension of STRIDE-2. Results Baseline serum uric acid was similar between groups. Increased serum uric acid was a significant risk factor for 1-year mortality and TtCW. Compared with placebo, sitaxentan 50 and 100 mg, and bosentan all reduced serum uric acid (p<0.05). Reduced serum uric acid correlated with increased 6MWD (p=0.0037). Conclusions Endothelin receptor antagonism reduces serum uric acid in PAH patients, and this reduction is associated with improved survival and longer TtCW. Further prospective studies are needed to investigate the pathogenic role of serum uric acid in PAH and its prognostic potential.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2014; · 3.54 Impact Factor
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    ABSTRACT: The 6 minutes walk test (6MWT) is often shown to be the best predictor of mortality in pulmonary hypertension (PH) probably because it challenges the failing heart to deliver adequate cardiac output. We hypothesised that the 6MWT elicits maximal cardiac output as measured during a maximal cardiopulmonary exercise testing (CPET). 18 patients with chronic thromboembolic pulmonary hypertension (n = 12) or pulmonary arterial hypertension (n = 6) and 10 healthy subjects performed a 6MWT and CPET with measurements of cardiac output (non invasive rebreathing device) before and directly after exercise. Heart rate was measured during 6MWT with a cardiofrequence meter. Cardiac output and heart rate measured at the end of the 6MWT were linearly related to 6MW distance (mean±SD: 490±87 m). Patients with a high NT-pro-BNP achieve a maximum cardiac output during the 6MWT, while in normal subjects and in patients with a low-normal NT-proBNP, cardiac output at the end of a 6MWT was lower than achieved at maximum exercise during a CPET. In both cases, heart rate is the major determinant of exercise-induced increase in cardiac output. However, stroke volume increased during CPET in healthy subjects, not in PH patients. Maximal cardiac output is elicited by 6MWT in PH patients with failing right ventricle. Cardiac output increase is dependent on chronotropic response in patients with PH.
    PLoS ONE 01/2014; 9(3):e92324. · 3.53 Impact Factor
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    ABSTRACT: Mutations affecting transforming growth factor-beta (TGF-β) superfamily receptors, activin receptor-like kinase (ALK)-1, and endoglin (ENG) occur in patients with pulmonary arterial hypertension (PAH). To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs) and pulmonary endothelial cells (PECs) from 14 patients with idiopathic PAH (iPAH) and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV) systolic pressure (RVSP), RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/-) and wild-type (Eng+/+) mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH.
    PLoS ONE 01/2014; 9(6):e100310. · 3.53 Impact Factor
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    ABSTRACT: Background Endothelin receptor antagonists improve pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2) predispose to PAH. Here, we sought to determine whether there might exist interactions between these two signaling pathways and their impact on the acquisition of the altered phenotype of pulmonary artery smooth muscle cells (PA-SMCs) observed in PAH. Methods Expression of BMPR2, of one BMP agonist (BMP4) and of two BMP antagonists (gremlin1 and gremlin2) was evaluated in lungs and in PA-SMCs from PAH patients (n=6) and controls (n=14), treated with endothelin-1. Endothelin-1 pre-treated PA-SMCs were assessed for proliferation, apoptosis and downstream signaling activation (Smad1/5/8, p38MAPK) after BMP2 treatment. Results In PA-SMCs from PAH patients, expression of BMPR2 and BMP4 decreased, while expression of gremlin1 and gremlin2 increased compared to controls. Treatment of control PA-SMCs with endothelin-1 induced a dose-dependent increase in gremlin1 and gremlin2, while BMPR2 and BMP4 expression decreased, reaching similar levels as those observed in PAH cells. In control PA-SMCs, endothelin-1 pre-treatment reduced Id1 expression and Smad1/5/8 activation induced by BMP2, while it enhanced p38MAPK activation. Moreover, BMP2 decreased serum-induced proliferation and increased pro-apoptotic Bax/Bcl-2 ratio. These effects were attenuated by endothelin-1 pre-treatment. In PA-SMCs from PAH patients, endothelin-1 did not alter BMPR2 signaling. Conclusions Endothelin-1 downregulates canonical BMPR2 signaling. This is related to decreased BMPR2 and increased anti-BMP gremlin expression associated to increased activation of p38MAPK, and results in PA-SMC proliferation.
    The Journal of Heart and Lung Transplantation. 01/2014;
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    ABSTRACT: Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation.
    Journal of the American College of Cardiology 12/2013; 62(25 Suppl):D22-33. · 14.09 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND A reduced pulmonary arterial compliance (Ca) is a marker of poor prognosis in idiopathic pulmonary arterial hypertension. We tested the hypothesis that Ca could be a predictor of outcome in patients with chronic heart failure (CHF). METHODS We enrolled 306 patients with CHF due to systolic left ventricular dysfunction (sLVD) who underwent a clinically driven right heart catheterization. Pulmonary arterial Ca was measured by the ratio between stroke volume and pulse pressure (SV/PP). The primary end-point was cardiovascular death; secondary end-point was the composite of cardiovascular death, urgent heart transplantation and appropriately detected and treated episode of ventricular fibrillation. RESULTS An inverse relationship was observed between SV/PP and pulmonary vascular resistance, the mean resistance-compliance product (RC-time) being 0.30 ± 0.2 seconds. In patients with pulmonary capillary wedge pressure < 15 mmHg the mean RC-time was 0.34 ± 0.14 sec and in patients with pulmonary capillary wedge pressure ≥ 15 mmHg it was 0.28 ± 0.22 sec. Eighty-seven patients died in a follow-up period of 50 ± 32 months. At receiver operating characteristic curve analysis, the optimal prognostic cut-off point of SV/PP was 2.15 ml/mmHg. An elevated (>2.15) SV/PP was more strongly associated with survival than any other hemodynamic variable; it was associated with poor prognosis both in patients with high (p=0.003) and in patients with normal pulmonary vascular resistance (p=0.005). CONCLUSIONS Pulmonary arterial compliance is a strong prognostic indicator in CHF patients with sLVD; most importantly, its prognostic role is retained in patients with normal pulmonary vascular resistance.
    Chest 12/2013; · 7.13 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND. Although transthoracic echocardiography (TTE) is an excellent non-invasive screening test for pulmonary hypertension, the physiologic range of echo-Doppler derived pulmonary pressures remains not completely investigated. The aim of the present study was therefore to explore the full spectrum of pulmonary pressures and RV functional indexes by TTE in healthy subjects and to investigate clinical and echocardiographic correlates. METHODS. A random sample of 1480 healthy individuals (mean age 36.1 ± 15.5 years, range 20-80 - 905 males) underwent a comprehensive TTE. Pulmonary artery systolic (PASP) and mean pressure, and pulmonary vascular resistance were estimated by standard echo-Doppler formulas. In addition, RV diastolic (Doppler transtricuspid inflow measurements) and systolic indices (RV fractional area change, RV tissue Doppler (TD) peak systolic velocity, tricuspid annular plane systolic excursion) were calculated. RESULTS. PASP and mean pulmonary artery pressure values were significantly higher in subjects > 50 years old and in those with a body mass index > 30 Kg/m2. In particular, a PASP > 40 mmHg was found in 118 subjects (8 %) of those > 50 years old and in 103 (7 %) of those with a BMI > 30 Kg/m2. No differences by age were registered in RV systolic indexes and in pulmonary vascular resistances. On multivariate analysis, in the overall study population, age, body mass index (BMI), mitral E/e' ratio and left ventricular stroke volume were the only independent predictors of PASP. CONCLUSIONS. This study delineates an estimate of pulmonary hemodynamics in a wide age range cohort of healthy subjects. Pulmonary pressures increased with age and BMI as expected.
    Chest 12/2013; · 7.13 Impact Factor

Publication Stats

7k Citations
2,038.62 Total Impact Points

Institutions

  • 1976–2014
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium
  • 1975–2014
    • Vrije Universiteit Brussel
      • • Department of Cardiology
      • • Physiology (FYSP)
      • • Department of Intensive Care Medicine
      • • Department of Internal Medicine
      Bruxelles, Brussels Capital Region, Belgium
  • 2013
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom
    • Monaldi Hospital
      Napoli, Campania, Italy
  • 2002–2013
    • Université Libre de Bruxelles
      • • Laboratory of Physiology and Physiopathology (PHYSIO)
      • • Department of Pathology
      • • Intensive Care Unit
      Brussels, BRU, Belgium
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
  • 1998–2013
    • Universitair Ziekenhuis Leuven
      • Department of Cardiology
      Leuven, VLG, Belgium
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2012
    • University of Cambridge
      Cambridge, England, United Kingdom
    • The University of Western Ontario
      London, Ontario, Canada
    • Université de Poitiers
      Poitiers, Poitou-Charentes, France
  • 2009–2012
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
    • University of Wisconsin, Madison
      • Department of Biomedical Engineering
      Madison, MS, United States
  • 2008–2012
    • VU University Medical Center
      • Institute for Cardiovascular Research (ICaR-VU)
      Amsterdamo, North Holland, Netherlands
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
    • Vienna General Hospital
      Wien, Vienna, Austria
    • Medical University of Bialystok
      Belostok, Podlasie, Poland
  • 2006
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • University-Hospital Brugmann UVC
      Bruxelles, Brussels Capital Region, Belgium
  • 2005–2006
    • Erasmushogeschool Brussel
      Bruxelles, Brussels Capital Region, Belgium
  • 2004–2005
    • University of Bologna
      • Institute of Cardiology
      Bologna, Emilia-Romagna, Italy
  • 2000
    • University Hospital of Lausanne
      • Service de médecine interne
      Lausanne, VD, Switzerland
  • 1979–1989
    • Centre Hospitalier Universitaire Saint-Pierre
      Bruxelles, Brussels Capital Region, Belgium