G Simonneau

Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud), Lutetia Parisorum, Île-de-France, France

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Publications (625)3650.74 Total impact

  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
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    Circulation 04/2012; 125(16):2045-7. · 15.20 Impact Factor
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    ABSTRACT: Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension.The aim of this study is to report clinical and haemodynamic characteristics of patients suffering of pulmonary hypertension associated with benfluorex exposure identified by the French pulmonary hypertension network.Eighty five cases of pulmonary hypertension associated with benfluorex exposure were identified by the French pulmonary hypertension network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary pulmonary hypertension. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for pulmonary hypertension was identified in 20/70 (30%) patients with pre-capillary pulmonary hypertension. A quarter of patients in this current series showed co-existing pulmonary hypertension and mild to moderate cardiac valve involvement.The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for pulmonary arterial hypertension.
    European Respiratory Journal 04/2012; · 6.36 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is a rare but potentially fatal complication of human immunodeficiency virus (HIV). It may occur in HIV-1 or 2 infection, irrespective of the route of transmission or the degree of immunosuppression. The improved survival of patients infected with HIV in the era of highly active antiretroviral therapy (HAART) justifies systematic screening for PAH according to an algorithm in patients with unexplained dyspnea. In all cases, right heart catheterization must be performed to establish the definitive diagnosis of pulmonary hypertension. The prevalence of PAH is about 0.5% in patients with HIV infection. A beneficial effect of HAART on the course of HIV-related PAH has not been clearly established. In contrast, PAH-specific therapies such as epoprostenol and bosentan have been demonstrated to be efficacious for short- and long-term outcomes in this context. Notably, some patients pulmonary hemodynamics and functional class normalized or near normalized with these treatments. Other PAH-specific therapies remain to be evaluated. The advent of HAART associated with the development of PAH-specific therapies has improved the prognosis of patients HIV-related PAH, with a survival rate of about 70% at 3 years.
    Revue des Maladies Respiratoires 04/2012; 29(4):491-500. · 0.50 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is a rare but potentially fatal complication of human immunodeficiency virus (HIV). It may occur in HIV-1 or 2 infection, irrespective of the route of transmission or the degree of immunosuppression. The improved survival of patients infected with HIV in the era of highly active antiretroviral therapy (HAART) justifies systematic screening for PAH according to an algorithm in patients with unexplained dyspnea. In all cases, right heart catheterization must be performed to establish the definitive diagnosis of pulmonary hypertension. The prevalence of PAH is about 0.5% in patients with HIV infection. A beneficial effect of HAART on the course of HIV-related PAH has not been clearly established. In contrast, PAH-specific therapies such as epoprostenol and bosentan have been demonstrated to be efficacious for short- and long-term outcomes in this context. Notably, some patients pulmonary hemodynamics and functional class normalized or near normalized with these treatments. Other PAH-specific therapies remain to be evaluated. The advent of HAART associated with the development of PAH-specific therapies has improved the prognosis of patients HIV-related PAH, with a survival rate of about 70% at 3 years.
    Revue des Maladies Respiratoires. 04/2012; 29(4):491–500.
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    ABSTRACT: Abstract BACKGROUND:Precapillary pulmonary hypertension (PH) is a complication of pulmonary Langerhans cell histiocytosis (PLCH) associated with increased mortality. However, outcomes and efficacy of pulmonary arterial hypertension (PAH) therapies in patients with PH complicating PLCH (PLCH-PH) remain unknown. METHODS:Consecutive PLCH patients with PH confirmed by right heart catheterization were included in the study. Characteristics at baseline and during follow-up as well as survival were analyzed. RESULTS:29 patients were studied. Baseline characteristics of PLCH-PH patients were: 83% of patients in World Health Organization (WHO) functional class III-IV, mean 6-min walk distance of 355 ± 95 m, mean pulmonary arterial pressure (mPAP) of 45 ± 14 mm Hg, cardiac index of 3.2 ± 0.9 L.min(-1).m(-2) and pulmonary vascular resistance (PVR) of 555 ± 253 dyn.s.cm(-5). Use of PAH therapy in 12 patients was followed by improvement in mPAP (56 ± 14 and 45 ± 12 mm Hg, P = 0.03) and PVR (701 ± 239 and 469 ± 210 dyn.s.cm(-5), P = 0.01) between baseline and follow up evaluations. No significant oxygen worsening was observed in the treated group. The 1-, 3- and 5-year survival estimates of the 29 patients were 96%, 92% and 73%, respectively. Except a trend toward a better survival associated with the use of PAH therapy, WHO functional class was the only variable significantly associated with death. CONCLUSIONS:In this group of patients, PAH therapies improved hemodynamic without oxygen worsening or pulmonary edema. WHO functional class was the only prognostic factor identified. Prospective clinical trials focusing on this population of patients are warranted.
    Chest 03/2012; · 7.13 Impact Factor
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    ABSTRACT: The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases of precapillary PH have been reported in patients who have chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. This study was designed to describe incident cases of dasatinib-associated PH reported in the French PH registry. From the approval of dasatinib (November 2006) to September 30, 2010, 9 incident cases treated by dasatinib at the time of PH diagnosis were identified. At diagnosis, patients had moderate to severe precapillary PH with functional and hemodynamic impairment. No other incident PH cases were exposed to other tyrosine kinase inhibitors at the time of PH diagnosis. Clinical, functional, or hemodynamic improvements were observed within 4 months of dasatinib discontinuation in all but 1 patient. Three patients required PH treatment with endothelin receptor antagonist (n=2) or calcium channel blocker (n=1). After a median follow-up of 9 months (min-max 3-36), the majority of patients did not demonstrate complete clinical and hemodynamic recovery, and no patients reached a normal value of mean pulmonary artery pressure (≤20 mm Hg). Two patients (22%) died at follow-up (1 of unexplained sudden death and 1 of cardiac failure in the context of septicemia, respectively, 8 and 12 months after dasatinib withdrawal). The lowest estimate of incident PH occurring in patients exposed to dasatinib in France was 0.45%. Dasatinib may induce severe precapillary PH fulfilling the criteria of pulmonary arterial hypertension, thus suggesting a direct and specific effect of dasatinib on pulmonary vessels. Improvement is usually observed after withdrawal of dasatinib.
    Circulation 03/2012; 125(17):2128-37. · 15.20 Impact Factor
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    ABSTRACT: Abstract:Rationale:Within the last decade biochemical markers have emerged as attractive tools to assess pulmonary arterial hypertension prognosis, being non-invasive and easily repeatable.ObjectivesTo determine whether biomarkers measured at initial diagnostic right heart catheterization predict 3-year all-cause mortality for incident cases of pulmonary arterial hypertension, independently of clinical and hemodynamic parameters.MethodsIncident cases of pulmonary arterial hypertension were enrolled between December 2003 and April 2006 in 6 centers from the French Network on Pulmonary Hypertension and followed during 3 years. Venous blood samples were taken during right heart catheterization and analyses were centralized.ResultsAmong 110 enrolled patients, 11 underwent lung or heart/lung transplantation and 27 died during follow-up. The Kaplan-Meier estimates of survival were 91%, 78% and 75% at 1, 2, and 3 years, respectively. Plasma big endothelin-1 (hazard ratio [HR] per 1 standard deviation [SD] increase, 1.48, 95% confidence interval [CI], 1.14 to 1.92), serum troponin T >0.01 mg/L (HR, 2.35, 95%CI, 1.05 to 5.29) and urinary F(2)-isoprostanes (15-F(2t)-isoprostane) (HR per 1 SD increase, 1.76, 95%CI, 1.31 to 2.36) were associated with increased unadjusted hazard of death. In multivariate analysis adjusting for patients' characteristics, urinary F(2)-isoprostanes were the only biomarker that remained independently associated with increased hazard of death (HR, 1.82 per 1 SD increase, 95%CI, 1.28 to 2.60).ConclusionThis study shows that urinary F(2)-isoprostane levels, biomarkers of lipid peroxidation, quantified at initial diagnostic right heart catheterization are independently associated with mortality in a cohort of patients with incident pulmonary arterial hypertension.
    Chest 03/2012; · 7.13 Impact Factor
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    ABSTRACT: In this phase 2 proof-of-concept study we examined the safety and efficacy of selexipag, an orally available, selective prostacyclin receptor (IP receptor) agonist, as a treatment for pulmonary arterial hypertension (PAH). 43 adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one to receive either selexipag or placebo. Dosage was up-titrated in 200-μg increments from 200 μg twice daily on day 1 to the maximum tolerated dose by day 35 (maximum allowed dose of 800 μg twice daily). Change in pulmonary vascular resistance at week 17 expressed as a percentage of the baseline value was the primary efficacy end-point, and was analysed in the per protocol set first and then in the all-treated set to assess robustness of results. A statistically significant 30.3% reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks' treatment with selexipag compared with placebo (95% confidence limits -44.7- -12.2; p=0.0045, Wilcoxon rank sum test). This was supported by a similar result from the all-treated set. Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect. Our results encourage the further investigation of selexipag for the treatment of PAH.
    European Respiratory Journal 02/2012; 40(4):874-80. · 6.36 Impact Factor
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    ABSTRACT: This retrospective, multicentre study evaluated patients with lymphangioleiomyomatosis (LAM) and pre-capillary pulmonary hypertension (PH) by right heart catheterisation. It was conducted in 20 females with a mean ± SD age of 49 ± 12 yrs and a mean ± SD time interval between LAM and PH diagnoses of 9.2 ± 9.8 yrs. All, except for one patient, were receiving supplemental oxygen. 6-min walking distance was mean ± SD 340 ± 84 m. Haemodynamic characteristics were: mean pulmonary artery pressure (PAP) 32 ± 6 mmHg, cardiac index 3.5 ± 1.1 L · min(-1) · m(-2) and pulmonary vascular resistance (PVR) 376 ± 184 dyn · s · cm(-5). Mean PAP was >35 mmHg in only 20% of cases. The forced expiratory volume in 1 s was 42 ± 25%, carbon monoxide transfer factor was 29 ± 13%, and arterial oxygen tension (P(a,O(2))) was 7.4 ± 1.3 kPa in room air. Mean PAP and PVR did not correlate with P(a,O(2)). In six patients who received oral pulmonary arterial hypertension (PAH) therapy, the PAP decreased from 33 ± 9 mmHg to 24 ± 10 mmHg and the PVR decreased from 481 ± 188 dyn · s · cm(-5) to 280 ± 79 dyn · s · cm(-5). The overall probability of survival was 94% at 2 yrs. Pre-capillary PH of mild haemodynamic severity may occur in patients with LAM, even with mild pulmonary function impairment. PAH therapy might improve the haemodynamics in PH associated with LAM.
    European Respiratory Journal 02/2012; 40(3):630-40. · 6.36 Impact Factor
  • G Simonneau, F Parent
    European Respiratory Journal 01/2012; 39(1):3-4. · 6.36 Impact Factor
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    ABSTRACT: Recent guidelines have proposed first-line combination therapy as a potential strategy for the treatment of functional class IV pulmonary arterial hypertension (PAH). We analyzed efficacy and safety of upfront epoprostenol and bosentan combination therapy in consecutive patients with idiopathic, heritable, or anorexigen-associated PAH and compared outcomes with matched controls treated by epoprostenol monotherapy. Data for 16 functional class III patients and 7 functional class IV patients were analyzed. Baseline 6-minute walk distance (6MWD) was 287 ± 133 meters, mean pulmonary artery pressure was 65 ± 12 mm Hg, cardiac index was 1.8 ± 0.3 L/min/m(2), and pulmonary vascular resistance (PVR) was 1493 ± 398 dynes/sec/cm(5). After 4 months, 6MWD and PVR significantly improved to 421 ± 100 meters and 784 ± 364 dynes/sec/cm(5), respectively. These improvements were maintained long-term (30 ± 19 months). At 1, 2, 3, and 4 years, overall survival estimates were 100%, 94%, 94%, and 74%, and transplant-free survival estimates were 96%, 85%, 77%, and 60%, respectively. Compared with matched controls started on epoprostenol monotherapy, there was a trend to an improvement in overall survival (p = 0.07). Initial combination therapy with epoprostenol and bosentan in patients with severe PAH is associated with improvements in important outcomes such as functional class, exercise capacity, and hemodynamics. This combination strategy might also favorably affect overall and transplant-free survival.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 12/2011; 31(2):150-8. · 3.54 Impact Factor
  • M Humbert, G Simonneau, L J Rubin
    European Respiratory Review 12/2011; 20(122):215-7.
  • O Sitbon, G Simonneau
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    ABSTRACT: Over the past decade, awareness among the medical profession of pulmonary arterial hypertension (PAH) being a treatable disease has increased. Despite this, approximately one-fifth of newly diagnosed patients are classified as being in the most severely compromised functional class (i.e. New York Health Association/World Health Organization functional class (NYHA/WHO FC) IV). The prognosis for patients in NYHA/WHO FC IV is poor, with 3-yr survival being around 40%, even with treatment. Poor prognosis coupled with severe functional impairment means it is vital that these patients receive optimal treatment. There are also subgroups of patients, who, although classified as NYHA/WHO FC III, may actually be severely haemodynamically compromised and at risk of rapid deterioration. Such subgroups include patients with PAH associated with systemic sclerosis or certain heritable mutations. These patients should be considered as being at the more severe end of the disease spectrum. In this article we will discuss the optimal management of patients with severe PAH. This includes newly emerging evidence from small-scale, open-label studies that use upfront combination therapy with intravenous epoprostenol plus oral PAH-specific drugs. We also review treatment strategies that may offer clinical benefits to patients with more severe PAH.
    European Respiratory Review 12/2011; 20(122):254-61.
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    ABSTRACT: Pulmonary veno-occlusive disease (PVOD), a rare form of pulmonary arterial hypertension (PAH), requires histological proof for definitive diagnosis; however, lung biopsy is not recommended in PAH. Recent conjoint European Respiratory Society/European Society of Cardiology guidelines suggest that nonmatched perfusion defects on ventilation/perfusion (V'/Q') lung scanning in PAH patients may suggest PVOD. The aim of our study was to evaluate V'/Q' lung scans in a large cohort of PVOD and idiopathic or heritable PAH patients. V'/Q' lung scans from 70 patients with idiopathic or heritable PAH and 56 patients with confirmed or highly probable PVOD were reviewed in a double-blind manner. The vast majority of V'/Q' lung scans were normal or without significant abnormalities in both groups. No differences in ventilation or perfusion lung scans were observed between PAH and PVOD patients (all p>0.05). Furthermore, no differences were observed between confirmed (n=31) or highly probable PVOD (n=25). Nonmatched perfusion defects were found in seven (10%) idiopathic PAH patients and four (7.1%) PVOD patients (p>0.05). Nonmatched perfusion defects were rarely seen in a large cohort of idiopathic or heritable PAH and PVOD patients. Future recommendations should be amended according to these results suggesting that V'/Q' lung scanning is not useful in discriminating PVOD from idiopathic PAH.
    European Respiratory Journal 11/2011; 40(1):75-83. · 6.36 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is characterised by remodelling of pulmonary arteries with enhanced vascular smooth muscle cell (VSMC) contraction, migration and proliferation. The authors investigated the presence of antibodies to human VSMCs in the serum of patients with systemic sclerosis with or without PAH and idiopathic PAH (iPAH). Antibodies to VSMCs were detected by immunofluorescence in sera from healthy controls and patients with scleroderma without PAH, scleroderma-associated PAH and iPAH. Serum IgG from these patients induced contraction of VSMCs in a collagen matrix in contrast with IgG from healthy controls. Several protein spots of interest and target antigens were identified by two-dimensional immunoblotting and MS, including stress-induced phosphoprotein 1 and α-enolase. Finally, antibodies to stress-induced phosphoprotein 1 were detected by ELISA in sera from 84%, 76% and 24% of patients with scleroderma without PAH, scleroderma-associated PAH and iPAH, respectively, compared with only 3% of healthy controls. The authors have identified IgG that binds to VSMCs in the serum of patients with scleroderma and iPAH. These antibodies may be pathogenic by modulating vascular contraction. The target antigens of these antibodies are stress-induced phosphoprotein 1 and α-enolase.
    Annals of the rheumatic diseases 11/2011; 71(4):596-605. · 8.11 Impact Factor

Publication Stats

24k Citations
3,650.74 Total Impact Points

Institutions

  • 2008–2014
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France
    • Armed Forces Biomedical Research Institute, France
      Bretigny, Île-de-France, France
  • 1991–2014
    • Université Paris-Sud 11
      • • Faculty of Pharmaceutical Sciences
      • • Service de Pneumologie
      • • Faculté de Médecine
      Orsay, Île-de-France, France
  • 2013
    • Mater Misericordiae University Hospital
      Dublin, Leinster, Ireland
    • University of Grenoble
      Grenoble, Rhône-Alpes, France
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2011–2013
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom
    • Institut Cochin
      Lutetia Parisorum, Île-de-France, France
  • 2006–2013
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 1988–2013
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
  • 2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • VU University Medical Center
      Amsterdamo, North Holland, Netherlands
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2002–2012
    • University of Bologna
      • Institute of Cardiology
      Bologna, Emilia-Romagna, Italy
    • Universitätsklinikum Jena
      Jena, Thuringia, Germany
  • 1990–2012
    • Centre Chirurgical Marie Lannelongue
      Plessis-Robinson, Île-de-France, France
  • 2007–2011
    • Columbia University
      • Department of Pediatrics
      New York City, NY, United States
  • 2001–2011
    • University of California, San Diego
      • • Department of Medicine
      • • Division of Pulmonary and Critical Care Medicine
      San Diego, CA, United States
  • 2010
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Internal Medicine
      Lille, Nord-Pas-de-Calais, France
  • 2009–2010
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
    • Université de Montréal
      Montréal, Quebec, Canada
    • Palmelit Francia
      Montferrier, Languedoc-Roussillon, France
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
    • Centre Hospitalier Universitaire de Brest
      Brest, Brittany, France
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2006–2010
    • Université René Descartes - Paris 5
      • • Faculté de Médecine
      • • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2002–2006
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2005
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Institut Universitaire de Cardiologie et de Pneumologie de Québec (Hôpital Laval)
      Québec, Quebec, Canada
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2004
    • Harbor-UCLA Medical Center
      Torrance, California, United States
    • CHRU de Strasbourg
      Strasburg, Alsace, France
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • Institute Mutualiste Montsouris
      Lutetia Parisorum, Île-de-France, France
    • The University of Sheffield
      • Medical School
      Sheffield, ENG, United Kingdom
  • 1997
    • Azienda Ospedaliera Niguarda Ca' Granda
      • Department of Pneumology
      Milano, Lombardy, Italy