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2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori, Marius Hoeper
European Respiratory Journal 2015 46: 903-975; DOI: 10.1183/13993003.01032-2015
Nazzareno Galiè
1Representing the European Society of Cardiology
Roles: (ESC Chairperson)
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  • For correspondence: nazzareno.galie@unibo.it marc.humbert@aphp.fr
Marc Humbert
2Representing the European Respiratory Society
Roles: (ERS Chairperson)
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  • For correspondence: nazzareno.galie@unibo.it marc.humbert@aphp.fr
Jean-Luc Vachiery
3Representing the International Society for Heart and Lung Transplantation
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Simon Gibbs
1Representing the European Society of Cardiology
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Irene Lang
1Representing the European Society of Cardiology
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Adam Torbicki
1Representing the European Society of Cardiology
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Gérald Simonneau
2Representing the European Respiratory Society
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Andrew Peacock
2Representing the European Respiratory Society
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Anton Vonk Noordegraaf
2Representing the European Respiratory Society
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Maurice Beghetti
4Representing the Association for European Paediatric and Congenital Cardiology
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Ardeschir Ghofrani
2Representing the European Respiratory Society
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Miguel Angel Gomez Sanchez
1Representing the European Society of Cardiology
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Georg Hansmann
4Representing the Association for European Paediatric and Congenital Cardiology
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Walter Klepetko
3Representing the International Society for Heart and Lung Transplantation
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Patrizio Lancellotti
1Representing the European Society of Cardiology
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Marco Matucci
5Representing the European League Against Rheumatism
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Theresa McDonagh
1Representing the European Society of Cardiology
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Luc A. Pierard
1Representing the European Society of Cardiology
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Pedro T. Trindade
1Representing the European Society of Cardiology
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Maurizio Zompatori
6Representing the European Society of Radiology. A full list of collaborators and document reviewers can be found in the Appendix
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Marius Hoeper
2Representing the European Respiratory Society
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  • FIGURE 1
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    FIGURE 1

    Diagnostic algorithm. CHD: congenital heart diseases; CT: computed tomography; CTD: connective tissue disease; CTEPH: chronic thromboembolic pulmonary hypertension; DLCO: carbon monoxide diffusing capacity; ECG: electrocardiogram; HIV: Human immunodeficiency virus; HRCT: high-resolution CT; mPAP: mean pulmonary arterial pressure; PA: pulmonary angiography; PAH: pulmonary arterial hypertension; PAWP: pulmonary artery wedge pressure; PFT: pulmonary function tests; PH: pulmonary hypertension; PVOD/PCH: pulmonary veno-occlusive disease or pulmonary capillary hemangiomathosis; PVR: pulmonary vascular resistance; RHC: right heart catheterisation; RV: right ventricular; V/Q: ventilation/perfusion. aCT pulmonary angiography alone may miss diagnosis of chronic thromboembolic pulmonary hypertension.

  • FIGURE 2
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    FIGURE 2

    Evidence based treatment algorithm for pulmonary arterial hypertension patients (for group 1 patients only; see description in the text). CCB: calcium channel blockers; DPAH: drug-induced PAH; HPAH: heritable PAH; IPAH: idiopathic PAH; i.v.: intravenous; PAH: pulmonary arterial hypertension; PCA: prostacyclin analogues; WHO-FC: World Health Organization functional class. aSome WHO-FC III patients may be considered high risk (see Table 13). bInitial combination with ambrisentan plus tadalafil has proven to be superior to initial monotherapy with ambrisentan or tadalafil in delaying clinical failure. cIntravenous epoprostenol should be prioritised as it has reduced the 3 months rate for mortality in high risk PAH patients also as monotherapy. dConsider also balloon atrial septostomy.

  • FIGURE 3
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    FIGURE 3

    Diagnostic algorithm for chronic thromboembolic pulmonary hypertension. CT: computed thomography; CTEPH: chronic thromboembolic pulmonary hypertension; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; V/Q: ventilation/perfusion. aCT pulmonary angiography alone may miss diagnosis of chronic thromboembolic pulmonary hypertension.

  • FIGURE 4
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    FIGURE 4

    Treatment algorithm for chronic thromboembolic pulmonary hypertension. BPA: balloon pulmonary angioplasty; CTEPH: chronic thromboembolic pulmonary hypertension; PH: pulmonary hypertension. aTechnically operable patients with non-acceptable risk/benefit ratio can be considered also for BPA. bIn some centers medical therapy and BPA are initiated concurrently.

Tables

  • Figures
  • Additional Files
  • TABLE 1

    Classes of recommendations

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  • TABLE 2

    Level of evidence

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  • TABLE 3

    Haemodynamic definitions of pulmonary hypertensiona

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    • CO: cardiac output; DPG: diastolic pressure gradient (diastolic PAP – mean PAWP); mPAP: mean pulmonary arterial pressure; PAWP: pulmonary arterial wedge pressure; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; WU: Wood units. aAll values measured at rest; see also section 8.0. bAccording to Table 4. cWood Units are preferred to dynes.s.cm−5.

  • TABLE 4

    Comprehensive clinical classification of pulmonary hypertension (updated from Simonneau et al. [5])

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    • BMPR2: bone morphogenetic protein receptor, type 2; EIF2AK4: eukaryotic translation initiation factor 2 alpha kinase 4; HIV: human immunodeficiency virus.

  • TABLE 5

    Important pathophysiological and clinical definitions

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  • TABLE 6

    Clinical classification of pulmonary arterial hypertension associated with congenital heart disease (updated from Simonneau et al. [5])

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    • PAH: pulmonary arterial hypertension; PVR: pulmonary vascular resistance. aWith surgery or intravascular percutaneous procedure. bThe size applies to adult patients. However, also in adults the simple diameter may be not sufficient for defining the haemodynamic relevance of the defect and also the pressure gradient, the shunt size and direction, and the pulmonary to systemic flows ratio should be considered (Web Table II).

  • TABLE 7

    Updated risk level of drugs and toxins known to induce pulmonary arterial hypertension

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    • aIncreased risk of persistent pulmonary hypertension in the newborns of mothers with intake of selective serotonin reuptake inhibitors; bAlkylating agents are possible causes of pulmonary veno-occlusive disease.

  • TABLE 8A

    Echocardiographic probability of pulmonary hypertension in symptomatic patients with a suspicion of pulmonary hypertension

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    • PH: pulmonary hypertension. aSee Table 8B.

  • TABLE 8B

    Echocardiographic signs suggesting pulmonary hypertension used to assess the probability of pulmonary hypertension in addition to tricuspid regurgitation velocity measurement in Table 8A

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    • PA: pulmonary artery. aEchocardiographic signs from at least two different categories (A/B/C) from the list should be present to alter the level of echocardiographic probability of pulmonary hypertension.

  • TABLE 9

    Diagnostic management suggested according to echocardiographic probability of pulmonary hypertension in patients with symptoms compatible with pulmonary hypertension, with or without risk factors for pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension

    Embedded Image
    • CTEPH: chronic thromboembolic pulmonary hypertension; Echo: echocardiographic; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; RHC: right heart catheterization. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dThese recommendations do not apply to patients with diffuse parenchymal lung disease or left heart disease. eDepending on the presence of risk factors for PH group 2, 3 or 5. Further investigation strategy may differ depending on whether risk factors/associated conditions suggest higher probability of PAH or CTEPH – see diagnostic algorithm.

  • TABLE 10

    Recommendations for right heart catheterization in pulmonary hypertension

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    • CTEPH: chronic thromboembolic pulmonary hypertension; LVEDP: left ventricular end-diastolic pressure; PAWP: pulmonary artery wedge pressure; PH: pulmonary hypertension; RHC: right heart catheterization. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 11

    Recommendations for vasoreactivity testing

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    • CCB: calcium channel blocker; HPAH: heritable pulmonary arterial hypertension; IPAH: idiopathic pulmonary arterial hypertension; PAP: pulmonary arterial pressure; PAH: pulmonary arterial hypertension. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 12

    Recommendations for diagnostic strategy

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    • CT: computed tomography; CTEPH: chronic thromboembolic pulmonary hypertension; DLCO: diffusing capacity of the lung for carbon monoxide; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 13

    Risk assessment in pulmonary arterial hypertension

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    • 6MWD: 6-minute walking distance; BNP: brain natriuretic peptide; CI: cardiac index; CMR: cardiac magnetic resonance; NT-proBNP: N-terminal pro-brain natriuretic peptide; pred.: predicted; RA: right atrium; RAP: right atrial pressure; SvO2: mixed venous oxygen saturation; VE/VCO2: ventilatory equivalents for carbon dioxide; VO2: oxygen consumption; WHO: World Health Organization. aMost of the proposed variables and cut-off values are based on expert opinion. They may provide prognostic information and may be used to guide therapeutic decisions, but application to individual patients must be done carefully. One must also note that most of these variables have been validated mostly for IPAH and the cut-off levels used above may not necessarily apply to other forms of PAH. Furthermore, the use of approved therapies and their influence on the variables should be considered in the evaluation of the risk. bOccasional syncope during brisk or heavy exercise, or occasional orthostatic syncope in an otherwise stable patient. cRepeated episodes of syncope, even with little or regular physical activity.

  • TABLE 14

    Suggested assessment and timing for the follow-up of patients with pulmonary arterial hypertension

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    • ALAT: alanine aminotransferase; ASAT: aspartate aminotransferase; BGA: blood gas analysis; BNP: brain natriuretic peptide; CPET: cardiopulmonary exercise testing; Echo: echocardiography; ECG: electrocardiogram; ERAs: endothelin receptor antagonists; FC: functional class; INR: international normalized ratio; lab: laboratory assessment; NT-proBNP: N-terminal pro-brain natriuretic peptide; RHC: right heart catheterization; TSH: thyroid stimulating hormone; 6MWT: 6-minute walking test. aIntervals to be adjusted according to patient needs. bBasic lab includes blood count, INR (in patients receiving vitamin K antagonists), serum creatinine, sodium, potassium, ASAT/ALAT (in patients receiving ERAs), bilirubin and BNP/NT-proBNP. cExtended lab includes TSH, troponin, uric acid, iron status (iron, ferritin, soluble transferrin receptor) and other variables according to individual patient needs. dFrom arterial or arterialized capillary blood; may be replaced by peripheral oxygen saturation in stable patients or if BGA is not available. eShould be considered. fSome centres perform RHCs at regular intervals during follow-up.

  • TABLE 15

    Recommendations for evaluation of the severity of pulmonary arterial hypertension and clinical response to therapy

    Embedded Image
    • PAH: pulmonary arterial hypertension. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 16

    Recommendations for general measures

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    • O2: oxygen; PAH: pulmonary arterial hypertension; WHO-FC: World Health Organization functional class. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 17

    Recommendations for supportive therapy

    Embedded Image
    • HPAH: heritable pulmonary arterial hypertension; IPAH: idiopathic pulmonary arterial hypertension; O2: oxygen; PAH: pulmonary arterial hypertension; RV: right ventricular. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dSee also recommendations for PAH associated with congenital cardiac shunts.

  • TABLE 18

    Recommendations for calcium channel blocker therapy in patients who respond to the acute vasoreactivity test

    Embedded Image
    • CCB: calcium channel blocker; DPAH: drug-induced PAH; HPAH: heritable PAH; IPAH: idiopathic PAH; PAH: pulmonary arterial hypertension; RHC: right heart catheterization; RV: right ventricular; WHO-FC: World Health Organization functional class.

  • TABLE 19

    Recommendations for efficacy of drug monotherapy for pulmonary arterial hypertension (group 1) according to World Health Organization functional class. The sequence is by pharmacological group, by rating and by alphabetical order

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    • EMA: European Medicines Agency; PAH: pulmonary arterial hypertension; RCT: randomized controlled trial; WHO-FC: World Health Organization functional class. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dOnly in responders to acute vasoreactivity tests = class I, for idiopathic PAH, heritable PAH and PAH due to drugs; class IIa, for conditions associated with PAH. eTime to clinical worsening as primary endpoint in RCTs or drugs with demonstrated reduction in all-cause mortality. fIn patients not tolerating the subcutaneous form. gThis drug is not approved by the EMA at the time of publication of these guidelines.

  • TABLE 20

    Recommendations for efficacy of initial drug combination therapy for pulmonary arterial hypertension (group 1) according to World Health Organization functional class. Sequence is by rating

    Embedded Image
    • ERA: endothelin receptor antagonist; i.v.: intravenous; PDE-5i: phosphodiesterase type 5 inhibitor; RCT: randomized controlled trial; s.c.: subcutaneous; WHO-FC: World Health Organization functional class. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dTime to clinical failure as primary endpoint in RCTs or drugs with demonstrated reduction in all-cause mortality (prospectively defined).

  • TABLE 21

    Recommendations for efficacy of sequential drug combination therapy for pulmonary arterial hypertension (group 1) according to World Health Organization functional class. Sequence is by rating and by alphabetical order

    Embedded Image
    • EMA: European Medicines Agency; ERA: endothelin receptor antagonist; PAH: pulmonary arterial hypertension; PDE-5i: phosphodiesterase type 5 inhibitor; RCT: randomized controlled trial; WHO-FC: World Health Organization functional class. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dTime to clinical worsening as primary endpoint in RCTs or drugs with demonstrated reduction in all-cause mortality (prospectively defined). eThis drug was not approved by the EMA at the time of publication of these guidelines.

  • TABLE 22

    Recommendations for efficacy of intensive care unit management, balloon atrial septostomy and lung transplantation for pulmonary arterial hypertension (group 1) according to World Health Organization functional class

    Embedded Image
    • BAS: Balloon atrial septostomy; ICU: intensive care unit; PH: pulmonary hypertension; WHO-FC: World Health Organization functional class. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 23

    Recommendations for paediatric pulmonary hypertension

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    • PAH: pulmonary arterial hypertension; PH: pulmonary hypertension. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dSee Ivy D et al. J Am Coll Cardiol 2013; 62(25): D117–D126.

  • TABLE 24

    Recommendations for correction of congenital heart disease with prevalent systemic-to-pulmonary shunts

    Embedded Image
    • PVR: pulmonary vascular resistance; PVRi: pulmonary vascular resistance index; WU: Wood units. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dWith surgery or intravascular percutaneous procedure.

  • TABLE 25

    Recommendations for pulmonary arterial hypertension associated with congenital heart disease

    Embedded Image
    • CCBs: calcium channel blockers; ERAs: endothelin receptor antagonists; O2: oxygen; PA: pulmonary artery; PDE-5is: phosphodiesterase type 5 inhibitors; WHO-FC: World Health Organization functional class. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 26

    Recommendations for pulmonary arterial hypertension associated with connective tissue disease

    Embedded Image
    • CTD: connective tissue disease; DLCO: diffusing capacity of the lung for carbon monoxide; IPAH: idiopathic pulmonary arterial hypertension; PAH: pulmonary arterial hypertension; RHC: right heart catheterization; SSc: systemic sclerosis. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 27

    Recommendations for pulmonary arterial hypertension associated with portal hypertension

    Embedded Image
    • PAH: pulmonary arterial hypertension; PH: pulmonary hypertension. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 28

    Recommendations for pulmonary arterial hypertension associated with human immunodeficiency virus infection

    Embedded Image
    • HIV: human immunodeficiency virus; IPAH: idiopathic pulmonary arterial hypertension; PAH: pulmonary arterial hypertension. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 29

    Recommendations for pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis

    Embedded Image
    • PAH: pulmonary arterial hypertension; PCH: pulmonary capillary haemangiomatosis; PH: pulmonary hypertension; PVOD: pulmonary veno-occlusive disease. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 30

    Examples of key factors suggestive of group 2 pulmonary hypertension

    Embedded Image
    • AF: atrial flutter; Afib: atrial fibrillation; ECG: electrocardiogram; IAS: inter-atrial septum; LA: left atrium; LAH: left atrial hypertrophy/dilatation; LBBB: left bundle branch block; LV: left ventricle; LVH: left ventricular hypertrophy; PA: pulmonary artery; RV: right ventricle.

  • TABLE 31

    Management of pulmonary hypertension in left heart disease

    Embedded Image
    • COPD: chronic obstructive pulmonary disease; CTEPH: chronic thromboembolic pulmonary hypertension; DPG: diastolic pressure gradient; LHD: left heart disease; LV: left ventricular; PE: pulmonary embolism; PH: pulmonary hypertension; PVR: pulmonary vascular resistance. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 32

    Haemodynamic classification of pulmonary hypertension due to lung disease [9]

    Embedded Image
    • CI: cardiac index; COPD: chronic obstructive pulmonary disease; CPFE: combined pulmonary fibrosis and emphysema; IPF: idiopathic pulmonary fibrosis; PAP: pulmonary artery pressure; PAPm: mean pulmonary arterial pressure; PH: pulmonary hypertension.

  • TABLE 33

    Recommendations for pulmonary hypertension due to lung diseases

    Embedded Image
    • CTEPH: chronic thromboembolic pulmonary hypertension; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; RHC: right heart catheterization. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations. dThis recommendation does not apply to patients with end-stage lung disease who are not considered candidates for lung transplantation.

  • TABLE 34

    Recommendations for chronic thromboembolic pulmonary hypertension

    Embedded Image
    • BPA: balloon pulmonary angioplasty; CTEPH: chronic thromboembolic pulmonary hypertension; PAH: pulmonary arterial hypertension; PE: pulmonary embolism; PEA: pulmonary endarterectomy. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • TABLE 35

    Recommendations for pulmonary hypertension referral centres

    Embedded Image
    • CTD: connective tissue disease; CTEPH: chronic thromboembolic pulmonary hypertension; DPAH: drug-induced pulmonary arterial hypertension; HPAH: heritable pulmonary arterial hypertension; IPAH: idiopathic pulmonary arterial hypertension; PAH: pulmonary arterial hypertension; PEA: pulmonary endarterectomy. aClass of recommendation. bLevel of evidence. cReference(s) supporting recommendations.

  • 13. To do and not to do messages from the guidelines

    Embedded Image

Additional Files

  • Figures
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  • Disclosures

    • N. Galiè
    • M. Humbert
    • J-L. Vachiery
    • S. Gibbs
    • I. Lang
    • A. Torbicki
    • G. Simonneau
    • A. Peacock
    • A. Vonk Noordegraaf
    • M. Beghetti
    • A. Ghofrani
    • M. Hoeper
  • Supplementary material

    Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

    Files in this Data Supplement:

    • 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension - web addenda
  • ERJ Podcast

    Duration: 25:19 min

    Presenter: Anh Tuan Dinh-Xuan, Deputy Chief Editor, ERJ

    Interviewee: Marc Humbert, Chief Editor, ERJ

    Articles discussed:

    • Lau EMT, Tamura Y, McGoon MD, et al. The 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: a practical chronicle of progress. Eur Respir J 2015; 46: 879-882. Full Text
    • Galiè N, Humber M, Vachiery J-L, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2015; 46: 903-975. Full Text

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2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori, Marius Hoeper
European Respiratory Journal Oct 2015, 46 (4) 903-975; DOI: 10.1183/13993003.01032-2015

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2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori, Marius Hoeper
European Respiratory Journal Oct 2015, 46 (4) 903-975; DOI: 10.1183/13993003.01032-2015
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  • Article
    • Abstract
    • Abstract
    • Table of Contents
    • Abbreviations and acronyms
    • 1. Preamble
    • 2. Introduction
    • 3. Definitions and classifications
    • 4. Epidemiology and genetics of pulmonary hypertension
    • 5. Pulmonary hypertension diagnosis
    • 6. Pulmonary arterial hypertension (group 1)
    • 7. Specific pulmonary (arterial) hypertension subsets
    • 8. Pulmonary hypertension due to left heart disease (group 2)
    • 9. Pulmonary hypertension due to lung diseases and/or hypoxia (group 3)
    • 10. Chronic thromboembolic pulmonary hypertension (group 4)
    • 11. Pulmonary hypertension with unclear and/or multifactorial mechanisms (group 5)
    • 12. Definition of a pulmonary hypertension referral centre
    • 14. Appendix
    • Footnotes
    • 16.  References
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