2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)

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

doi:10.1183/13993003.01032-2015

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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.
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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.
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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.
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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
TABLE 2
Level of evidence
TABLE 3
Haemodynamic definitions of pulmonary hypertension^a
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])
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
TABLE 6
Clinical classification of pulmonary arterial hypertension associated with congenital heart disease (updated from Simonneau et al. [5])
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
^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
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
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
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
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
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
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
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
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
PAH: pulmonary arterial hypertension. ^aClass of recommendation. ^bLevel of evidence. ^cReference(s) supporting recommendations.
TABLE 16
Recommendations for general measures
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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]
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
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
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
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

Additional Files

Figures
Tables

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

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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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