BOX 2

Selected revised recommendations (R) and new recommendations (N)

New or revisedRecommendation in 2015 versionClassaRecommendation in 2022 versionClassa
Right heart catheterization and vasoreactivity testing – Recommendation Table 1
NIt is recommended that RHC comprises a complete set of haemodynamics and is performed following standardized protocolsI
RAdenosine should be considered for performing vasoreactivity testing as an alternative
Inhaled iloprost may be considered for performing vasoreactivity testing as an alternative
IIaInhaled nitric oxide, inhaled iloprost, or i.v. epoprostenol are recommended for performing vasoreactivity testingI
Diagnostic strategy – Recommendation Table 2
NIt is recommended to assign an echocardiographic probability of PH, based on an abnormal TRV and the presence of other echocardiographic signs suggestive of PH (see Table 10)I
NIt is recommended to maintain the current threshold for TRV (>2.8 m/s) for echocardiographic probability of PH according to the updated haemodynamic definitionI
NBased on the probability of PH by echocardiography, further testing should be considered in the clinical context (i.e. symptoms and risk factors or associated conditions for PAH/CTEPH)IIa
NIn symptomatic patients with intermediate echocardiographic probability of PH, CPET may be considered to further determine the likelihood of PHIIb
Screening and improved detection of pulmonary arterial hypertension and chronic thrombo-embolic pulmonary hypertension – Recommendation Table 3
NIn patients with SSc, an annual evaluation of the risk of having PAH is recommendedI
RResting echocardiography is recommended as a screening test in asymptomatic patients with SSc, followed by annual screening with echocardiography, DLCO, and biomarkersIIn adult patients with SSc of >3 years’ disease duration, an FVC ≥40%, and a DLCO <60%, the DETECT algorithm is recommended to identify asymptomatic patients with PAHI
NIn patients with SSc, where breathlessness remains unexplained following non-invasive assessment, RHC is recommended to exclude PAHI
NAssessing the risk of having PAH, based on an evaluation of breathlessness, in combination with echocardiogram or PFTs and BNP/NT-proBNP, should be considered in patients with SScIIa
NPolicies to evaluate the risk of having PAH should be considered in hospitals managing patients with SScIIa
RRHC is recommended in all cases of suspected PAH associated with CTDIIn symptomatic patients with SSc, exercise echocardiography or CPET, or CMR may be considered to aid decisions to perform RHCIIb
NIn patients with CTD with overlap features of SSc, an annual evaluation of the risk of PAH may be consideredIIb
RIn PE survivors with exercise dyspnoea, CTEPH should be consideredIIaIn patients with persistent or new-onset dyspnoea or exercise limitation following PE, further diagnostic evaluation to assess for CTEPH/CTEPD is recommendedI
NFor symptomatic patients with mismatched perfusion lung defects beyond 3 months of anticoagulation for acute PE, referral to a PH/CTEPH centre is recommended after considering the results of echocardiography, BNP/NT-proBNP, and/or CPETI
NCounselling regarding the risk of PAH, and annual screening is recommended in individuals who test positive for PAH-causing mutations and in first-degree relatives of patients with HPAHI
NIn patients referred for liver transplantation, echocardiography is recommended as a screening test for PHI
NFurther tests (echocardiography, BNP/NT-proBNP, PFTs, and/or CPET) should be considered in symptomatic patients with CTD, portal hypertension, or HIV to screen for PAHIIa
Evaluating the disease severity and risk of death in patients with pulmonary arterial hypertension – Recommendation Table 4
NFor risk stratification at the time of diagnosis, the use of a three-strata model (low, intermediate, and high risk) is recommended, taking into account all available data including haemodynamicsI
NFor risk stratification during follow-up, the use of a four-strata model (low, intermediate–low, intermediate–high, and high risk) based on WHO-FC, 6MWD, and BNP/NT-proBNP is recommended, with additional variables taken into account as necessaryI
RAchievement/maintenance of an intermediate-risk profile should be considered an inadequate treatment response for most patients with PAHIIaIn some PAH aetiologies and in patients with comorbidities, optimization of therapy should be considered on an individual basis while acknowledging that a low-risk profile is not always achievableIIa
General measures and special circumstances – Recommendation Table 5
RSupervised exercise training should be considered in physically deconditioned PAH patients under medical therapyIIaSupervised exercise training is recommended in patients with PAH under medical therapyI
RImmunization of PAH patients against influenza and pneumococcal infection is recommendedIImmunization of patients with PAH against SARS-CoV-2, influenza, and Streptococcus pneumoniae is recommendedI
RCorrection of anaemia and/or iron status may be considered in PAH patientsIIbIn the presence of iron-deficiency anaemia, correction of iron status is recommended in patients with PAHI
NIn the absence of anaemia, iron repletion may be considered in patients with PAH with iron deficiencyIIb
ROral anticoagulant treatment may be considered in patients with IPAH, HPAH, and PAH due to use of anorexigensIIbAnticoagulation is not generally recommended in patients with PAH but may be considered on an individual basisIIb
RThe use of angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists, beta-blockers, and ivabradine is not recommended in patients with PAH unless required by comorbidities (i.e. high blood pressure, coronary artery disease, or left HF)IIIThe use of ACEis, ARBs, ARNIs, SGLT-2is, beta-blockers, or ivabradine is not recommended in patients with PAH unless required by comorbidities (i.e. high blood pressure, coronary artery disease, left HF, or arrhythmias)III
RIn-flight O2 administration should be considered for patients in WHO-FC III and IV and those with arterial blood O2 pressure consistently <8 kPa (60 mmHg)IIaIn-flight oxygen administration is recommended for patients using oxygen or whose arterial blood oxygen pressure is <8 kPa (60 mmHg) at sea levelI
RIn elective surgery, epidural rather than general anaesthesia should be preferred whenever possibleIIaFor interventions requiring anaesthesia, multidisciplinary consultation at a PH centre to assess risk and benefit should be consideredIIa
Women of childbearing potential – Recommendation Table 6
RIt is recommended that PAH patients avoid pregnancyIIt is recommended that women of childbearing potential with PAH are counselled at the time of diagnosis about the risks and uncertainties associated with becoming pregnant; this should include advice against becoming pregnant, and referral for psychological support where neededI
NIt is recommended to provide women of childbearing potential with PAH with clear contraceptive advice, considering the individual needs of the woman but recognizing that the implications of contraceptive failure are significant in PAHI
NIt is recommended that women with PAH who consider pregnancy or who become pregnant receive prompt counselling in an experienced PH centre to facilitate genetic counselling and shared decision-making, and to provide psychological support to the patients and their families where neededI
NFor women with PAH having termination of pregnancy, it is recommended that this be performed in PH centres, with psychological support provided to the patient and their familyI
NFor women with PAH who desire to have children, where available, adoption and surrogacy with pre-conception genetic counselling may be consideredIIb
NAs teratogenic potential has been reported in preclinical models for endothelin receptor antagonists and riociguat, these drugs are not recommended during pregnancyIII
Treatment of vasoreactive patients with idiopathic, heritable, or drug-associated pulmonary arterial hypertension – Recommendation Table 7
RContinuation of high doses of CCBs is recommended in patients with IPAH, HPAH, and DPAH in WHO-FC I or II with marked haemodynamic improvement (near normalization)IContinuing high doses of CCBs is recommended in patients with IPAH, HPAH, or DPAH in WHO-FC I or II with marked haemodynamic improvement (mPAP <30 mmHg and PVR <4 WU)I
NIn patients with a positive vasoreactivity test but insufficient long-term response to CCBs who require additional PAH therapy, continuation of CCB therapy should be consideredIIa
Treatment of non-vasoreactive patients with idiopathic, heritable, or drug-associated pulmonary arterial hypertension who present without cardiopulmonary comorbiditiesb – Recommendation Table 8
NIn patients with IPAH/HPAH/DPAH who present at high risk of death, initial combination therapy with a PDE5i, an ERA, and i.v./s.c. prostacyclin analogues should be consideredcIIa
NIn patients with IPAH/HPAH/DPAH who present at intermediate–low risk of death while receiving ERA/PDE5i therapy, addition of selexipag should be consideredIIa
NIn patients with IPAH/HPAH/DPAH who present at intermediate–high or high risk of death while receiving ERA/PDE5i therapy, the addition of i.v./s.c. prostacyclin analogues and referral for lung transplantation evaluation should be consideredIIa
NIn patients with IPAH/HPAH/DPAH who present at intermediate–low risk of death while receiving ERA/PDE5i therapy, switching from PDE5i to riociguat may be consideredIIb
Initial oral drug combination therapy for patients with idiopathic, heritable, or drug-associated pulmonary arterial hypertensionwithout cardiopulmonary comorbidities – Recommendation Table 9
RAmbrisentan + tadalafilIInitial combination therapy with ambrisentan and tadalafil is recommendedI
NInitial combination therapy with macitentan and tadalafil is recommendedI
ROther ERA + PDE-5iIIaInitial combination therapy with other ERAs and PDE5is should be consideredIIa
NInitial combination therapy with macitentan, tadalafil, and selexipag is not recommendedIII
Sequential drug combination therapy for patients with idiopathic, heritable, or drug-associated pulmonary arterial hypertension – Recommendation Table 10
NIt is recommended to base treatment escalations on risk assessment and general treatment strategies (see treatment algorithm)I
RMacitentan added to sildenafilIAddition of macitentan to PDE5is or oral/inhaled prostacyclin analogues is recommended to reduce the risk of morbidity/mortality eventsI
NAddition of oral treprostinil to ERA or PDE5i/riociguat monotherapy is recommended to reduce the risk of morbidity/mortality eventsI
RBosentan added to sildenafilIIbAddition of bosentan to sildenafil is not recommended to reduce the risk of morbidity/mortality eventsIII
RRiociguat added to bosentanIAddition of riociguat to bosentan should be considered to improve exercise capacityIIa
Treatment of non-vasoreactive patients with idiopathic, heritable, or drug-associated pulmonary arterial hypertensionwho present with cardiopulmonary comorbiditiesb – Recommendation Table 11
NIn patients with IPAH/HPAH/DPAH and cardiopulmonary comorbidities, initial monotherapy with a PDE5i or an ERA should be consideredIIa
NIn patients with IPAH/HPAH/DPAH with cardiopulmonary comorbidities who present at intermediate or high risk of death while receiving PDE5i or ERA monotherapy, additional PAH medications may be considered on an individual basisIIb
Efficacy of intensive care management for pulmonary arterial hypertension – Recommendation Table 12
NWhen managing patients with right HF in the ICU, it is recommended to involve physicians with expertise, treat causative factors, and use supportive measures including inotropes and vasopressors, fluid management, and PAH drugs as appropriateI
NMechanical circulatory support may be an option for selected patients as a bridge to transplantation or to recovery, and interhospital transfer should be considered if such resources are not available on siteIIa
Lung transplantation – Recommendation Table 13
RLung transplantation is recommended soon after inadequate clinical response on maximal medical therapyIIt is recommended that potentially eligible candidates are referred for LTx evaluation when they have an inadequate response to oral combination therapy, indicated by an intermediate–high or high risk or by a REVEAL risk score >7I
NIt is recommended to list patients for LTx who present with a high risk of death or with a REVEAL risk score ≥10 despite receiving optimized medical therapy including s.c. or i.v. prostacyclin analoguesI
Pulmonary arterial hypertensionassociated with drugs or toxins – Recommendation Table 14
NIt is recommended to make a diagnosis of drug- or toxin-associated PAH in patients who had relevant exposure and in whom other causes of PH have been excludedI
NIn patients with suspected drug- or toxin-associated PAH, it is recommended to discontinue the causative agent immediately whenever possibleI
NImmediate PAH therapy should be considered in patients who present with intermediate/high-risk PAH at diagnosisIIa
NPatients with low-risk PAH should be re-evaluated 3–4 months after discontinuing the suspected drug or toxin, and PAH therapy may be considered when the haemodynamics have not normalizedIIb
Pulmonary arterial hypertension associated with connective tissue disease – Recommendation Table 15
NIn patients with PAH associated with CTD, treatment of the underlying condition according to current guidelines is recommendedI
Pulmonary arterial hypertension associated with human immunodeficiency virus infection – Recommendation Table 16
NIn patients with PAH associated with HIV infection, antiretroviral treatment according to current guidelines is recommendedI
NIn patients with PAH associated with HIV infection, initial monotherapy should be considered, followed by sequential combination if necessary, taking into consideration comorbidities and drug–drug interactionsIIa
PAH associated with portal hypertension – Recommendation Table 17
REchocardiographic assessment for signs of PH is recommended in symptomatic patients with liver disease or portal hypertension and in all candidates for liver transplantationIEchocardiography is recommended in patients with liver disease or portal hypertension with signs or symptoms suggestive of PH, and as a screening tool in patients evaluated for liver transplantation or transjugular portosystemic shuntI
RIt is recommended that the treatment algorithm for patients with other forms of PAH should be applied to patients with PAH associated with portal hypertension, taking into account the severity of liver diseaseIIn patients with PAH associated with portal hypertension, initial monotherapy should be considered, followed by sequential combination if necessary, taking into consideration the underlying liver disease and indication for liver transplantationIIa
RLiver transplantation may be considered in selected patients responding well to PAH therapyIIbLiver transplantation should be considered on an individual basis in patients with PAH associated with portal hypertension, as long as PVR is normal or near normal with PAH therapyIIa
NDrugs approved for PAH are not recommended for patients with portal hypertension and unclassified PH (i.e. elevated mPAP, high CO, and a normal PVR)III
Shunt closure in patients with pulmonary-systemic flow ratio >1.5:1 based on calculated pulmonary vascular resistance – Recommendation Table 18
NIn patients with ASD, VSD, or PDA and a PVR <3 WU, shunt closure is recommendedI
NIn patients with ASD, VSD, or PDA and a PVR of 3–5 WU, shunt closure should be consideredIIa
NIn patients with ASD and a PVR >5 WU that declines to <5 WU with PAH treatment, shunt closure may be consideredIIb
NIn patients with VSD or PDA and a PVR >5 WU, shunt closure may be considered after careful evaluation in specialized centresIIb
NIn patients with ASD and a PVR >5 WU despite PAH treatment, shunt closure is not recommendedIII
Pulmonary arterial hypertension associated with adult congenital heart disease – Recommendation Table 19
NRisk assessment is recommended for patients with persistent PAH after defect closureI
NRisk assessment should be considered in patients with Eisenmenger syndromeIIa
RBosentan is recommended in WHO-FC III patients with Eisenmenger syndromeIBosentan is recommended in symptomatic patients with Eisenmenger syndrome to improve exercise capacityI
RThe use of supplemental iron treatment may be considered in patients with low ferritin plasma levelsIIbSupplemental iron treatment should be considered in patients with iron deficiencyIIa
RCombination drug therapy may be considered in patients with Eisenmenger syndromeIIbIn patients with PAH after corrected adult CHD, initial oral combination therapy with drugs approved for PAH should be considered for patients at low and intermediate risk, while initial combination therapy including i.v./s.c. prostacyclin analogues should be considered for patients at high riskIIa
RCombination drug therapy may be considered in patients with Eisenmenger syndromeIIbIn patients with adult CHD, including Eisenmenger syndrome, sequential combination therapy should be considered if patients do not meet treatment goalsIIa
NIn women with Eisenmenger syndrome, pregnancy is not recommendedIII
RIf symptoms of hyperviscosity are present, phlebotomy with isovolumic replacement should be considered, usually when the haematocrit is >65%IIaIn patients with Eisenmenger syndrome, routine phlebotomy to lower elevated haematocrit is not recommendedIII
Pulmonary arterial hypertension with signs of venous/capillary involvement – Recommendation Table 20
RA combination of clinical findings, physical examination, bronchoscopy, and radiological findings is recommended to diagnose PVOD/PCHIA combination of clinical and radiological findings, ABG, PFTs, and genetic testing is recommended to diagnose PAH with signs of venous and/or capillary involvement (PVOD/PCH)I
NIn patients with PVOD/PCH, the use of drugs approved for PAH may be considered with careful monitoring of clinical symptoms and gas exchangeIIb
NLung biopsy is not recommended to confirm a diagnosis of PVOD/PCHIII
Paediatric pulmonary hypertension – Recommendation Table 21
NIt is recommended to perform the diagnostic work-up, including RHC and acute vasodilator testing, and treat children with PH at centres with specific expertise in paediatric PHI
RA PH diagnostic algorithm work-up is recommended for diagnosis and definition of the specific aetiology group in paediatric PH patientsIIn children with PH, a comprehensive work-up for confirming diagnosis and specific aetiology is recommended (similar to that in adults, but adapted for age)I
NFor confirming PH diagnosis, RHC is recommended, preferably before initiating any PAH therapyI
NIn children with IPAH/HPAH, acute vasoreactivity testing is recommended to detect those who may benefit from calcium channel blocker therapyI
NIt is recommended to define a positive response to acute vasoreactivity testing in children similar to adults by a reduction of mPAP ≥10 mmHg to reach an absolute value of mPAP ≤40 mmHg, with an increased or unchanged COI
RA PAH-specific therapeutic algorithm is recommended in paediatric PH patientsIIn children with PAH, a therapeutic strategy based on risk stratification and treatment response is recommended, extrapolated from that in adults but adapted for ageI
RSpecific paediatric determinants of risk should be consideredIIaIt is recommended to monitor the treatment response in children with PAH by serially assessing a panel of data derived from clinical assessment, echocardiographic evaluation, biochemical markers, and exercise tolerance testsI
NAchieving and maintaining a low-risk profile should be considered as an adequate treatment response for children with PAHIIa
NIt is recommended to screen infants with bronchopulmonary dysplasia for PHI
NIn infants with (or at risk of) bronchopulmonary dysplasia and PH, treating lung disease, including hypoxia, aspiration, and structural airway disease, and optimizing respiratory support is recommended before initiating PAH therapyI
NIn neonates and infants, a diagnostic and therapeutic approach to PH distinct from that in older children and adults should be considered, given the frequent association with developmental vascular and parenchymal lung diseaseIIa
Pulmonary hypertension associated with left heart disease – Recommendation Table 22
NRHC is recommended for suspected PH in patients with LHD, if it aids management decisionsI
NRHC is recommended in patients with severe tricuspid regurgitation with or without LHD prior to surgical or interventional valve repairI
RPatients with PH-LHD and a severe pre-capillary component as indicated by a high DPG and/or high PVR should be referred to an expert PH centre for a complete diagnostic work-up and an individual treatment decisionIIaFor patients with LHD and suspected PH with features of a severe pre-capillary component and/or markers of RV dysfunction, referral to a PH centre for a complete diagnostic work-up is recommendedI
NIn patients with LHD and CpcPH with a severe pre-capillary component (e.g. PVR >5 WU), an individualized approach to treatment is recommendedI
NWhen patients with PH and multiple risk factors for LHD, who have a normal PAWP at rest but an abnormal response to exercise or fluid challenge, are treated with PAH drugs, close monitoring is recommendedI
NIn patients with PH at RHC, a borderline PAWP (13–15 mmHg) and features of HFpEF, additional testing with exercise or fluid challenge may be considered to uncover post-capillary PHIIb
Pulmonary hypertension associated with lung disease and/or hypoxia – Recommendation Table 23
REchocardiography is recommended for the non-invasive diagnostic assessment of suspected PH in patients with lung diseaseIIf PH is suspected in patients with lung disease, it is recommended that echocardiographyd be performed and results interpreted in conjunction with ABG, PFTs including DLCO, and CT imagingI
ROptimal treatment of the underlying lung disease, including long-term O2 therapy in patients with chronic hypoxaemia, is recommended in patients with PH due to lung diseasesIIn patients with lung disease and suspected PH, it is recommended to optimize treatment of the underlying lung disease and, where indicated, hypoxaemia, sleep-disordered breathing, and/or alveolar hypoventilationI
RReferral to an expert centre is recommended in patients with echocardiographic signs of severe PH and/or severe right ventricular dysfunctionIIn patients with lung disease and suspected severe PH, or where there is uncertainty regarding the treatment of PH, referral to a PH centre is recommendedeI
NIn patients with lung disease and severe PH, an individualized approach to treatment is recommendedI
NIt is recommended to refer eligible patients with lung disease and PH for LTx evaluationI
RRHC is not recommended for suspected PH in patients with lung disease, unless therapeutic consequences are to be expected (e.g. LTx, alternative diagnoses such as PAH or CTEPH, potential enrolment in a clinical trial)IIIIn patients with lung disease and suspected PH, RHC is recommended if the results are expected to aid management decisionsI
NInhaled treprostinil may be considered in patients with PH associated with ILDIIb
NThe use of ambrisentan is not recommended in patients with PH associated with IPFIII
NThe use of riociguat is not recommended in patients with PH associated with IIPIII
Chronic thrombo-embolic pulmonary hypertension and chronic thrombo-embolic pulmonary disease without pulmonary hypertension – Recommendation Table 24
RLifelong anticoagulation is recommended in all patients with CTEPHILifelong therapeutic doses of anticoagulation are recommended in all patients with CTEPHI
NAntiphospholipid syndrome testing is recommended in patients with CTEPHI
NIn patients with CTEPH and antiphospholipid syndrome, anticoagulation with VKAs is recommendedI
RIt is recommended that all patients with CTEPH receive assessment of operability and decisions regarding other treatment strategies made by a multidisciplinary team of expertsIIt is recommended that all patients with CTEPH are reviewed by a CTEPH team for the assessment of multimodality managementI
RSurgical PEA in deep hypothermia circulatory arrest is recommended for patients with CTEPHIPEA is recommended as the treatment of choice for patients with CTEPH and fibrotic obstructions within pulmonary arteries accessible by surgeryI
RInterventional BPA may be considered in patients who are technically inoperable or carry an unfavourable risk:benefit ratio for PEAIIbBPA is recommended in patients who are technically inoperable or have residual PH after PEA and distal obstructions amenable to BPAI
RRiociguat is recommended in symptomatic patients who have been classified as having persistent/recurrent CTEPH after surgical treatment or inoperable CTEPH by a CTEPH team including at least one experienced PEA surgeonIRiociguat is recommended for symptomatic patients with inoperable CTEPH or persistent/recurrent PH after PEAI
NLong-term follow-up is recommended after PEA and BPA, as well as for patients with CTEPH established on medical therapyI
NA multi-modality approach should be considered for patients with persistent PH after PEA and for patients with inoperable CTEPHIIa
NIn patients with CTEPD without PH, long-term anticoagulant therapy should be considered on individual basisfIIa
NPEA or BPA should be considered in selected symptomatic patients with CTEPD without PHIIa
NTreprostinil s.c. may be considered in patients in WHO-FC III–IV who have inoperable CTEPH or persistent/recurrent PH after PEAIIb
ROff-label use of drugs approved for PAH may be considered in symptomatic patients who have been classified as having inoperable CTEPH by a CTEPH team including at least one experienced PEA surgeonIIbOff-label use of drugs approved for PAH may be considered in symptomatic patients who have inoperable CTEPHIIb
NIn patients with inoperable CTEPH, a combination of sGC stimulator/PDE5i, ERA, or parenteral prostacyclin analogues may be consideredIIb
NBPA may be considered for technically operable patients with a high proportion of distal disease and an unfavourable risk:benefit ratio for PEAIIb
Pulmonary hypertension centres – Recommendation Table 25
NIt is recommended that PH centres maintain a patient registryI
NIt is recommended that PH centres collaborate with patient associationsI
NAccreditation of the PH centres should be considered (e.g. https://ec.europa.eu/health/ern/assessment_en)IIa
RIt should be considered that a referral centre follow at least 50 patients with PAH or CTEPH and should receive at least two new referrals per month with documented PAH or CTEPHIIaPH centres should follow-up a sufficient number of patients to maintain expertise (at least 50 patients with PAH or CTEPH and at least two new referrals per month with documented PAH or CTEPH), and consider establishing collaborations with high-volume centresIIa

6MWD, 6-minute walking distance; ABG, arterial blood gas analysis; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor–neprilysin inhibitor; ASD, atrial septal defect; BNP, brain natriuretic peptide; BPA, balloon pulmonary angioplasty; CCB, calcium channel blocker; CHD, congenital heart disease; CI, cardiac index; CMR, cardiac magnetic resonance; CO, cardiac output; CpcPH, combined post- and pre-capillary pulmonary hypertension; CPET, cardiopulmonary exercise testing; CT, computed tomography; CTD, connective tissue disease; CTEPD, chronic thrombo-embolic pulmonary disease; CTEPH, chronic thrombo-embolic pulmonary hypertension; DLCO, lung diffusion capacity for carbon monoxide; DPAH, drug-associated pulmonary arterial hypertension; DPG, diastolic pressure gradient; ERA, endothelin receptor antagonist; FVC, forced vital capacity; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HIV, human immunodeficiency virus; HPAH, heritable pulmonary arterial hypertension; ICU, intensive care unit; IIP, idiopathic interstitial pneumonia; ILD, interstitial lung disease; IPAH, idiopathic pulmonary arterial hypertension; IPF, idiopathic pulmonary fibrosis; i.v., intravenous; LHD, left heart disease; LTx, lung transplantation; mPAP, mean pulmonary arterial pressure; NT-proBNP, N-terminal pro-brain natriuretic peptide; PAH, pulmonary arterial hypertension; PAP, pulmonary arterial pressure; PAWP, pulmonary arterial wedge pressure; PCH, pulmonary capillary haemangiomatosis; PDA, patent ductus arteriosus; PDE5i, phosphodiesterase 5 inhibitor; PE, pulmonary embolism; PEA, pulmonary endarterectomy; PFTs, pulmonary function tests; PH, pulmonary hypertension; PH-LHD, pulmonary hypertension associated with left heart disease; PVOD, pulmonary veno-occlusive disease; PVR, pulmonary vascular resistance; RAP, mean right atrial pressure; RHC, right heart catheterization; RV, right ventricle; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; s.c., subcutaneous; sGC, soluble guanylate cyclase; SGLT-2i, sodium–glucose cotransporter-2 inhibitor; SSc, systemic sclerosis; SVI, stroke volume index; TRV, tricuspid regurgitation velocity; VKA, vitamin K antagonist; VSD, ventricular septal defect; VTE, venous thrombo-embolism; WHO-FC, World Health Organization functional class; WU, Wood units. aClass of recommendation. bCardiopulmonary comorbidities are predominantly encountered in elderly patients and include risk factors for HFpEF, such as obesity, diabetes, coronary heart disease, a history of hypertension, and/or a low DLCO. cInitial triple-combination therapy including i.v./s.c. prostacyclin analogues may also be considered in patients presenting at intermediate risk but severe haemodynamic impairment (e.g. RAP ≥20 mmHg, CI <2.0 L/min/m2, SVI <31 mL/m2, and/or PVR ≥12 WU). dAssessments should ideally be made when the patient is clinically stable, as exacerbations can significantly raise PAP. eThis recommendation does not apply to patients with end-stage lung disease who are not considered candidates for LTx. fLong-term anticoagulant therapy is recommended when the risk of PE recurrence is intermediate or high, or when there is no history of VTE.