Summary

Fourth-edition joint ESC/ERS guideline on diagnosis and treatment of pulmonary hypertension covering all five PH groups, with emphasis on PAH and CTEPH. Key changes from 2015: lowered hemodynamic definition (mPAP >20 mmHg, PVR >2 WU), introduction of exercise PH definition, four-strata follow-up risk model, simplified treatment algorithm distinguishing patients with vs without cardiopulmonary comorbidities, new CTEPD-without-PH concept, and upgraded role of balloon pulmonary angioplasty plus medical therapy in CTEPH.

Key Recommendations

Confirm PH diagnosis by right heart catheterization at experienced centers using standardized complete hemodynamic protocols.
Perform vasoreactivity testing only in IPAH/HPAH/DPAH using inhaled NO, inhaled iloprost, or IV epoprostenol; positive response = mPAP drop ≥10 mmHg to absolute ≤40 mmHg with preserved/increased CO.
Use V/Q lung scan (not CTPA alone) to rule out CTEPH in any unexplained PH; refer symptomatic PE survivors with mismatched defects beyond 3 months of anticoagulation to a PH/CTEPH center.
Screen patients with systemic sclerosis annually for PAH; use DETECT algorithm in SSc patients with >3 years disease, FVC ≥40%, DLCO <60%.
Initial therapy in IPAH/HPAH/DPAH without cardiopulmonary comorbidities: combination ERA + PDE5i (ambrisentan+tadalafil or macitentan+tadalafil) for low/intermediate risk; add IV/SC prostacyclin analogue for high risk.
In PAH patients with cardiopulmonary comorbidities, start with PDE5i or ERA monotherapy and escalate individually.
At follow-up use four-strata model (WHO-FC, 6MWD, BNP/NT-proBNP); intermediate-low → add selexipag or switch PDE5i to riociguat; intermediate-high/high → add IV/SC prostacyclin and refer for lung transplant.
Achieve and maintain a low-risk profile as the treatment goal; refer to LTx when REVEAL >7 or intermediate-high/high risk despite oral combination therapy.
Strongly advise against pregnancy in PAH; stop ERAs, riociguat, and selexipag if pregnancy occurs; provide effective contraception counseling.
Do not use PAH-approved drugs routinely in PH-LHD; PDE5is are not recommended in HFpEF with isolated post-capillary PH.
In CTEPH: lifelong therapeutic anticoagulation, multidisciplinary team review, PEA as treatment of choice for surgically accessible disease; BPA + riociguat for inoperable/residual disease.
Supervised exercise training is recommended for all clinically stable PAH patients on medical therapy; immunize against influenza, pneumococcus, and SARS-CoV-2.

Thresholds & Doses

Pulmonary hypertension: mPAP >20 mmHg at rest
Pre-capillary PH: mPAP >20 mmHg + PAWP ≤15 mmHg + PVR >2 WU
Isolated post-capillary PH: mPAP >20, PAWP >15, PVR ≤2 WU; Combined post/pre-capillary: PAWP >15 and PVR >2 WU
Exercise PH: mPAP/CO slope >3 mmHg/L/min between rest and exercise
Echocardiographic PH probability: peak TRV >2.8 m/s threshold maintained
Severe PH in lung disease: PVR >5 WU
Positive vasoreactivity: mPAP drop ≥10 mmHg to absolute ≤40 mmHg with unchanged/increased CO
Sustained CCB response criteria: WHO-FC I/II with mPAP <30 mmHg and PVR <4 WU at 3–6 month reassessment
Four-strata risk by BNP: <50, 50–199, 200–800, >800 ng/L; NT-proBNP: <300, 300–649, 650–1100, >1100 ng/L
Four-strata 6MWD cutoffs: >440, 320–440, 165–319, <165 m
Low-risk hemodynamics: RAP <8 mmHg, CI ≥2.5 L/min/m², SVI >38 mL/m², SvO2 >65%
Drug doses: amlodipine 15–30 mg/d, diltiazem 120–360 mg bid, ambrisentan 5–10 mg od, bosentan 125 mg bid, macitentan 10 mg od, sildenafil 20 mg tid, tadalafil 40 mg od, riociguat up to 2.5 mg tid, selexipag up to 1600 µg bid
Long-term/in-flight oxygen indicated when PaO2 <8 kPa (60 mmHg) or SaO2 <92%
Iron deficiency: ferritin <100 µg/L, or ferritin 100–299 with transferrin saturation <20%
Shunt closure: PVR <3 WU recommended; 3–5 WU consider; >5 WU generally not recommended (ASD)
REVEAL risk score: >7 refer for LTx evaluation; ≥10 list for transplant
PH center volume: ≥50 PAH/CTEPH patients followed and ≥2 new referrals/month; CTEPH centers ideally >50 PEAs/year and >30 BPA patients (>100 procedures)/year
Inhaled treprostinil target dose: 72 µg four times daily (INCREASE trial for PH-ILD)

Citations

Section 3.1 Definitions, Table 5 — updated hemodynamic definitions of PH
Section 6.2.7 / Tables 16 and 18 — three-strata and four-strata risk assessment models
Recommendation Tables 8–10, Figure 9 — PAH treatment algorithm and combination therapy
Recommendation Table 7 — vasoreactivity testing and CCB therapy criteria
Recommendation Table 13 — lung transplantation referral and listing criteria
Recommendation Tables 22–23 — group 2 (LHD) and group 3 (lung disease) management
Recommendation Table 24 / Figures 14–15 — CTEPH multimodality management (PEA, BPA, riociguat)
Section 2.1 ‘What is new’ — summary of changes from 2015 guideline
Table 19 — PAH drug dosing in adults