ESC 2026 Pulmonary Hypertension: Diagnosis and Risk-Stratified Management
Hemodynamic Definition and Diagnostic Confirmation
Right-heart catheterization is mandatory to confirm pulmonary hypertension before initiating any disease-targeted therapy; pulmonary hypertension is defined as mean pulmonary artery pressure >20 mmHg with pulmonary vascular resistance >3 Wood units for precapillary PH. 1
- The diagnostic threshold has been lowered from the previous ≥25 mmHg to >20 mmHg, with PVR >2 Wood units defining a precapillary component 2, 3
- Pulmonary artery wedge pressure ≤15 mmHg distinguishes precapillary from postcapillary PH 1, 4
- RHC must be performed at expert centers with morbidity ~1.1% and mortality ~0.055% 5
- Zero the pressure transducer at mid-thoracic line (halfway between anterior sternum and bed surface) in the supine position 5
- Measure pressures at end-expiration; average multiple readings because spontaneous variability can reach ±20 mmHg 4
Clinical Classification (Five Groups)
Group 1: Pulmonary Arterial Hypertension (PAH)
- Idiopathic, heritable (BMPR2, ALK1, endoglin mutations), drug/toxin-induced 5
- Associated PAH: connective tissue disease, HIV, portal hypertension, congenital heart disease, schistosomiasis, chronic hemolytic anemia 5
Group 2: PH Due to Left Heart Disease
- Mean PAP ≥25 mmHg with PAWP >15 mmHg 5, 4
- Includes systolic dysfunction, diastolic dysfunction, valvular disease 5
- PAH-specific drugs are contraindicated and may be harmful 5, 1
Group 3: PH Due to Lung Disease/Hypoxia
- COPD, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation 4
- PAH-specific therapies are not recommended 5, 1
Group 4: Chronic Thromboembolic PH (CTEPH)
- Requires perfusion imaging (V/Q scan) to exclude at diagnostic work-up 5
- Surgical pulmonary endarterectomy in deep hypothermia with circulatory arrest is first-line treatment 5, 1
Group 5: Unclear/Multifactorial Mechanisms
- Hematologic, systemic, metabolic disorders 4
Diagnostic Algorithm
Initial Screening (All Suspected PAH Patients)
- Pulmonary function tests including DLCO at diagnostic work-up 5
- Transthoracic echocardiography—most important non-invasive test 5, 6
- Right heart catheterization to confirm diagnosis 5, 1
- Perfusion imaging (V/Q scan) to exclude CTEPH 5
- Screen for connective tissue disease 5
Vasoreactivity Testing (Specific Indications Only)
- Perform only in idiopathic, heritable, or drug-induced PAH—never in other PAH subtypes or PH groups 5, 1
- Use inhaled nitric oxide as preferred agent; IV epoprostenol or adenosine are alternatives 1
- Positive response: ≥10 mmHg fall in mean PAP to absolute value ≤40 mmHg with stable/increased cardiac output 1
- Only ~10% of idiopathic PAH patients respond positively 1
- Critical pitfall: Never start calcium-channel blockers without documented positive vasoreactivity—can cause life-threatening hypotension and RV ischemia 1
Risk Stratification at Diagnosis
Assess all PAH patients using WHO functional class, NT-proBNP, and 6-minute walk test at diagnosis to determine risk category. 5, 1
- Use validated ESC/ERS risk assessment tool to stratify into low, intermediate, or high risk 5
- Assess quality of life using validated instrument 5
- Target parameters for low risk: WHO FC I-II, 6MWT >440 m (>500 m optimal), NT-proBNP <50 ng/L, no pericardial effusion, RAP <8 mmHg, cardiac index >2.5 L/min/m² 1
Risk-Stratified Initial Treatment (Group 1 PAH Only)
Vasoreactive Patients (~10% of Idiopathic PAH)
- High-dose calcium-channel blockers are first-line: nifedipine 120-240 mg daily, diltiazem 240-720 mg daily, or amlodipine up to 20 mg daily 1
- Mandatory re-assessment with repeat RHC at 3-4 months; if not WHO FC I-II with marked hemodynamic improvement, add PAH-specific therapy 1
Low or Intermediate Risk (Non-Vasoreactive)
- Initial oral combination therapy with ambrisentan plus tadalafil is recommended—targets endothelin and nitric-oxide-cGMP pathways and delays clinical worsening 7, 1
- Alternative: initial combination with PDE5 inhibitor plus endothelin receptor antagonist 5
High Risk
- Initial combination therapy including intravenous prostacyclin analogue (epoprostenol preferred) reduces 3-month mortality 7, 1
- Consider initial triple combination therapy 2
Sequential Escalation
- If inadequate response to initial therapy, escalate to double or triple oral/IV combination targeting multiple pathways 7, 1
- Contraindication: Never combine riociguat with PDE5 inhibitor due to safety concerns 1
Essential Supportive Care (All PAH Patients)
- Diuretics for right ventricular failure and fluid retention 5, 7, 1
- Supplemental oxygen when PaO₂ <60 mmHg or to maintain saturation >90% 7, 1
- Oral anticoagulation (INR 1.5-2.5) in idiopathic, heritable, and drug-induced PAH 1
- Pregnancy is absolutely contraindicated—30-50% maternal mortality risk 5, 7, 1
- Influenza and pneumococcal vaccination 1
- Avoid high altitude (>1,500-2,000 m) without supplemental oxygen 1
- Supervised exercise rehabilitation for deconditioned patients 7, 1
Follow-Up Monitoring
Reassess stable patients every 3-6 months with WHO functional class, 6-minute walk distance, NT-proBNP, and echocardiography. 5, 7, 1
- Primary goal: achieve and maintain low-risk status (WHO FC I-II) 7, 1
- Track right ventricular size/function and pericardial effusion on echo 1
Advanced Therapies and Rescue
- Refer for lung transplantation after inadequate response to maximal combination therapy 7, 1
- Balloon atrial septostomy as palliative/bridging procedure after failure of maximal medical therapy 1
- Veno-arterial ECMO as bridge to transplantation in awake end-stage patients 1
Critical Pitfalls to Avoid
- Never initiate PAH-specific drugs without RHC confirmation of Group 1 PAH—can cause harm in Group 2 PH (left heart disease) 1
- Never perform vasoreactivity testing in connective tissue disease, congenital heart disease, HIV-associated PAH, portopulmonary hypertension, or Groups 2-5 PH 1
- Never use PAH-approved therapies in Group 2 or Group 3 PH outside clinical trials 5, 1
- Do not use ACE inhibitors, ARBs, or beta-blockers in PAH unless required for comorbidities 7