How should I diagnose and manage pulmonary hypertension, including confirmation with right‑heart catheterisation, WHO (World Health Organization) group classification, supportive measures (oxygen therapy, low‑salt diet, diuretics), acute vasoreactivity testing, and appropriate pharmacologic (e.g., calcium‑channel blockers, phosphodiesterase‑5 inhibitors, endothelin‑receptor antagonists, soluble guanylate cyclase stimulators, prostacyclin analogues) and procedural therapies (e.g., pulmonary endarterectomy, lung transplantation) for each WHO group?

Pulmonary Hypertension Management

Right-heart catheterization is mandatory to confirm the diagnosis of pulmonary hypertension before initiating any therapy, and all patients must be classified into one of five WHO groups because treatment differs fundamentally by group. 1

Diagnostic Confirmation

Right-Heart Catheterization (RHC)

• RHC must be performed at expert centers to confirm PH and document hemodynamics before any treatment decisions. 1
• Diagnostic criteria for Group 1 PAH: mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 3 Wood units. 2
• Measure all parameters in triplicate: mPAP, right atrial pressure, cardiac output (by thermodilution or Fick method), and PAWP. 3
• When PAWP is unreliable, perform left-heart catheterization to measure left ventricular end-diastolic pressure. 1
• RHC is required for congenital cardiac shunts to determine operability and guide surgical correction. 1
• RHC is mandatory before lung or heart-lung transplantation in Group 2 or Group 3 PH. 1

Essential Pre-RHC Work-Up

• Transthoracic echocardiography estimates pulmonary artery pressure, assesses right-ventricular function (including TAPSE), evaluates left-heart disease, detects valvular abnormalities, and identifies pericardial effusion. 3
• Ventilation-perfusion (V/Q) scan is mandatory in all patients to exclude chronic thromboembolic PH (CTEPH); a normal scan has 90–100% sensitivity. 2, 3
• High-resolution CT chest identifies interstitial lung disease, emphysema, and pulmonary veno-occlusive disease. 3
• Pulmonary function tests (spirometry, lung volumes, DLCO) characterize obstructive or restrictive patterns. 3
• Laboratory tests: complete blood count, thyroid function (TSH, free T4), autoimmune serology (ANA, anti-Scl-70, anti-centromere, anti-RNP, rheumatoid factor), HIV serology, hepatitis B and C serology, liver function tests, and abdominal ultrasound for portal hypertension. 3

WHO Group Classification & Treatment

Group 1: Pulmonary Arterial Hypertension (PAH)

Acute Vasoreactivity Testing

• Perform vasoreactivity testing ONLY in idiopathic PAH, heritable PAH, and drug-induced PAH. 1
• Vasoreactivity testing is contraindicated in connective-tissue disease PAH, congenital heart disease PAH, HIV-PAH, portopulmonary hypertension, pulmonary veno-occlusive disease, and all Groups 2–5. 1, 2
• Testing must be performed only at expert centers. 1
• Preferred agent: inhaled nitric oxide. 1
• Alternative agents: intravenous epoprostenol (Class I), adenosine (Class IIa), or inhaled iloprost (Class IIb). 1
• Oral or intravenous calcium-channel blockers must NEVER be used during acute testing. 1
• Positive response criteria (all three required): ↓ mPAP ≥ 10 mmHg, absolute mPAP ≤ 40 mmHg, and cardiac output unchanged or increased. 1, 2
• Only ~10–15% of idiopathic PAH patients test positive. 2

Calcium-Channel Blocker (CCB) Therapy for Vasoreactive Patients

• High-dose CCBs are first-line therapy ONLY for patients with documented positive vasoreactivity. 2, 4
• Drug selection by resting heart rate:
  • HR < 70–75 bpm: extended-release nifedipine 120–240 mg daily or amlodipine up to 20 mg daily. 2
  • HR > 75–80 bpm: diltiazem 240–720 mg daily. 2
• Mandatory reassessment: repeat RHC at 3–4 months to identify non-responders. 2, 4
• Long-term response criteria: WHO functional class I–II with marked hemodynamic improvement (mPAP ideally < 25 mmHg). 2
• Approximately 50% of acute responders lose efficacy and require escalation to PAH-specific therapy. 2
• Absolute contraindications to CCBs: no documented positive vasoreactivity test, PAH associated with connective-tissue disease/HIV/portopulmonary hypertension/pulmonary veno-occlusive disease, presence of right-heart failure, or any Group 2–5 PH. 2

PAH-Specific Pharmacologic Therapy (Non-CCB)

• Low- or intermediate-risk patients: initial oral combination therapy with ambrisentan plus tadalafil (phosphodiesterase-5 inhibitor + endothelin-receptor antagonist) is superior to monotherapy in delaying clinical failure. 4
• High-risk patients: initial combination therapy must include intravenous prostacyclin analogue; intravenous epoprostenol is preferred because it reduces 3-month mortality. 4, 5
• Sequential escalation: if response is inadequate, escalate to double or triple oral/intravenous combination therapy. 4
• Riociguat (soluble guanylate cyclase stimulator) plus phosphodiesterase-5 inhibitor is contraindicated due to safety concerns. 4
• Alternative monotherapy options (if combination not tolerated): endothelin-receptor antagonists (bosentan 125 mg twice daily, ambrisentan) or phosphodiesterase-5 inhibitors (sildenafil, tadalafil). 4

Supportive Measures for Group 1 PAH

• Diuretics are indicated for signs of right-ventricular failure and fluid retention. 1, 4
• Continuous long-term oxygen when arterial oxygen tension is consistently < 60 mmHg (8 kPa) to maintain saturations > 90%. 1, 4
• Oral anticoagulation (target INR 1.5–2.5) should be considered in idiopathic, heritable, and anorexigen-induced PAH. 1, 4
• Pregnancy is absolutely contraindicated because maternal mortality is 30–50%. 1, 4
• Vaccination against influenza and pneumococcal disease. 1, 4
• Supervised exercise rehabilitation for deconditioned patients (Class IIa). 1, 4
• Avoid excessive physical activity that leads to distressing symptoms. 1

Group 2: PH Due to Left Heart Disease

• PAH-specific drugs (endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclins) are NOT recommended and may be harmful. 4
• Management focuses on optimal treatment of the underlying cardiac condition (systolic dysfunction, diastolic dysfunction, valvular disease) and diuretics for volume control. 4
• RHC may be considered to assist in differential diagnosis and support treatment decisions. 1

Group 3: PH Due to Lung Disease

• PAH-specific therapies are NOT recommended. 4
• Treatment is directed at the underlying lung pathology (COPD, interstitial lung disease, pulmonary fibrosis) and long-term oxygen therapy where appropriate. 4
• RHC is required if organ transplantation is considered. 1

Group 4: Chronic Thromboembolic PH (CTEPH)

• Surgical pulmonary endarterectomy is the treatment of choice and must be performed at experienced centers using deep hypothermia with circulatory arrest. 4
• Operability assessment must be performed by a multidisciplinary expert team. 4
• RHC is mandatory to confirm diagnosis and support treatment decisions. 1
• Riociguat (soluble guanylate cyclase stimulator) is the only licensed targeted therapy for inoperable or persistent/recurrent CTEPH. 6
• Oral anticoagulation (target INR 2–3) is required. 7

Group 5: PH with Unclear/Multifactorial Mechanisms

• Therapy is directed at the underlying disease. 4
• PAH-specific agents are not advised. 4

Monitoring & Treatment Goals

• Routine follow-up every 3–6 months should include WHO functional class, 6-minute walk distance (target > 440 m), BNP/NT-proBNP (target < 50 ng/L), ECG, echocardiography, and basic laboratory tests. 1, 4
• Primary therapeutic goal: achieve and maintain low-risk profile (WHO functional class I–II, 6-minute walk > 500 m, normal BNP/NT-proBNP, no pericardial effusion, right atrial pressure < 8 mmHg, cardiac index > 2.5 L/min/m²). 1, 4
• RHC should be considered to assess treatment effect of drugs in Group 1 PAH. 1

Advanced Therapies & Rescue Options

• Lung or heart-lung transplantation should be considered for WHO functional class III–IV patients refractory to maximal medical therapy. 4
• Balloon atrial septostomy may be considered as a palliative or bridging procedure after failure of maximal medical therapy. 4
• Veno-arterial ECMO can be employed in awake, end-stage PH patients as a bridge to lung transplantation. 4

Critical Pitfalls to Avoid

• Do NOT perform vasoreactivity testing in connective-tissue disease PAH, congenital heart disease PAH, HIV-PAH, portopulmonary hypertension, or any Group 2–5 PH; it offers no benefit and adds risk. 1, 2
• Do NOT start CCBs without documented positive vasoreactivity testing; doing so can cause life-threatening hypotension, reflex tachycardia, and right-ventricular ischemia. 2, 4
• Do NOT omit the 3–4-month repeat RHC in patients treated with CCBs; failure to identify non-responders delays necessary therapy escalation. 2, 4
• Do NOT use CCBs empirically for symptom relief in PH patients who are not vasoreactive; they are not general pulmonary vasodilators and can be dangerous. 2
• Do NOT initiate PAH-specific drugs without confirmed Group 1 PAH by RHC, especially in Group 2 PH, to avoid harm. 4
• Do NOT rely on CT pulmonary angiography alone to exclude CTEPH; V/Q scan is more sensitive. 3
• Do NOT perform open or thoracoscopic lung biopsy in PAH patients due to high procedural risk and limited diagnostic yield. 3

Urgent/Critical Care Situations

• ICU admission is indicated for hemodynamic instability (heart rate > 110 bpm, systolic BP < 90 mmHg, oliguria, rising lactate). 4
• Inotropic support should be provided to hypotensive patients. 4