Pulmonary Hypertension

Pulmonary hypertension (PH) is defined by mean pulmonary artery pressure over 20 mmHg at rest on right heart catheterisation. Pulmonary arterial hypertension (PAH) requires also pulmonary artery wedge pressure 15 mmHg or less and pulmonary vascular resistance over 2 Wood units.

WHO groups

• Group 1: pulmonary arterial hypertension (idiopathic, heritable BMPR2, drugs such as fenfluramine and dasatinib, connective tissue disease especially systemic sclerosis, HIV, portal hypertension, congenital heart disease, schistosomiasis), pulmonary veno occlusive disease.
• Group 2: left heart disease (commonest, 65 to 80%).
• Group 3: lung disease and hypoxia (COPD, ILD, sleep apnoea, altitude).
• Group 4: chronic thromboembolic pulmonary hypertension and pulmonary artery obstruction.
• Group 5: unclear or multifactorial (sickle cell disease, sarcoidosis, myeloproliferative disease, chronic kidney disease).
• Idiopathic PAH incidence 1 to 2 per million; prevalence 15 to 50 per million; women 3:1; untreated median survival 2.8 years, now over 7 years with modern therapy.
• Risk stratification using functional class, 6 minute walk distance, BNP/NT proBNP, echo and haemodynamics (ESC/ERS three strata; REVEAL).

• Progressive exertional dyspnoea, fatigue, exertional syncope, chest pain, palpitations, haemoptysis, Ortner syndrome.
• Loud P2, right ventricular heave, tricuspid regurgitation, raised JVP with large v wave, hepatomegaly, ascites, oedema; cyanosis.
• Signs of underlying cause (scleroderma, liver disease, congenital heart disease).

• Transthoracic echocardiography (tricuspid regurgitant velocity over 2.8 m/s, right ventricular enlargement, septal flattening, TAPSE under 17 mm).
• Right heart catheterisation to confirm and classify; vasoreactivity testing with inhaled nitric oxide 20 ppm in idiopathic, heritable, drug associated PAH (positive: mean pressure fall of 10 mmHg or more to below 40 mmHg with preserved output).
• Ventilation perfusion scan (sensitive for chronic thromboembolic disease), CT pulmonary angiography, HRCT chest, pulmonary function tests with DLCO, polysomnography.
• Blood tests: NT proBNP, ANA, anti centromere, anti Scl 70, HIV, liver tests, thyroid, haemoglobin; genetic testing (BMPR2) in idiopathic and familial PAH.
• Six minute walk test, cardiopulmonary exercise testing, cardiac MRI.

General

• Supervised exercise, vaccinations, avoid pregnancy (maternal mortality 30 to 50%), diuretics (furosemide 20 to 80 mg, spironolactone), oxygen to keep saturations above 90%, iron correction, anticoagulation (warfarin) in selected idiopathic PAH.
• Calcium channel blockers (nifedipine 120 to 240 mg or diltiazem 240 to 720 mg or amlodipine 20 mg) only in vasoreactive responders (about 5 to 10% of idiopathic PAH).

Targeted PAH therapy (group 1)

• Initial combination for most: ambrisentan 5 to 10 mg or macitentan 10 mg (endothelin receptor antagonists) with tadalafil 40 mg daily or sildenafil 20 mg three times daily; add selexipag 200 to 1600 micrograms twice daily or inhaled/oral treprostinil.
• High risk or class IV: parenteral prostacyclin (epoprostenol IV 2 ng/kg/min titrated, treprostinil SC/IV) with combination.
• Sotatercept 0.3 mg/kg then 0.7 mg/kg SC every 3 weeks (activin signalling inhibitor) added to background therapy improves exercise capacity and outcomes.
• Riociguat 1 to 2.5 mg three times daily for PAH and CTEPH (not with PDE5 inhibitors).
• Monitor monthly liver tests (bosentan), teratogenicity (endothelin antagonists: contraception, pregnancy tests).

Other groups

• Group 2: optimise left heart disease and valve treatment (no PAH drugs).
• Group 3: oxygen, treat lung disease; inhaled treprostinil for PH ILD.
• Group 4: pulmonary endarterectomy, balloon pulmonary angioplasty, riociguat, lifelong anticoagulation.

Advanced

• Atrial septostomy, lung or heart lung transplantation referral early for high risk disease despite therapy.
• Palliative care and decision making. Follow up every 3 to 6 months with risk re assessment.