Pulmonary hypertension
Overview
•Elevated pulmonary arterial pressure - mean PAP (mPAP) ≥20 mmHg on right heart catheterisation
•Not a single disease - a haemodynamic state with many causes; WHO group determines management
Presentation
•Exertional dyspnoea - cardinal and earliest symptom; fixed elevated PVR prevents increased cardiac output on demand
•Exertional syncope/pre-syncope - sinister; RV cannot increase output → drop in systemic cardiac output and cerebral hypoperfusion
•Fatigue, chest pain (RV ischaemia), haemoptysis (uncommon)
•Signs of RV failure (cor pulmonale): raised JVP, parasternal heave, loud P2, tricuspid regurgitation murmur, hepatomegaly, peripheral oedema
Investigations
•First-line screening: transthoracic echocardiogram (TTE) - estimates RVSP from TR jet velocity; peak TR velocity >3.4 m/s = high probability PH
•ECG: right axis deviation, RBBB, P pulmonale, RV strain (T-wave inversion V1-V4)
•CXR: enlarged hilar pulmonary arteries, peripheral pruning, RV enlargement
•V/Q scan: essential to exclude Group 4 CTEPH - more sensitive than CTPA for chronic thromboembolic disease; normal V/Q effectively excludes CTEPH
•Bloods: BNP/NT-proBNP (RV strain/prognosis), autoimmune screen (ANA, anti-Scl-70, anti-centromere for SSc), HIV, TFTs, FBC
•PFTs + DLCO: exclude Group 3; DLCO typically reduced in PAH
•Gold standard - right heart catheterisation (RHC): directly measures mPAP, PCWP, PVR, cardiac output; also allows vasoreactivity testing
Pre-capillary vs post-capillary PH on RHC
| Parameter | Pre-capillary (Groups 1,3,4,5) | Post-capillary (Group 2) |
|---|---|---|
| mPAP | ≥20 mmHg | ≥20 mmHg |
| PCWP | ≤15 mmHg | >15 mmHg |
| PVR | ≥2 Wood units | Normal/low |
| Targeted PAH therapy | Appropriate | Harmful - avoid |
Management
•General (all groups): treat underlying cause, supplemental oxygen if hypoxic, diuretics for RV failure, anticoagulation in CTEPH
•Group 1 PAH - targeted vasodilator therapies (3 pathways):
•Endothelin receptor antagonists (ERAs): ambrisentan, bosentan, macitentan
•PDE-5 inhibitors: sildenafil, tadalafil
•Prostacyclin pathway: epoprostenol (IV), iloprost (inhaled), selexipag (oral)
•Combination therapy (e.g. ERA + PDE-5i) is standard of care in Group 1
•Vasoreactivity testing (RHC): positive responders (minority) can be treated with nifedipine or other CCBs
•Group 4 CTEPH: riociguat (soluble guanylate cyclase stimulator); surgical pulmonary endarterectomy if operable - potentially curative
•Advanced/refractory disease: lung transplantation (or heart-lung transplant)
Complications
•Right ventricular failure (cor pulmonale) - principal cause of death
•Atrial arrhythmias - AF/flutter due to RA dilatation; poorly tolerated
•Eisenmenger syndrome - longstanding unrepaired left-to-right shunt reverses with cyanosis; precludes surgical repair
•Pregnancy - very high maternal mortality (up to 30-50%) in severe PAH; strongly contraindicated
Prognosis
•Untreated idiopathic PAH: median survival ~2.8 years from diagnosis
•Modern combination therapy: 5-year survival ~60-70% in Group 1
•Group 4 CTEPH: best prognosis if surgically resectable endarterectomy successful
Classification (WHO Groups)
•Group 1 - Pulmonary arterial hypertension (PAH): idiopathic, heritable (BMPR2 mutation), CTD-associated (esp. systemic sclerosis), congenital heart disease, drugs/toxins
•Group 2 - Left heart disease: most common cause of PH overall (HFpEF, HFrEF, valve disease)
•Group 3 - Lung disease/hypoxia: COPD, ILD, OSA
•Group 4 - CTEPH: chronic thromboembolic pulmonary hypertension - only potentially curable form (surgical endarterectomy)
•Group 5 - Unclear/multifactorial: sarcoidosis, haematological disorders