pulmonary hypertension
Contents
Pulmonary hypertension (mPAP > 20 mmHg) is classified into five WHO groups by aetiology — the distinction matters because only group 1 (PAH) responds to targeted vasodilator therapy. Most PH encountered in hospital medicine is group 2 (left heart disease) or group 3 (lung disease). The 2022 ESC/ERS guidelines lowered the haemodynamic threshold and introduced risk-stratification-driven combination therapy as standard of care. See PAH Targeted Therapy for group 1 management, CTEPH for group 4, and Right Heart Failure for RV failure management.
quick recognition
- Young(er) patient with unexplained exertional dyspnoea, syncope, or signs of right heart failure
- Loud P2, parasternal heave, tricuspid regurgitation murmur, elevated JVP
- Peripheral oedema, hepatomegaly, ascites out of proportion to left-sided disease
- CXR: prominent central pulmonary arteries with peripheral oligaemia
- CT: PA diameter > 3 cm or PA:aorta ratio > 1
- Echo: elevated RVSP, RV dilatation, septal flattening, tricuspid regurgitant velocity (TRV) > 2.8 m/s
As the RV fails, pulmonary artery pressures may decrease — falling pressures in a deteriorating patient signal decompensation, not improvement.
when to suspect
Conceptual framework — all elevated PA pressures result from one (or more) of three mechanisms:
- High resistance (precapillary vasculopathy, lung disease, CTEPH)
- High back-pressure (LV dysfunction, valvular disease)
- High flow (anaemia, AV fistula, cirrhosis)
Many patients have overlapping mechanisms — the diagnostic workup exists to tease these apart.
Red flags for PH in a patient with known lung disease:
- Exertional dyspnoea or hypoxaemia disproportionate to the severity of parenchymal disease
- Rapid desaturation on exercise
- Features of right heart failure (elevated JVP, peripheral oedema, hepatomegaly)
- DLCO reduced out of proportion to spirometric abnormality (strong marker of pulmonary vascular disease)
- PA diameter > 29 mm on CT (sensitivity 89%, specificity 83%)
Social history — explicitly ask about methamphetamine use and appetite suppressants (definite PAH risk factors). Dasatinib, mitomycin C, and carfilzomib are under-recognised drug causes (definite association per updated classification).
Do not assess for PH during an acute exacerbation — hypoxic vasoconstriction transiently elevates pulmonary pressures and may be misconstrued as chronic PH. Similarly, acute anaemia, volume overload, and atelectasis can all artifactually raise estimated PASP on echo.
classification
| Group | Mechanism | Common causes |
|---|---|---|
| 1 — PAH | Precapillary vasculopathy | Idiopathic, heritable (BMPR2), CTD (scleroderma), CHD, HIV, portopulmonary, drugs, schistosomiasis |
| 2 — Left heart disease | Postcapillary | HFrEF, HFpEF, valvular disease |
| 3 — Lung disease/hypoxia | Hypoxic vasoconstriction + remodelling | COPD, ILD, CPFE, OSA/OHS |
| 4 — PA obstruction | Mechanical obstruction | CTEPH, PA sarcoma |
| 5 — Multifactorial | Mixed | Sarcoidosis, myeloproliferative, sickle cell, CKD |
haemodynamic definitions
| Category | mPAP | PAWP | PVR |
|---|---|---|---|
| Precapillary (groups 1, 3, 4) | > 20 mmHg | ≤ 15 mmHg | > 2 WU |
| Isolated postcapillary (group 2) | > 20 mmHg | > 15 mmHg | ≤ 2 WU |
| Combined pre- & postcapillary | > 20 mmHg | > 15 mmHg | > 2 WU |
Indicators suggesting severe pulmonary vascular disease in group 3 PH (warrant PH centre referral): PVR > 5 WU, mPAP ≥ 35 mmHg, or low cardiac index (CI < 2.0 L/min/m²). These are not formal guideline-defined thresholds but are commonly used to identify patients who may benefit from targeted therapy evaluation.
diagnosis / investigations
step 1: clinical suspicion
See when to suspect above. Key triggers: disproportionate dyspnoea, exertional syncope, RV failure signs, low DLCO relative to spirometry.
step 2: echocardiography
| TRV | Interpretation |
|---|---|
| < 2.8 m/s | PH unlikely (unless other echo signs present) |
| 2.8–3.4 m/s | Possible — correlate with ≥ 2 additional signs (RV dilatation, septal flattening, IVC plethora, PA acceleration time < 105 ms) |
| > 3.4 m/s | Probable PH |
Tricuspid regurgitation is absent in many patients with proven PH — a “normal” estimated PASP does not exclude the diagnosis. Echo also overestimates or underestimates pressures by ≥ 10 mmHg in up to 50% of patients with advanced lung disease.
step 3: determine aetiology
- V/Q scan: mandatory to exclude CTEPH (sensitivity > 95%, superior to CTPA for chronic disease)
- PFTs + DLCO: identifies group 3; disproportionately low DLCO suggests vascular disease or PVOD
- Overnight oximetry / polysomnography: if sleep-disordered breathing suspected
- Blood work: ANA (all patients), extended CTD panel if ANA positive, HIV, TSH, LFTs (portal hypertension screen), NT-proBNP
- HRCT chest: parenchymal lung disease, mediastinal lymphadenopathy, centrilobular ground-glass nodularity (PVOD)
- Abdominal ultrasound: portal hypertension screening
step 4: right heart catheterisation
Gold standard — confirms diagnosis, classifies haemodynamics, guides therapy.
Indications for RHC:
- Suspected group 1 PAH (all patients before starting targeted therapy)
- Suspected moderate–severe group 3 PH (ePASP ≥ 40 mmHg)
- Diagnostic uncertainty (group 2 vs. group 1; overlap syndromes)
- Transplant evaluation
- Vasoreactivity testing
Not required: mild group 3 PH (ePASP 20–39 mmHg, no RV dysfunction) — observe clinically.
vasoreactivity testing
- Only in groups 1.1–1.3 (idiopathic, heritable, drug-induced PAH)
- Agent: inhaled nitric oxide (preferred), IV epoprostenol, or IV adenosine
- Positive response: mPAP falls ≥ 10 mmHg to absolute mPAP < 40 mmHg with stable or increased cardiac output
- ~12% of PAH patients are vasoreactive; only ~50% of those maintain long-term response to CCBs
Vasodilator challenge may precipitate fatal pulmonary oedema in pulmonary veno-occlusive disease.
management
general measures (all groups)
- Supplemental O₂ to maintain SpO₂ > 92% (> 90% at altitude)
- Diuretics for volume overload — loop diuretics ± thiazide; aggressive decongestion often needed
- Supervised exercise rehabilitation (improves functional capacity in stable PAH)
- Influenza and pneumococcal vaccination
- Contraception counselling for women of childbearing age (pregnancy carries 30–50% mortality in severe PAH)
- Psychosocial support and advance care planning
- Anticoagulation: the 2022 ESC/ERS guidelines make no recommendation for or against routine anticoagulation in PAH — a deliberate shift away from prior practice where warfarin was often used empirically. Individualise: consider when other indications exist (atrial fibrillation, central line, hypercoagulable state). Avoid in SSc-PAH (registry data suggest potential harm). If used, target INR 1.5–2.5.
- Beta-blockers — generally avoid (reduce RV contractility and chronotropic reserve). May be tolerated in select patients with compelling cardiac indications (e.g. atrial fibrillation with rapid ventricular response), but use with caution and close monitoring.
- Systemic vasodilators (nitrates, ACE inhibitors, ARBs) — drop preload without reducing PVR
- Alpha-agonists (phenylephrine, noradrenaline at high doses) — increase PVR
- Verapamil (negative inotropy on RV) — contraindicated. Diltiazem also generally avoided, though used cautiously in vasoreactive patients on CCB therapy.
group 1 PAH — targeted therapy
See PAH Targeted Therapy for risk stratification, drug classes, treatment algorithms, and monitoring.
group 2 PH — left heart disease
- Treat the underlying cause — optimise GDMT for HF, address valvular disease
- PH-targeted therapy is not indicated and may cause harm:
- Epoprostenol → ↑ mortality in HFrEF
- Endothelin antagonists (bosentan, macitentan) → no benefit, possible harm
- PDE5i (sildenafil) → no clear benefit in RCTs
- sGC stimulators → no clear benefit
HFpEF and PAH are frequently confused, leading to inappropriate PAH-targeted therapy. Features favouring HFpEF over PAH:
- Demographics: age > 60, obesity, HTN, DM, CAD, atrial fibrillation
- ECG: left axis deviation, LVH, LBBB
- Echo: LA enlargement (LAVI > 34 mL/m²), LVH, E/e’ > 12, diastolic dysfunction — without RV dilatation or septal flattening
- CT: LA area > 27 cm²
When unclear, RHC with fluid challenge (PAWP > 18 mmHg after 500 mL saline) or exercise testing unmasks occult LV dysfunction.
group 3 PH — lung disease
- Treat underlying lung disease — optimise bronchodilators, O₂ therapy, treat OSA
- Most patients have mild–moderate PH (mPAP 20–35 mmHg); < 5% have severe PH
- PH severity correlates with severity of underlying disease, hypoxaemia, and hypercapnia
Echo overestimates or underestimates pressures by ≥ 10 mmHg in ~50% of patients with advanced lung disease. RHC is needed if moderate–severe PH is suspected.
when to refer for RHC in group 3
| Echo finding | Action |
|---|---|
| ePASP 20–39 mmHg, no RV dysfunction | Observe — clinical diagnosis of mild group 3 PH |
| ePASP 40–59 mmHg | Consider RHC (case-by-case) |
| ePASP ≥ 60 mmHg, or RV dysfunction | Refer to PH centre for RHC |
COPD-PH
- PVR > 5 WU is the strongest mortality predictor in moderate airflow obstruction and defines severe PH-COPD
- Severe PH-COPD (PVR > 5 WU): refer to PH centre — no proven targeted therapy, but may be considered on individual basis
ILD-PH
- PH present in 8–15% of IPF patients at diagnosis, > 60% in end-stage disease
- DLCO predicts PH better than spirometry
- Inhaled treprostinil is the only approved agent for group 3 PH-ILD (INCREASE (2021) — improved 6MWD by 31 m; higher doses = greater benefit). Consider when mPAP ≥ 25 mmHg and PVR > 3 WU with worsening symptoms, elevated NT-proBNP, or pulmonary vascular limitation to exercise.
CPFE
- Combined pulmonary fibrosis and emphysema: disproportionately severe PH (30–50% prevalence) with severe DLCO reduction but near-normal FEV₁/FVC — a classic exam pattern
OSA
- PH in 20–30%, usually mild; rarely the sole cause — always exclude coexistent group 2 or lung disease
severity stratification (RHC-based)
- Non-severe (PVR ≤ 5 WU): general measures + treat underlying disease; monitor every 6–12 months
- Severe (PVR > 5 WU, or indicators above): refer to PH centre
PAH-directed vasodilators may worsen V/Q mismatch and gas exchange in patients with parenchymal lung disease. Specific evidence of harm:
- Inhaled treprostinil in COPD: RCT stopped early due to ↑ serious adverse events
- Ambrisentan in IPF: ↑ disease progression, ↑ hospitalisations, worsening oxygenation — do not use
- Riociguat in IIP-PH: phase II trial terminated early due to ↑ adverse events and mortality
- Bosentan / macitentan in IPF: ineffective (not tested specifically in IPF-PH)
Do not use oral PAH drugs for group 3 PH outside of expert centres / clinical trials.
Exception — suspected overlap with group 1: patients with mild lung disease but disproportionately severe PH (especially scleroderma with ILD) may have a group 1 component and benefit from PAH-directed therapy. Requires expert evaluation to distinguish true group 3 from group 1 with coexistent lung disease.
Lung transplantation: refer eligible patients with progressive group 3 PH despite therapy. Bilateral lung transplant preferred in severe PH (single lung transplant associated with ↑ 90-day mortality in the presence of PH).
group 4 PH — CTEPH
See CTEPH for diagnosis, operability assessment, PEA, BPA, and medical therapy.
what NOT to do
- Do not start PAH-targeted therapy without RHC confirmation and haemodynamic classification
- Do not use PDE5i + riociguat together (severe hypotension)
- Do not perform vasoreactivity testing in suspected PVOD
- Do not use CCBs in non-vasoreactive PAH (may cause cardiovascular collapse)
- Do not use PAH-specific drugs for group 2 PH
- Do not give fluid boluses to decompensated RV failure (worsens septal shift)
- Avoid beta-blockers in PAH unless a compelling cardiac indication exists (see drugs to avoid callout)
- Do not abruptly discontinue IV epoprostenol (rebound crisis, death)
- Do not use ambrisentan in patients with IPF (↑ disease progression)
- Do not delay CTEPH referral for PEA assessment — secondary distal vasculopathy develops over time and reduces surgical success
- Do not close a patent foramen ovale or ASD in patients with significant PH (acts as pressure relief for the RV)
special populations
connective tissue disease
- Screen all scleroderma patients annually with echo ± DLCO (DETECT algorithm)
- PAH component treated as group 1; ILD component may warrant inhaled treprostinil
- Distinguish pure PAH from PH driven by ILD or LV diastolic dysfunction — RHC often needed
portopulmonary hypertension
- Pre-capillary PH in the setting of portal hypertension (sPAP > 20 mmHg, PVR > 2 WU, PAWP ≤ 15 mmHg)
- Macitentan preferred ERA (PORTICO (2023))
- CCBs contraindicated (worsen splanchnic vasodilatation); beta-blockers harm cardiac output
- TIPS contraindicated
- Liver transplant criteria: mPAP < 35 mmHg with PVR < 5 WU; mPAP > 45 mmHg is absolute contraindication
PVOD / pulmonary capillary haemangiomatosis
- Suspect when PAH patient develops pulmonary oedema after starting vasodilators
- CT clues: centrilobular ground-glass nodularity, septal thickening, pleural effusions with normal LA size
- Genetic: biallelic EIF2AK4 mutations are diagnostic
- Vasoreactivity testing contraindicated; PAH-specific drugs may cause pulmonary oedema
- Lung transplantation is only definitive therapy; 70% one-year mortality without transplant
pregnancy
- Absolute contraindication in severe PAH (mortality 30–50%)
- Counsel on effective contraception; ERAs and riociguat are teratogenic
- If pregnancy occurs: multidisciplinary management at expert centre; planned early delivery
Eisenmenger syndrome
- Bosentan improves exercise capacity
- Shunt closure is contraindicated (removes RV “pop-off valve”)
- Prefer SC treprostinil over IV epoprostenol (central line → paradoxical embolism risk)