What is pulmonary hypertension and how is it different from normal high blood pressure?

Regular high blood pressure (hypertension) refers to elevated pressure in the systemic arteries — the blood vessels supplying the body. Pulmonary hypertension is a separate condition affecting only the arteries supplying the lungs. The right side of the heart pumps blood through these pulmonary arteries, so when the pressure in them is elevated the right ventricle has to work harder, eventually causing it to enlarge and weaken. Pulmonary hypertension has five distinct clinical groups with different causes — left heart disease, lung disease, clots, rare vascular conditions, and others — and the treatments differ fundamentally between groups.

Why does misidentifying the group of pulmonary hypertension matter?

The drugs developed for Group 1 (pulmonary arterial hypertension) — such as sildenafil, bosentan, and riociguat — work by dilating the pulmonary arteries. In Group 2 pulmonary hypertension (caused by left-sided heart disease), the lung pressure is elevated because the left heart is not working well, causing a back-pressure. Giving pulmonary arterial dilators to a patient with Group 2 increases blood flow into the lungs faster than the left heart can cope with, potentially causing acute pulmonary oedema. Multiple clinical trials have confirmed this risk. The ESC/ERS 2022 guideline categorises PAH-specific drugs as contraindicated in Group 2.

What are the symptoms that should trigger investigation for pulmonary hypertension?

The most common and earliest symptom is breathlessness on exertion that is out of proportion to apparent fitness levels — often misattributed to deconditioning for months or years. Other important symptoms include: fatigue and reduced exercise tolerance; near-fainting or fainting on exertion (pre-syncope or syncope); chest pain with exercise (right ventricular angina); palpitations (from atrial arrhythmias); and, in later stages, ankle swelling and abdominal distension from right heart failure. The typical diagnostic delay is approximately two years from symptom onset to diagnosis, largely because early symptoms are non-specific.

What is CTEPH and can it be cured?

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in some patients after a pulmonary embolism (blood clot in the lungs). The clots fail to resolve fully and instead organise into fibrous obstruction of the pulmonary arteries, causing persistently elevated pressures. For patients whose obstructions are surgically accessible, pulmonary endarterectomy (PEA) — a complex open-heart surgery — can remove the organised clots and normalise pulmonary pressures. Australia's PEA centre is at Royal Prince Alfred Hospital in Sydney; referral is through the PHSANZ specialist network. Even for patients unsuitable for surgery, balloon pulmonary angioplasty and riociguat (PBS-listed for inoperable CTEPH) improve symptoms and prognosis.

Why is pregnancy so dangerous for women with pulmonary arterial hypertension?

Pulmonary arterial hypertension during pregnancy carries an estimated maternal mortality of 30–50%, despite modern treatments. The cardiovascular demands of pregnancy — increased blood volume, heart rate and cardiac output — place an extreme burden on the right ventricle, which is already working at its limit in PAH. Labour and delivery are particularly high-risk periods. The ESC/ERS 2022 guideline categorises pregnancy as a Class III recommendation (harm outweighs benefit) in PAH. Effective contraception is essential and should be discussed with every woman with PAH of reproductive age. A progestogen intrauterine device (Mirena) avoids oestrogen-containing preparations, which carry additional thromboembolic risk.

What drugs are used for pulmonary arterial hypertension and are they on the PBS?

Group 1 PAH is treated with targeted vasodilator therapy, typically as upfront combination treatment for intermediate- and high-risk patients. Drug classes include endothelin-receptor antagonists (ambrisentan, bosentan, macitentan), PDE5 inhibitors (sildenafil, tadalafil), soluble guanylate cyclase stimulators (riociguat — cannot be combined with PDE5i), and prostacyclin pathway agents (epoprostenol IV, treprostinil, iloprost inhaled, selexipag oral). These are PBS Section 100 Highly Specialised Drugs — available at approved specialist centres for confirmed Group 1 PAH or inoperable Group 4 CTEPH, with Authority prescription requirements. They are not available for Groups 2 or 3.

Pulmonary hypertension

Pulmonary hypertension: five groups, targeted therapies and AU pathway

By Dr HB Lo, FACRRM Reviewed 12 August 2026 10 min read

Pulmonary hypertension — elevated pressure in the lung's arteries — has five clinical groups with completely different causes and treatments. The drugs used in Group 1 (pulmonary arterial hypertension) are harmful in Group 2 (left-sided heart disease), which is the most common form at roughly 65% of all cases.

Workup begins with echocardiography and ECG, then specialist referral for right-heart catheterisation. In Australia, targeted Group 1 therapies are funded through PBS Section 100 for specialist-confirmed cases. Group 4 (chronic thromboembolic PH after pulmonary embolism) may be curable with pulmonary endarterectomy at Royal Prince Alfred Hospital in Sydney.

Pulmonary hypertension (PH) is not a single disease. It is a haemodynamic state — elevated blood pressure in the arteries supplying the lungs — that arises from at least five distinct clinical mechanisms, each requiring a different treatment approach. This matters profoundly: the targeted drug therapies developed for one group are actively harmful in another, and arriving at the correct diagnosis requires specialist investigation including right-heart catheterisation.

The 2022 ESC/ERS guideline and the 6th World Symposium on Pulmonary Hypertension (WSPH 2018) define pulmonary hypertension as a mean pulmonary artery pressure (mPAP) above 20 mmHg at rest on right-heart catheterisation — revised down from the previous threshold of 25 mmHg, capturing earlier disease with prognostic significance. Importantly, this haemodynamic definition must be interpreted in the context of pulmonary vascular resistance and left-heart filling pressures to correctly classify the type.

In general practice, the role is to recognise progressive unexplained dyspnoea and exertional pre-syncope, initiate echocardiography and basic workup, and refer appropriately. The typical delay from symptom onset to diagnosis is approximately two years — earlier recognition from general practice can meaningfully change outcomes.

A. Core clinical — the AU general-practice framework

The five WSPH clinical groups

Group 1 — Pulmonary Arterial Hypertension (PAH): disease of the pulmonary arterial wall (muscularis media, intima, and adventitia) causing intrinsic obstruction and vasoconstriction. Includes idiopathic PAH, heritable PAH (most commonly from BMPR2 mutation, autosomal dominant with variable penetrance), drug- and toxin-associated PAH (anorectic drugs, methamphetamine, dasatinib for CML), connective tissue disease-associated PAH (systemic sclerosis is the dominant CTD risk, followed by mixed CTD, lupus, and rheumatoid arthritis), HIV-associated, portopulmonary, congenital heart disease-associated, and schistosomiasis. In Australia, methamphetamine-associated PAH has emerged as a recognised entity given Australia’s high crystal methamphetamine use prevalence.

Group 2 — PH due to left heart disease: the most common form, comprising approximately 65% of all pulmonary hypertension. Elevated left atrial pressure from HFpEF, HFrEF, mitral valve disease, or aortic valve disease creates passive pulmonary venous hypertension. Treatment is of the underlying left-heart condition. PAH-specific drugs are contraindicated and harmful in this group.

Group 3 — PH due to lung disease or hypoxia: hypoxic pulmonary vasoconstriction and parenchymal destruction cause elevated pulmonary pressures. Most common underlying conditions: COPD, interstitial lung disease (IPF and other ILDs), obstructive sleep apnoea, obesity-hypoventilation syndrome. Primary treatment is of the underlying lung disease plus long-term oxygen therapy.

Group 4 — Chronic Thromboembolic PH (CTEPH): develops in approximately 2–4% of patients following acute pulmonary embolism. Organised thrombus and fibrotic obstruction of pulmonary arteries causes fixed elevated pressures. Potentially curative with pulmonary endarterectomy (PEA). All patients with CTEPH should be referred to the Australian PEA centre at Royal Prince Alfred Hospital in Sydney for surgical assessment.

Group 5 — Multifactorial or unclear mechanisms: includes haematological conditions (sickle cell disease, myeloproliferative neoplasms, splenectomy), systemic disorders (sarcoidosis, neurofibromatosis, Gaucher disease), metabolic (thyroid disorders, glycogen storage), and others (chronic renal failure on dialysis, fibrosing mediastinitis).

Who is at risk — AU epidemiology

Total PH prevalence in Australia is estimated at 50–70 per 100,000 (predominantly Groups 2 and 3). Pulmonary arterial hypertension (Group 1) affects approximately 15–50 persons per million — around 1,500 PAH patients nationally. The Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) maintains a voluntary national registry.

Idiopathic PAH has historically been more common in women (approximately 3:1 female predominance), though the ratio is narrowing with the rise of methamphetamine-associated PAH. CTEPH affects men and women approximately equally.

Symptoms and examination

Early and classical symptoms:

Dyspnoea on exertion — the dominant presenting symptom, often progressive over months to years and initially attributed to deconditioning or obesity
Fatigue and reduced exercise tolerance
Pre-syncope or syncope on exertion — a high-risk feature indicating significant haemodynamic compromise
Exertional chest pain — right ventricular (RV) ischaemia
Palpitations from atrial arrhythmias (atrial fibrillation, flutter)

Later-stage symptoms (right heart failure):

Peripheral oedema, ascites, abdominal distension
Right upper quadrant discomfort from hepatic congestion

Examination findings:

Loud, palpable P2 (pulmonary component of second heart sound) — a characteristic finding
Left parasternal RV heave
Elevated jugular venous pressure with prominent V-wave
Tricuspid regurgitation murmur (pansystolic, lower left sternal edge, louder with inspiration)
Peripheral oedema, hepatomegaly, ascites in advanced disease
Connective tissue features if relevant: sclerodactyly, telangiectasia, Raynaud’s phenomenon, digital ulcers

Investigations in general practice

Initial workup before specialist referral:

ECG — right axis deviation, RV strain pattern, right bundle branch block, peaked P waves in lead II (P-pulmonale), atrial arrhythmias
Chest X-ray — prominent main pulmonary artery, cardiomegaly with right-sided predominance, peripheral vascular pruning
Transthoracic echocardiography (TTE) — estimates pulmonary artery systolic pressure from tricuspid regurgitation jet velocity; assesses RV size and function, LV systolic and diastolic function, valvular disease, pericardial effusion; PASP above 40 mmHg or RV dysfunction should trigger specialist referral
NT-proBNP or BNP — elevated in PH; prognostic
Pulmonary function tests — spirometry and DLCO; DLCO disproportionately reduced in PAH out of proportion to spirometric impairment
Sleep study — if obstructive sleep apnoea or obesity hypoventilation suspected (Group 3)
V/Q scan — the gold standard to exclude CTEPH; mismatched perfusion defects strongly suggest CTEPH; a normal V/Q scan effectively excludes it
Connective tissue screen — ANA, ENA, anti-centromere, anti-Scl-70, RNA Pol III for systemic sclerosis-associated PAH
HIV serology; LFTs for portopulmonary; TFTs; FBC and iron studies

Right-heart catheterisation — the gold standard diagnostic test, performed by specialists. It directly measures mPAP, pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), and cardiac output. Only RHC can definitively confirm PH and classify it as pre- or post-capillary — the essential step for correct group assignment.

B. Evidence: combination therapy and surgical options

Upfront combination therapy in PAH

The AMBITION trial (Galiè et al., NEJM, 2015) randomised treatment-naive PAH patients to upfront combination therapy with ambrisentan plus tadalafil versus monotherapy with either agent. Combination therapy reduced the risk of clinical failure events by 50% (hazard ratio 0.50, 95% CI 0.35–0.72) compared with monotherapy pooled. Six-minute walk distance and NT-proBNP improvements were also significantly superior. This trial, incorporated into ESC/ERS 2022 guidance as a Class I recommendation, established upfront dual combination therapy as the standard of care for intermediate- and high-risk PAH.

For the highest-risk patients — Group 1 PAH WHO functional Class IV, rapidly deteriorating — intravenous epoprostenol (prostacyclin) remains the most potent and evidence-based treatment and has shown survival benefit in early pivotal trials.

Surgical cure of CTEPH

Pulmonary endarterectomy — surgical removal of organised thrombus from the pulmonary arteries via cardiopulmonary bypass and hypothermic circulatory arrest — can normalise pulmonary pressures and functionally cure CTEPH in patients with surgically accessible disease. Five-year survival post-PEA approaches 80%, compared with approximately 30% with medical management alone for comparable-severity CTEPH.

For patients with inoperable distal CTEPH, the CHEST-1 trial (Ghofrani et al., NEJM, 2013) showed that riociguat (a soluble guanylate cyclase stimulator) significantly improved six-minute walk distance and haemodynamics — it is now the first-line PAH-specific drug for inoperable CTEPH in ESC/ERS 2022 guidance and is PBS Section 100-listed in Australia.

Balloon pulmonary angioplasty (BPA) — catheter-based dilation of distal pulmonary arterial obstructions — is an emerging option at expert centres for inoperable CTEPH.

Exercise rehabilitation

The Mereles et al. exercise training RCT (Circulation, 2006) showed significant improvements in six-minute walk distance and quality of life with supervised exercise rehabilitation in patients with severe PAH. Subsequent studies have confirmed this across multiple centres. Supervised exercise rehabilitation — not unsupervised exertion — is now incorporated into ESC/ERS 2022 as a standard component of PAH management.

C. Group-specific treatment summary

Group 1 — PAH (specialist-led):

Upfront combination ERA + PDE5i for most patients
IV epoprostenol for highest-risk Group 1
VATS pleurodesis or lung transplantation for advanced refractory PAH
Iron repletion (target ferritin 50–300 µg/L) as standard supportive care
Vaccinations: influenza annually, pneumococcal, COVID-19
Contraception counselling — progestogen IUD preferred (avoids oestrogen-associated thrombosis)
Pregnancy: counsel against; if pregnancy occurs, urgent multidisciplinary high-risk management

Group 2 — Left heart disease:

Heart failure guideline-directed therapy — ARNI/ACEi/ARB, beta-blocker, mineralocorticoid receptor antagonist, SGLT2 inhibitor, diuretics
Mitral or aortic valve repair or replacement if indicated
PAH-specific drugs are contraindicated and must not be initiated

Group 3 — Lung disease and hypoxia:

Treat the underlying lung disease optimally
Long-term oxygen therapy (LTOT) if resting PaO₂ below 55 mmHg (or 56–59 with cor pulmonale)
CPAP for obstructive sleep apnoea
BiPAP for obesity-hypoventilation syndrome
PAH-specific drugs generally not used; selected cases with disproportionate pulmonary hypertension may be considered at specialist centres

Group 4 — CTEPH:

Lifelong anticoagulation (warfarin or DOAC)
Refer all patients to the PHSANZ network and the PEA centre at Royal Prince Alfred Hospital
Riociguat (PBS Section 100) for inoperable CTEPH
Balloon pulmonary angioplasty at experienced centres

D. Australian operations

Specialist centres: the PHSANZ network includes Royal Prince Alfred Hospital (Sydney — national PEA centre and PAH), Alfred Hospital (Melbourne), Princess Alexandra Hospital (Brisbane), Royal Adelaide Hospital, Sir Charles Gairdner Hospital (Perth), and others. Lung transplantation is available at Alfred Melbourne, RPA Sydney, Prince Charles Brisbane, and Sir Charles Gairdner WA.

MBS billing in general practice:

Initial consultation and ongoing shared care: items 23, 36, 44
ECG requested from general practice: items 11700/11701
Spirometry and DLCO: items 11506/11512/11519
V/Q scan: items 61350/61351
Echocardiography — billed by specialist: items 55135/55136
Six-minute walk test: item 12203 for eligible PAH or heart failure patients
Right-heart catheterisation — specialist: items 38253/38256
Annual health assessment: item 715
Telehealth for shared care follow-up: items 91890/91891

PBS Section 100 (Highly Specialised Drugs) for PAH — Group 1: Ambrisentan, bosentan, macitentan, sildenafil, tadalafil, riociguat, selexipag, epoprostenol, treprostinil, and iloprost are all listed under Section 100 with Authority prescription requirements. Prescribing is restricted to specialist-confirmed Group 1 PAH or Group 4 inoperable CTEPH. These drugs are not available on general schedule for Groups 2, 3, or 5.

NDIS, DSP, and travel subsidies: severe PAH or CTEPH meets NDIS functional impairment criteria. The Disability Support Pension is available for advanced PAH affecting work capacity. Patients travelling interstate for PEA surgery or lung transplantation assessment are eligible for state patient travel assistance schemes (IPTAAS in NSW, VPTAS in Victoria, PATS in Queensland, etc.).

E. Special populations

Systemic sclerosis (scleroderma): the highest-risk connective tissue disease for PAH development; approximately 8–12% of systemic sclerosis patients develop PAH. Annual echocardiographic screening is recommended by the PHSANZ and CSANZ for systemic sclerosis patients given the prognostic importance of early detection.

Congenital heart disease: PAH associated with uncorrected or late-corrected left-to-right shunts (Eisenmenger syndrome) requires specialised cardiology input. These patients may develop cyanosis, polycythaemia, and paradoxical embolism. Management is highly specialised and centre-based.

Methamphetamine use: Australia has a high crystal methamphetamine use prevalence. Methamphetamine-induced PAH is now a recognised Group 1 entity — pathophysiologically similar to idiopathic PAH and responsive to the same targeted therapies. Abstinence does not reliably reverse established pulmonary vascular disease. Coordinate with an alcohol and other drugs service alongside PHSANZ specialist management.

Mental health comorbidities: depression and anxiety are highly prevalent in PAH — the diagnostic journey is lengthy, treatment is complex, and the prognosis is confronting. Routine mental health screening and referral to PHSANZ-affiliated peer support and psychology services is recommended. The PHSANZ patient community provides peer support for Australian patients.

Older adults: Group 2 and Group 3 pulmonary hypertension are most common in older patients due to the prevalence of left heart disease and COPD. Frailty assessments inform surgical risk discussions for PEA candidates. Cardiac rehabilitation programmes through the Heart Foundation are appropriate for Group 2 patients.

When to escalate

Refer the same day (or via 000) if:

Pre-syncope or syncope on exertion in a patient with known PH — indicates severe haemodynamic compromise
Rapid clinical deterioration with rising NT-proBNP, worsening oedema, or new haemoptysis
New or worsening right heart failure: tachycardia, hypotension, oliguria, cold peripheries

Semi-urgent specialist referral for:

Echocardiography showing PASP above 40 mmHg or RV dysfunction without a clear explanation
Unexplained progressive dyspnoea on exertion not explained by spirometry, cardiac function, or deconditioning
Previous pulmonary embolism with ongoing symptoms — CTEPH screening
Suspected CTD with pulmonary symptoms — scleroderma screening
Abnormal DLCO disproportionate to spirometric impairment

GP shared care responsibilities for established PH:

Annual influenza and pneumococcal vaccinations; COVID-19 boosters
Contraception counselling for women of reproductive age with Group 1 PAH
Monitoring for drug interactions (riociguat is incompatible with PDE5 inhibitors; sildenafil and tadalafil have significant interactions with nitrates and antihypertensives)
Iron studies and repletion — common deficiency in PAH adversely affects exercise capacity

What this article is and is not

This is general health information drawn from the ESC/ERS 2022 Pulmonary Hypertension Guideline (Humbert et al.), WSPH 2018 clinical classification (Simonneau et al.), Therapeutic Guidelines (eTG), the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ), Cardiac Society of Australia and New Zealand (CSANZ), Lung Foundation Australia, and the AMBITION, CHEST-1, INCREASE, and Mereles exercise trials. It is not personal medical advice and does not create a doctor–patient relationship.

For Australian consumer resources: Lung Foundation Australia, PHSANZ patient information, HealthDirect — Pulmonary hypertension, Better Health Channel.

Sources cited

Frequently asked questions

What is pulmonary hypertension and how is it different from normal high blood pressure?

Regular high blood pressure (hypertension) refers to elevated pressure in the systemic arteries — the blood vessels supplying the body. Pulmonary hypertension is a separate condition affecting only the arteries supplying the lungs. The right side of the heart pumps blood through these pulmonary arteries, so when the pressure in them is elevated the right ventricle has to work harder, eventually causing it to enlarge and weaken. Pulmonary hypertension has five distinct clinical groups with different causes — left heart disease, lung disease, clots, rare vascular conditions, and others — and the treatments differ fundamentally between groups.
Why does misidentifying the group of pulmonary hypertension matter?

The drugs developed for Group 1 (pulmonary arterial hypertension) — such as sildenafil, bosentan, and riociguat — work by dilating the pulmonary arteries. In Group 2 pulmonary hypertension (caused by left-sided heart disease), the lung pressure is elevated because the left heart is not working well, causing a back-pressure. Giving pulmonary arterial dilators to a patient with Group 2 increases blood flow into the lungs faster than the left heart can cope with, potentially causing acute pulmonary oedema. Multiple clinical trials have confirmed this risk. The ESC/ERS 2022 guideline categorises PAH-specific drugs as contraindicated in Group 2.
What are the symptoms that should trigger investigation for pulmonary hypertension?

The most common and earliest symptom is breathlessness on exertion that is out of proportion to apparent fitness levels — often misattributed to deconditioning for months or years. Other important symptoms include: fatigue and reduced exercise tolerance; near-fainting or fainting on exertion (pre-syncope or syncope); chest pain with exercise (right ventricular angina); palpitations (from atrial arrhythmias); and, in later stages, ankle swelling and abdominal distension from right heart failure. The typical diagnostic delay is approximately two years from symptom onset to diagnosis, largely because early symptoms are non-specific.
What is CTEPH and can it be cured?

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in some patients after a pulmonary embolism (blood clot in the lungs). The clots fail to resolve fully and instead organise into fibrous obstruction of the pulmonary arteries, causing persistently elevated pressures. For patients whose obstructions are surgically accessible, pulmonary endarterectomy (PEA) — a complex open-heart surgery — can remove the organised clots and normalise pulmonary pressures. Australia's PEA centre is at Royal Prince Alfred Hospital in Sydney; referral is through the PHSANZ specialist network. Even for patients unsuitable for surgery, balloon pulmonary angioplasty and riociguat (PBS-listed for inoperable CTEPH) improve symptoms and prognosis.
Why is pregnancy so dangerous for women with pulmonary arterial hypertension?

Pulmonary arterial hypertension during pregnancy carries an estimated maternal mortality of 30–50%, despite modern treatments. The cardiovascular demands of pregnancy — increased blood volume, heart rate and cardiac output — place an extreme burden on the right ventricle, which is already working at its limit in PAH. Labour and delivery are particularly high-risk periods. The ESC/ERS 2022 guideline categorises pregnancy as a Class III recommendation (harm outweighs benefit) in PAH. Effective contraception is essential and should be discussed with every woman with PAH of reproductive age. A progestogen intrauterine device (Mirena) avoids oestrogen-containing preparations, which carry additional thromboembolic risk.
What drugs are used for pulmonary arterial hypertension and are they on the PBS?

Group 1 PAH is treated with targeted vasodilator therapy, typically as upfront combination treatment for intermediate- and high-risk patients. Drug classes include endothelin-receptor antagonists (ambrisentan, bosentan, macitentan), PDE5 inhibitors (sildenafil, tadalafil), soluble guanylate cyclase stimulators (riociguat — cannot be combined with PDE5i), and prostacyclin pathway agents (epoprostenol IV, treprostinil, iloprost inhaled, selexipag oral). These are PBS Section 100 Highly Specialised Drugs — available at approved specialist centres for confirmed Group 1 PAH or inoperable Group 4 CTEPH, with Authority prescription requirements. They are not available for Groups 2 or 3.

Source quality

Sources grouped by evidence tier. AU primary tier first; international where AU is silent or lagging; named-author reconstruction where guidelines have not yet caught up. How tiers work.