Pulmonary arterial hypertension

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

PAH is characterised by progressive pulmonary arteriolar remodelling, vasoconstriction and thrombosis that raise pulmonary vascular resistance. The right ventricle first hypertrophies, then dilates as afterload exceeds its reserve. Death is usually related to right-heart failure rather than failure of oxygenation alone. Clinical status can deteriorate abruptly with infection, arrhythmia, anaemia, pregnancy, surgery or interruption of therapy.

Diagnosis is deliberately staged. Non-invasive testing estimates probability and looks for a cause, while the designated centre confirms haemodynamics by right-heart catheterisation and completes classification. Left atrial hypertension, COPD, interstitial lung disease, hypoventilation and CTEPH are common alternative mechanisms. Treating the wrong mechanism with a pulmonary vasodilator can cause harm.

Modern care uses repeated risk assessment rather than one drug ladder. Functional class, exercise capacity, right-ventricular imaging, biomarkers, haemodynamics, symptoms and trajectory determine therapy escalation and transplant referral. Verify specialist regimens, contraception requirements and commissioning criteria against the current pulmonary-hypertension-centre protocol.

Key points

Pulmonary hypertension is a haemodynamic state with several causes; pulmonary arterial hypertension is the pre-capillary group after chronic thromboembolism, significant lung disease and left-heart disease have been excluded.
PAH may be idiopathic, heritable, drug-associated or linked to connective-tissue disease, congenital heart disease, portal hypertension or HIV.
Early symptoms are nonspecific: exertional breathlessness, fatigue, chest pressure and reduced exercise tolerance. Exertional presyncope or syncope is a high-risk feature.
ECG, chest radiograph and natriuretic peptide can support suspicion but may be normal early. Echocardiography estimates probability and assesses right-heart consequence.
Right-heart catheterisation at a designated centre is required before definitive classification and targeted treatment; an estimated echo pressure is not enough.
A V/Q scan is required to exclude chronic thromboembolic disease even when a CTPA is not reported to show emboli.
Treatment is based on multidimensional risk and commonly uses combination therapy across endothelin, nitric-oxide and prostacyclin pathways, initiated and monitored only by designated services.
Do not give PAH drugs empirically for pulmonary hypertension from left-heart or parenchymal lung disease; vasodilation can worsen pulmonary oedema or gas exchange.
Pregnancy carries major maternal risk in PAH and several therapies are teratogenic. Ask reproductive intentions early and arrange specialist contraception and preconception counselling.
NHS England updated its targeted-therapy commissioning policy in July 2026; eligibility and combinations must be checked live, with separate arrangements in devolved nations.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Idiopathic or heritable disease

Some patients have no associated condition, while pathogenic variants affecting pulmonary vascular signalling create familial or apparently sporadic susceptibility.

Connective-tissue disease

Systemic sclerosis and other autoimmune disorders cause pulmonary arteriopathy, sometimes alongside interstitial or left-heart disease that changes classification.

Congenital and portal vascular disease

Systemic-to-pulmonary shunts, portal hypertension and selected developmental conditions expose pulmonary vessels to abnormal flow or signalling.

Drugs, toxins and infection

Certain appetite suppressants, stimulants, toxins, HIV and schistosomiasis are recognised associations requiring a careful exposure and epidemiological history.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Endothelial imbalance
Reduced vasodilator and antiproliferative signalling combines with increased vasoconstrictive and growth pathways in small pulmonary arteries.
2
Vascular remodelling
Smooth-muscle, intimal and complex plexiform changes narrow vessel lumens and reduce the compliant pulmonary vascular bed.
3
Rising right-ventricular afterload
Pulmonary vascular resistance increases, limiting flow augmentation during exercise and progressively loading the right ventricle, which links the underlying lesion to the observed respiratory dysfunction.
4
Right-heart decompensation
Initially adaptive hypertrophy gives way to dilation, tricuspid regurgitation, low cardiac output and systemic venous congestion.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Early pulmonary vascular limitation

Unexplained exertional breathlessness, fatigue or chest discomfort with declining exercise capacity may precede obvious examination signs, especially in systemic sclerosis or a family with heritable PAH.

Established right-heart pressure load

A loud pulmonary second sound, parasternal heave, right-sided third heart sound, raised JVP and functional tricuspid regurgitation support advanced pulmonary vascular disease.

High-risk PAHRed flag

Presyncope or syncope, rapid symptom progression, rest symptoms, hypotension, cool peripheries, rising natriuretic peptide, severe right-ventricular dysfunction or pericardial effusion indicates urgent specialist review.

Decompensated right-heart failureRed flag

Peripheral oedema, ascites, hepatic congestion, oliguria, confusion and low output may coexist with clear lungs. Atrial arrhythmia or sepsis can precipitate rapid collapse.

Associated PAH phenotype

Raynaud phenomenon, sclerodactyly, congenital shunt, portal hypertension, HIV risk, appetite-suppressant or toxin exposure, or a family history guides aetiological testing and counselling.

A different pulmonary-hypertension group

Orthopnoea and left-atrial disease, substantial emphysema or fibrosis, sleep-disordered breathing, or mismatched perfusion defects point away from isolated PAH and alter treatment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
ECG, chest radiograph and natriuretic peptideFirst step
Why
Support pulmonary-hypertension suspicion, identify right-heart strain and provide prognostic baseline.
Interpretation and limitations
Right-axis deviation, right-ventricular hypertrophy, enlarged central pulmonary arteries or raised BNP/NT-proBNP support disease but normal results do not exclude early PAH.
02
Transthoracic echocardiography
Why
Estimate pulmonary-hypertension probability, assess right-ventricular size and function, and identify left-heart or congenital disease.
Interpretation and limitations
Use multiple echo signs rather than a single estimated systolic pressure. Severe right-heart dysfunction or pericardial fluid increases risk and urgency.
03
Pulmonary function, gas transfer, oximetry and thoracic CT
Why
Identify significant airway, parenchymal or hypoventilation-related disease and quantify physiological burden.
Interpretation and limitations
A disproportionately low gas transfer can support pulmonary vascular disease but is nonspecific. The extent of lung disease determines classification and whether targeted therapy is appropriate.
04
Ventilation–perfusion scan
Why
Exclude chronic thromboembolic pulmonary hypertension as a treatable alternative.
Interpretation and limitations
Mismatched segmental defects require a CTEPH pathway. A normal perfusion scan makes chronic thromboembolic obstruction unlikely.
05
Aetiology blood tests and clinical screening
Why
Look for connective-tissue disease, HIV, liver disease, thyroid disease, anaemia and other associated conditions.
Interpretation and limitations
Select tests from history and phenotype; autoantibodies without compatible clinical disease should not be allowed to shortcut haemodynamic classification.
06
Right-heart catheterisation with selective vasoreactivity testing
Why
Confirm haemodynamics, distinguish pre- from post-capillary disease and identify the rare vasoreactive phenotype.
Interpretation and limitations
Testing and fluid or exercise challenges are specialist procedures. A positive vasoreactivity result applies to a small defined group and should not prompt community calcium-channel blocker use.
07
Functional and risk assessment
Why
Combine WHO functional class, walk or exercise testing, biomarkers, imaging and haemodynamics to guide therapy intensity.
Interpretation and limitations
No single measure is sufficient. Direction of change and right-ventricular reserve are more informative than an isolated estimated pressure.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Left-heart pulmonary hypertension

Elevated left-sided filling pressure from ventricular or valve disease defines a post-capillary mechanism rather than PAH.

Chronic thromboembolic pulmonary hypertension

Mismatched perfusion defects and organised thrombus identify a potentially operable vascular obstruction, making dedicated pulmonary-hypertension pathway assessment important before another vascular label is accepted.

Lung-disease-associated hypertension

Substantial emphysema, fibrosis, hypoxia or sleep-disordered breathing may explain raised pressure through parenchymal and hypoxic mechanisms.

Deconditioning or anaemia

Exertional breathlessness with normal pulmonary haemodynamics may arise from low fitness, reduced oxygen carriage or systemic illness.

Pulmonary veno-occlusive disease

Characteristic CT findings, very low gas transfer and pulmonary oedema with vasodilator exposure suggest rare post-capillary small-vein obstruction.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SuspectFrom unexplained breathlessness to referralFirst stepSymptoms, high-risk condition or examination suggests pulmonary vascular disease.

1Assess urgency, oxygenation, ECG, chest radiograph, natriuretic peptide and routine causes of breathlessness including anaemia and thyroid disease.
2Obtain echocardiography and targeted lung assessment; do not diagnose PAH from symptoms or an echo estimate alone.
3Arrange V/Q scanning when pulmonary hypertension is suspected so CTEPH is not missed.
4Refer moderate or high echo probability, unexplained right-heart changes or a concerning high-risk phenotype to a designated PH centre.

02ClassifyConfirm the mechanism before treatmentNon-invasive testing indicates possible pulmonary hypertension.

1The specialist service integrates echo, lung imaging and physiology, perfusion imaging, associated-condition testing and previous treatment.
2Right-heart catheterisation confirms the haemodynamic pattern and measures severity; selective vasoreactivity testing is used only when indicated.
3Assign the pulmonary-hypertension group and identify modifiable contributors such as hypoxaemia, shunt, portal disease or drug exposure.
4Discuss the case in the specialist MDT and record diagnosis, risk, treatment goals and shared-care responsibilities.

03TreatRisk-directed specialist PAH therapyPAH is confirmed at a designated centre.

1Optimise supportive care, vaccination, supervised activity, oxygen when hypoxaemic, diuresis for congestion and associated-condition treatment.
2Initiate commissioned pathway-targeted therapy, commonly combination treatment, after reviewing hypotension, interactions, liver function, pregnancy risk and patient preference.
3EscalationReassess risk at defined intervals; escalate oral, inhaled, subcutaneous or intravenous therapy when the low-risk goal is not reached.
4Refer early for transplant assessment when high risk persists despite maximal treatment rather than waiting for refractory shock.

04EmergencyDecompensated PAH and right-heart failureSyncope, low output, hypotension, arrhythmia or rapidly worsening congestion.

1Contact the patient’s PH centre immediately, use monitored ABCDE care and correct hypoxaemia while seeking the precipitant.
2Continue established PAH therapy, especially continuous prostacyclin, and confirm that pumps, lines and supply are functioning.
3Use cautious diuresis or specialist vasoactive support based on congestion and perfusion; avoid reflex fluid loading and unplanned intubation.
4Discuss critical-care transfer, rescue therapy, transplant options and treatment ceilings with the expert team and patient where possible.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Augments nitric-oxide signalling as part of risk-directed single or combination PAH therapy.

PDE5 inhibitor such as sildenafil

Initiated at a designated pulmonary-hypertension centre using the current commissioned regimen and BNF, with dose review for interactions and organ dysfunction.

Do not combine with nitrates or riociguat. Watch hypotension, visual symptoms and CYP interactions; community initiation for unclassified pulmonary hypertension is unsafe.

Reduces endothelin-mediated vasoconstriction and remodelling in confirmed PAH.

Endothelin-receptor antagonist

Specialist selection and dosing follow the current NHS policy, product monograph and centre protocol; combinations are risk- and eligibility-dependent.

Agents differ in hepatic, haemoglobin, oedema, interaction and pregnancy risks. Teratogenicity requires a documented pregnancy-prevention programme where relevant.

Provides potent pulmonary vasodilation and antiproliferative therapy, particularly in high-risk or inadequately controlled PAH.

Prostacyclin-pathway therapy

Oral, inhaled, subcutaneous or continuous intravenous treatment is titrated only by the expert centre to efficacy and tolerability.

Abrupt interruption of continuous therapy can cause fatal rebound deterioration. Pump or line failure is an emergency; adverse effects and line infection require specialist management.

Relieves systemic venous congestion and improves symptoms in right-heart failure.

Loop diuretic for congestion

Titrate oral or intravenous treatment to weight, oedema, renal function, electrolytes, blood pressure and specialist-defined dry weight.

Over-diuresis lowers preload and cardiac output, while under-treatment worsens organ congestion. Monitor creatinine, sodium, potassium and symptoms closely.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Right-heart failure

Progressive pressure overload causes oedema, ascites, hepatic congestion, renal dysfunction and low cardiac output, creating an additional need for recognition and targeted treatment.

Syncope

The restricted pulmonary circulation cannot increase cardiac output during exertion, causing transient cerebral hypoperfusion and marking advanced physiological limitation.

Arrhythmia

Right-atrial dilation and pressure stress promote atrial tachyarrhythmias that can abruptly reduce ventricular filling and output.

Haemoptysis

Distended bronchial collateral vessels or pulmonary vascular injury can bleed, occasionally severely, particularly when baseline cardiopulmonary reserve is limited.

Sudden death

Acute right-ventricular failure, arrhythmia or massive haemorrhage may cause abrupt collapse in advanced disease, and potentially prolonging treatment and functional recovery.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

At each review document WHO functional class, syncope, chest pain, activity, oxygenation, blood pressure, JVP, oedema and signs of low output.
Use the centre risk tool combining exercise capacity, natriuretic peptide, right-heart imaging and haemodynamics rather than following estimated pulmonary pressure alone.
Apply therapy-specific liver, haemoglobin, renal, blood-pressure, interaction and pregnancy-prevention monitoring exactly as directed by the PH service.
Confirm continuous-therapy pump function, line integrity, emergency supplies and out-of-hours contacts at every transition of care.
Review vaccination, supervised rehabilitation, psychosocial support, travel and altitude planning, and reproductive goals.
Escalate new arrhythmia, infection, anaemia, haemoptysis, syncope or rapid functional decline because minor physiological insults can destabilise the right ventricle.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Pressure is not the whole disease

Right-ventricular adaptation and cardiac output largely determine symptoms and survival. A modest pressure estimate can coexist with advanced failing-right-ventricle physiology.

Vasoreactivity is a narrow exception

Only a small specialist-defined subgroup benefits from high-dose calcium-channel blockers. An empirical community trial risks hypotension and right-heart collapse.

Intubation can be hazardous

Induction, positive pressure and loss of sympathetic tone can sharply reduce venous return and right-ventricular perfusion. Expert haemodynamic planning is required.

Pregnancy discussion is routine care

Maternal risk and teratogenic therapies make preconception counselling and reliable contraception essential, while respecting autonomy and involving maternal-medicine expertise.

Do not forget CTEPH

A V/Q scan remains necessary because identifying surgically treatable chronic thromboembolism changes prognosis more than choosing among PAH tablets.

11Common pitfallsFrequent interpretation and management errors.

01
Calling an elevated echo pressure pulmonary arterial hypertension.
02
Skipping V/Q scanning because CTPA shows no acute embolus.
03
Prescribing PAH vasodilators for left-heart or hypoxic lung disease without specialist classification.
04
Giving large fluid boluses to a congested, pressure-loaded right ventricle.
05
Interrupting a prostacyclin infusion during admission, imaging or transfer.
06
Ignoring reproductive intentions and medicine teratogenicity.
07
Waiting for rest symptoms before referring a high-risk associated condition such as systemic sclerosis.