01OverviewDefinition, clinical context and the essential points that orientate the chapter.
PH is a haemodynamic state with five broad groups: PAH; PH due to left-heart disease; lung disease/hypoxia; pulmonary artery obstruction including CTEPH; and unclear/multifactorial mechanisms. Treatments differ fundamentally by group.
Symptoms reflect limited RV reserve and are often nonspecific. Referral should accelerate when there is exertional syncope, rapid progression, RV dysfunction, suspected PAH or evidence of chronic thromboembolism.
Key points
- Pulmonary hypertension is haemodynamically defined by mean pulmonary artery pressure greater than 20 mmHg at rest on right-heart catheterisation.
- Pre-capillary PH also requires pulmonary artery wedge pressure 15 mmHg or less and pulmonary vascular resistance greater than 2 Wood units.
- Echo estimates probability; it does not confirm PH or distinguish all five clinical groups.
- Use a three-step approach: clinical suspicion, echocardiographic detection, then confirmation/classification in a PH centre.
- Always consider left-heart disease, lung/hypoxic disease and chronic thromboembolic PH before labelling PAH.
- A ventilation-perfusion scan is the key screening test for CTEPH; a normal perfusion scan makes it unlikely.
- PAH-targeted drugs should be initiated and escalated by a specialist PH service, generally using risk-based combination therapy.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Pulmonary arterial hypertension
Idiopathic, heritable or drug-associated disease, connective-tissue disorders, portal hypertension, HIV and congenital shunts can remodel small pulmonary arteries and raise precapillary vascular resistance.
Left-heart disease
Left-ventricular dysfunction, impaired relaxation or valve disease can raise left-atrial and pulmonary venous pressure, producing post-capillary pulmonary hypertension and sometimes secondary vascular remodelling.
Lung disease and hypoxia
Chronic parenchymal lung disease can reduce the pulmonary vascular bed, while sustained hypoxia, including from some sleep-related breathing disorders, drives vasoconstriction and may promote vascular remodelling.
Chronic pulmonary arterial obstruction
Organised thromboembolic material can obstruct pulmonary arteries after venous thromboembolism. Other multifactorial conditions may also elevate pressure through combined vascular, cardiac and systemic mechanisms.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Pulmonary vascular load develops
Vascular remodelling, hypoxic constriction, chronic obstruction or transmitted left-atrial pressure can increase the pressure required from the right ventricle to eject blood.
- 2Right-ventricular adaptation
The right ventricle initially hypertrophies and increases contractility to preserve stroke volume against the higher afterload, often masking symptoms until cardiovascular reserve becomes limited.
- 3Maladaptation and dilatation
Persistent load may eventually cause right-ventricular dilatation, ischaemia and reduced contractility. Annular enlargement can add functional tricuspid regurgitation and further volume stress.
- 4Ventricular interaction
A dilated, pressure-loaded right ventricle displaces the interventricular septum, reducing left-ventricular filling and systemic cardiac output, particularly during exertion when demand rises.
- 5Systemic congestion and low output
Falling forward flow causes fatigue, syncope and hypotension, while rising systemic venous pressure produces oedema, ascites and congestive renal or liver dysfunction.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Progressive exertional dyspnoea, fatigue, reduced exercise capacity, chest pressure or palpitations without a sufficient alternative explanation.
Loud P2, RV heave, tricuspid regurgitation murmur, raised JVP, hepatomegaly, ascites and oedema.
Exertional syncope, hypotension, WHO functional class IV symptoms or rapidly worsening right-heart failure.
Connective-tissue disease, portal hypertension, HIV, congenital shunt, appetite-suppressant/toxin exposure, lung disease or prior PE should direct classification.
Persistent dyspnoea after PE, mismatched perfusion defects or chronic thromboembolic signs on CT warrants expert operability assessment.
05InvestigationsWhat to request, why it matters and how to interpret it.
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 basic blood testsFirst step - Why
- Look for RV strain, alternative disease, anaemia, renal/liver dysfunction, thyroid disease and treatment constraints.
- Interpretation and limitations
- Normal ECG does not exclude mild PH; advanced RV strain increases concern.
- 02
BNP or NT-proBNP - Why
- Assess RV wall stress and prognosis.
- Interpretation and limitations
- Interpret with age, renal function and rhythm; use trends within a validated risk model rather than a single diagnostic cutoff.
- 03
Transthoracic echocardiography - Why
- Estimate PH probability and assess RV/LV, valves and congenital shunts.
- Interpretation and limitations
- Use tricuspid-regurgitation velocity plus additional signs; an estimated pressure alone is insufficient.
- 04
Pulmonary function tests, arterial gases and chest CT - Why
- Identify parenchymal lung disease, hypoxia and other thoracic causes.
- Interpretation and limitations
- A disproportionately low gas transfer can support pulmonary vascular disease but is not specific.
- 05
Ventilation-perfusion scan - Why
- Screen for CTEPH in newly diagnosed or unexplained PH.
- Interpretation and limitations
- Mismatched perfusion defects require CTEPH-centre imaging and operability review.
- 06
Right-heart catheterisation - Why
- Confirm PH, measure PAWP/PVR/cardiac output and classify haemodynamics.
- Interpretation and limitations
- Required before PAH-specific treatment; vasoreactivity testing is reserved for idiopathic, heritable or drug-associated PAH in expert centres.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Left-sided heart failure
Left-atrial enlargement, ventricular or valve abnormalities and raised filling pressure favour left-heart disease; specialist catheter measurements separate this from a precapillary pulmonary arterial phenotype.
Parenchymal lung disease
Prominent airflow limitation, abnormal gas transfer and characteristic chest imaging favour chronic lung disease, although pulmonary hypertension may coexist when vascular burden is disproportionate.
Chronic thromboembolic disease
Previous embolism and mismatched perfusion defects suggest chronic thromboembolic pulmonary hypertension; a normal perfusion study makes this mechanism substantially less likely.
Anaemia or thyroid disease
Fatigue, breathlessness and palpitations may arise from systemic illness; blood tests identify these contributors, while right-heart signs and vascular imaging support pulmonary hypertension.
Coronary disease or deconditioning
Exertional chest pressure or breathlessness may reflect myocardial ischaemia or poor conditioning. These can coexist with pulmonary hypertension, so right-heart or pulmonary-vascular abnormalities still need an explanation.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01FirstClinical suspicionFirst stepUnexplained dyspnoea, syncope, RV signs or a condition associated with PAH/CTEPH.+
- 1Assess acuity, oxygen saturation, ECG, chest radiograph, FBC, renal/liver/thyroid tests and BNP/NT-proBNP.
- 2Obtain expert echocardiography to grade PH probability and examine left heart, RV and shunts.
- 3Investigate common causes with lung testing/imaging and a V/Q scan rather than assuming idiopathic PAH.
- 4Refer intermediate/high echo probability, suspected PAH or CTEPH to an NHS specialist PH centre.
02NextConfirm and classifySpecialist evaluation for likely PH.+
- 1Complete cause-specific serology, imaging, functional assessment and congenital/portal/HIV evaluation as indicated.
- 2Perform right-heart catheterisation with accurate zeroing, wedge pressure and cardiac output measurement.
- 3Classify pre- versus post-capillary physiology and assign the clinical PH group.
- 4For CTEPH, obtain multidisciplinary pulmonary endarterectomy, balloon angioplasty and medical-therapy assessment.
03TreatmentRisk-based specialist therapyConfirmed PAH or CTEPH after classification.+
- 1Optimise oxygenation, volume status, exercise/rehabilitation, vaccination and the underlying condition.
- 2For PAH, use guideline risk assessment to select initial oral combination therapy or parenteral prostacyclin-based treatment in high risk.
- 3Reassess early using symptoms, WHO class, 6-minute walk distance, biomarkers, RV imaging and haemodynamics when needed.
- 4EscalationEscalate combination therapy and consider transplantation if a low-risk profile is not achieved.
04EscalationAcute right-heart failureEscalationSyncope, hypotension, rising lactate, oliguria, severe congestion or arrhythmia.+
- 1Admit to critical care with immediate PH-centre involvement and search for infection, PE, anaemia, arrhythmia and treatment interruption.
- 2Maintain systemic pressure and RV perfusion; use carefully titrated diuresis for congestion and avoid indiscriminate fluid loading.
- 3Continue established PAH therapy and never abruptly interrupt a prostacyclin infusion.
- 4EscalationEscalate inotropes/vasopressors, inhaled pulmonary vasodilators or mechanical/transplant support through the expert team.
Key medicines and prescribing safety4 treatments · regimens, roles and cautions+
Sildenafil
20 mg orally three times daily for PAH.Contraindicated with nitrates and riociguat; hypotension, visual effects and CYP3A interactions.
Bosentan
62.5 mg orally twice daily for 4 weeks, then 125 mg twice daily if tolerated.Teratogenic; monthly liver tests, haemoglobin monitoring and major drug interactions including reduced hormonal-contraceptive reliability.
Macitentan
10 mg orally once daily.Specialist initiation; teratogenicity, anaemia, oedema and liver assessment. Ensure effective pregnancy prevention.
Riociguat
Start 1 mg orally three times daily for 2 weeks. If systolic BP is at least 95 mmHg without hypotensive symptoms, increase by 0.5 mg three times daily every 2 weeks to a maximum 2.5 mg three times daily; reduce by 0.5 mg three times daily if systolic BP falls below 95 mmHg with symptoms.Do not combine with PDE-5 inhibitors or nitrates and do not start when systolic BP is below 95 mmHg. Contraindicated in pregnancy and severe hepatic impairment; not recommended when creatinine clearance is below 30 mL/min. Smoking lowers exposure, so starting or stopping smoking can require specialist dose review.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Progressive right-sided heart failure
Sustained afterload may eventually exhaust right-ventricular compensation, causing venous congestion, oedema, ascites, hepatic discomfort and repeated decompensation with a worsening prognosis.
Functional tricuspid regurgitation
Right-ventricular and annular dilatation prevent leaflet coaptation. Regurgitant volume then aggravates chamber enlargement, systemic venous pressure and congestive symptoms of right-sided failure.
Arrhythmia
Right-atrial stretch and chamber remodelling predispose to atrial tachyarrhythmias, which reduce filling and output and can precipitate abrupt clinical deterioration.
Syncope, shock and sudden death
A failing right ventricle cannot increase output during exertion or acute stress. Systemic hypotension may impair right-coronary perfusion, creating a spiral towards shock or arrest.
Congestive organ dysfunction
Persistently raised venous pressure impairs renal filtration and causes hepatic congestion, while low output further compromises organ perfusion and complicates fluid management.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- At specialist reviews, record WHO functional class, syncope, right-heart-failure signs and treatment adherence.
- Trend 6-minute walk or cardiopulmonary exercise capacity, BNP/NT-proBNP and RV imaging within a risk model.
- Monitor blood pressure, oxygenation, weight/volume status, renal/liver function and medicine-specific laboratory tests.
- Repeat haemodynamics when clinical response is unclear, before major escalation or as the PH centre recommends.
- Review contraception/pregnancy risk, anticoagulation indication, vaccinations, exercise and emergency contact plan.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Echo is a probability test
Right-heart catheterisation establishes the diagnosis and separates pre- from post-capillary physiology.
V/Q before reassurance
CT pulmonary angiography can miss chronic distal disease; V/Q scanning remains the screening test for CTEPH.
Treat the group
PAH drugs are not routine therapy for PH caused by left-heart or lung disease and may cause harm.
The RV drives prognosis
Symptoms, natriuretic peptides and outcomes reflect the ability of the RV to adapt to afterload.
Never stop prostacyclin abruptly
Interruption of continuous epoprostenol or treprostinil can cause rapid rebound PH and collapse.
11Common pitfallsFrequent interpretation and management errors.
- 01
Diagnosing PH from an echo-estimated systolic pressure alone.
- 02
Starting PAH-targeted therapy before right-heart catheterisation and classification.
- 03
Failing to obtain a V/Q scan when CTEPH is possible.
- 04
Giving large empiric fluid boluses in decompensated RV failure.
- 05
Combining sildenafil with nitrates or riociguat.