Eisenmenger syndrome

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

Pulmonary resistance eventually approaches or exceeds systemic resistance, reversing flow across a VSD, PDA, ASD or more complex communication. Chronic hypoxaemia affects blood viscosity, haemostasis, kidneys, urate, iron balance and multiple organs.

Care is centralised in an ACHD-pulmonary-hypertension service. Treatment aims to preserve systemic perfusion, reduce pulmonary vascular load, correct reversible contributors and recognise complications early rather than normalise the oxygen saturation.

Key points

Eisenmenger syndrome is severe pulmonary vascular disease caused by a longstanding systemic-to-pulmonary shunt, with bidirectional or right-to-left reversal and cyanosis.
Never close the causal shunt once Eisenmenger physiology is established.
Secondary erythrocytosis is an appropriate response to hypoxaemia; routine venesection is harmful.
Check iron status because iron deficiency worsens symptoms and makes microcytic blood less deformable despite a lower haemoglobin.
Avoid dehydration, systemic hypotension, air in intravenous lines and unplanned general anaesthesia.
Routine anticoagulation is not recommended without a separate indication because thrombosis and bleeding coexist.
Pregnancy carries very high maternal and fetal risk; provide expert pre-pregnancy counselling and Pregnancy Heart Team care if pregnancy occurs.

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

Large ventricular or arterial shunts

An unrepaired ventricular septal defect or persistent arterial duct exposes pulmonary vessels to systemic pressure and high flow. These post-tricuspid communications often drive pulmonary vascular disease relatively early.

Atrial-level shunts

A large atrial septal communication mainly creates pulmonary volume overload at lower pressure. Pulmonary vascular resistance may still rise over years, eventually permitting bidirectional or right-to-left flow.

Complex congenital communications

Atrioventricular septal defects and other complex lesions can provide unrestricted systemic-to-pulmonary flow. Lesion anatomy, size, associated abnormalities and duration before repair determine the pulmonary vascular burden.

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

1
Persistent left-to-right flow
A large congenital communication initially directs oxygenated systemic blood back to the pulmonary circulation. Excess flow, and sometimes systemic pressure, repeatedly stresses the pulmonary arterial endothelium.
2
Pulmonary vascular remodelling
Endothelial dysfunction, vasoconstriction and structural thickening progressively narrow pulmonary vessels. Pulmonary vascular resistance rises and, once Eisenmenger physiology is established, is usually no longer safely reversible by closing the shunt.
3
Shunt reversal
When pulmonary resistance approaches or exceeds systemic resistance, flow becomes bidirectional or right-to-left. The communication then decompresses the pressure-loaded right ventricle and helps preserve cardiac output.
4
Systemic hypoxaemia
Deoxygenated blood bypasses the lungs and enters the systemic circulation, producing central cyanosis and clubbing. Exercise or systemic vasodilation may increase right-to-left flow and worsen desaturation.
5
Multisystem adaptation
Chronic hypoxaemia stimulates erythropoietin and secondary erythrocytosis, which supports oxygen carriage. Concomitant abnormalities of haemostasis, renal handling, iron balance and urate metabolism contribute to the wider bleeding, thrombotic and metabolic complications.

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

Chronic cyanosis

Central cyanosis, digital clubbing, reduced exercise tolerance and secondary erythrocytosis in a person with a large congenital shunt.

Pulmonary-hypertension signs

Right-ventricular heave, loud P2, tricuspid regurgitation murmur, raised JVP and right-heart failure.

Hyperviscosity-like symptoms

Headache, dizziness, visual disturbance, fatigue or paraesthesia first require assessment for dehydration and iron deficiency.

Haemostatic complexity

Haemoptysis, epistaxis or bruising can coexist with in-situ pulmonary thrombosis and paradoxical embolism.

Acute decompensationRed flag

Syncope, rapidly falling saturation, arrhythmia, infection, haemoptysis or fluid overload is high risk.

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
Pulse oximetry at rest and with exertionFirst step
Why
Document cyanosis and functional change.
Interpretation and limitations
Trend against the person's baseline; an abrupt fall suggests an acute precipitant rather than simple disease progression.
02
FBC, ferritin and transferrin saturation
Why
Assess secondary erythrocytosis and iron deficiency.
Interpretation and limitations
Haemoglobin must be interpreted against saturation; a seemingly normal value may represent relative anaemia in a markedly cyanosed patient.
03
Renal, liver, urate and haemolysis profile
Why
Identify multisystem complications and medicine constraints.
Interpretation and limitations
Creatinine can be misleading with altered muscle mass; interpret trends and clinical state.
04
ECG, echocardiography and CMR
Why
Define anatomy, shunt, right-heart size/function, valves and pulmonary pressures.
Interpretation and limitations
Serial RV function and clinical risk markers guide therapy; echo pressure estimates do not replace specialist haemodynamics.
05
Right-heart catheterisation
Why
Confirm haemodynamics when diagnosis or targeted-therapy strategy is uncertain.
Interpretation and limitations
Perform only in an expert congenital PH centre with meticulous air avoidance and interpretation of shunt physiology.

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

Cyanotic congenital heart disease without Eisenmenger physiology

Some congenital lesions cause right-to-left flow from their anatomy rather than acquired pulmonary vascular reversal. Cyanosis from infancy and lesion-specific imaging without severe pulmonary resistance support this distinction.

Idiopathic or heritable pulmonary arterial hypertension

Severe pulmonary hypertension may open a small patent foramen ovale and cause desaturation. Absence of a large causal congenital shunt on expert imaging argues against Eisenmenger syndrome.

Chronic thromboembolic pulmonary hypertension

Organised pulmonary emboli can cause pulmonary hypertension, right-heart failure and exertional syncope. Mismatched perfusion defects and chronic thromboembolic changes on dedicated imaging provide the discriminating evidence.

Pulmonary arteriovenous malformation

An intrapulmonary right-to-left connection can produce cyanosis, clubbing and paradoxical emboli. Delayed contrast passage on bubble echocardiography and vascular lesions on chest imaging distinguish it.

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

01FirstNew suspected Eisenmenger physiologyFirst stepCongenital shunt plus cyanosis or severe pulmonary hypertension.

1Do not arrange shunt closure; document anatomy, resting/exercise saturation and signs of right-heart failure.
2Check FBC with iron indices, renal/liver function, ECG and expert echo.
3DefinitiveRefer promptly to a combined ACHD-pulmonary-hypertension service for definitive classification and risk assessment.
4Give written advice on hydration, air filters for IV access, pregnancy, anaesthesia and emergency symptoms.

02NextStable specialist managementConfirmed Eisenmenger syndrome without acute decompensation.

1Correct iron deficiency and other reversible contributors; avoid routine oxygen unless it produces clinical benefit or treats another indication.
2Use WHO functional class, exercise capacity, biomarkers and RV assessment to guide PAH-targeted therapy.
3EscalationFor symptomatic patients, use an endothelin-receptor antagonist-based strategy and escalate combination therapy if response is inadequate.
4Plan dental care, vaccination, contraception, procedures and travel through the specialist service.

03EscalationHaemoptysis or decompensationEscalationSignificant haemoptysis, syncope, arrhythmia, infection or right-heart failure.

1Stabilise airway, breathing and circulation while avoiding systemic hypotension and air embolism; contact the expert centre immediately.
2Stop and reassess antithrombotics when bleeding is present and investigate the source with specialist imaging.
3Correct dehydration, iron deficiency, infection and rhythm disturbance carefully; use diuresis cautiously if congested.
4EscalationEscalate targeted therapy and assess transplant options when clinical risk remains high despite treatment.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Endothelin-receptor antagonist with licensed evidence in PAH associated with congenital shunts and Eisenmenger physiology.

Bosentan

62.5 mg orally twice daily for 4 weeks, then 125 mg twice daily if tolerated.

Specialist initiation; teratogenic. Check liver transaminases before treatment and monthly and monitor haemoglobin. Bosentan reduces hormonal-contraceptive reliability: use effective additional or alternative contraception and perform monthly pregnancy testing.

PDE-5 inhibitor used alone or in specialist combination therapy when appropriate.

Sildenafil

20 mg orally three times daily for PAH.

Never combine with nitrates or riociguat; consider hypotension, visual effects and CYP3A interactions. Specialist initiation and monitoring are required.

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

Right-heart failure

Progressive pulmonary vascular load can overwhelm the hypertrophied right ventricle, causing raised venous pressure, oedema, hepatic congestion and low output. Decompensation carries substantial short-term risk.

Arrhythmia and sudden death

Chamber enlargement, myocardial fibrosis and hypoxaemia promote atrial and ventricular arrhythmias. Loss of coordinated filling or a rapid rhythm can abruptly destabilise the pressure-loaded right heart.

Thrombosis and paradoxical embolism

Sluggish pulmonary flow and abnormal haemostasis favour in-situ thrombosis, while right-to-left shunting allows venous clot or air to reach systemic arteries, causing stroke or other infarction.

Bleeding and haemoptysis

Fragile hypertensive pulmonary vessels, platelet dysfunction and coagulation abnormalities can cause haemoptysis, epistaxis or procedural bleeding. This coexisting risk makes routine anticoagulation potentially hazardous.

Iron deficiency and hyperviscosity-like symptoms

Blood loss or inappropriate venesection may cause iron deficiency and less-deformable microcytic red cells, impairing oxygen delivery. Dehydration can worsen headache, dizziness, visual disturbance or fatigue; both causes should be assessed before attributing symptoms to erythrocytosis alone.

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

Specialist review of WHO functional class, syncope, haemoptysis, saturation and signs of right-heart failure.
Serial FBC and iron indices; treat iron deficiency and avoid haemoglobin targets derived from non-cyanotic adults.
Renal/liver function, urate and treatment-specific safety tests, including monthly liver tests with bosentan.
ECG/rhythm assessment, natriuretic peptide trend, echo/CMR and objective exercise capacity as appropriate.
Review contraception, pregnancy intentions, dental health, vaccination, travel and any planned anaesthesia at each suitable opportunity.

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

Relative anaemia

A haemoglobin in the laboratory normal range may be inappropriately low for the degree of cyanosis and signal iron deficiency or bleeding.

Venesection is exceptional

Only severe persistent hyperviscosity after correcting dehydration and iron deficiency may justify isovolumic venesection in an expert centre.

Air is dangerous

Right-to-left shunting permits venous air to enter the systemic circulation; use meticulous de-airing and filters on IV lines.

Bleeding and clotting coexist

Abnormal platelets/coagulation and fragile pulmonary vessels do not prevent pulmonary thrombosis or paradoxical embolism.

The shunt is protective late

Once pulmonary vascular disease is irreversible, the communication supports cardiac output by decompressing the right ventricle.

11Common pitfallsFrequent interpretation and management errors.

01
Closing the congenital shunt after Eisenmenger physiology has developed.
02
Performing routine venesection for a high haematocrit without symptoms, hydration and iron assessment.
03
Giving routine anticoagulation without a clear indication and bleeding review.
04
Allowing unfiltered intravenous access or avoidable dehydration.
05
Understating the extreme pregnancy risk or managing pregnancy outside a Pregnancy Heart Team.