Eisenmenger Syndrome

📋 Key Information Summary

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Eisenmenger syndrome (ES) is irreversible pulmonary arterial hypertension (PAH) caused by a large, longstanding left-to-right shunt that has reversed to bidirectional or right-to-left shunting, resulting in central cyanosis.
Most commonly arises from unrepaired large ventricular septal defect (VSD), atrioventricular septal defect (AVSD), or patent ductus arteriosus (PDA) — typically presenting in the second to fourth decade of life in Australia.
Diagnosis requires: (1) an underlying congenital systemic-to-pulmonary shunt, (2) severe PAH with pulmonary vascular resistance >800 dyn·s·cm⁻⁵, and (3) bidirectional or right-to-left shunting at rest.
Closure of the underlying defect is CONTRAINDICATED once Eisenmenger physiology is established — surgical or percutaneous closure worsens right ventricular failure and may be fatal.
Doppler echocardiography is the primary non-invasive diagnostic tool; right heart catheterisation is the gold standard for confirming haemodynamics and reversibility testing.
Complications include haemoptysis (most common cause of death), brain abscess, stroke, arrhythmias (particularly atrial), iron-deficiency anaemia, gout, cholelithiasis, and erythrocytosis with hyperviscosity.
PAH-targeted therapy (endothelin receptor antagonists, PDE-5 inhibitors, prostanoids) improves functional class and exercise capacity — bosentan has the strongest trial evidence in ES (BREATHE-5 trial).
Avoid dehydration, phlebotomy (unless symptomatic hyperviscosity with haematocrit >65%), high-altitude travel, general anaesthesia where possible, and nephrotoxic agents.
Heart–lung transplantation or bilateral lung transplantation with intracardiac repair is the definitive treatment for refractory disease; timing of referral is critical (NYHA III–IV, recurrent haemoptysis).
Women with Eisenmenger syndrome have a 30–50% maternal mortality rate with pregnancy — contraception counselling and avoidance of oestrogen-containing preparations is essential.
Pregnancy is absolutely contraindicated (WHO Category IV); long-acting reversible contraception (LARC) with progesterone-only methods or copper IUD is recommended.
Endocarditis prophylaxis is no longer routinely recommended per ESC/AHA 2020 guidelines, but should be considered on a case-by-case basis in prosthetic material or prior endocarditis.
Iron-deficiency anaemia must be corrected with intravenous iron (avoid phlebotomy); routine venesection is harmful and worsens hyperviscosity symptoms.
Multidisciplinary care at a specialised adult congenital heart disease (ACHD) centre (e.g., Royal Adelaide Hospital, Westmead Hospital, Monash Heart) is essential for ongoing management.

Introduction & Australian Epidemiology

Eisenmenger syndrome is a severe, progressive condition characterised by irreversible pulmonary arterial hypertension (PAH) arising from a longstanding, large congenital systemic-to-pulmonary shunt. The progressive rise in pulmonary vascular resistance ultimately exceeds systemic vascular resistance, causing shunt reversal to bidirectional or right-to-left flow. The resultant central cyanosis and multi-organ sequelae define the syndrome.

The condition was first described by Paul Wood in 1958, building on Victor Eisenmenger's original 1897 case report of a patient with a large VSD and pulmonary hypertension. Eisenmenger syndrome represents the end-stage consequence of unrepaired congenital heart disease (CHD) and is now increasingly seen in low- and middle-income countries or in patients whose defects were undiagnosed or managed conservatively in the pre-surgical era.

Australian epidemiology:

The prevalence of Eisenmenger syndrome has declined dramatically in Australia due to universal neonatal screening, early echocardiographic diagnosis, and timely surgical repair of large defects.
An estimated 200–400 adults with Eisenmenger syndrome are living in Australia, managed primarily through specialised Adult Congenital Heart Disease (ACHD) centres.
Median age at diagnosis in Australian cohorts is 25–35 years; patients born before the era of routine paediatric cardiac surgery (pre-1980s) are the most affected.
VSD (40–50%) is the most common underlying defect, followed by AVSD (20–25%), PDA (10–15%), and ASD (rarely — only large, longstanding secundum or primum defects).
In Aboriginal and Torres Strait Islander communities, delayed access to paediatric cardiac services in remote and regional areas may contribute to higher rates of undiagnosed CHD and late presentation (see ATSI section).
Survival has improved with PAH-targeted therapies: 10-year survival is approximately 70–80% with modern treatment compared to 40–50% in historical series.
Key Australian referral centres include the Adult Congenital Heart Disease service at Royal Adelaide Hospital, Westmead Adult Congenital Heart Centre (Sydney), Monash Heart (Melbourne), and the Queensland Adult Congenital Heart Service.

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Critical principle: Eisenmenger syndrome is the paradigmatic example of "too little, too late" — had the underlying defect been repaired before irreversible pulmonary vascular disease developed, the syndrome would not occur. Once Eisenmenger physiology is established, closing the defect is dangerous and contraindicated, as the shunt acts as a "pop-off valve" decompressing the failing right ventricle.

Pathophysiology (Shunt Reversal)

The pathophysiology of Eisenmenger syndrome is a progressive, staged process driven by chronic volume and pressure overload of the pulmonary vasculature.

Stages of Pulmonary Vascular Remodelling

1

Phase 1 — Large Left-to-Right Shunt (Heath–Edwards Grade I–II)

In the neonatal period and infancy, a large unrestricted defect (VSD, AVSD, PDA) permits high-volume, high-pressure pulmonary blood flow. The pulmonary vasculature initially accommodates this with medial hypertrophy of pulmonary arterioles and intimal proliferation. Pulmonary vascular resistance (PVR) remains low; shunt ratio (Qp:Qs) is typically >2:1.

2

Phase 2 — Progressive Pulmonary Vascular Disease (Heath–Edwards Grade III–IV)

Chronic shear stress, turbulent flow, and endothelial dysfunction trigger obliterative vascular remodelling: intimal fibrosis, concentric laminar fibrosis, plexiform lesions, and necrotising arteriopathy. PVR rises progressively toward systemic levels. The shunt becomes bidirectional — predominantly left-to-right at rest with right-to-left components during exercise, Valsalva, or with rising PVR.

3

Phase 3 — Eisenmenger Physiology (Heath–Edwards Grade V–VI)

PVR exceeds systemic vascular resistance (SVR). The shunt reverses to predominantly right-to-left, causing systemic arterial desaturation (cyanosis). The large shunt effectively acts as a pressure-relief valve for the right ventricle, paradoxically preventing acute right heart failure but at the cost of chronic cyanosis. The right ventricle adapts with concentric hypertrophy; eventually, RV dilatation and systolic dysfunction supervene.

Key Pathophysiological Concepts

Mechanism	Consequence	Clinical Relevance
Endothelial dysfunction	Reduced NO, prostacyclin; increased endothelin-1, thromboxane A₂	Target for PAH-specific therapy (bosentan, sildenafil, epoprostenol)
Plexiform arteriopathy	Obliterative lesions in small pulmonary arteries	Irreversible — explains why shunt closure is contraindicated
Right-to-left shunting	Systemic desaturation, erythrocytosis, secondary polycythaemia	Iron deficiency worsens hyperviscosity despite lower Hb
RV pressure overload	RV hypertrophy → dilatation → systolic failure	Prognostic marker; serial echo assessment essential
Chronic hypoxaemia	Clubbing, gout, cholelithiasis, coagulopathy	Multi-organ complications drive morbidity
Thrombotic tendency	In-situ pulmonary artery thrombosis, paradoxical embolism	Anticoagulation controversial — case-by-case decision

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Important distinction: ASD-type shunts (secundum, primum) rarely cause Eisenmenger syndrome before the third decade because the low-pressure left-to-right shunt produces slower vascular remodelling. VSD and PDA shunts are high-pressure and typically produce Eisenmenger physiology by age 10–20 if unrepaired.

Clinical Features & Complications

Presenting Features

Patients typically present in the second to fourth decade with progressive exertional dyspnoea and central cyanosis. The clinical presentation is heterogeneous and depends on the degree of shunt reversal, compensatory erythrocytosis, and downstream organ damage.

Symptom / Sign	Mechanism	Prevalence
Central cyanosis	Right-to-left shunting, desaturated blood reaching systemic circulation	100%
Exertional dyspnoea	Reduced cardiac output, increased R→L shunt during exercise	90–95%
Digital clubbing	Chronic hypoxaemia, capillary proliferation	70–80%
Fatigue / exercise intolerance	Low cardiac output, impaired oxygen delivery	80–90%
Haemoptysis	Rupture of fragile bronchial collaterals or pulmonary arterioles	20–30%
Palpitations / syncope	Arrhythmias (atrial flutter/fibrillation), reduced cerebral perfusion	25–35%
Peripheral oedema	Right ventricular failure, elevated CVP	30–50%
Loud P2 / right ventricular heave	Pulmonary hypertension, RV hypertrophy	95%
Systolic murmur (tricuspid regurgitation)	RV dilatation, annular dilatation	60–70%

Major Complications

Common

Erythrocytosis & Hyperviscosity

Secondary polycythaemia (Hct >55–65%) from chronic hypoxaemia. Symptoms: headache, visual disturbance, paraesthesiae, fatigue. Iron deficiency dramatically worsens hyperviscosity through production of small, rigid microcytes despite lower Hb.

Management: IV iron replacement; phlebotomy only if symptomatic with Hct >65%

Serious

Haemoptysis

Most common cause of death in Eisenmenger syndrome. Results from rupture of fragile bronchial collaterals, pulmonary arterioles, or in-situ pulmonary artery thrombosis. Can be massive and life-threatening.

Management: ICU admission, transfusion, interventional radiology embolisation; consider transplant referral

Critical

Brain Abscess

Right-to-left shunting allows paradoxical embolisation of bacteria, bypassing pulmonary capillary filtration. Incidence 5–10% lifetime. Presenting with headache, fever, focal neurological signs in a cyanotic patient.

Management: IV antibiotics (metronidazole + ceftriaxone), neurosurgical drainage; MRI brain is essential

Additional Complications

Arrhythmias: Atrial flutter and fibrillation occur in 20–40%; ventricular arrhythmias are less common but carry high mortality. Treatment is challenging — digoxin and beta-blockers may worsen RV function.
Stroke / paradoxical embolism: Right-to-left shunt permits venous thrombi to enter systemic circulation. Annual stroke risk 1–3%.
Paradoxical embolism via PFO or septal defect: Deep venous thrombosis must be aggressively treated and prevented.
Iron-deficiency anaemia: Occurs in up to 30% of patients due to chronic consumption, phlebotomy, GI bleeding, or menorrhagia. Confounds the clinical picture by lowering Hb while worsening hyperviscosity through microcytosis.
Hyperuricaemia and gout: Increased red cell turnover leads to hyperuricaemia; gout flares occur in 10–20% of patients.
Cholelithiasis: Bilirubin overproduction from chronic haemolysis causes pigment gallstones.
Renal dysfunction: Chronic hypoxaemia, reduced renal blood flow, and renal tubular acidosis. Nephrolithiasis from hyperuricosuria.
Coagulopathy: Paradoxical combination of thrombotic tendency (in-situ PA thrombosis) and bleeding risk (thrombocytopenia, acquired von Willebrand syndrome).
Infective endocarditis: Risk persists with turbulent flow across the defect.

Investigations & Diagnosis

Diagnostic Criteria

Diagnosis of Eisenmenger syndrome requires all three of:

An underlying congenital systemic-to-pulmonary shunt (VSD, AVSD, PDA, ASD, or complex CHD)
Severe PAH — mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest with pulmonary vascular resistance >800 dyn·s·cm⁻⁵ (10 Wood units)
Bidirectional or right-to-left shunting at rest (cyanosis, SpO₂ <95% room air)

Baseline & Ongoing Investigations

Essential

Transthoracic Echocardiography (TTE)

MBS Item 55118. First-line non-invasive assessment. Estimates RVSP via TR jet velocity, assesses RV size and function (TAPSE, FAC, RV S'), identifies shunt anatomy, quantifies bidirectional shunting with agitated saline contrast. Perform 6–12 monthly.

Essential

Right Heart Catheterisation (RHC)

Gold standard for confirming haemodynamics. MBS Item 38218. Measures mPAP, PCWP, PVR, CO/CI, Qp:Qs. Acute vasoreactivity testing with inhaled NO (iNO) — a positive response (↓mPAP ≥10 mmHg to <40 mmHg with preserved CO) does NOT predict benefit from shunt closure in established Eisenmenger but may identify candidates for calcium channel blocker therapy (rare).

Essential

Pulse Oximetry & ABG

Resting and exercise SpO₂ (six-minute walk test). ABG for accurate SaO₂, PaO₂, PaCO₂. Serial monitoring of oxygenation trajectory.

Available

Full Blood Count, Iron Studies, Haemolysis Markers

FBC with blood film (microcytosis, target cells), serum ferritin, transferrin saturation, LDH, haptoglobin, reticulocyte count. Critical for detecting iron deficiency, which worsens hyperviscosity despite lower Hb.

Available

CT Pulmonary Angiography (CTPA)

MBS Item 56805. Identifies in-situ pulmonary artery thrombosis, bronchial collaterals, pulmonary artery anatomy, and rules out acute PE. Use cautiously due to contrast nephrotoxicity risk.

Available

Cardiac MRI

MBS Item 63509. Gold standard for RV volumetric assessment, quantification of shunt fraction, and tissue characterisation (fibrosis). Useful for serial RV function monitoring. Requires specialised CHD imaging protocols.

Available

Six-Minute Walk Test (6MWT)

Functional assessment — distance, SpO₂ nadir, heart rate response. Used for longitudinal monitoring and treatment response evaluation. Reproducible in outpatient setting.

Available

Cardiopulmonary Exercise Testing (CPET)

Peak VO₂, VE/VCO₂ slope, exercise capacity. Prognostic value — peak VO₂ <10.6 mL/kg/min is an independent predictor of mortality and threshold for transplant consideration.

Available

ECG & 24-hour Holter Monitor

ECG: right axis deviation, RV hypertrophy (dominant R in V1, ST changes). Holter for detection of atrial and ventricular arrhythmias — monitor annually in NYHA III–IV.

Available

NT-proBNP / BNP

Baseline and serial monitoring. NT-proBNP >1400 pg/mL is a poor prognostic marker. Useful for detecting RV failure progression and guiding treatment escalation.

Available

Uric Acid, Renal Function, LFTs

Hyperuricaemia monitoring, eGFR for drug dosing (PAH therapies), liver function for bosentan/ambrisentan monitoring.

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MBS Note: Right heart catheterisation (Item 38218) and cardiac MRI (Item 63509) are available at major tertiary centres with ACHD services. Patients in regional and remote Australia may require interstate transfer for specialised invasive testing. Telehealth echo review and hub-and-spoke models are increasingly used.

Management — PAH Therapy, Transplant & Supportive Care

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ABSOLUTE CONTRAINDICATION: Surgical or percutaneous closure of the underlying defect is CONTRAINDICATED in established Eisenmenger syndrome. The shunt acts as a decompression valve for the right ventricle. Closure eliminates this safety mechanism, causing acute RV failure and catastrophic haemodynamic collapse. Reversibility testing at RHC does NOT predict benefit from closure once Eisenmenger physiology is established.

General Principles & Avoidance Measures

All care should be coordinated through a specialised ACHD centre with PAH expertise.
Avoid dehydration (reduces preload, worsens R→L shunt).
Avoid high-altitude travel (>1500 m) — reduced FiO₂ worsens hypoxaemia and increases PVR.
Avoid strenuous isometric exercise; encourage moderate aerobic activity within symptom limits.
Use local or regional anaesthesia where possible; general anaesthesia carries very high risk.
Pre-operative assessment for any procedure must include anaesthetic/cardiology review at an ACHD centre.
Annual influenza vaccination and pneumococcal vaccination (per ATAGI schedule).
Smoking cessation — absolute requirement.

PAH-Targeted Therapy

Three major pathways are targeted by current PAH therapies: the endothelin pathway, the NO–cGMP pathway, and the prostacyclin pathway. Evidence in Eisenmenger syndrome, while extrapolated from broader PAH trials, supports initiation of therapy in symptomatic patients (WHO/NYHA functional class II–IV).

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Bosentan

Tracleer® · Endothelin receptor antagonist (dual ETA/ETB)

Adult dose 62.5 mg PO BD for 4 weeks, then 125 mg PO BD

Paediatric dose ≥2 years: weight-based dosing — <10 kg: 15 mg BD; 10–20 kg: 31.25 mg BD; 20–40 kg: 62.5 mg BD; >40 kg: 62.5 mg BD → 125 mg BD

Key notes Strongest evidence in ES — BREATHE-5 trial demonstrated improved 6MWD and functional class. Monthly LFTs required (hepatotoxicity 10%). Teratogenic — Pregnancy Prevention Programme mandatory.

PBS status Authority Required

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Ambrisentan

Volibris® · Selective endothelin receptor antagonist (ETA)

Adult dose 5 mg PO OD, titrate to 10 mg PO OD after 4 weeks if tolerated

Key notes Lower hepatotoxicity than bosentan. Less evidence specifically in ES; extrapolated from PAH trials (ARIES-1, ARIES-2). Peripheral oedema common.

PBS status Authority Required

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Macitentan

Opsumit® · Endothelin receptor antagonist (dual ETA/ETB)

Adult dose 10 mg PO OD

Key notes Tissue-penetrating ERA with favourable safety profile. SERAPHIN trial showed reduced morbidity/mortality in PAH. Limited specific ES data. Pregnancy prevention required.

PBS status Authority Required

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Sildenafil

Revatio® · PDE-5 inhibitor

Adult dose 20 mg PO TDS (6-hourly)

Paediatric dose ≥1 year: 0.5–1 mg/kg/dose PO TDS (max 20 mg TDS)

Key notes Improves exercise capacity and haemodynamics in ES. Used as first-line or in combination with ERA. Well tolerated — headache, flushing, visual disturbance. Avoid with nitrates.

PBS status PBS Restricted Benefit

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Tadalafil

Cialis® / Adcirca® · PDE-5 inhibitor

Adult dose 40 mg PO OD

Key notes

Once-daily alternative to sildenafil. PHIRST trial evidence. Longer half-life (17.5 hours). Same drug interactions as sildenafil.

PBS status PBS Restricted Benefit

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Epoprostenol (Prostacyclin)

Flolan® / Veletri® · Prostacyclin analogue

Adult dose Continuous IV infusion; start 1–2 ng/kg/min, titrate by 1–2 ng/kg/min every 15 min during initiation; maintenance typically 20–40 ng/kg/min

Key notes Reserved for severe/refractory PAH (NYHA III–IV). Requires indwelling central venous catheter and continuous infusion pump. Risk of line infection, rebound PAH if interrupted. Available at specialist centres.

PBS status Authority Required

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Selexipag

Uptravi® · Selective IP receptor agonist (oral prostacyclin pathway)

Adult dose Start 200 µg PO BD, titrate by 200 µg BD weekly to maximum tolerated dose (up to 1600 µg BD)

Key notes GRIPHON trial showed reduced composite morbidity/mortality in PAH. Oral alternative to IV epoprostenol. GI side effects (diarrhoea, nausea) common during uptitration.

PBS status Authority Required

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Riociguat

Adempas® · Soluble guanylate cyclase stimulator

Adult dose Start 1 mg PO TDS, titrate every 2 weeks to maximum 2.5 mg PO TDS

Key notes PATENT-1 trial evidence in PAH. Unique mechanism — stimulates sGC directly. CONTRAINDICATED with PDE-5 inhibitors (severe hypotension). Pregnancy contraindication — mandatory contraception.

PBS status Authority Required

Combination Therapy Strategy

Current ESC/ERS guidelines recommend initial combination therapy (ERA + PDE-5 inhibitor) for PAH patients in WHO/NYHA functional class II–IV, with escalation to triple therapy (adding prostanoid) if response is inadequate. This strategy is applied to Eisenmenger syndrome patients based on extrapolation and expert consensus:

1

First-line (FC II–III)

Bosentan 125 mg BD (or ambrisentan/macitentan) PLUS sildenafil 20 mg TDS (or tadalafil 40 mg OD). Monitor response at 3–4 months with 6MWT, echo, NT-proBNP.

2

Escalation (inadequate response FC III–IV)

Add inhaled treprostinil (Tyvaso®), oral selexipag, or IV epoprostenol. Consider switching to riociguat (if not on PDE-5i). Reassess at ACHD centre.

3

Transplant referral (refractory FC IV)

Heart–lung or bilateral lung transplant with intracardiac repair. Refer early (see below).

Management of Specific Complications

Complication	Management
Iron-deficiency anaemia	IV iron infusion (ferric carboxymaltose 500–1000 mg IV, or iron polymaltose). Target ferritin >50 µg/L, TSAT >20%. Avoid oral iron (poor absorption, GI intolerance). NEVER venesection for anaemia.
Symptomatic erythrocytosis	Phlebotomy ONLY if symptomatic hyperviscosity (headache, visual changes, TIA-like symptoms) AND Hct >65%. Remove 250–500 mL, replace with isovolumic normal saline. Target Hct 55–60%. Ensure iron replete first.
Haemoptysis	Mild: observation, tranexamic acid 1 g IV/PO. Moderate–massive: ICU, transfusion, bronchial artery embolisation (interventional radiology). Urgent transplant reassessment.
Atrial arrhythmias	DC cardioversion for haemodynamic instability. Rate control with diltiazem or low-dose beta-blocker (caution — may reduce CO). Amiodarone for rhythm control. Avoid class IC agents.
Gout	Colchicine 500 µg OD prophylaxis; acute flares: colchicine 500 µg stat then 250 µg hourly (max 3 mg/day) or NSAIDs (short courses with caution). Allopurinol for chronic hyperuricaemia — adjust for renal function.
Brain abscess	IV metronidazole 400–500 mg TDS + ceftriaxone 2 g BD (or meropenem 1 g TDS if penicillin allergy). Neurosurgical drainage/aspiration. 6–8 weeks total antibiotics. MRI surveillance.
Anticoagulation	Not routinely recommended. Consider in: in-situ PA thrombosis, AF/Flutter (with extreme caution — bleeding risk), prior thromboembolic event. Use warfarin (INR 1.5–2.5) — DOACs less studied. Assess bleeding risk case-by-case.

Transplantation

Heart–lung transplantation (HLT) or bilateral lung transplantation (BLT) with intracardiac repair is the only definitive treatment for Eisenmenger syndrome refractory to medical therapy. Transplant listing in Australia is managed through the Transplantation Society of Australia and New Zealand (TSANZ).

Consider Referral

Indicators for Transplant Referral

NYHA/WHO FC III–IV despite optimal PAH therapy
Recurrent or life-threatening haemoptysis
Peak VO₂ <10.6 mL/kg/min on CPET
RV failure with progressive dilatation/dysfunction
Syncope or refractory arrhythmias
Progressive renal or hepatic dysfunction
NT-proBNP >1400 pg/mL (rising trend)

Refer to: Alfred Hospital (Melbourne), St Vincent's Hospital (Sydney), Prince Charles Hospital (Brisbane)

Transplant Options

Surgical Approaches

Bilateral lung transplant + intracardiac repair: Preferred when RV is recoverable (preserved RV function at transplant assessment). Defect is closed at the time of transplant.
Heart–lung transplant: Reserved for severe biventricular failure or complex anatomy not amenable to repair. Limited donor availability is the major barrier.
Post-transplant outcomes in ES: 1-year survival ~75–80%, 5-year survival ~50–60% (comparable to other PAH transplant indications).

Donor organ allocation: managed by DonateLife and TSANZ OrganMatch

Perioperative & Procedural Risk

Any surgical or procedural intervention in Eisenmenger syndrome carries extremely high mortality risk (estimated 7–30% for non-cardiac surgery). Key principles:

Elective surgery should be avoided where possible.
All procedures require pre-assessment at an ACHD centre with anaesthetic and cardiology input.
Regional anaesthesia preferred over general anaesthesia when feasible.
Avoid epidural anaesthesia if coagulopathy or thrombocytopenia present.
Intraoperative monitoring: arterial line, central venous access, transoesophageal echocardiography.
Maintain preload, avoid hypotension, avoid air bubbles in IV lines (paradoxical embolism risk).
Postoperative HDU/ICU monitoring mandatory.

Special Populations

🤰

Pregnancy

Risk Category: WHO Category IV — ABSOLUTE CONTRAINDICATION

Maternal mortality 30–50% in published series. Haemodynamic changes of pregnancy (increased plasma volume, decreased SVR) exacerbate R→L shunting and right heart failure. Miscarriage rate ~40%.

Contraception — essential

Long-acting reversible contraception (LARC): progesterone-only implant (Implanon NXT®) or copper IUD preferred. Avoid combined oral contraceptive pill (oestrogen increases thrombotic risk). Barrier methods alone are insufficient. Pregnancy termination should be discussed if unplanned pregnancy occurs.

If pregnancy occurs

Managed at tertiary centre with ACHD + obstetric medicine + anaesthetic input. Early multidisciplinary planning. High risk of peripartum deterioration. Vaginal delivery with epidural and assisted second stage preferred over caesarean (less haemodynamic fluctuation). Avoid oxytocin bolus — slow infusion only. IV iron for postpartum haemorrhage.

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Paediatric Considerations

Prevention is paramount

Timely repair of large VSD, AVSD, and PDA in infancy prevents Eisenmenger syndrome. Universal neonatal pulse oximetry screening (now standard in Australian maternity hospitals) detects critical CHD.

Transition to adult care

Adolescents with unrepaired CHD at risk of Eisenmenger physiology require structured transition programme from paediatric to ACHD service. Many Australian states have formal transition clinics (e.g., HeartKids Transition Programme, The Heart Centre for Children at Westmead).

PAH therapy in children

Bosentan and sildenafil are used off-label in paediatric Eisenmenger syndrome. Dose adjustment by weight. Limited RCT data — most evidence extrapolated from adult trials and paediatric PAH registries.

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Elderly Patients

Competing comorbidities

Coronary artery disease, renal impairment, and frailty complicate management. Dose-adjust PAH therapies for hepatic and renal function. Lower threshold for transplant referral given age-related decline in physiological reserve.

Polypharmacy risk

Many PAH therapies interact with common medications (PDE-5i with nitrates — absolute contraindication; bosentan CYP3A4/2C9 interactions). Medication reconciliation essential at each visit.

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Renal Impairment

Chronic kidney disease

Present in 20–30% due to chronic hypoxaemia, reduced renal perfusion, hyperuricaemia. Renal impairment limits use of NSAIDs for gout, IV contrast for CTPA, and requires dose adjustment for riociguat (avoid if eGFR <15). Monitor eGFR and uric acid regularly.

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Hepatic Impairment

Bosentan hepatotoxicity

Baseline LFTs required; monthly LFT monitoring for bosentan. Discontinue if transaminases >5× ULN. Ambrisentan or macitentan preferred in patients with hepatic impairment or elevated baseline LFTs.

Congestive hepatopathy

RV failure causes hepatic congestion, leading to deranged LFTs, ascites, and synthetic dysfunction. Progressive hepatopathy is an indicator for transplant evaluation.

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Immunocompromised

Post-transplant immunosuppression

Standard triple immunosuppression (tacrolimus + mycophenolate + prednisolone) after lung/heart–lung transplant. Increased infection risk (CMV, PJP, aspergillosis). Prophylaxis protocols per TSANZ guidelines.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Aboriginal and Torres Strait Islander peoples experience a higher burden of congenital heart disease and its complications, including Eisenmenger syndrome, due to systemic inequities in healthcare access, delayed diagnosis, and barriers to specialist cardiac services in remote and regional communities.

Epidemiology & burden

CHD prevalence in Indigenous Australian neonates may be higher than reported due to underdiagnosis in remote birth centres. AIHW data show that Indigenous Australians are 1.5–2× more likely to have undiagnosed or late-presenting CHD. Eisenmenger syndrome, now rare in non-Indigenous Australians, persists as a clinical concern in communities with limited access to paediatric echocardiography and cardiac surgery.

Geographic & access barriers

Many Indigenous communities in the Northern Territory, Western Australia, and Far North Queensland are >500 km from the nearest paediatric cardiac centre (Royal Darwin Hospital lacks paediatric cardiac surgery). Retrieval and transfer delays mean that large shunts may go unrepaired during the critical window (infancy) before irreversible pulmonary vascular disease develops.

Diagnostic delays

Limited availability of echocardiography in remote Aboriginal Community Controlled Health Services (ACCHS). Reliance on fly-in/fly-out specialist outreach clinics. Telehealth echocardiography (store-and-forward) is expanding but not yet universally available.

Treatment access

PAH-targeted therapies (bosentan, sildenafil, ambrisentan) require Authority PBS approval and ongoing specialist monitoring (monthly LFTs for bosentan). Remote patients may have difficulty attending regular follow-up. Supply chain interruptions to remote pharmacies can cause abrupt therapy cessation — rebound PAH risk.

Cultural safety

Care must be delivered in a culturally safe framework. Engage Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers in ACHD multidisciplinary teams. Respect kinship obligations and sorry business. Use interpreter services (e.g., NT Aboriginal Interpreter Service) for patients whose first language is not English.

Comorbidities

Higher rates of rheumatic heart disease (RHD) in Indigenous Australians — RHD with severe mitral/aortic valve disease can cause secondary PAH and Eisenmenger-like physiology. RHDAustralia registers and guidelines apply. Chronic kidney disease, diabetes, and smoking prevalence further complicate management.

Strategies for improvement

Support national CHD screening programmes in remote areas. Expand paediatric cardiac outreach via the National Rheumatic Heart Disease Strategy and Closing the Gap initiatives. Strengthen telehealth pathways for ACHD review. Fund AHW positions within ACHD services. Ensure reliable medication supply chains to remote pharmacies. Integrate Eisenmenger/PAH care with existing chronic disease management programmes in ACCHS.

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Key resource: RHDAustralia (www.rhdaustralia.org.au) provides clinical guidelines for RHD management that overlap with PAH/Eisenmenger care in Indigenous communities. The Australian Indigenous HealthInfoNet (www.healthinfonet.ecu.edu.au) maintains cardiovascular health summaries for Aboriginal and Torres Strait Islander peoples.

📚 References

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