Eisenmenger syndrome requires confirmation of fixed pulmonary vascular disease and shunt physiology, exclusion of reversible mimics, avoidance of destabilizing interventions, and individualized PAH-directed therapy in an adult congenital heart disease–pulmonary hypertension center.

Diagnosis

Confirm Eisenmenger physiology before treating the shunt

The critical diagnostic decision is whether severe pulmonary vascular disease has rendered the communication nonclosable.

Establish the anatomic lesion, direction of shunting, ventricular function, and pulmonary hypertension phenotype with transthoracic echocardiography plus advanced imaging when anatomy is incompletely defined. CMR can quantify shunt magnitude and avoids ionizing radiation; CTA or CMR is superior to echocardiography for extracardiac vascular anatomy when pulmonary venous or complex vascular connections are relevant.AHA JournalsAHA Journals2018 AHA/ACC Guideline for the Management of Adults ...

Perform cardiac catheterization at an adult congenital heart disease and pulmonary hypertension center when Eisenmenger syndrome is suspected or management will depend on operability. Obtain pulmonary and systemic pressures, pulmonary vascular resistance, ventricular filling pressures, and a detailed shunt run. A single elevated pulmonary pressure does not establish Eisenmenger syndrome without demonstrating the relevant shunt physiology and excluding competing causes.AHA Journals+1AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...PubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf

Specifically investigate alternative drivers of bidirectional or right-to-left flow: postcapillary pulmonary hypertension, flow streaming from a valvular regurgitant lesion, and RV pressure overload from RV outflow tract obstruction. If RVOT obstruction, rather than irreversible pulmonary vascular disease, is the source of right-to-left shunting, relieve the RVOT obstruction rather than treating the patient as Eisenmenger syndrome.AHA Journals+1AHA Journals2018 AHA/ACC Guideline for the Management of Adults ...AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...

Use pulse oximetry at rest and with exertion to document cyanosis and desaturation; obtain CBC and iron studies to characterize secondary erythrocytosis and iron deficiency.PubMedPubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf
Obtain ECG and assess ventricular function because arrhythmias, progressive heart failure, and sudden cardiac death are major Eisenmenger complications.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...
Consider pulmonary function testing when lung disease or hypoxemia from a noncardiac pulmonary process could contribute to pulmonary hypertension.PubMedPubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf

Diagnostic branches that alter the next intervention.AHA Journals+1AHA Journals2018 AHA/ACC Guideline for the Management of Adults ...AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...
Finding	Interpretation	Next step
Large intracardiac or great-artery communication with high PVR and bidirectional shunting	Eisenmenger physiology is likely after hemodynamic confirmation.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...	Manage in an ACHD-PH center; do not proceed directly to defect closure.AHA Journals+1AHA Journals2018 AHA/ACC Guideline for the Management of Adults ...AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...
Right-to-left shunt with RVOT obstruction	The obstruction may be the treatable cause of shunting rather than irreversible pulmonary vascular disease.AHA JournalsAHA Journals2018 AHA/ACC Guideline for the Management of Adults ...	Define anatomy and assess for RVOT-directed intervention.AHA JournalsAHA Journals2018 AHA/ACC Guideline for the Management of Adults ...
Elevated pulmonary pressures with high left-sided filling pressures	Postcapillary pulmonary hypertension may be contributing to shunt reversal.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...	Treat and characterize left-heart disease before assigning Eisenmenger-directed management.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...
Apparent shunt reversal with significant valvular regurgitation	Regurgitant-flow streaming can create misleading saturation or shunt findings.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...	Use imaging and catheterization data to define the flow mechanism before therapy.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...

Acute Care

Stabilize without disrupting fragile shunt-dependent physiology

Acute care should preserve systemic perfusion and avoid interventions that increase right-to-left shunting.

Treat new hemoptysis, syncope, decompensated heart failure, sustained arrhythmia, or rapidly worsening hypoxemia as indications for urgent evaluation in an ACHD-PH center. Eisenmenger syndrome carries high arrhythmic risk, progressive heart failure, thrombotic and bleeding diatheses, and premature mortality; acute changes should not be attributed to baseline cyanosis without reassessment.jaccjaccEisenmenger Syndrome: JACC State-of-the-Art Review

Avoid nonindicated defect closure and avoid routine volume-depleting or hemodynamically destabilizing interventions. The right-to-left shunt can preserve systemic cardiac output at the cost of oxygen saturation; abrupt systemic vasodilation can increase shunting and reduce pulmonary flow.PubMed+1PubMedCongenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC PubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC

Do not perform routine phlebotomy for secondary erythrocytosis. Increased red-cell mass is adaptive for oxygen transport; phlebotomy can worsen iron deficiency and oxygen delivery. Evaluate iron status and use replacement therapy for iron deficiency, which has been associated with improved exercise capacity and quality of life in cyanotic congenital heart disease and Eisenmenger syndrome.ACC+1ACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology ScienceDirectEisenmenger Syndrome: A Multisystem Disorder—Do Not Destabilize the Balanced but Fragile Physiology - ScienceDirect

If pulmonary artery thrombosis is documented, balance anticoagulation against hemoptysis and hemorrhage risk rather than anticoagulating solely for Eisenmenger physiology.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology
Pulmonary artery thrombosis has been reported in up to 20% of affected patients; older age, pulmonary artery dilatation, and biventricular dysfunction increase risk.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology
When paradoxical embolism is a concern, avoid unfiltered intravascular air and ensure meticulous IV-line handling; pregnancy-related systemic vasodilation further increases shunting and paradoxical embolism risk.PubMedPubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC

Common management pitfalls in Eisenmenger syndrome.AHA Journals+2AHA Journals2018 AHA/ACC Guideline for the Management of Adults ...PubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC ACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology
Pitfall	Why it is harmful	Preferred action
Closing an established Eisenmenger shunt	Surgical repair of open shunts with severe pulmonary vascular disease has prohibitively high morbidity and mortality.AHA JournalsAHA Journals2018 AHA/ACC Guideline for the Management of Adults ...	Confirm physiology invasively and manage as inoperable PAH-CHD unless expert reassessment identifies a different mechanism.AHA Journals+1AHA Journals2018 AHA/ACC Guideline for the Management of Adults ...AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...
Routine phlebotomy for elevated hematocrit	Secondary erythrocytosis supports oxygen delivery; repeated phlebotomy can aggravate iron deficiency.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology	Check iron studies and treat iron deficiency rather than phlebotomizing routinely.ScienceDirect+1ScienceDirectEisenmenger Syndrome: A Multisystem Disorder—Do Not Destabilize the Balanced but Fragile Physiology - ScienceDirect ACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology
Routine anticoagulation	Thrombosis risk coexists with hemoptysis and hemorrhage risk.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology	Reserve anticoagulation for individualized indications such as documented pulmonary artery thrombosis after bleeding-risk assessment.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology
Pregnancy	Systemic vasodilation increases shunting, cyanosis, low cardiac output, and paradoxical embolism risk.PubMedPubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC	Advise against pregnancy and provide preconception counseling.jacc+1jacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines PubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC

Disease Modification

Select PAH-directed therapy by symptoms, ventricular function, and defect type

Treat in collaboration with clinicians experienced in both adult congenital heart disease and pulmonary hypertension.

For adults with Eisenmenger syndrome, LVEF greater than 40%, and either symptoms or reduced exercise capacity, current ACC/AHA guidance recommends initial monotherapy with PAH-directed therapy to improve symptoms, hemodynamics, and overall survival.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Expert-center treatment is important because evidence, safety, and prognostic interpretation differ from idiopathic PAH.jaccjaccEisenmenger Syndrome: JACC State-of-the-Art Review

Bosentan is a reasonable treatment for symptomatic Eisenmenger syndrome associated with shunts other than ASD, VSD, or great-artery shunts, including patent ductus arteriosus, aortopulmonary window, complex congenital lesions, or Down syndrome.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Prior ESC/ERS guidance specified bosentan as initial therapy for symptomatic Eisenmenger syndrome; the BREATHE-5 trial is the pivotal randomized trial supporting its use in this population.PubMed+1PubMedUpdate on Eisenmenger syndrome – Review of pathophysiology and recent progress in risk assessment and management ACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology

For symptomatic Eisenmenger syndrome associated with ASD, VSD, or great-artery shunts, PDE-5 inhibition with sildenafil or tadalafil is reasonable.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines In patients who worsen clinically despite bosentan, one cohort added sildenafil 20 mg orally three times daily after right-heart catheterization; clinical status, oxygen saturation, 6-minute walk performance, laboratory testing, and hemodynamics were reassessed at 6 months.PubMedPubMedBosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology - PubMed

Use functional status, exercise capacity, oxygen saturation, ventricular function, and hemodynamics to judge treatment response; do not rely on an idiopathic-PAH risk score alone.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review PubMedCongenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC
A 6-minute walk distance threshold should not be interpreted in isolation, particularly in Down syndrome, where noncardiac factors can substantially reduce distance.PubMedPubMedUpdate on Eisenmenger syndrome – Review of pathophysiology and recent progress in risk assessment and management
Escalate persistent clinical worsening to an ACHD-PH team for reassessment of anatomy, hemodynamics, adherence, complications, and combination-therapy candidacy.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review PubMedBosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology - PubMed

PAH-directed treatment choices supported by contemporary ACHD guidance.jacc+2jacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines PubMedUpdate on Eisenmenger syndrome – Review of pathophysiology and recent progress in risk assessment and management PubMedBosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology - PubMed
Clinical setting	Therapy approach	Key monitoring decision
Symptomatic or reduced exercise capacity, LVEF >40%	Start PAH-directed monotherapy.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines	Assess symptoms, functional capacity, oxygenation, ventricular function, and clinical deterioration longitudinally.jacc+1jacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines PubMedCongenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC
Symptomatic ASD, VSD, or great-artery shunt	PDE-5 inhibitor therapy, such as sildenafil or tadalafil, is reasonable.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines	Reassess clinical response and do not infer operability from symptomatic improvement alone.AHA Journals+1AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...jacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Symptomatic PDA, aortopulmonary window, complex lesion, or Down syndrome	Bosentan is reasonable.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines	Monitor treatment response in an ACHD-PH center.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review jacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Clinical worsening on bosentan	In one cohort, sildenafil 20 mg orally three times daily was added after RHC, with reassessment at 6 months.PubMedPubMedBosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology - PubMed	Use invasive reassessment and individualized bleeding, oxygenation, and hemodynamic review before escalation.PubMedPubMedBosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology - PubMed

Risk assessment limitations

Risk models derived from idiopathic PAH should not be directly extrapolated to Eisenmenger syndrome. Patients may have better exercise performance or lower natriuretic peptide levels than expected for their pulmonary vascular resistance because an adapted hypertrophied RV and right-to-left shunt can preserve output despite severe disease.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review PubMedCongenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC

Trend WHO functional class, 6-minute walk distance, oxygen saturation, biomarkers, echocardiographic RV and ventricular parameters, and clinical events rather than using a single score as a treatment trigger.ScienceDirect+1ScienceDirectReview Risk stratification in Eisenmenger syndrome PubMedCongenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC

Follow-up

Monitor multisystem complications and reassess when the trajectory changes

Stable Eisenmenger physiology is fragile; new symptoms should prompt targeted evaluation rather than empiric escalation alone.

Follow patients in a multidisciplinary ACHD-PH center because chronic cyanosis, abnormal loading conditions, and altered systemic and pulmonary perfusion can produce multiorgan dysfunction, systolic or diastolic dysfunction, arrhythmias, and sudden cardiac death.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ... Serial evaluation should include oxygen saturation, CBC and iron studies, functional capacity, ECG, echocardiography, and clinical assessment for hemoptysis, thrombosis, heart failure, and arrhythmia.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review PubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf

Routine follow-up invasive hemodynamics are generally not needed after Eisenmenger syndrome has been established. Reconsider catheterization when clinical worsening, a potential therapeutic change, uncertain shunt mechanism, or possible alternative contributor to pulmonary hypertension would change management.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...

Interpret falling exercise capacity, escalating functional class, worsening cyanosis, new edema, syncope, palpitations, hemoptysis, or thrombotic events as potential evidence of progression or a superimposed complication. Reassess structural anatomy, ventricular function, rhythm, iron status, and pulmonary vascular hemodynamics according to the presenting change.jacc+2jaccEisenmenger Syndrome: JACC State-of-the-Art Review AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...PubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf

Assess women of childbearing potential before conception; pregnancy should be actively discouraged because guideline recommendations identify excess maternal morbidity and mortality.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Provide contraception and coordinate any unavoidable pregnancy-related care through a high-risk cardio-obstetric and PH team; PAH-CHD recognized during pregnancy may otherwise be missed until gestation.PubMedPubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC
Do not equate preserved 6-minute walk distance or a relatively low NT-proBNP level with low risk in Eisenmenger physiology.PubMedPubMedCongenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC

Triggered reassessment during longitudinal Eisenmenger care.jacc+2jaccEisenmenger Syndrome: JACC State-of-the-Art Review AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...PubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf
Clinical change	Targeted assessment	Management implication
New syncope, palpitations, or heart-failure symptoms	ECG and ventricular assessment; evaluate for arrhythmia and systolic or diastolic dysfunction.jacc+1jaccEisenmenger Syndrome: JACC State-of-the-Art Review AHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...	Urgent ACHD-PH review because arrhythmia and progressive heart failure carry substantial risk.jaccjaccEisenmenger Syndrome: JACC State-of-the-Art Review
Hemoptysis or suspected thrombosis	Evaluate bleeding source and pulmonary artery thrombosis; reassess anticoagulation risk-benefit.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology	Avoid routine anticoagulation; individualize treatment when thrombosis is documented.ACCACCAn Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology
Worsening cyanosis or exercise limitation	Rest and exertional pulse oximetry, 6-minute walk assessment, CBC and iron studies, and cardiac imaging.PubMedPubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf	Correct iron deficiency and assess for PAH progression, ventricular deterioration, or alternative hemodynamic drivers.ScienceDirect+1ScienceDirectEisenmenger Syndrome: A Multisystem Disorder—Do Not Destabilize the Balanced but Fragile Physiology - ScienceDirect PubMedEisenmenger Syndrome - StatPearls - NCBI Bookshelf
Unexplained deterioration or planned major treatment change	Repeat catheterization with detailed shunt evaluation when results will alter management.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...	Exclude postcapillary PH, valvular streaming, and RVOT obstruction before changing the Eisenmenger treatment plan.AHA JournalsAHA Journals2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the ...

Prevention

Make pregnancy avoidance a routine treatment decision

Pregnancy risk counseling is a core component of longitudinal Eisenmenger management.

Advise adults with Eisenmenger syndrome against pregnancy. ACC/AHA guidance classifies this as harm prevention because pregnancy carries excess maternal morbidity and mortality.jaccjacc2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Explain the hemodynamic mechanism during preconception counseling: pregnancy-related systemic vasodilation increases right-to-left shunting and decreases pulmonary blood flow, leading to worsening cyanosis, reduced cardiac output, and paradoxical embolism risk.PubMedPubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC Involve congenital cardiology, pulmonary hypertension, and high-risk obstetric specialists early if pregnancy occurs.PubMedPubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC

Do not defer risk counseling until pregnancy is established; PAH-CHD may first be recognized during pregnancy, complicating assessment and timing of invasive testing.PubMedPubMedPregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC