# Eisenmenger Syndrome

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.

**Clinical question:** How should physicians confirm, treat, and longitudinally manage Eisenmenger syndrome while avoiding harmful interventions?

Updated: 2026-08-24T17:13:34.122119+00:00

## What matters in practice
- Confirm Eisenmenger physiology with expert imaging and invasive hemodynamics, including a detailed shunt run, before labeling an unrepaired shunt inoperable or considering closure.[5][6]
- Exclude postcapillary pulmonary hypertension, valvular-regurgitation streaming, and RV outflow obstruction as alternative causes of bidirectional or right-to-left shunting; management differs materially for each.[5][6]
- Do not close an established Eisenmenger shunt; morbidity and mortality are prohibitively high with repair of open shunts once severe pulmonary vascular disease is present.[5]
- For symptomatic adults with LVEF >40% or reduced exercise capacity, initial PAH-directed monotherapy is recommended; drug selection should reflect defect type and be directed by ACHD-PH specialists.[9]
- Avoid routine phlebotomy and routine anticoagulation: secondary erythrocytosis supports oxygen delivery, while simultaneous thrombosis and bleeding risks require indication-specific decisions.[1][24]
- Pregnancy is contraindicated because systemic vasodilation can worsen right-to-left shunting, cyanosis, low cardiac output, and paradoxical embolism.[9][19]

## 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.[5]

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.[6][22]

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.[5][6]
- 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.[22]
- Obtain ECG and assess ventricular function because arrhythmias, progressive heart failure, and sudden cardiac death are major Eisenmenger complications.[1][6]
- Consider pulmonary function testing when lung disease or hypoxemia from a noncardiac pulmonary process could contribute to pulmonary hypertension.[22]

*Diagnostic branches that alter the next intervention.[5][6]*

| Finding | Interpretation | Next step |
| --- | --- | --- |
| Large intracardiac or great-artery communication with high PVR and bidirectional shunting | Eisenmenger physiology is likely after hemodynamic confirmation.[6] | Manage in an ACHD-PH center; do not proceed directly to defect closure.[5][6] |
| Right-to-left shunt with RVOT obstruction | The obstruction may be the treatable cause of shunting rather than irreversible pulmonary vascular disease.[5] | Define anatomy and assess for RVOT-directed intervention.[5] |
| Elevated pulmonary pressures with high left-sided filling pressures | Postcapillary pulmonary hypertension may be contributing to shunt reversal.[6] | Treat and characterize left-heart disease before assigning Eisenmenger-directed management.[6] |
| Apparent shunt reversal with significant valvular regurgitation | Regurgitant-flow streaming can create misleading saturation or shunt findings.[6] | Use imaging and catheterization data to define the flow mechanism before therapy.[6] |

## 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.[1]

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.[20][19]

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.[24][13]
- If pulmonary artery thrombosis is documented, balance anticoagulation against hemoptysis and hemorrhage risk rather than anticoagulating solely for Eisenmenger physiology.[24]
- Pulmonary artery thrombosis has been reported in up to 20% of affected patients; older age, pulmonary artery dilatation, and biventricular dysfunction increase risk.[24]
- 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.[19]

*Common management pitfalls in Eisenmenger syndrome.[5][19][24]*

| 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.[5] | Confirm physiology invasively and manage as inoperable PAH-CHD unless expert reassessment identifies a different mechanism.[5][6] |
| Routine phlebotomy for elevated hematocrit | Secondary erythrocytosis supports oxygen delivery; repeated phlebotomy can aggravate iron deficiency.[24] | Check iron studies and treat iron deficiency rather than phlebotomizing routinely.[13][24] |
| Routine anticoagulation | Thrombosis risk coexists with hemoptysis and hemorrhage risk.[24] | Reserve anticoagulation for individualized indications such as documented pulmonary artery thrombosis after bleeding-risk assessment.[24] |
| Pregnancy | Systemic vasodilation increases shunting, cyanosis, low cardiac output, and paradoxical embolism risk.[19] | Advise against pregnancy and provide preconception counseling.[9][19] |

## 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.[9] Expert-center treatment is important because evidence, safety, and prognostic interpretation differ from idiopathic PAH.[1]

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.[9] 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.[18][24]

For symptomatic Eisenmenger syndrome associated with ASD, VSD, or great-artery shunts, PDE-5 inhibition with sildenafil or tadalafil is reasonable.[9] 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.[23]
- 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.[1][20]
- A 6-minute walk distance threshold should not be interpreted in isolation, particularly in Down syndrome, where noncardiac factors can substantially reduce distance.[18]
- Escalate persistent clinical worsening to an ACHD-PH team for reassessment of anatomy, hemodynamics, adherence, complications, and combination-therapy candidacy.[1][23]

### 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.[1][20]
- 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.[12][20]

*PAH-directed treatment choices supported by contemporary ACHD guidance.[9][18][23]*

| Clinical setting | Therapy approach | Key monitoring decision |
| --- | --- | --- |
| Symptomatic or reduced exercise capacity, LVEF >40% | Start PAH-directed monotherapy.[9] | Assess symptoms, functional capacity, oxygenation, ventricular function, and clinical deterioration longitudinally.[9][20] |
| Symptomatic ASD, VSD, or great-artery shunt | PDE-5 inhibitor therapy, such as sildenafil or tadalafil, is reasonable.[9] | Reassess clinical response and do not infer operability from symptomatic improvement alone.[6][9] |
| Symptomatic PDA, aortopulmonary window, complex lesion, or Down syndrome | Bosentan is reasonable.[9] | Monitor treatment response in an ACHD-PH center.[1][9] |
| Clinical worsening on bosentan | In one cohort, sildenafil 20 mg orally three times daily was added after RHC, with reassessment at 6 months.[23] | Use invasive reassessment and individualized bleeding, oxygenation, and hemodynamic review before escalation.[23] |

## 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.[1][6] Serial evaluation should include oxygen saturation, CBC and iron studies, functional capacity, ECG, echocardiography, and clinical assessment for hemoptysis, thrombosis, heart failure, and arrhythmia.[1][22]

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.[6]

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.[1][6][22]
- Assess women of childbearing potential before conception; pregnancy should be actively discouraged because guideline recommendations identify excess maternal morbidity and mortality.[9]
- 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.[19]
- Do not equate preserved 6-minute walk distance or a relatively low NT-proBNP level with low risk in Eisenmenger physiology.[20]

*Triggered reassessment during longitudinal Eisenmenger care.[1][6][22]*

| 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.[1][6] | Urgent ACHD-PH review because arrhythmia and progressive heart failure carry substantial risk.[1] |
| Hemoptysis or suspected thrombosis | Evaluate bleeding source and pulmonary artery thrombosis; reassess anticoagulation risk-benefit.[24] | Avoid routine anticoagulation; individualize treatment when thrombosis is documented.[24] |
| Worsening cyanosis or exercise limitation | Rest and exertional pulse oximetry, 6-minute walk assessment, CBC and iron studies, and cardiac imaging.[22] | Correct iron deficiency and assess for PAH progression, ventricular deterioration, or alternative hemodynamic drivers.[13][22] |
| Unexplained deterioration or planned major treatment change | Repeat catheterization with detailed shunt evaluation when results will alter management.[6] | Exclude postcapillary PH, valvular streaming, and RVOT obstruction before changing the Eisenmenger treatment plan.[6] |

## 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.[9]

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.[19] Involve congenital cardiology, pulmonary hypertension, and high-risk obstetric specialists early if pregnancy occurs.[19]
- Do not defer risk counseling until pregnancy is established; PAH-CHD may first be recognized during pregnancy, complicating assessment and timing of invasive testing.[19]

## References
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2. Eisenmenger Syndrome: A Clinical Perspective in a New Therapeutic Era of Pulmonary Arterial Hypertension — www.jacc.org — https://www.jacc.org/doi/10.1016/j.jacc.2008.11.025
3. Sotatercept in Congenital Heart Disease–Associated ... — www.jacc.org — https://www.jacc.org/doi/10.1016/j.jaccas.2026.108814
4. Clinical Evaluation and Management of Pulmonary ... — www.ahajournals.org — https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.006976?doi=10.1161%2FCIRCULATIONAHA.114.006976
5. 2018 AHA/ACC Guideline for the Management of Adults ... — www.ahajournals.org — https://www.ahajournals.org/doi/10.1161/CIR.0000000000000603
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7. The Eisenmenger Syndrome in Adults — annals.org — http://annals.org/aim/article/711368/eisenmenger-syndrome-adults
8. Echocardiographic Predictors of Outcome in Eisenmenger ... — www.ahajournals.org — https://www.ahajournals.org/doi/10.1161/circulationaha.112.091421
9. 2025 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 — www.jacc.org — https://www.jacc.org/doi/10.1016/j.jacc.2025.09.006
10. Risk stratification for adult patients with pulmonary arterial ... — academic.oup.com — https://academic.oup.com/eurjhf/advance-article/doi/10.1093/ejhf/xuag059/8512130
11. Biventricular longitudinal strain analysis using ... — www.sciencedirect.com — https://www.sciencedirect.com/science/article/pii/S1097664724011438
12. Review Risk stratification in Eisenmenger syndrome — www.sciencedirect.com — https://www.sciencedirect.com/science/article/pii/S1875213625000944
13. Eisenmenger Syndrome: A Multisystem Disorder—Do Not Destabilize the Balanced but Fragile Physiology - ScienceDirect — www.sciencedirect.com — https://www.sciencedirect.com/science/article/abs/pii/S0828282X19312991
14. Sildenafil therapy for pulmonary arterial hypertension associated with atrial septal defects - ScienceDirect — www.sciencedirect.com — https://www.sciencedirect.com/science/article/abs/pii/S0167527306007844
15. Guidelines on diagnosis and treatment of pulmonary ... — academic.oup.com — https://academic.oup.com/eurheartj/article-pdf/25/24/2243/17887941/2243.pdf
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17. portopulmonary hypertension and pulmonary arterial ... — academic.oup.com — https://academic.oup.com/eurheartjsupp/article/21/Supplement_K/K37/5678710
18. Update on Eisenmenger syndrome – Review of pathophysiology and recent progress in risk assessment and management — pmc.ncbi.nlm.nih.gov — https://pmc.ncbi.nlm.nih.gov/articles/PMC11658362
19. Pregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension—A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals - PMC — pmc.ncbi.nlm.nih.gov — https://pmc.ncbi.nlm.nih.gov/articles/PMC9033133
20. Congenital Heart Disease and Pulmonary Arterial Hypertension: Current Perspectives - PMC — pmc.ncbi.nlm.nih.gov — https://pmc.ncbi.nlm.nih.gov/articles/PMC13036531
21. The Adult Patient with Eisenmenger Syndrome: A Medical Update After Dana Point Part I: Epidemiology, Clinical Aspects and Diagnostic Options — pmc.ncbi.nlm.nih.gov — https://pmc.ncbi.nlm.nih.gov/articles/PMC3083816
22. Eisenmenger Syndrome - StatPearls - NCBI Bookshelf — www.ncbi.nlm.nih.gov — https://www.ncbi.nlm.nih.gov/books/NBK507800
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24. An Approach to Pulmonary Arterial Hypertension in the Adult Patient With Congenital Heart Disease - American College of Cardiology — www.acc.org — https://www.acc.org/latest-in-cardiology/articles/2014/07/18/12/56/an-approach-to-pulmonary-arterial-hypertension-in-the-adult-patient-with-congenital-heart-disease

## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.