What is the best management approach for a patient with Eisenmenger syndrome, a history of congenital heart defects, and pulmonary hypertension?

Management of Eisenmenger Syndrome

Bosentan (an endothelin receptor antagonist) should be initiated as first-line therapy for patients with Eisenmenger syndrome who are in WHO functional class III, as this represents the only Class I, Level B evidence-based recommendation for medical treatment of this condition. 1, 2

Diagnostic Confirmation and Initial Evaluation

Before initiating treatment, comprehensive evaluation at a specialized adult congenital heart disease center is mandatory to confirm the diagnosis and exclude other causes of right-to-left shunting 1:

• Confirm true Eisenmenger physiology by excluding alternative causes of right-to-left shunting: subpulmonary ventricular outflow obstruction, abnormal subpulmonary chamber compliance, thromboembolic disease, or vascular streaming 1
• Cardiac catheterization is essential to document pulmonary vascular resistance at or exceeding systemic vascular resistance and to confirm shunt reversal 1
• Baseline testing must include: finger and toe oximetry, complete blood count with indices and ferritin, renal and hepatic function tests, 6-minute walk test, pulmonary function tests with CO2 diffusion, CT chest with pulmonary embolism protocol, and echocardiography 1, 2

Medical Therapy Algorithm

First-Line Treatment

• Bosentan is the only medication with Class I, Level B evidence for WHO functional class III Eisenmenger patients 1, 2
• Demonstrated improvement in 6-minute walk distance, hemodynamics, and functional capacity in randomized controlled trials specifically in Eisenmenger syndrome with ASD or VSD 1

Second-Line and Alternative Options

• Other endothelin receptor antagonants, phosphodiesterase-5 inhibitors (sildenafil), and prostanoids should be considered as alternative or additional therapy (Class IIa, Level C evidence) 1, 2, 3
• These agents may improve functional class, oxygen saturation, and hemodynamics 4
• Combination therapy may be considered in symptomatic patients, though evidence is limited (Class IIb, Level C) 1

Contraindicated Therapy

• Calcium channel blockers are contraindicated in Eisenmenger syndrome (Class III, Level C evidence) 1, 2, 3

Critical Supportive Care Measures

Oxygen Therapy

• Use supplemental oxygen only if it produces a consistent, documented increase in arterial oxygen saturation AND reduces symptoms (Class IIa, Level C) 1, 2
• Oxygen-unresponsive hypoxemia warrants further investigation for alternative pathology 1

Phlebotomy Management

• Perform phlebotomy with isovolumic replacement only when ALL of the following are present: 2, 3
  • Moderate to severe symptoms of hyperviscosity (headache, fatigue, visual disturbances)
  • Hematocrit exceeds 65%
  • No evidence of dehydration
  • Iron stores are replete
• Avoid routine phlebotomy as it can worsen iron deficiency and paradoxically increase blood viscosity 1, 5

Anticoagulation

• Consider oral anticoagulation in patients with atrial fibrillation, documented pulmonary artery thrombosis, or signs of heart failure, provided there is no significant hemoptysis risk (Class IIa, Level C) 1, 3
• Anticoagulation carries both potential benefits and risks in this population; decision requires careful individualized risk-benefit assessment 1

Essential Safety Protocols

Prevention of Paradoxical Embolization

• Meticulous exclusion of air bubbles in ALL intravenous tubing is mandatory to prevent paradoxical embolization through the right-to-left shunt 1, 2
• Consider air filters on all venous catheters 1

Procedural Considerations

• All noncardiac surgery and cardiac catheterization must be performed only at centers with Eisenmenger expertise 1, 2
• In emergent situations where transfer is impossible, sustained consultation with designated Eisenmenger experts is required throughout care 1
• Rigorous medication review is required for all drugs to assess potential effects on systemic blood pressure, loading conditions, intravascular shunting, and renal/hepatic function (Class IIa, Level C) 1, 2

Situations That Must Be Avoided

The following circumstances can precipitate acute decompensation and must be strictly avoided 1, 2, 5:

• Pregnancy (associated with extremely high maternal and fetal mortality)
• Dehydration (increases blood viscosity and thrombosis risk)
• High altitude exposure (worsens hypoxemia)
• Iron deficiency (produces iron-deplete red cells that increase viscosity despite lower hematocrit)
• Extreme exertion
• General anesthesia without expert planning
• Nephrotoxin exposure
• Large intravascular volume shifts

Monitoring and Follow-Up

• Specialized follow-up at a grown-up congenital heart (GUCH) center at least every 12 months is required 2
• Monitor exercise capacity, right ventricular function, arrhythmias, and hematological parameters at each visit 2, 3
• Promptly treat any infections, as infectious diseases are a leading cause of mortality 6, 7

Prognostic Considerations

• Eisenmenger syndrome has markedly better survival than idiopathic pulmonary arterial hypertension: 77% three-year survival versus 35% for untreated idiopathic PAH 1, 2, 3
• Many patients survive into their third or fourth decade, with some reaching their seventh decade 1, 2
• Negative prognostic factors include: decreased arterial oxygen saturation, WHO functional class III-IV, impaired exercise tolerance, syncope, iron deficiency, pre-tricuspid shunts, arrhythmias, elevated brain natriuretic peptide, right ventricular dysfunction on echocardiography, and hospitalization for heart failure 6, 7
• Leading causes of death are sudden cardiac death, progressive heart failure, and infectious diseases 6, 7