What is Eisenmenger Syndrome?

Eisenmenger Syndrome

Eisenmenger syndrome is defined as a congenital heart defect that initially causes a large systemic-to-pulmonary shunt, which induces severe pulmonary vascular disease and pulmonary arterial hypertension (PAH), resulting in reversal of the shunt direction and central cyanosis. 1

Pathophysiology

Eisenmenger syndrome develops through a sequence of pathological changes:

1. Initial phase: A congenital heart defect (typically large VSD, ASD, or PDA) creates a left-to-right shunt
2. Progressive phase: The pulmonary vasculature is exposed to increased blood flow and pressure
3. Irreversible phase: Development of pulmonary vascular obstructive disease occurs
4. Final phase: As pulmonary vascular resistance (PVR) approaches or exceeds systemic resistance, the shunt reverses direction (becomes right-to-left) 1

The pathological changes in the pulmonary vasculature include:

• Initial reversible changes: Medial hypertrophy and intimal proliferation
• Advanced irreversible changes: Plexiform lesions and arteritis 1

Clinical Classification

The European Society of Cardiology classifies PAH associated with congenital heart disease into four categories:

1. Eisenmenger syndrome: Large systemic-to-pulmonary shunts with severe PAH and reversed/bidirectional shunting
2. Moderate to large shunts: With severe PAH but without shunt reversal (no cyanosis)
3. Small defects: With PAH (clinical picture similar to idiopathic PAH)
4. PAH after repair: Persisting or recurring PAH after correction of congenital heart defect 1

Clinical Presentation

Patients with Eisenmenger syndrome typically present with:

• Central cyanosis: Due to right-to-left shunting
• Dyspnea and exercise intolerance: Often well-compensated for years
• Hemoptysis: From rupture of dilated bronchial arteries
• Syncope: Due to inadequate cardiac output or arrhythmias
• Abnormal hemostasis: At risk for both bleeding and thrombosis
• Cerebrovascular events: From paradoxical embolization, venous thrombosis, or intracranial hemorrhage
• Heart failure symptoms: Uncommon until advanced disease, indicating poor prognosis 1

Multisystem Complications

Eisenmenger syndrome affects multiple organ systems:

• Hematologic: Secondary erythrocytosis, iron deficiency, bleeding disorders
• Neurological: Stroke, brain abscess, headaches from hyperviscosity
• Renal: Progressive dysfunction
• Cardiac: Right heart failure, arrhythmias
• Respiratory: Hemoptysis, pulmonary infections
• Musculoskeletal: Joint pain, hypertrophic osteoarthropathy 2, 3

Diagnosis

Diagnosis requires:

• Comprehensive anatomical assessment of the underlying congenital defect
• Documentation of shunt direction and severity of PAH
• Assessment of oxygen saturation, complete blood count, iron studies
• Evaluation of renal and hepatic function
• 6-minute walk test, pulmonary function tests
• ECG, chest X-ray
• Echocardiography for ventricular function assessment 2

Right heart catheterization is essential to confirm the diagnosis and assess pulmonary vascular resistance.

Management

Patients with Eisenmenger syndrome should be managed exclusively in specialized centers with expertise in adult congenital heart disease and pulmonary arterial hypertension. 2

Pulmonary Vasodilator Therapy

• Endothelin receptor antagonists (ERAs): Bosentan is recommended as first-line therapy for WHO functional class III patients 2
• Phosphodiesterase-5 inhibitors: Consider for symptomatic patients
• Combination therapy: May be considered in patients not responding adequately to monotherapy 2
• Contraindicated: Calcium channel blockers (can cause catastrophic systemic vasodilation) 2

Supportive Care

• Oxygen therapy: Consider when it produces consistent increase in arterial oxygen saturation and reduces symptoms 2
• Phlebotomy: Only for patients with moderate/severe hyperviscosity symptoms (headache, poor concentration) with hematocrit >65%, always with isovolumic replacement 1
• Iron supplementation: Avoid iron deficiency and treat when present 2
• Anticoagulation: Consider in patients with pulmonary artery thrombosis, heart failure, atrial fibrillation, or low bleeding risk 2

Important Precautions

• Avoid destabilizing situations: Volume shifts, extreme fatigue, high-altitude exposure, dehydration 2
• Pregnancy: Absolutely contraindicated due to extremely high maternal and fetal mortality 2
• Non-cardiac surgery: Should only be performed in specialized centers 2
• IV lines: Avoid air bubbles to prevent paradoxical embolism 2

Prognosis

Survival of patients with Eisenmenger syndrome is better than that of subjects with idiopathic PAH with comparable functional class. In one study, actuarial survival of Eisenmenger patients was 97% at 1 year, 89% at 2 years, and 77% at 3 years, compared to 77%, 69%, and 35%, respectively, for patients with idiopathic PAH 1.

Follow-up

• Regular assessment at specialized centers every 6-12 months
• Monitoring of exercise capacity, oxygen saturation, blood tests
• Echocardiography to assess ventricular function
• Vigilance for complications including arrhythmias, heart failure progression, bleeding, thrombosis, and infections 2

Eisenmenger syndrome is a preventable condition, highlighting the importance of early detection and management of congenital heart defects before irreversible pulmonary vascular disease develops 3.