Eisenmenger Syndrome
When an atrial septal defect develops pulmonary hypertension severe enough to reverse the shunt from left-to-right to right-to-left (or bidirectional), this is called Eisenmenger syndrome. 1
Definition and Pathophysiology
Eisenmenger syndrome specifically refers to any congenital systemic-to-pulmonary shunt (including ASD, VSD, or PDA) that leads to severe elevation in pulmonary vascular resistance, resulting in reversed (pulmonary-to-systemic) or bidirectional shunt flow with associated cyanosis, erythrocytosis, and multiple organ involvement. 1
The pathophysiologic sequence occurs as follows:
- Initially, the ASD creates a left-to-right shunt due to lower right-sided pressures 1
- Chronic exposure of pulmonary vasculature to increased blood flow triggers pulmonary vascular remodeling with medial thickening and plexiform lesions 1
- Progressive pulmonary arterial hypertension develops with increasing pulmonary vascular resistance 1, 2
- When pulmonary vascular resistance approaches or exceeds systemic vascular resistance, shunt reversal occurs 1
- The resulting right-to-left shunt causes oxygen-unresponsive hypoxemia and cyanosis 1, 3
Clinical Presentation
Key clinical features that distinguish Eisenmenger syndrome from simple ASD include:
- Cyanosis at rest (the hallmark finding differentiating this from uncomplicated left-to-right shunts) 1, 3
- Digital clubbing 4, 2
- Erythrocytosis with elevated hematocrit (often >65%) 1, 5
- Multiple organ system involvement affecting cardiac, hematologic, neurologic, respiratory, and other systems 2
Important Clinical Distinction
Not all right-to-left shunting through an ASD represents Eisenmenger syndrome. Rare cases of right-to-left shunting can occur without pulmonary hypertension due to transient interatrial pressure gradients from timing differences in cardiac cycle phases between right and left chambers 6. However, when cyanosis and right-to-left shunting occur in the context of elevated pulmonary vascular resistance and pulmonary arterial pressure at systemic levels, the diagnosis is Eisenmenger syndrome 1.
Prognosis and Timing
- ASDs carry relatively lower risk of developing Eisenmenger syndrome compared to VSDs or other post-tricuspid shunts 1
- When Eisenmenger syndrome develops from ASD, it typically presents later in life (often recognized during pregnancy or middle age) rather than in the first decade 1, 3
- Patients with Eisenmenger syndrome have better survival than idiopathic pulmonary arterial hypertension, with 3-year survival rates of 77% versus 35% for untreated idiopathic PAH 1
Management Implications
Surgery is absolutely contraindicated once Eisenmenger physiology develops 1. The presence of shunt reversal with exercise-induced desaturation or when pulmonary vascular resistance exceeds 2/3 of systemic values precludes surgical closure 1, 7. Treatment focuses on pulmonary arterial hypertension-specific therapies (endothelin receptor antagonists like bosentan, phosphodiesterase-5 inhibitors, prostacyclin analogues) and supportive care 1, 7, 2.