From the Guidelines
Eisenmenger syndrome is a severe complication of untreated congenital heart defects characterized by pulmonary hypertension and reversed or bidirectional shunting of blood, with the fundamental cause being elevated pulmonary vascular resistance driving right-to-left intracardiac or great arterial shunting leading to systemic arterial desaturation. The pathophysiology of Eisenmenger syndrome begins with a congenital heart defect that creates a left-to-right shunt, such as ventricular septal defect, atrial septal defect, or patent ductus arteriosus 1. Initially, this shunt causes increased blood flow to the pulmonary circulation, leading to progressive damage to the pulmonary vasculature, including intimal hyperplasia, medial hypertrophy, and fibrosis of pulmonary arterioles. These changes cause increased pulmonary vascular resistance and pulmonary arterial pressure, eventually leading to pulmonary hypertension. When pulmonary pressure exceeds systemic pressure, the shunt reverses direction (becoming right-to-left), resulting in deoxygenated blood entering the systemic circulation. This reversal causes cyanosis, hypoxemia, erythrocytosis (increased red blood cell production), and multiple organ complications.
Key Factors Contributing to Eisenmenger Syndrome
- Congenital heart defects with left-to-right shunting
- Increased pulmonary blood flow leading to pulmonary vascular damage
- Elevated pulmonary vascular resistance and pulmonary arterial pressure
- Reversal of shunt direction from left-to-right to right-to-left
- Systemic arterial desaturation and cyanosis
The condition typically develops over years or decades and is irreversible once established. Management focuses on supportive care rather than correction of the original defect, as surgical repair at this stage carries extremely high risk and may worsen outcomes 1. The most recent guidelines recommend the use of endothelin receptor antagonists, such as bosentan, and phosphodiesterase-5 inhibitors, such as sildenafil or tadalafil, to improve functional capacity and hemodynamics in adults with Eisenmenger syndrome 1. Accurate diagnosis of Eisenmenger syndrome and exclusion of other potential contributors to right-to-left shunting or pulmonary hypertension are crucial prerequisites to optimize therapy.
Important Considerations for Management
- Accurate diagnosis of Eisenmenger syndrome
- Exclusion of other potential contributors to right-to-left shunting or pulmonary hypertension
- Use of endothelin receptor antagonists and phosphodiesterase-5 inhibitors to improve functional capacity and hemodynamics
- Supportive care rather than surgical repair of the original defect.
From the Research
Pathophysiology of Eisenmenger Syndrome
The pathophysiology of Eisenmenger syndrome is complex and involves multiple systems. Key aspects include:
- A large nonrestrictive systemic left-to-right shunt that triggers the development of pulmonary vascular disease and progressive pulmonary arterial hypertension 2
- Increasing pulmonary vascular resistance at the systemic level, which ultimately results in shunt reversal 2, 3
- Chronic hypoxemia, which leads to various systemic manifestations, including hematologic, cardiovascular, renal, neurologic, and immune consequences 4
Disease Progression
Disease progression in Eisenmenger syndrome involves:
- Pulmonary vascular remodeling and pulmonary arterial hypertension 5
- Shunt reversal and central cyanosis 3, 5
- Multiorgan disease, including involvement of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal, and endocrinological systems 2
Clinical Presentation
The clinical presentation of Eisenmenger syndrome includes:
- Central cyanosis, dyspnea, fatigue, hemoptysis, syncope, and right-sided heart failure 5
- Progressive deterioration of function over time 5
- Multiple organ involvement, with each system informing management 4
Management
Management of Eisenmenger syndrome involves:
- Multidisciplinary care, with a focus on preventing disease progression and managing complications 2, 6
- Pulmonary arterial hypertension therapies, which have improved quality of life and outcome for many patients 3, 6
- Supportive care, including recommendations for physical activity, pregnancy, infections, air travel, and elective surgery 5
- Consideration of lung transplantation or combined heart-lung transplantation for patients with a poor prognosis 5