What is Eisenmenger Syndrome?

From the Guidelines

Eisenmenger syndrome is a severe heart condition that requires prompt diagnosis and treatment to reduce morbidity and mortality, and improve quality of life, with bosentan being beneficial in symptomatic adults with Eisenmenger syndrome with ASD or VSD, as supported by the 2018 AHA/ACC guideline for the management of adults with congenital heart disease 1.

Diagnosis and Treatment

Eisenmenger syndrome typically develops when congenital heart defects like ventricular septal defects, atrial septal defects, or patent ductus arteriosus go untreated in childhood, leading to increased blood flow to the lungs, pulmonary hypertension, and reversed blood flow through the defect. The hallmark of this condition is the reversal of the initial left-to-right shunt to a right-to-left shunt, causing deoxygenated blood to bypass the lungs and enter the systemic circulation. Patients experience symptoms including:

• Bluish skin (cyanosis)
• Shortness of breath
• Fatigue
• Chest pain
• Fainting
• Heart rhythm abnormalities Management focuses on treating symptoms rather than curing the condition, with medications like:
• Endothelin receptor antagonists (bosentan, ambrisentan)
• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil)
• Prostacyclins (epoprostenol) to reduce pulmonary pressure

Recommendations

The 2018 AHA/ACC guideline for the management of adults with congenital heart disease recommends:

• Confirming diagnostic imaging and cardiac catheterization data accuracy and excluding other potential contributors to right-to-left shunting or pulmonary hypertension 1
• Using bosentan in symptomatic adults with Eisenmenger syndrome with ASD or VSD 1
• Considering combination therapy with bosentan and PDE-5 inhibitors in symptomatic adults with Eisenmenger syndrome who do not respond to either medication alone 1
• Using PDE-5 inhibitors (e.g., sildenafil, tadalafil) to treat symptomatic adults with Eisenmenger syndrome with ASD, VSD, or great artery shunt 1

Lifestyle Modifications

Patients with Eisenmenger syndrome should:

• Avoid pregnancy
• Avoid high altitudes
• Avoid dehydration
• Avoid excessive physical exertion
• Consider iron supplementation for iron deficiency
• Consider phlebotomy for severe polycythemia Heart-lung transplantation is the only definitive treatment but carries significant risks. The condition develops because the initial heart defect allows excessive blood flow to the lungs, damaging pulmonary blood vessels and causing them to narrow, which increases resistance and eventually reverses blood flow through the defect.

From the Research

Definition and Pathophysiology of Eisenmenger Syndrome

• Eisenmenger syndrome (ES) develops in association with unrepaired, non-restrictive cardiac shunt lesions at the atrial, ventricular or arterial level over time 2.
• It is the most severe and extreme phenotype of pulmonary arterial hypertension associated with congenital heart disease 3.
• A large nonrestrictive systemic left-to-right shunt triggers the development of pulmonary vascular disease, progressive pulmonary arterial hypertension, and increasing pulmonary vascular resistance at the systemic level, which ultimately results in shunt reversal 3.

Clinical Features and Complications

• Central cyanosis with secondary erythrocytosis is one of the key features of patients with ES 2.
• Clinical consequences of longstanding hypoxia can lead to other organ complications, that involve other organs than the heart alone 2.
• Multiorgan disease is an integral manifestation of Eisenmenger syndrome and includes involvement of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal, and endocrinological systems 3.
• The leading reasons for mortality are sudden cardiac death, progressive heart failure, and infectious diseases 2, 4.

Diagnosis and Management

• Care in tertiary specialist cardiac centers with access to multidisciplinary subspecialities is required 2.
• Follow-up and care at specialist congenital heart disease centers is highly recommended to prevent, to early diagnose and to timely manage complications of ES 2.
• Advanced pulmonary arterial hypertension therapies are indicated in patients with Eisenmenger syndrome and World Health Organization functional class II or higher symptoms to improve functional capacity, quality of life, and-less well documented-survival 3.
• Endothelin receptor antagonists are used as first-line treatment in symptomatic patients, while phosphodiesterase-5 inhibitors may be added 4.

Treatment Options

• The dual endothelin receptor antagonist bosentan was demonstrated to improve hemodynamics and exercise capacity without compromising oxygen saturation, both in the short and long term 5.
• The phosphodiesterase type V inhibitor sildenafil may improve functional class, oxygen saturation, and hemodynamics in patients with ES 5.
• Combination therapy with bosentan and sildenafil in Eisenmenger syndrome has been evaluated in a randomized, placebo-controlled, double-blinded trial, which showed that bosentan improved the 6 min walk distance, pulmonary vascular resistance, and pulmonary blood flow, while adding sildenafil to bosentan did not significantly improve walking distance but did increase saturation at rest 6.