NORD gratefully acknowledges Nancy Kong, NORD Editorial Intern from the Massachusetts College of Pharmacy and Health Sciences, and Konstantinos Dimopoulos, MD, MSc, PhD, FESC, Consultant Cardiologist, Professor of Practice in ACHD and PH, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital and Imperial College, London, UK, for assistance in the preparation of this report.
Eisenmenger syndrome is a rare condition that affects both the heart and the lungs. The disease is characterized by high blood pressure and abnormal blood flow through the heart. The type of high blood pressure experienced by affected individuals is called pulmonary artery hypertension, which affects the blood vessels in the lungs and the right heart chambers. Generally, patients with Eisenmenger syndrome are born with a heart defect (congenital heart defect) that was not corrected with surgery or other intervention at an early age.
The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition, known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The valves allow for blood to be pumped through the chambers. Blood travels from the right ventricle through the pulmonary artery to the lungs where it receives oxygen. The blood returns to the heart through pulmonary veins and enters the left ventricle. The left ventricle sends the now oxygen-filled blood into the main artery of the body (aorta). The aorta carries the blood to the body.
Individuals with Eisenmenger syndrome often have a ventricular septal defect or a “hole in the heart” between the left and right pumping chambers in the heart. This results in significant shunting of blood from the left side of the heart to the right at birth, which progresses to pulmonary vascular disease. Once pulmonary vascular disease has developed, the heart defect is no longer repairable. Eventually blood flow through the defect (shunt) can become bidirectional, which leads to cyanosis (reduced oxygen concentration in the blood).
The specific symptoms of Eisenmenger syndrome vary greatly from person to person. Although the heart defect is present at birth, Eisenmenger syndrome with cyanosis often develops around puberty, but may develop earlier or later depending on the location and severity of the congenital heart defect. The symptoms and complications result from a combination of the effects of the heart defect, reduced oxygen in the blood and high pressures in the lungs.
The most notable symptom is called cyanosis, which is the bluish discoloration of the skin and mucous membranes. Individuals affected with Eisenmenger syndrome develop cyanosis, particularly of the lips, fingers and toes, which is more pronounced during physical efforts. Patients typically have an increased number of blood cells (red blood cells or erythrocytes) that transport oxygen to the body (i.e., erythrocytosis), compensating for the inadequate oxygen supply to tissues.
Additional signs may include rounding of the tips of the fingers and toes (clubbing), shortness of breath, fatigue, lethargy or arrhythmias. Those with Eisenmenger syndrome are also at higher risk for stroke, coughing up blood (hemoptysis) or gout.
Specific genes that cause Eisenmenger syndrome have not been identified and the condition is not thought to be inherited.
Eisenmenger syndrome is caused by a defect in the structure of the heart, more specifically a ventricular septal defect (VSD) or other shunt. A VSD is a hole in the heart in the region that connects the left ventricle and the right ventricle. At birth, this hole allows large amounts of blood to flow between the two chambers, increase the volume of blood traveling to the lungs and increasing lung pressures, damaging the small blood vessels in the lungs. The rise in lung pressures due to often irreversible changes in the lung vessels (pulmonary vascular disease) is called pulmonary arterial hypertension.
Without early surgical correction of the underlying defect, the damage in the small arteries within the lung leads to increasing resistance to blood flow. The increasing pressure in the right ventricle can surpass that of the left ventricle and, when this happens, “blue” blood flow from the right to the left ventricle through the VSD (bidirectional, reversed or right-to-left shunt), leading to insufficient oxygen supply to the body (hypoxia), bluish discoloration of the skin and mucous membranes (cyanosis), elevated levels of circulating red blood cells, and other findings characteristic of Eisenmenger syndrome.
Eisenmenger syndrome appears to affect males and females in relatively equal numbers. Individuals with Down syndrome represent between 25-50% of the adult Eisenmenger population.
The diagnosis of Eisenmenger syndrome is not particularly complex but may require cardiac catheterization, an invasive procedure to measure pressures in the heart and lungs. Other tests include pulse oximetry, which checks oxygen levels in the blood, chest x-ray, EKG, pulmonary function test, iron levels and complete blood count (CBC). Echocardiography is fundamental in identifying the heart defect and raising the suspicion of high pressures in the lungs. Other imaging modalities (e.g. cardiac MRI) can provide valuable anatomic information.
The treatment of Eisenmenger syndrome should be managed by a medical team with expertise in both congenital heart disease (cardiologist) and pulmonary hypertension (cardiologist or pulmonologist), with help from other specialists, e.g. hematologists, radiologists, anesthetists etc. The goal of treatment is to minimize symptoms, and the treatment often aligns with patients who are being treated for other types of pulmonary arterial hypertension.
Currently, Eisenmenger patients are treated with pulmonary arterial hypertension therapies aimed at reducing the lung resistances and increase the amount of blood flowing through the lungs, hence delivering more oxygen to the body and reducing the load to the heart. Additional medications used include diuretics that reduce the amount of fluid in the body and, at times, medication to prevent blood clots. Beta blockers and especially calcium channel blockers are avoided, because they have a negative effect on the right ventricle. Iron supplementation may be necessary for individuals with iron deficiency anemia.
Affected individuals may have an increased risk of developing bacterial infections of the heart lining and valves (bacterial endocarditis); therefore, disease management includes the administration of appropriate antibiotics (antibiotic prophylaxis) prior to dental visits, for certain oral procedures. In addition, anesthesia and sedation carry significant risks and should be avoided. Careful monitoring during anesthesia is essential for any patients undergoing essential unavoidable surgical procedures, which should be performed in expert centers.
Pregnancy should be avoided in women with pulmonary hypertension and Eisenmenger syndrome since it carries significant risks for both the mother and the developing fetus. Thus, it is essential that affected women have a thorough understanding of such risks and receive information, support, and guidance from their physicians and other members of their healthcare team concerning appropriate options to prevent pregnancy. Oxygen therapy has also been met with controversial reviews. There is no data to support its use as a mean for increasing exercise capacity or survival in adult patients. However, it has been seen to help patients with advanced disease in need of a heart-lung transplant or for nocturnal support.
Individuals with Eisenmenger syndrome should avoid dehydration, high altitudes, and activities that could cause a sudden drop in blood pressure such as saunas, steam rooms or hot tubs. Extreme physical exercise should also be limited. In severely affected patients with physical deterioration, a heart-lung transplant may be necessary.
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