(See also Overview of Congenital Cardiovascular Anomalies Overview of Congenital Cardiovascular Anomalies Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births ( 1). Among birth defects, congenital heart disease is the leading cause of infant mortality... read more .)
Congenital heart anomalies that, if untreated, may result in Eisenmenger syndrome include (in approximate order of occurrence— 1 General reference Eisenmenger syndrome is a complication of uncorrected large intracardiac or aortic to pulmonary artery left-to-right shunts. Increased pulmonary resistance may develop over time, eventually... read more )
Partial anomalous venous return (PAPVR, whereby some of the pulmonary veins connect to the right atrium instead of the left atrium)
Rare patients with single ventricle variants or with transposition of the great arteries Transposition of the Great Arteries (TGA) Transposition of the great arteries (in this case, dextro-transposition) occurs when the aorta arises directly from the right ventricle and the pulmonary artery arises from the left ventricle... read more with a persistent patent ductus arteriosus and/or ventricular septal defect may develop Eisenmenger syndrome if untreated, though the vast majority of these patients die early in infancy if the anomaly is not recognized and treated. In the United States, the incidence has markedly decreased because of early diagnosis and definitive repair of the causative anomaly.
Right-to-left shunting due to Eisenmenger syndrome results in cyanosis and its complications. Systemic oxygen desaturation leads to clubbing of fingers and toes, secondary polycythemia Perinatal Polycythemia and Hyperviscosity Syndrome Polycythemia is an abnormal increase in red blood cell mass, defined in neonates as a venous hematocrit ≥ 65%; this increase can lead to hyperviscosity with sludging of blood within vessels... read more , hyperviscosity, hemoptysis, central nervous system events (eg, brain abscess or stroke), pulmonary artery thrombosis, and sequelae of increased red blood cell turnover (eg, hyperuricemia causing gout, hyperbilirubinemia causing cholelithiasis, iron deficiency with or without anemia).
1. Diller GP, Korten MA,Bauer UMM, et al: Current therapy and outcome of Eisenmenger syndrome: data of the German National Register for congenital heart defects. Eur Heart J 37(18): 1449–1455, 2016. doi: 10.1093/eurheartj/ehv743
Symptoms and Signs of Eisenmenger Syndrome
Symptoms of Eisenmenger syndrome develop at different ages depending on the cause.
Patients with pre-tricuspid left-to-right shunts (ASD, partial anomalous pulmonary venous return) usually do not develop symptoms until later in life (age 20 to 40 years). However, patients with unrepaired post-tricuspid shunts (VSD, PDA, or more complex congenital heart disease) may develop irreversible, symptomatic pulmonary vascular disease within the first few years of life.
Symptoms include cyanosis, syncope, dyspnea during exertion, fatigue, chest pain, and palpitations. Some patients die suddenly.
Hemoptysis is a late symptom. Manifestations of cerebral emboli Ischemic Stroke Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more , brain abscess Brain Abscess A brain abscess is an intracerebral collection of pus. Symptoms may include headache, lethargy, fever, and focal neurologic deficits. Diagnosis is by contrast-enhanced MRI or CT. Treatment is... read more , or endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more may develop.
Secondary polycythemia Secondary Erythrocytosis Secondary erythrocytosis is erythrocytosis that develops secondary to disorders that cause tissue hypoxia, inappropriately increased erythropoietin production, or increased sensitivity to erythropoietin... read more commonly causes symptoms (eg, transient ischemic attacks with slurred speech or other neurologic symptoms, vision problems, headaches, increased fatigue, signs of thromboembolism). Abdominal pain may result from cholelithiasis Cholelithiasis Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder. Gallstones tend to be asymptomatic. The most common symptom is biliary colic; gallstones do not cause dyspepsia... read more . Painful gouty arthritis Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more may result from hyperuricemia.
Physical examination detects central cyanosis and digital clubbing. Signs of right ventricular failure Heart failure (eg, hepatomegaly, peripheral edema, jugular venous distention) may be present. Palpation may reveal a right ventricular heave. A holosystolic murmur of tricuspid regurgitation may be present at the lower left sternal border. An early diastolic, decrescendo, high-pitched murmur of pulmonic regurgitation may be audible along the left sternal border. A loud, single second heart sound (S2) is a constant finding; a pulmonary ejection sound (click) is common.
An unusual finding of clubbing and cyanosis of only the lower extremities indicates the cause of the cyanosis is right-to-left shunting through an unrepaired large PDA directed primarily to the descending aorta.
Diagnosis of Eisenmenger Syndrome
Chest x-ray and ECG
Echocardiography or cardiac catheterization
Diagnosis of Eisenmenger syndrome is suspected by history of uncorrected cardiac anomalies, supported by chest x-ray and ECG findings, and established by 2-dimensional echocardiography with color flow and Doppler studies. Cardiac catheterization is often done to measure pulmonary artery pressure, pulmonary vascular resistance, and response to pulmonary vasodilators.
Laboratory testing shows polycythemia with hematocrit > 55%. Increased red blood cell turnover may be reflected as an iron deficiency state (eg, microcythemia), hyperuricemia, and hyperbilirubinemia. Iron deficiency should be suspected if the mean corpuscular volume (MCV) is low; iron deficiency can be identified by measuring transferrin saturation and ferritin.
Chest x-ray usually shows prominent central pulmonary arteries, peripheral pulmonary vessel pruning, and right heart enlargement.
ECG shows right ventricular hypertrophy, right axis deviation, and, occasionally, right atrial enlargement.
Treatment of Eisenmenger Syndrome
Medications to treat pulmonary arterial hypertension (eg, prostacyclin analogs, endothelin antagonists, phosphodiesterase-5 inhibitors)
"Treat and repair" approach
Heart and lung transplantation
Ideally, corrective operations should have been done earlier to prevent Eisenmenger syndrome. There is no specific treatment once the syndrome develops, other than heart and lung transplantation, but medications that may lower pulmonary artery pressure have been shown to have at least a modest beneficial effect on survival (1, 2 Treatment references Eisenmenger syndrome is a complication of uncorrected large intracardiac or aortic to pulmonary artery left-to-right shunts. Increased pulmonary resistance may develop over time, eventually... read more ).
Prostacyclin analogs (eg, treprostinil, epoprostenol), endothelin antagonists (eg, bosentan), and phosphodiesterase-5 inhibitors (eg, sildenafil, tadalafil) have been shown to improve performance on 6-minute walk tests and to reduce N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. In a small number of patients, aggressive therapy with pulmonary vasodilating drugs has resulted in net left-to-right shunting, allowing surgical repair of the underlying cardiac defect and significant reduction in mean pulmonary artery pressure. This has been called the treat and repair approach.
Supportive treatment includes avoidance of conditions that may exacerbate the syndrome (eg, pregnancy, volume depletion, isometric exercise, high altitudes, smoking). Supplemental oxygen may provide some benefit.
Symptomatic polycythemia can be treated by cautious phlebotomy to lower hematocrit to 55 to 65% plus simultaneous volume replacement with normal saline. However, compensated and asymptomatic polycythemia does not require phlebotomy, regardless of hematocrit. Phlebotomy eventually leads to iron deficiency, which is associated with a higher risk of adverse outcomes. In case of confirmed iron deficiency, supplemental iron should be carefully administered to replenish iron stores.
Hyperuricemia can be treated with allopurinol 300 mg orally once a day.
Anticoagulation therapy is controversial because the risk of pulmonary artery thrombosis and other thromboembolic phenomena must be balanced with the risk of pulmonary hemorrhage. Warfarin therapy is potentially harmful due to the risk of pulmonary hemorrhage, so anticoagulant use should be individualized (1 Treatment references Eisenmenger syndrome is a complication of uncorrected large intracardiac or aortic to pulmonary artery left-to-right shunts. Increased pulmonary resistance may develop over time, eventually... read more ). Although there is no clear evidence, low-dose aspirin potentially may prevent thrombotic complications.
Life expectancy depends on type and severity of the underlying congenital anomaly and ranges from 20 to 50 years. In untreated patients, low exercise tolerance and secondary complications severely limit quality of life. Use of advanced pulmonary vasodilator therapies has been shown to improve functional capacity and appears to improve survival.
Heart and lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. (See also Overview... read more or lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. (See also Overview... read more with cardiac repair may be an option, but transplantation is reserved for patients with severe symptoms and unacceptable quality of life. Long-term prognosis after transplantation is guarded.
All patients should be given endocarditis prophylaxis Prevention Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more before dental or surgical procedures that are likely to cause bacteremia.
1. Diller GP, Korten MA, Bauer UMM, et al: Current therapy and outcome of Eisenmenger syndrome: data of the German National Register for congenital heart defects. Eur Heart J 37(18):1449–1455, 2016. doi: 10.1093/eurheartj/ehv743
2. Kempny A, Hjortshoj CS, Gu H, et al: Predictors of death in contemporary adult patients with Eisenmenger syndrome: a multicenter study. Circulation 135(15): 1432–1440, 2017. doi: 10.1161/CIRCULATIONAHA.116.023033
Cardiac anomalies that involve large intracardiac left-to-right shunts often eventually cause increased pulmonary resistance, which first causes bidirectional shunting and ultimately right-to-left shunting (shunt reversal).
With shunt reversal, deoxygenated blood enters the systemic circulation, causing hypoxia and its complications (eg, clubbing of fingers and toes, secondary polycythemia); polycythemia may cause hyperviscosity, stroke, or other thromboembolic disorders, and/or hyperuricemia.
Symptoms usually do not occur until age 20 to 40 years in patients with pre-tricuspid shunting; in patients with a post-tricuspid shunt, symptoms can occur during the first few years of life.
Symptoms include cyanosis, syncope, dyspnea during exertion, fatigue, chest pain, palpitations, atrial and ventricular arrhythmias, hemoptysis, right heart failure, and sudden death.
Doing a corrective operation for the underlying cardiac anomaly at the appropriate age should prevent Eisenmenger syndrome.
There is no specific treatment once the syndrome develops, other than heart and lung transplantation, but drugs that may lower pulmonary vascular resistance (eg, prostacyclin analogs, endothelin antagonists, phosphodiesterase-5 inhibitors) are useful.
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American Heart Association: Common Heart Defects: Provides overview of common congenital heart defects for parents and caregivers
American Heart Association: Infective Endocarditis: Provides an overview of infective endocarditis, including summarizing prophylactic antibiotic use, for patients and caregivers
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