(Eisenmenger's Syndrome; Pulmonary Vascular Obstructive Disease)
(See also Overview of Congenital Cardiovascular Anomalies.)
Eisenmenger syndrome is a complication of uncorrected large intracardiac left-to-right shunts. Increased pulmonary resistance may develop over time, eventually leading to bidirectional shunting and then to right-to-left shunting. Deoxygenated blood enters the systemic circulation, causing symptoms of hypoxia. Murmurs and heart sounds depend on the underlying anomaly. Diagnosis is by echocardiography or cardiac catheterization. Treatment is generally supportive, but heart and lung transplantation may be an option when symptoms are severe. Endocarditis prophylaxis is recommended.
Congenital heart anomalies that, if untreated, may result in Eisenmenger syndrome include
In the US, 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, hyperviscosity, hemoptysis, CNS events (eg, brain abscess or cerebrovascular accident), and sequelae of increased RBC turnover (eg, hyperuricemia causing gout, hyperbilirubinemia causing cholelithiasis, iron deficiency with or without anemia).
Symptoms of Eisenmenger syndrome usually do not occur until age 20 to 40 yr; they include cyanosis, syncope, dyspnea during exertion, fatigue, chest pain, palpitations, atrial and ventricular arrhythmias, and rarely right heart failure (eg, hepatomegaly, peripheral edema, jugular venous distention).
Hemoptysis is a late symptom. Signs of cerebral embolic phenomena, brain abscess, or endocarditis may develop.
Secondary polycythemia commonly causes symptoms (eg, transient ischemic attacks with slurred speech or other neurologic symptoms, visual problems, headaches, increased fatigue, signs of thromboembolism). Abdominal pain may result from cholelithiasis.
Physical examination detects central cyanosis and digital clubbing. Rarely, signs of right ventricular failure may be present. A holosystolic murmur of tricuspid regurgitation may be present at the lower left sternal border. An early diastolic, decrescendo, high-pitched murmur of pulmonary insufficiency may be audible along the left sternal border. A loud, single 2nd heart sound (S2) is a constant finding; an ejection click is common. Scoliosis is present in about one third of patients.
Diagnosis of Eisenmenger syndrome is suspected by history of uncorrected cardiac anomalies, supported by chest x-ray and ECG, 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 Hct > 55%. Increased RBC turnover may be reflected as an iron deficiency state (eg, microcythemia), hyperuricemia, and hyperbilirubinemia.
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.
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 drugs that may lower pulmonary artery pressure are being studied.
Prostacyclin antagonists (eg, treprostinil, epoprostenol), endothelin antagonists (eg, bosentan), and nitric oxide enhancers (eg, sildenafil) have been shown to improve performance on 6-min walk tests and to reduce N-terminal pro-brain natriuretic peptide (NT-proBNP). In a small number of patients, aggressive therapy with advanced pulmonary vasodilating drugs has resulted in net left-to-right shunt, 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) and use of supplemental oxygen.
Symptomatic polycythemia can be treated by cautious phlebotomy to lower Hct to 55 to 65% plus simultaneous volume replacement with normal saline. However, compensated and asymptomatic polycythemia does not require phlebotomy, regardless of Hct; phlebotomy eventually leads to iron deficiency and does not change the natural history.
Hyperuricemia can be treated with allopurinol 300 mg po once/day. Anticoagulation therapy with warfarin is potentially harmful and its use should be individualized, but aspirin 81 mg po once/day is indicated to prevent thrombotic complications.
Life expectancy depends on type and severity of the underlying congenital anomaly and ranges from 20 to 50 yr; median age at death is 37 yr. However, low exercise tolerance and secondary complications severely limit quality of life.
Heart transplantation and lung transplantation may be an option but is reserved for patients with severe symptoms and unacceptable quality of life. Long-term survival after transplantation is not promising.
All patients should be given endocarditis prophylaxis before dental or surgical procedures that are likely to cause bacteremia.
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 yr; they include cyanosis, syncope, dyspnea during exertion, fatigue, chest pain, palpitations, atrial and ventricular arrhythmias, and rarely right heart failure.
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 artery pressure (eg, prostacyclin antagonists, endothelin antagonists, nitric oxide enhancers) are being studied.