(See also Overview of Congenital Cardiovascular Anomalies.)
Congenital heart anomalies that, if untreated, may result in Eisenmenger syndrome include
Rare patients with single ventricle variants or with transposition of the great arteries 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. 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 stroke), and sequelae of increased RBC turnover (eg, hyperuricemia causing gout, hyperbilirubinemia causing cholelithiasis, iron deficiency with or without anemia).
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 yr). 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 will die suddenly.
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. Signs of right ventricular 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 2nd heart sound (S2) is a constant finding; a pulmonary ejection click is common.
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 Hct > 55%. Increased RBC turnover may be reflected as an iron deficiency state (eg, microcythemia), hyperuricemia, and hyperbilirubinemia. 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.
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 analogs (eg, treprostinil, epoprostenol), endothelin antagonists (eg, bosentan), and phosphodiesterase-5 inhibitors (eg, sildenafil, tadalafil) have been shown to improve performance on 6-min 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 Hct. 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 po once/day.
Anticoagulation therapy with warfarin is potentially harmful due to the risk of pulmonary hemorrhage, so anticoagulant use should be individualized. 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. 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 transplantation and lung transplantation may be an option, but transplantation 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 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, and 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 analogs, endothelin antagonists, phosphodiesterase-5 inhibitors) are useful.