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A rare respiratory disease associated with unoperated congenital heart disease and characterized by congenital heart malformations with reversed or bi-directional shunting through an intra-cardiac or intervascular (usually aorto-pulmonary) communication with the development of PAH.
ORPHA:97214Classification level: Disorder
- Synonym(s): -
- Prevalence: 1-9 / 1 000 000
- Inheritance: Not applicable
- Age of onset: Adolescent, Childhood, Adult
- ICD-10: I27.2
- OMIM: -
- UMLS: C0013743
- MeSH: -
- GARD: 6323
- MedDRA: 10058554
The disease is thought to be rare and affects both males and females equally. The incidence of the syndrome is decreasing in the developed world as the vast majority of causative cardiac lesions are now readily treatable. Incidence may still be higher in the less developed regions of the world as perinatal survival is higher but surgical treatment remains unaffordable for many.
The disease generally develops in children before puberty, but may develop in adolescence or early adulthood. Infants born with a large ventricular septal defect, an atrio-ventricular septal defect, or a persistently patent arterial duct are most susceptible. Pulmonary hypertension can also be associated with atrial septal defects but it is more controversial as to whether this is more accurately a form of idiopathic pulmonary hypertension (possibly accelerated by the shunt) than directly due to the atrial shunt. Clinical manifestations include exertional dyspnea, fatigue, lethargy, central cyanosis, chest pain, palpitations, atrial and ventricular arrhythmias. Right heart failure (with hepatomegaly, jugular venous distention and peripheral edema, is a very late complication). Dizziness and syncope due to low cardiac output is much rarer in Eisenmenger's syndrome than in PAH without intracardiac shunts. Clubbing and hemoptysis may occur. Precordial signs of ES are loud (often palpable) second heart sound and right ventricular heave. A pulmonary ejection click may be heard; Murmurs are variable and include those of pulmonary and tricuspid regurgitation. Complications include infective endocarditis, hyperviscosity, iron deficiency, bleeding disorders, hyperuricemia, stroke and cerebral abscess. Patients are at extremely high risk of death or major complications during pregnancy and the puerperium.
The disease results from communication between right and left sides of the circulation, permitting oxygenated blood to recirculate at high pressure within the pulmonary vasculature. This increase blood pressure +/- increased flow promotes endothelial dysfunction and proliferation; which leads to vascular remodeling, and pulmonary hypertension. Reversal of shunt and development of cyanosis is regarded as Eisenmenger syndrome.
Diagnosis is based on the clinical features, pulse oximetry findings, an abnormal electrocardiogram (right axis deviation, right ventricular hypertrophy and right atrial enlargement), echocardiography (underlying lesion, site of shunt and estimating pulmonary arterial pressure) and imaging (MRI and CT). Right-heart catheterization (saturation, hemodynamics and pulmonary vasoreactivity study if appropriate) is usual to establish the diagnosis and may be clinically useful in planning treatment / assessing efficacy. Routine lab testing (total blood count, liver function test, urea, creatinine, electrolytes, uric acid and iron status) is sought to detect emerging complications.
Differential diagnoses include idiopathic pulmonary hypertension, tetralogy of Fallot, tricuspid atresia, transposition of the great arteries, persistent newborn pulmonary hypertension, pulmonary infection and respiratory failure.
Management and treatment
The disease can be avoided if appropriate repair of the underlying heart defect is undertaken prior to the establishment of irreversible changes to the pulmonary vascular bed. Management includes maintaining fluid balance, prophylaxis against infective endocarditis, iron supplementation and avoiding precipitating factors (pregnancy, isometric exercise, high altitude). Targeted pharmacological therapies are recommended for symptomatic patients; prostacyclin analogues (treprostinil), endothelin antagonists (bosentan, macitantan), nitric oxide, phosphodiesterase inhibitor (sildenafil). Heart and lung transplantation (or lung transplantation with intracardiac repair) is an option for patients with a poor prognosis who fail to respond to medical therapy.
Life expectancy depends on the type and severity of the underlying defect and right ventricular function, and ranges from 20 to 50 years. In patients with the syndrome the maternal mortality rate exceeds 50%. The chances of preterm delivery and low birth weight are extremely high and the likelihood of livebirth drops dramatically with lower maternal oxygen saturation levels (to below 10% in some series) if maternal resting oxygen saturations are less than 85%.
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