Eisenmenger's Syndrome

Eisenmenger's syndrome is defined as obstructive pulmonary vascular disease that develops as a consequence of a large pre-existing left-to-right shunt causing pulmonary artery pressures to increase and approach systemic levels, such that the direction of blood flow then becomes bi-directional or right-to-left^[1].

The frequency of pulmonary hypertension and development of reversed shunting vary depending on the specific heart defect and operative interventions. Early development of Eisenmenger's syndrome is more commonly associated with persistent truncus arteriosus and unrestricted pulmonary blood flow, common atrioventricular canal, ventricular septal defect (VSD), patent ductus arteriosus (PDA) and transposition of the great arteries.

The high pulmonary vascular resistance is usually established by age 2 years and can sometimes be present from birth. It is less common and occurs later in life in patients with a large secundum atrial septal defect (ASD).

Epidemiology

• The frequency of pulmonary hypertension and the development of reversed shunting vary depending on the specific heart defect and operative interventions.
• 50% of infants with a large, non-restrictive VSD or PDA develop pulmonary hypertension by early childhood.
• 10% of patients with a large secundum ASD progress to pulmonary hypertension but usually not until after the third decade of life.

Presentation

See the separate articles on Congenital Heart Disease in Children, Heart Murmurs in Children and Heart Auscultation. A thorough clinical examination is essential.

The main clinical symptoms include cyanosis due to secondary erythrocytosis, resulting in increased blood viscosity, iron-deficiency anaemia (enhanced by unnecessary phlebotomies), blood clotting disturbances, heart failure and serious supraventricular and ventricular arrhythmias^[2].

• Dyspnoea, fatigue, syncope; exercise intolerance (dyspnoea and fatigue) is proportional to the degree of hypoxaemia or cyanosis.
• Chest pain.
• Haemoptysis.
• Examination reveals:
  • Cyanosis, clubbing and plethora.
  • Right ventricular heave with palpable, loud pulmonary component of the second heart sound.
  • Loud second heart sound with a narrow split.
  • Ejection systolic murmur audible along the left sternal border.
  • Graham Steell murmur: a diastolic murmur audible along the left sternal border due to functional incompetence of the pulmonary valve in patients with pulmonary hypertension. The Graham Steell murmur is a high-pitched, decrescendo murmur, loudest during inspiration.

Differential diagnosis

• Primary pulmonary hypertension.
• Cyanotic congenital heart disease - eg Fallot's tetralogy.

Investigations

Initial investigations include:

• FBC, renal function and electrolytes, uric acid, LFTs (raised conjugated bilirubin), ferritin and clotting profile.
• Pulse oximetry at rest, and occasionally with exertion (if the saturation at rest is more than 90%).
• ECG: almost always abnormal; shows features suggestive of right heart hypertrophy (with tall R wave in V1, deep S wave in V6, ST and T wave abnormalities, P pulmonale) as well as abnormalities associated with the underlying defect.
• CXR: radiological features of a particular condition (such as PDA, VSD) but the lungs are no longer plethoric.
• Echocardiogram.

Further investigations may include:

• MRI: to assess the defect(s) between the pulmonary and systemic circulations, to evaluate the size of the proximal pulmonary arteries, and the presence of mural or obstructive thrombi.
• Transoesophageal echocardiography (rarely) to assess defects further between the pulmonary and systemic circulations.
• Spiral/high-resolution CT chest scan in patients with haemoptysis, to rule out the possibility of major pulmonary haemorrhage, especially when the CXR shows pulmonary infiltrate.
• Heart catheterisation with pulmonary vasodilators primarily to determine pulmonary artery pressures and resistances.
• Open lung biopsy should only be considered when the reversibility of the pulmonary hypertension is uncertain.

Advice to patients

• Take medication only after consultation with your physician.
• Avoid dehydration.
• Avoid smoking.
• Tell the responsible cardiologist if you need non-cardiac surgery or have suffered serious illness or injury.
• Avoid excessive physical activity.
• Avoid needless high-altitude exposure, especially when combined with significant physical activity.
• Flying on commercial airline flights can be safely performed with stable patients and SaO₂ on room air >85%.

Management

• Treat heart failure and arrhythmias.
• Calcium-channel blockers (may increase the right-to-left shunt), antiplatelet agents and anticoagulants have not been shown to be beneficial and may cause further complications - eg, hypotension, worsening cyanosis, increased hyperuricaemia or haemorrhage.
• Prevention of infective endocarditis:
  • The National Institute for Health and Care Excellence (NICE) recommends that if a person at risk of infective endocarditis is receiving antimicrobial therapy because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected infection, the person should receive an antibiotic that covers organisms that cause infective endocarditis.
  • Any episodes of infection in people at risk of infective endocarditis should be investigated and treated promptly to reduce the risk of endocarditis developing.
• Patients with significant polycythaemia may be helped by repeated venesection and volume replacement. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is above 65%^[3].
• Chronic use of oxygen or pulmonary vasodilators is controversial and under investigation.
• With continued improvements in the diagnosis, pre-operative management, refinement of surgical techniques and postoperative management strategies, patients with Eisenmenger's syndrome might be amenable to, and benefit from, repair in the modern era^[4].
• Ultimately, heart-lung transplant may be indicated^[5].

Pregnancy and contraception

• Pregnancy should be avoided. If it occurs, early termination is advised. If pregnancy is continued, maternal mortality approaches 50% with each pregnancy and fetal loss is similar.
• Tubal ligation is recommended for contraception. Intrauterine devices should be avoided, as they may cause significant menorrhagia and increase the risk of endocarditis.
• Combined oral contraceptive pills (COCPs) should be avoided.
• The risk of congenital heart defects in offspring is approximately 10% but depends on the initial cardiac defect.

Other risks

Apart from pregnancy, the following also carry increased risk in patients with Eisenmenger's syndrome:

• General anaesthesia.
• Dehydration.
• Haemorrhage.
• Non-cardiac surgery and cardiac surgery.
• Certain drugs - eg, vasodilators, diuretics, COCPs, danazol.
• Anaemia (prevention of iron deficiency is important).
• Cardiac catheterisation.
• Intravenous lines (risk of paradoxical air embolism and infection).
• Altitude exposure.
• Lung infections.

Complications

• Haemoptysis.
• Bleeding disorders.
• Hyperuricaemia, gout, nephrolithiasis.
• Polycythaemia, hyperviscosity syndrome.
• Angina pectoris.
• Arrhythmias (atrial fibrillation/atrial flutter).
• Syncope.
• Sudden death, stroke, transient ischaemic attacks.
• Paradoxical emboli.
• Infective endocarditis.
• Pulmonary arterial aneurysm/calcification.
• Brain abscess.
• Progressive valvar stenosis or regurgitation.
• Renal dysfunction (especially proteinuria).
• Hyperbilirubinaemia may cause gallstones.
• Hypertrophic osteoarthropathy.

Prognosis

• Eisenmenger's syndrome is a devastating condition that has a considerable impact on patients' lives^[6].
• The most common causes of death are sudden death, congestive heart failure and haemoptysis.
• Pregnancy, perioperative mortality following non-cardiac surgery, and infectious causes (brain abscesses and endocarditis) account for most of the other deaths.
• Reduced systemic blood flow and elevated right atrial pressure are associated with high mortality rates in adults with Eisenmenger's syndrome^[7].