Eisenmenger's syndrome

What is 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

Pulmonary hypertension is defined as a mean pulmonary arterial pressure of 25 mmHg or higher. Pulmonary hypertension is a relatively common complication of congenital heart disease, with adult prevalence between 5 and 10%.²

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 early childhood and can sometimes be present even from birth. It is less common and occurs later in life in patients with a large secundum atrial septal defect (ASD).

See also the articles on Congenital Heart Disease in Children and Congenital Heart Disease in Adults.

Eisenmenger's syndrome epidemiology

In developed countries, cardiac defects are being operated on in a timely manner, before pulmonary vascular disease develops. However, in lower income countries, shunt lesions that are not amenable for repair, as pulmonary vascular disease has already established, are more common.³

Eisenmenger's syndrome symptoms (presentation)³

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.⁴

• 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. Central cyanosis with secondary erythrocytosis is a key feature.

  • 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.

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%.

Eisenmenger's syndrome treatment and management¹

• Heart failure management.

• Management of arrhythmias.

• Therapy for pulmonary artery hypertension: bosentan, a dual endothelin receptor antagonist (ERA), was the first drug to be studied and was recommended as a first-class drug in symptomatic patients. Macitentan, a newer-generation ERA, has also been assessed. Trials on phosphodiesterase type 5 (PDE-5) inhibitors also showed positive haemodynamic and functional effects. Limited data exist on the use of intravenous, subcutaneous, or inhaled prostanoids in symptomatic patients, and usually used as third-line therapy.

• The use of anticoagulation remains a controversial issue and should be carefully considered on a case-by-case basis. Current guidelines state that anticoagulation should be offered for atrial arrhythmias and in the presence of pulmonary artery thrombus or embolism in patients at low bleeding risk. Anticoagulation is therefore not routinely recommended.¹

• Prevention of infective endocarditis:⁵
  

  • 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.

• Routine therapeutic venesections have no place in treatment, as they cause or exacerbate iron deficiency and reduce oxygen tissue delivery, thus increasing the risk of cerebrovascular events. Venesection should only be considered for patients with significantly elevated haemoglobin concentration and hematocrit.

• Chronic use of oxygen or pulmonary vasodilators is controversial.

• 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.⁶

• Ultimately, heart-lung transplant may be indicated.⁷

Pregnancy and contraception¹

• Pregnancy leads to a reduction in systemic vascular resistance with a consequent increase in right-to-left shunting, hypoxaemia, and in the context of induced thrombophilia, increased risk of paradoxical embolism.

• In general, pregnancy is very high risk for adverse outcomes, including maternal and fetal death. Maternal mortality risk is reported as 30%-50%, with a perinatal fetal loss or morbidity of approximately 30%.

• For contraception, high-dose oestrogen therapy should be avoided because of the risk of thromboembolism.

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.

Prognosis³

Eisenmenger's syndrome is a devastating condition that has a considerable impact on patients' lives.⁸ .

• Although Eisenmenger's syndrome has a better prognosis compared to other patients with pulmonary arterial hypertension, it grossly affects quality of life and morbidity is frequent.

• Long-term prognosis remains unfavourable, despite recent advances in medical management: 5-year survival is estimated between 74% and 81%, and long-term survival is even lower, with 57% of patients surviving 10 years.

• The leading reasons for mortality are sudden cardiac death, progressive heart failure, and infectious diseases.

• Various factors have been shown to be associated with mortality, such as decreased arterial oxygen saturation, functional class, impaired exercise tolerance, syncopal events, iron deficiency, presence of pre-tricuspid shunts, arrhythmias, increased (NT-pro) brain natriuretic peptide, echocardiographic variables of right ventricular dysfunction, and hospitalisation for heart failure.