What is Eisenmenger syndrome? Cardiology Basics

What is Eisenmenger syndrome? Cardiology Basics

Eisenmenger syndrome is a late complication of congenital heart diseases with large left to right shunts. Fortunately, it is rare now-a-days because most conditions which can cause Eisenmenger syndrome later, are detected by neonatal screening and treated early so that this complication does not develop later. Eisenmenger syndrome is a condition in which long standing high pulmonary blood flow leads to irreversible pulmonary hypertension with reversal of shunt. Right to left shunt causes reduced systemic oxygen saturation with cyanosis.

This is an echocardiogram showing a left to right shunt from the left ventricle to the right ventricle. Left to right shunt occurs in VSD because the left ventricular pressure is normally much higher than that in the right ventricle.

This diagram illustrates a left to right shunt across a patent ductus arteriosus. Normally ductus arteriosus which is present in the fetus closes soon after birth because of higher oxygen saturation when lungs start functioning. Strongest stimulus for constriction of a mature ductus is oxygen. Ductus arteriosus in a premature infant does not respond that well to oxygen and that is why incidence of PDA is higher in preterm infants. In PDA, blood flows from the aorta at systemic pressure to the pulmonary artery which has a much lower pressure after birth.

When there is an atrial septal defect, there is a left to right shunt from the left atrium to right atrium. The excessive load causes dilatation of right atrium, right ventricle and pulmonary artery. Pulmonary blood flow will be very high when there is a large atrial septal defect. The ratio between the pulmonary and systemic blood flows is known as the shunt ratio, which is more than 2:1 in large ASD.

In case of ventricular septal defect, the shunt is from the left ventricle at higher pressure to the right ventricle at lower pressure.  Pulmonary blood flow is high in a large ventricular septal defect with left to right shunt. The extra blood flow due to the shunt returns to the left atrium and then to the left ventricle. Excessive flow in the circuit can cause heart failure in an infant. This is because the immature left ventricle of the infant has more of mitochondria than contractile elements and cannot accommodate the higher workload.

For a variable period of time depending on the size of the shunt, the lung accommodates the increased flow by pulmonary vasodilatation. In this phase there can be flow related hyperdynamic pulmonary hypertension, which is reversible after closure of the defect. After some time this mechanism fails and there is disproportionate pulmonary hypertension which is known as reactive pulmonary hypertension. When the pressure in the pulmonary artery rises above that in the aorta, the shunt across the PDA, reverses so that blood flows from pulmonary artery to aorta. This usually causes cyanosis of the lower limbs, known as differential cyanosis. Upper limbs are not cyanosed because the ductus joins the aorta beyond the origin of left subclavian artery.

Similarly, when the right ventricular pressure rises above that in left ventricle, the flow across the ventricular septal defect reverses. Blood flows from right ventricle to the left ventricle. Eisenmenger VSD causes uniform central cyanosis. In both VSD and PDA, the pulmonary pressure can rise up to the level of the systemic pressures, but not beyond that because of the unrestrictive communication.

Similar reversal can also occur across the ASD so that blood flows from right atrium to left atrium. All these right to left shunts due to pulmonary hypertension are called Eisenmenger syndrome. By the time it occurs, severe damage would have occurred in the pulmonary arterial tree due to long-standing high pulmonary blood flow. Reactive pulmonary hypertension becomes obliterative because of vascular pathology. The rapidity with which this complication occurs depends on the size of the initial left to right shunt. Development of Eisenmenger syndrome may be earlier in certain conditions like Trisomy 21. In ASD Eisenmenger, the pulmonary arterial pressures can be suprasystemic.

Cyanosis and reduced systemic oxygen saturation occurs in all the three types of right to left shunts. Hypoxia stimulates the secretion of erythropoietin which causes polycythemia. Though this allows blood to carry more oxygen, it leads to increased viscosity of blood.

Though polycythemia is initially beneficial, it leads to clogging of microcirculation due to increased viscosity of the blood. Venesection can reduce viscosity of the blood and can alleviate symptoms of hyperviscosity temporarily. But there is a chance of development of microcytes due to iron deficiency. Microcytes being less deformable, can cause higher microvascular obstruction. Resulting renal hypoxia increases erythropoietin secretion and sets in a vicious cycle of decompensated erythrocytosis.

So Eisenmenger syndrome is better prevented than treated. Neonatal screening is helpful in early detection and treatment of left to right shunts. All left to right shunts may not need surgery or device closure. Shunts detected in early life can decrease spontaneously and disappear later. This has been documented in all three types, though it is more typical of VSD. A detailed echocardiogram will decide the need and suitability for procedures. This image shows an atrial septal device positioned for release across and ASD.

Small defects will not cause pulmonary hypertension and are left alone, except in the case of a PDA. In case of PDA, even small defects will be closed as the procedural risk is low. Small defects have a risk of infection at some point in life. But procedure risk being higher than this risk, small ASDs and VSDs are left alone. They will be followed up regularly with prompt treatment for infections elsewhere in the body.

Once Eisenmenger syndrome has developed, potential complications like stroke, brain abscess, pulmonary hemorrhage with hemoptysis and hyperuricemia due to increased red cell turnover can occur. Most children who had heart failure due to large left to right shunts in early infancy will get relief when Eisenmenger syndrome develops as pulmonary blood flow comes down. This may be mistaken for spontaneous decrease in size of the defect. An echocardiogram done in suspected situations can very well tell whether it is improvement due to spontaneous decrease in size of the defect or development of Eisenmenger syndrome.

Many persons with Eisenmenger syndrome go on for a long time with mild symptoms. Among the Eisenmenger syndromes, the prognosis is thought to be worst for ASD Eisenmenger because of the possibility for suprasystemic pulmonary hypertension. But development of Eisenmenger reaction is less common in ASD than in VSD and PDA as the shunt gets established only later in life in case of ASD. In the unfortunate few who are really disabled due to Eisenmenger syndrome, heart lung transplantation is a final option.