Eisenmenger syndrome

Eisenmenger syndrome refers to any untreated congenital cardiac defect with intracardiac
communication that leads to pulmonary hypertension, reversal of flow, and cyanosis. The
previous left-to-right shunt is converted into a right-to-left shunt secondary to elevated
pulmonary artery pressures and associated pulmonary vascular disease.
Lesions in Eisenmenger syndrome, such as large septal defects, are characterized by high
pulmonary pressure and/or a high pulmonary flow state. Development of the syndrome
represents a point at which pulmonary hypertension is irreversible and is an indication that
the cardiac lesion is likely inoperable. (Pulmonary hypertension is defined as a mean
pulmonary artery pressure of more than 25 mm Hg at rest or more than 30 mm Hg during
exercise)

Epidemiology
Eisenmenger syndrome usually develops before puberty but may develop in adolescence
and early adulthood. Patients in underdeveloped countries are more likely to present late
with uncorrected congenital cardiac lesions and a markedly elevated pulmonary vascular
resistance (PVR).

Etiology and Patophysiology

A congenital cardiac defect will allow an intracardiac communication of blood flow
between the chambers. Because the pressures in the left side of the heart are normally
greater than those in the right side of the heart, an opening between the left and right
sides of the heart will cause blood to flow from the left side of the heart into the right
side. This left-to-right shunting causes increased blood flow into the blood vessels of the
lungs. The increased blood flow in the lungs blood vessels causes increased pressure in
these vessels (pulmonary hypertension).
If the pulmonary hypertension continues without treatment, the pressure in the right side
of the heart may increase to the point that the right side pressure is greater than the left.
When this occurs, blood will flow from the right side of the heart to the left (right-to-left
shunt), which means that oxygen-poor blood is mixed with the oxygen-rich blood
normally pumped out to the body from the left ventricle.

This reversal of the shunt (right-to-left shunt) causes insufficient oxygen in the blood. In
addition, high pressure in the lungs causes progressive changes in the pulmonary blood
vessels that result in irreversible damage to the lining of these blood vessels. Fibrosis
(the growth of scar tissue following an infection, inflammation, or injury), and thrombus
(clotting) may also occur. The changes inside the lung blood vessels may be referred to
as pulmonary vascular obstructive disease (PVOD) or secondary pulmonary arterial
hypertension (PAH).
Examples of congenital heart disease subtypes that may cause pulmonary vascular
disease and proceed to Eisenmenger syndrome include the following:
Increased pulmonary arterial flow - Atrial septal defect (ASD), systemic arteriovenous
fistulae, total anomalous pulmonary venous return
Increased pulmonary arterial pressure and flow - Large VSD, large PDA, truncus
arteriosus, single ventricle with unobstructed pulmonary blood flow
Elevated pulmonary venous pressure - Mitral stenosis, cor triatriatum, obstructed
pulmonary venous return

Transposition of the great arteries

Symptoms and Signs

Symptoms usually do not occur until age 20 to 40 yr; they include cyanosis, syncope,
dyspnea during exertion, fatigue, chest pain, palpitations, atrial and ventricular
arrhythmias, and rarely right heart failure (eg, hepatomegaly, peripheral edema, jugular
venous distention). Hemoptysis is a late symptom. Signs of cerebral embolic phenomena,
brain abscess, or endocarditis may develop.
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.
Cardiovascular findings in Physical examination include the following:

Central cyanosis (differential cyanosis in the case of a PDA)

Clubbing

Jugular venous pulse wave may be A-wave dominant, and, in the presence of a
significant tricuspid regurgitation, the V wave may be prominent; central venous
pressure may be elevated.

Precordial palpation reveals a right ventricular heave and, frequently, a palpable S2.

Loud P2

A holosystolic murmur of tricuspid regurgitation may be present at the lower left

sternal border

High-pitched early diastolic murmur of pulmonic insufficiency

Right-sided fourth heart sound

Pulmonary ejection click

Single S2

Diagnosis

Blood tests. Laboratory testing shows polycythemia with Hct > 55%. Increased RBC
turnover may be reflected as an iron deficiency state (eg, microcythemia),
hyperuricemia, and hyperbilirubinemia.

Chest X-ray. There may be changes that take place in the lungs due to extra blood
flow that can be seen on an X-ray. Chest x-ray usually shows prominent central
pulmonary arteries, peripheral pulmonary vessel pruning, and right heart enlargement.

Electrocardiogram (ECG). ECG might shows right ventricular hypertrophy, right

axis deviation, and, occasionally, right atrial enlargement.

Echocardiogram (echo). A procedure that evaluates the structure and function of the
heart by using sound waves recorded on an electronic sensor that produce a moving
picture of the heart and heart valves. An echo can show the direction of blood flow
through the source of a shunting lesion, such as a PDA, and determine how large the
opening is, as well as estimate the amount of blood passing through it.

Cardiac catheterization. A cardiac catheterization is an invasive procedure that gives

very detailed information about the structures inside the heart.This is often done to
measure pulmonary artery pressure, pulmonary vascular resistance, and response to
pulmonary vasodilators.

Magnetic resonance imaging (MRI). The MRI may be used to clarify the amount
and direction of blood shunting.

Complications
Clinically, patients gradually develop the following complications of advanced
pulmonary vascular disease:
Dyspnea upon exertion

Congestive heart failure

Syncope

Dysrhythmia

Chest pain

Hyperviscosity complications

Stroke

Pulmonary hemorrhage/hemoptysis

Brain abscess

Endocarditis

Cyanosis

 Treatment
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 and other supportive teraphy are being studied. The goals of treatment for
Eisenmenger syndrome are aimed at decreasing the pulmonary artery pressure,
improving oxygenation, and decreasing degree of cyanosis and erythrocytosis.
o

Drugs to lower pulmonary artery pressure. These medications include

calcium channel blockers, They include prostacyclin antagonists (eg, treprostinil,
epoprostenol), endothelin antagonists (eg, bosentan), and nitric oxide enhancers (eg,
sildenafil).

Oxygen. Supplemental oxygen may be used during sleep periods or while

resting. Use of oxygen may progress to continuous use for symptom relief.

Phlebotomy. Phlebotomy is generally done only when symptoms are severe

and/or the hematocrit (the percentage of blood that is made up of red blood cells)
becomes extremely elevated. Symptomatic polycythemia can be treated by cautious
phlebotomy to lower Hct to 55 to 65% plus simultaneous volume replacement with
normal saline.

Other treatments. Hyperuricemia can be treated with allopurinol 300 mg po

once/day. Anticoagulation therapy with warfarin is potentially harmful and its use
should be individualized, but aspirin 81 mg po once/day is indicated to prevent
thrombotic complications. All patients should be given endocarditis prophylaxis
before dental or surgical procedures that are likely to cause bacteremia.

Prognosis
Eisenmenger syndrome is uniformly fatal; however, some patients survive into the
sixth decade of life. The usual life expectancy of a patient with Eisenmenger syndrome is
20-50 years if the syndrome is diagnosed promptly and treated with vigilance. The onset
of pulmonary hemorrhage is usually the hallmark of a rapid progression of the disease.
The complications of chronic cyanotic heart disease affect multiple organ systems,
including the hematologic, skeletal, renal, and neurologic systems, causing significant
morbidity and mortality.

 The quality of life is poor in patients with Eisenmenger syndrome because exercise
tolerance is extremely limited (due to limited oxygen uptake resulting from an inability
to increase pulmonary blood flow) and complications are profound. Poor prognosis is
predicted by syncope, elevated-right sided pressures, and hypoxemia.
A study by Salehian et al reported that left ventricular dysfunction (defined as left
ventricular ejection fraction [LVEF] < 50%), right ventricular hypertrophy, and signs and
symptoms of heart failure predict mortality in patients with Eisenmenger syndrome. A
simple echocardiographic score relying on right ventricular and right atrial characteristics
was found to predict adverse outcomes in patients with Eisenmenger syndrome that is
not associated with complex congenital heart disease.
Uncorrected congenital heart disease with development of Eisenmenger complex
portends an insidious progression to near complete physical disability.

Reference :

Mikhael F El-Chami, MD. Eisenmenger Syndrome. MedScape, section Drugs and

Diseases. http://emedicine.medscape.com/article/154555-clinical. Updated: Nov 23,
2014. Accessed March 30, 2015.
Jeanne Marie Baffa, MD. Eisenmenger Syndrome. Merck Manuals, Trusted Medical and
Veterinary Information.
http://www.merckmanuals.com/professional/pediatrics/congenital_cardiovascular_an
omalies/eisenmenger_syndrome.html. Updated : March 2014. Accessed March 30, 2015.
Stanford Children's Health. Eisenmenger Syndrome. Lucile Packard Childrens Hospital
Stanford. http://www.stanfordchildrens.org/en/topic/default?id=eisenmengers-syndrome90-P08482. Accessed March 30, 2015.