AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Eisenmenger syndrome was initially described in 1897 when Eisenmenger reported a patient with symptoms of dyspnea and cyanosis from infancy who subsequently developed heart failure and succumbed to massive hemoptysis.¹ The autopsy revealed a large ventricular septal defect (VSD) and an overriding aorta.

The syndrome is often secondary to uncorrected congenital heart disease. If left uncorrected, lesions with high pulmonary pressure and flow states, such as a large VSD, eventually lead to pulmonary hypertension and reversal of the usual left-to-right intracardiac shunt. The presence of right-to-left shunting and the associated cyanosis is referred to as Eisenmenger syndrome; it represents a point at which the pulmonary hypertension is irreversible and is an indication that the cardiac lesion is inoperable.

Recent advances in the medical treatment of patients with severe pulmonary hypertension may improve survival and may potentially reverse the process in selected patients to a point that they again become candidates for surgical repair.

Definition

Pulmonary hypertension is defined by a mean pulmonary artery pressure of more than 25 mm Hg at rest or more then 30 mm Hg during exercise. The World Health Organization (WHO) has published a classification system of various etiologies of pulmonary hypertension.

Eisenmenger syndrome refers to untreated congenital cardiac defects with intracardiac communications that lead to pulmonary hypertension and reversal of flow. The previous left-to-right shunt is converted into a right-to-left shunt secondary to the elevated pulmonary artery pressures and associated pulmonary vascular disease.

Anatomy

An intracardiac communication allows high pulmonary artery pressures to develop and produce right-to-left intracardiac blood flow. Originally described with a large VSD, the syndrome can also manifest with a patent ductus arteriosus (PDA) and, more infrequently, with other congenital cardiac anomalies.

Subtypes

Examples of congenital heart disease subtypes that may cause pulmonary vascular disease include the following:

• Elevated pulmonary venous pressure - Mitral stenosis, cor triatriatum, obstructed pulmonary venous return
• Increased pulmonary arterial flow - Atrial septal defect (ASD), systemic arteriovenous fistulae, total anomalous pulmonary venous return
• Increased pulmonary arterial pressure and flow - Large VSDs, large PDA, truncus arteriosus, single ventricle with unobstructed pulmonary blood flow

Pathophysiology

If left unchecked, increased pulmonary blood flow and/or elevated pulmonary arterial pressure can result in remodeling of the pulmonary microvasculature with subsequent obstruction to pulmonary blood flow. This is commonly referred to as pulmonary vascular obstructive disease (PVOD).

According to Ohms law, flow (Q) is inversely related to resistance (R) and is directly proportional to pressure (P), as represented by the equation Q = P/R. Any increase in flow, as is observed in patients with intracardiac defects and initial left-to-right shunts, results in increased pulmonary artery pressures. Additionally, any increase in resistance, as occurs in PVOD, results in a decrease in effective flow at the same pressure.

The progression to Eisenmenger physiology is represented by a spectrum of morphologic changes that progress from reversible lesions to eventual irreversibility. In 1958, Heath and Edwards proposed a histologic classification to describe these changes (see Histologic Findings).² Stages I and II represent disease that is most likely reversible. Stage III may still be reversible, but progression to stages IV-VI is thought to be irreversible. Pulmonary biopsies are rarely performed today for this condition. 
 
In general, cardiac catheterization provides all information necessary to define the severity of the pulmonary hypertension. Evaluation during catheterization can determine the degree of hypertension through direct measurement of intracardiac and pulmonary artery pressures.  Additionally, one can assess whether the pulmonary hypertension is reversible or partially reversible with hyperoxic and nitric oxide challenges to determine whether patients are eligible for surgical therapy.

Patients with true Eisenmenger syndrome are considered inoperable. Their pulmonary hypertension is fixed, and the PVOD is considered irreversible. Closure of the defect and elimination of the right-to-left shunt (now a physiologic "pop-off" for the high right-sided pressures) results in right ventricular failure.

Natural history

Failure to reduce pulmonary pressures in the first 2 years of life may result in the failure of the normal regression of the intimal smooth muscle. This is followed by the progressive changes described by Heath and Edwards.² The condition then progresses to irreversible pulmonary hypertension, defined as unresponsiveness to inhalation of 100% oxygen or nitric oxide. This point usually correlates to a pulmonary vascular resistance (PVR) of more than 12 Woods units.

Clinically, patients gradually develop dyspnea upon exertion, syncope, chest pain, stroke, brain abscess, cyanosis, congestive heart failure, dysrhythmia, hyperviscosity complications, pulmonary hemorrhage/hemoptysis, and endocarditis as complications of advanced pulmonary vascular disease.

The timeframe for this process depends on the nature of the lesion and conditions, such as trisomy 21 (Down syndrome), that are known to accelerate the development of PVOD. Without intervention, reversal of flow may happen in early childhood or around puberty, and progression of symptoms may lead to death by the second or third decade of life.

Frequency

United States

Eisenmenger syndrome is rare in persons younger than 1 year. However, if left untreated, patients with a large PDA, D-transposition of the great arteries and a VSD, truncus arteriosus, or a VSD may develop advanced pulmonary vascular lesions within the first 6 months of life.

Complete atrioventricular canal (AVC) is a lesion that is particularly susceptible to the development of increased PVR. Most individuals develop pulmonary hypertension within the first 2 years of life, and the process can be accelerated in certain patients (such as patients with trisomy 21).

Systemic–to–pulmonary artery shunts may also be associated with the development of pulmonary hypertension, but this is comparatively rare (around 10%). Other shunts, such as Waterston shunts, have a higher rate of pulmonary hypertension and are rarely used.

Large ASDs may also cause pulmonary hypertension, but they tend to do so much less rapidly and are often not associated with complications until the second or third decade of life.

International

Patients in underdeveloped countries are more likely to present late with uncorrected congenital cardiac lesions and a markedly elevated PVR. They are more likely to be inoperable secondary to Eisenmenger physiology.

Mortality/Morbidity

• Hypoxemia, right ventricular dysfunction, and an inability to increase pulmonary blood flow severely limit exercise tolerance and significantly alter the quality of life.
• Death can be sudden and can be caused by a massive pulmonary hemorrhage and hemoptysis. Patients also succumb to severe hypoxemia and lethal arrhythmias.
• Survival varies; many patients survive to adulthood, but few survive into the fifth decade of life. The quality of life is poor because exercise tolerance is extremely limited and complications are profound.

Sex

No definite differences are observed between sexes.

Age

The development of Eisenmenger physiology is dependent on the size of the intracardiac lesion and other factors, such as the presence of Down syndrome.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients who develop Eisenmenger syndrome may be asymptomatic for long periods of time. The elevated pulmonary vascular resistance (PVR) prevents pulmonary overcirculation and the symptoms of heart failure. This can result in a delay in diagnosis.

• In the first weeks of life when the PVR begins to fall toward adult levels, an infant with a large atrial septal defect (ASD), ventricular septal defect (VSD), or patent ductus arteriosus (PDA) may present with congestive heart failure symptoms due to the large left-to-right shunt. This may simply be reflected by poor weight gain.
• Infants with the same defects who maintain a high PVR have less left-to-right intracardiac shunting and less pulmonary blood flow. Therefore, developing Eisenmenger physiology may remain undetected in infants with a high PVR and relatively large defects because they lack a loud systolic murmur and/or diastolic rumble and the symptoms of heart failure.
• Patients may have a period of poor weight gain, reflecting congestive heart failure, that improves as pulmonary pressures increase and overcirculation decreases. Clues to the diagnosis may include only dyspnea upon exertion and exercise intolerance. These symptoms become increasingly evident with advancing age, particularly at adolescence, and may progress to lethargy and syncopal episodes.
• Erythrocytosis secondary to chronic cyanosis is an adaptation to low levels of circulating oxyhemoglobin and is present in most patients. Excessive polycythemia may result in hematocrit levels greater than 65% and hyperviscosity syndrome. Hyperviscosity may lead to thromboembolic events, cerebrovascular complications, gout, chest pain from pulmonary infarction, and hemoptysis. Most of the symptoms are nonspecific and are confirmed if they are relieved by phlebotomy.
• Any of the multitude of multisystem complications that occur in patients with congenital heart disease may be present.

Physical

Examination findings vary with the progression of the disease. Early in life, infants with a large systemic-to-pulmonary communication may demonstrate mild pulmonary overcirculation with symptoms of cor pulmonale. Initially, cyanosis is absent, and infants present with the signs and symptoms of heart failure. Physical examination may reveal the following:

• Tachypnea, nasal flaring, grunting, retractions, and tachycardia may be observed.
• An ausculatory examination may reveal a hyperactive precordium, systolic flow murmur, diastolic rumble, and hepatosplenomegaly.
• Delayed capillary refill may be present, indicating low cardiac output.

As the PVR increases, the pulmonary circulation receives less blood flow with gradually advancing pulmonary artery pressure. Symptoms of congestive heart failure wane. The right ventricle may become hypertrophied, and the chest, when examined, may be asymmetric, with a right ventricular heave and a palpable P₂ (ie, a pulmonary closure sound that is so forceful that it can be felt).

As pulmonary resistance increases over time, a relative decrease in the left-to-right intracardiac shunt occurs, initially with periods of subclinical right-to-left and bidirectional shunt, followed by frank cyanosis, clubbing, and polycythemia (a ruddy appearance to the skin).

A hallmark of Eisenmenger syndrome is this seemingly improved clinical condition, despite the lack of change in therapy for congestive heart failure. It represents a physiologically normalized condition caused by the progressively worsening pulmonary vascular obstructive disease (PVOD), with resolution of pulmonary overcirculation and heart failure.

Causes

• Potential causes of PVOD and Eisenmenger syndrome include the following:
• • High-pressure and high-volume shunts
  • • A large VSD
    • Single ventricle or unbalanced defects with a large interventricular communication (eg, double outlet right ventricle, truncus arteriosus)
    • PDA
    • Aortopulmonary communication (aortopulmonary window)
  • High-volume low-pressure communications
  • • ASD
    • Partial or total anomalous venous connection without obstruction
    • Partial or incomplete atrioventricular canal/ASD
  • High–pulmonary venous pressure states
  • • Cor triatriatum or stenosing supravalvar mitral ring
    • Obstructed anomalous pulmonary venous connection
    • Pulmonary vein stenosis
    • Mitral stenosis
• Syndromes associated with a more rapid progression of pulmonary vascular disease include trisomy 21.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC count
• • RBCs - Polycythemia (ie, an increased number of RBCs), especially in iron deficient states (microcytic, hypochromic)
  • Hemoglobin and hematocrit - Increase in response to worsening cyanosis
  • Mean corpuscular hemoglobin and mean corpuscular volume
• Uric acid and bilirubin levels: These are increased with polycythemia.
• Pulse oximetry: Cyanosis and decreased saturations may be present.
• ABG: Both the PaO₂ and P_CO2 may be decreased secondary to right-to-left shunting and resting tachypnea, respectively.

Imaging Studies

• Chest radiography
• • In the early stages, chest radiography may reveal a typical appearance of increased pulmonary flow with right ventricular or biventricular enlargement, right atrial or biatrial enlargement, pulmonary vascular plethora, and enlarged main pulmonary artery.
  • Advancing pulmonary vascular disease has a normal cardiac silhouette with dilated main and branch pulmonary arteries without evidence of pulmonary overcirculation.
  • In patients with severe advanced pulmonary vascular disease, chest radiography may reveal a normal-sized heart, pruning of the pulmonary vasculature (ie, diminished distal/peripheral pulmonary vascularity), pulmonary infarction, and/or calcification of a patent ductus arteriosus (PDA).
• Echocardiography
• • Two-dimensional transthoracic imaging can reveal the particular features of the structural cardiac defect.
  • Color-flow Doppler interrogation is useful in demonstrating the direction of intracardiac blood flow.
  • Pulsed and continuous wave Doppler measurements enable quantification of intracardiac shunt, right ventricular pressures, and estimation of pulmonary artery systolic/diastolic and mean pressures by means of the modified Bernoulli equation.

Other Tests

A 12-lead EKG may reveal signs of underlying cardiac defect and signs of right ventricular hypertrophy, including tall R wave in V1, deep S wave in V6 ± ST and T-wave abnormalities, P pulmonale, and atrial and ventricular arrhythmias.

Procedures

• Cardiac catheterization permits the following:
• • Examination of the intracardiac structure and exclusion of potentially reversible causes of pulmonary hypertension
  • Assessment of ventricular function (systolic and diastolic)
  • Examination of the intracardiac shunt
  • Determination of pulmonary artery pressure and flow
  • Calculation of pulmonary vascular resistance (PVR)
  • Determination of the reversibility of the pulmonary hypertension: If the pulmonary artery pressures do not fall with inhalation of 100% oxygen or nitric oxide, the pulmonary hypertension is considered irreversible, and the patient is not a candidate for surgical repair.
• Pulmonary angiography can reveal structural alterations in the pulmonary vascular bed. Irreversible changes (consistent with Heath-Edwards III severity) can be visualized and can include a loss of normal arborization, as well as tortuosity, narrowing, or cut-off of small pulmonary arteries.

Histologic Findings

In 1958, Heath and Edwards proposed a histologic grading of pulmonary vascular disease that corresponds to the duration and severity of injury caused by increased pressure and volume load.² This grading is a histopathologic classification from isolated portions of the lung. A biopsy of various segments of the lung could possibly be performed at the same time, yielding different histologic grades. Currently, performing lung biopsies is rarely necessary. The combination of pulmonary angiography and measurement of pulmonary vascular hemodynamics is usually sufficient to guide therapy.

Staging

Stages of pulmonary vascular pathology are presented here with respect to the histopathologic criteria presented by Heath and Edwards.²

• Stage I - Medial hypertrophy (reversible)
• Stage II - Cellular Intimal hyperplasia in an abnormally muscular artery (reversible)
• Stage III - Lumen occlusion from intimal hyperplasia of fibroelastic tissue (partially reversible)
• Stage IV - Arteriolar dilation and medial thinning (irreversible)
• Stage V - Plexiform lesion, which is an angiomatoid formation (terminal and irreversible)
• Stage VI - Fibrinoid/necrotizing arteritis (terminal and irreversible)

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• The treatment of Eisenmenger syndrome widely varies depending on the patient's age, the degree of cyanosis, and subsequent polycythemia.
• Resources for patients with pulmonary hypertension can be found at the Pulmonary Hypertension Association Web site.
• Asymptomatic patients require periodic evaluation with anticipation of potential needs. All patients with intracardiac right-to-left shunts have potential for the following:
• • Syncope, paradoxical embolus, stroke, and/or brain abscess
  • Polycythemia, hemoptysis, and pulmonary infarction
  • Congestive heart failure
  • Endocarditis for which subacute bacterial endocarditis (SBE) prophylaxis must be practiced at times of preventable risk
• Much of the therapy currently used for Eisenmenger syndrome has been studied in idiopathic pulmonary hypertension (IPAH). Because of the similarities between the two entities, therapies found useful for IPAH are very attractive for use in Eisenmenger physiology. Therapies include the following:
• • Supplemental Oxygen: Although supplemental oxygen has not been shown to have a benefit in mortality rates, it is commonly used in patients with pulmonary hypertension. Nocturnal supplementation may be used, and use is also considered for airline travel.
  • Vasodilator Therapy: Studies of patients with IPAH have shown an imbalance between vasoconstrictors (endothelin, thromboxane) and vasodilators (prostacyclin, nitric oxide) in the pulmonary vasculature, and current therapy is directed at correcting this imbalance. Most studies are in adults and reveal a significant improvement in exercise tolerance, 6-minute walk distance, or New York Heart Association (NYHA) class failure. Subgroups, as well as smaller studies, have shown improvement in pulmonary hypertension caused by congenital heart disease.
  • Calcium channel blocker therapy: Calcium channel blockers have been studied the longest in patients with pulmonary hypertension. Unfortunately, their use should be restricted to patients that show response to vasodilator challenge during cardiac catheterization; they have not otherwise been shown to have benefit.
  • Prostacyclin replacement
  • • The oldest preparation, epoprostenol (Flolan) requires a continuous intravenous infusion via a central catheter because of its short half-life (5 min). Patients must carry a portable pump in a waist pack and must maintain the drug at a cool temperature during the infusion. This therapy is extremely expensive (more than $100,000 annually). It has been shown to improve pulmonary pressure, 6-minute walk distance, oxygenation, and quality of life in patients.
    • Treprostinil (Remodulin) is a prostacyclin analogue that is administered by continuous subcutaneous infusion. Data on its use in children with pulmonary hypertension is limited.
    • Iloprost (Ventavis) is an inhaled prostacyclin administered intermittently 6-9 times per day via nebulizer and is approved for adults with IPAH.  Preliminary evidence suggests that it may have efficacy in children with pulmonary hypertension due to cardiac lesions; however, it may cause bronchospasms, and its use may be limited.
  • Endothelin-receptor antagonists
  • • Endothelin is a potent vasoconstrictor, and the endothelin-receptor antagonist bosentan (Tracleer) has been approved for patients with IPAH. Its benefit has been shown in patients with Eisenmenger syndrome; improvement in pulmonary artery pressure, 6-minute walk distance, NYHA class, and oxygen saturation has been observed.
    • Ambrisentan (Letairis) has recently been approved for IPAH and is a specific endothelium-receptor 1 type A antagonist. Data on its use in Eisenmenger syndrome is limited.
  • Nitric oxide replacement: Innovative home nitric oxide delivery devices have been described and have been used on a compassionate basis for patients with severe pulmonary hypertension.
  • Phosphodiesterase inhibitors: Sildenafil has recently been approved for IPAH. It acts as an inhibitor of phosphodiesterase 5, resulting in an increase in cyclic guanosine monophosphate (cGMP) and vascular relaxation. It works synergistically with inhaled nitric oxide. In patients with Eisenmenger syndrome, it has been shown to decrease pulmonary artery pressure and 6-minute walk distance; pediatric experience is increasing.
• Patients with Eisenmenger syndrome may also be treated for the following:
• • Anticoagulation: Although an increased risk of thrombosis is observed in patients with Eisenmenger syndrome, an increased risk of bleeding and pulmonary hemorrhage is also recognized; thus, treatment is controversial.
  • Right heart failure: Treatment is directed at symptom relief. Diuretics and digoxin are commonly used.
  • Endocarditis: Patients are at risk for endocarditis and should be given adequate prophylaxis.
  • Polycythemia and hyperviscosity syndrome: This syndrome (ie, increasing fatigue, headaches, exertional dyspnea) may require therapeutic phlebotomy. Iron replacement therapy is usually required to correct the resultant hypochromic microcytosis.
• • Therapeutic erythropheresis: The amount of blood to be withdrawn to achieve a desired hematocrit equals [(patient hematocrit - desired hematocrit)/patient hematocrit] X (kg body weight X 100).
• Drugs are discussed in more detail in the Medication section.

Surgical Care

No surgical care is available to correct the congenital cardiac defect that caused the pathologic pulmonary vascular changes once Eisenmenger syndrome has developed to the irreversible stage.

For patients with systemic or suprasystemic pulmonary artery pressures and impending right ventricular failure, creation of an atrial septal defect (ASD) can be palliative. For example, a patient with an increased pulmonary vascular resistance (PVR) secondary to pulmonary vein obstruction may benefit from a surgical ASD to serve as "pop-off" for the right ventricle.

Heart-lung transplantation and single or bilateral sequential lung transplantation with and without repair of relatively simple congenital cardiovascular anomalies are viable transplant procedures and are the only surgical options for a patient with Eisenmenger syndrome.

• Indications
• • Lung transplantation only - Pulmonary hypertension and Eisenmenger syndrome with surgically correctable congenital anomalies and maintained right ventricular function
  • Heart-lung transplantation - Patients with single ventricle or complex congenital heart defects and those with severe right ventricular failure
• Results: Excellent results can be obtained, with return to normal pulmonary function. However, several donor-specific issues complicate the use of transplantation. Fewer donors are acceptable for lung or heart-lung donation than heart donation alone. In addition, the strategy of oversized donors is limited in heart-lung transplants. A weight mismatch of over 20% is generally contraindicated for heart-lung transplants. Five- and 10-year survival rates are markedly decreased when heart-lung transplantation is compared with heart transplantation alone.

Consultations

In the course of therapy, the following consultations may be appropriate:

• Hematologist - To assist with therapeutic phlebotomy, coagulopathy, and bleeding diatheses secondary to hyperviscosity, polycythemia, and platelet dysfunction or thrombocytopenia
• Nephrologist - To assist with patients who are hyperuricosuric and, ultimately, to assist with the management problems of patients with congestive heart failure, poor cardiac output, decreased renal blood flow, and coincident renal insufficiency in its terminal stages
• Infectious-disease specialist - Management of potential bacteriologic complications (eg, endocarditis, brain abscess)
• Surgeon - Placement of central venous access devices for use in long-term treatment of endocarditis or therapeutic phlebotomies
• Cardiologist - For optimal inpatient and outpatient treatment of patients who require a cardiologist with a special interest in congenital cardiology or adults with congenital heart disease (Enrollment in clinical trials may be required for access to newer treatment modalities.)
• Cardiothoracic surgeon - Evaluation for heart-lung transplantation or repair of lesion with lung transplantation

Diet

• When congestive heart failure develops, a no-added-salt or a salt-restricted diet must be maintained.
• Attention to weight control is important because excess weight places additional strain on the cardiovascular system. In addition, significant obesity is a contraindication to transplantation.

Activity

Physical activity is important for the patient with Eisenmenger syndrome to maintain cardiovascular fitness; however, physical activity should be limited to milder forms, such as walking and stretching. Strenuous exercise is contraindicated.

• Smoking is absolutely contraindicated because of the deleterious effects on the heart, blood vessels, and lungs.
• Alcohol may exacerbate myocardial dysfunction, hypovolemia, and worsening hyperviscosity and can result in systemic hypotension with an exacerbation of the right-to-left shunt.
• Air travel at high altitudes exacerbates cyanosis because a pressurized airplane cabin is only pressurized to the equivalent atmosphere represented by an altitude of 5000 feet above sea level. Travelers should ensure that they have adequate oxygen for their trip and, if necessary, identify an oxygen source at their destination and have oxygen waiting. They should get up and walk multiple times during the flight to avoid deep venous thromboses. An extra week of medication beyond what is anticipated should be packed in case of travel delays. Patients using Flolan should travel with ice and a premixed dose. Patients on Remodulin should bring an extra pump.
• Scuba diving is contraindicated in any patients with an intracardiac shunt. Even patients with a predominant left-to-right shunt run the risk of transient right-to-left shunts and air embolism.
• Uncorrected congenital heart disease with development of Eisenmenger complex portends an insidious progression to near complete physical disability.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Inotropic agents

Inotropic agents are used to enhance cardiac contractility as an adjunct to treating congestive heart failure. They are used to augment the function of the failing right ventricle.

Drug Category: Diuretics

Diuretics are used as an adjunct in the treatment of congestive heart failure.

Drug Category: Prostaglandin analogues

Naturally produced prostaglandins and manufactured analogues such as epoprostenol dilate blood vessels such as the pulmonary arteries. Studies have shown a reduction in mortality and improvement in functional symptoms in pediatric patients.

Drug Category: Endothelin receptor antagonists

Endothelin causes vasoconstriction in the pulmonary circulation. Blockade of endothelin receptors ameliorates the effect of endothelin and produces vasodilatation in some patients.

Drug Category: Phosphodiesterase (type 5) Enzyme Inhibitor

These agents act synergistically with nitric oxide to promote smooth muscle relaxation.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients do not require hospitalization for therapeutic erythropheresis but may need attention for infectious disease complications and/or other hematologic concerns.
• Vasodilator therapy initiation may require inpatient observation.

Further Outpatient Care

• Good dental hygiene is required to prevent infectious concerns, such as infective endocarditis or brain abscess.

In/Out Patient Meds

• A partial list of medications includes aspirin to prevent thrombotic complications, allopurinol for gout, iron supplementation for microcytosis, and digitalis and diuretics for symptoms of heart failure.
• Supplemental oxygen is a powerful pulmonary arterial vasodilator and remains a critical component of the treatment for pulmonary hypertension.

Transfer

• Nonurgent transfers are made to a tertiary facility because this disease, by nature, is a chronic and terminal condition.

Deterrence/Prevention

• Prevention is critical. When recognized in a timely fashion, congenital cardiac defects can be effectively treated with minimal morbidity and mortality. Eisenmenger syndrome is, by definition, an untreated lesion that has progressed to the point of inoperability.
• Many congenital heart defects can be identified in utero when families receive appropriate prenatal care. Continued perinatal care and routine follow-up with a qualified pediatrician leads to identification of most lesions not identified prenatally.

Complications

• Syncope and sudden death
• Polycythemia and hyperviscosity syndrome
• Congestive heart failure
• Dysrhythmia
• Surgical complications
• Brain abscess and stroke
• Pulmonary infarction and hemorrhage
• Hyperuricemia
• Infective endocarditis

Prognosis

• This disease 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.

Patient Education

• Inform patients that diet and weight control are essential.
• Educate patients to avoid smoking.
• Provide an exercise prescription.
• Advise abstinence from or moderate intake of alcohol.
• Educate patients about contraception options and pregnancy risk.
  • The mortality rate in pregnant patients with Eisenmenger syndrome is approximately 50%.
  • Contraception by means of tubal ligation (with SBE prophylaxis) may be recommended. Oral or implantable contraceptives might promote pulmonary infarction through activation of the coagulation cascade.
• Educate patients about the signs and symptoms of polycythemia and hyperviscosity.
• Inform patients of the importance of dental hygiene.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose the initial congenital heart defect
• Failure to treat appropriately
• Failure to evaluate and diagnose potential complications (eg, cor pulmonale, endocarditis)
• Failure to anticipate risks (eg, increased risk of perioperative complications of cardiac catheterization, cardiac and noncardiac operative procedures)

Special Concerns

• The high rate of complications and the approximate 50% mortality rate make pregnancy an absolute contraindication.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Eisenmenger V. Die angeborenen Defecte der Kammerscheidewand des Herzens. Z Klin Med. 1897;32:1-28.
2. Heath D, Edwards JE. The pathology of hypertensive pulmonary vascular disease; a description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation. Oct 1958;18(4 Part 1):533-47. [Medline].
3. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. Jun 2007;131(6):1917-28. [Medline].
4. Balzer DT, Kort HW, Day RW, et al. Inhaled Nitric Oxide as a Preoperative Test (INOP Test I): the INOP Test Study Group. Circulation. Sep 24 2002;106(12 Suppl 1):I76-81. [Medline].
5. Barst RJ, Ivy D, Dingemanse J, et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther. Apr 2003;73(4):372-82. [Medline].
6. Castaneda AR, Jonas RA, Hanley FL, Mayer JE. Surgery for infants with congenital heart defects. In: Cardiac Surgery of the Neonate and Infant. Philadelphia, Pa: WB Saunders Co; 1994.
7. Chau EM, Fan KY, Chow WH. Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension. Int J Cardiol. Sep 3 2007;120(3):301-5. [Medline].
8. Das BB, Wolfe RR, Chan KC, et al. High-altitude pulmonary edema in children with underlying cardiopulmonary disorders and pulmonary hypertension living at altitude. Arch Pediatr Adolesc Med. Dec 2004;158(12):1170-6. [Medline].
9. Dyer K, Lanning C, Das B, et al. Noninvasive Doppler tissue measurement of pulmonary artery compliance in children with pulmonary hypertension. J Am Soc Echocardiogr. Apr 2006;19(4):403-12. [Medline].
10. Esmore DS, Brown R, Buckland M. Techniques and results in bilateral sequential single lung transplantation. The National Heart & Lung Replacement Service. J Card Surg. Jan 1994;9(1):1-14. [Medline].
11. Fyler DC, ed. Ventricular septal defect. In: Nadas' Pediatric Cardiology. Philadelphia, PA: Hanley & Belfus Inc; 1991:449-51.
12. Hopkins WE. Severe pulmonary hypertension in congenital heart disease: a review of Eisenmenger syndrome. Curr Opin Cardiol. Sep 1995;10(5):517-23. [Medline].
13. Hopkins WE, Ochoa LL, Richardson GW, Trulock EP. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. J Heart Lung Transplant. Jan 1996;15(1 Pt 1):100-5. [Medline].
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Article Last Updated: Nov 29, 2007