Definition

The Eisenmenger syndrome is a secondary form of pulmonary hypertension, in which, due to a heart defect with an originally left-to-right shunt, increased pulmonary resistance leading to a shunt reversal has occurred.

As a result of the left-to-right shunt with increased pulmonary blood flow, the pulmonary arterial resistance increases more and more until it becomes irreversible due to pulmonary vascular remodeling (fixed increased pulmonary vascular resistance). When the pulmonary arterial resistance exceeds the systemic resistance, shunt reversal occurs with right-to-left shunt and cyanosis. An Eisenmenger syndrome is not a congenital heart defect, but rather the long-term result of an uncorrected shunt defect.

Epidemiology

Patients with Eisenmenger syndrome are now rare in industrialized nations, since nearly all congenital heart defects are surgically corrected before an Eisenmenger reaction has occurred. Most patients with Eisenmenger are now adults, for example, patients with trisomy 21 and an AVSD channel whose defects were not previously corrected surgically, or patients with complex congenital heart defects who were treated with a palliative aortopulmonary shunt.

Pathogenesis

As a result of a congenital heart defect with left-to-right shunt, there is increased pulmonary blood flow. In addition, in a large VSD, for example, the pressure of systemic circulation is transferred unprotected to the pulmonary circulation. Over time, the increased pulmonary blood flow, in particular in combination with pressure overload, leads to remodeling of the pulmonary vascular circulation. Histologically, hypertrophy of the media, proliferation of the intima, and fibrosis of the pulmonary vessels develop. The result is a gradual increase in pulmonary vascular resistance. If the pulmonary resistance exceeds systemic resistance, the blood flow in the lungs is impeded, leading to a reversal of the original left-to-right shunt; a right-to-left shunt with cyanosis develops. Moreover, cardiac output cannot be adequately increased during exercise due to limited pulmonary arterial blood flow.

Etiology

In theory, an Eisenmenger reaction can occur with any heart defect with a relevant left-to-right shunt, but it is most often found with the following diseases:

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  Complete AVSD channel

  
  
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  Truncus arteriosus

  
  
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  d-TGA with VSD

  
  
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  VSD

  
  
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  PDA

  
  
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  Aortopulmonary window

  
  
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  After surgical creation of an aortopulmonary shunt for palliative treatment of a complex congenital heart defect

Symptoms

The morphological changes of the pulmonary vessels associated with Eisenmenger syndrome usually begin in childhood. However, the affected children often have few symptoms. With increasing pulmonary resistance, the symptoms of heart failure in shunt defects initially even decrease. Severe symptoms usually do not occur in Eisenmenger patients until adolescence or adulthood. The main symptoms are severe cyanosis and increasing deterioration of physical capacity. Later, severe heart failure develops.

Later complications

The complications are mainly the result of chronic hypoxemia or the inability to adequately increase pulmonary blood flow under stress.

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  Cardiac complications:

  
  
  
  
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    Increasing heart failure as a result of hypoxemia

    
    
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    Arrhythmias (especially atrial flutter/fibrillation)

    
    
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    Angina pectoris

    
    
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    Syncopes, sudden cardiac death (e.g., as a result of arrhythmias or the inability to increase the cardiac output under stress due to limited pulmonary blood flow)

    
    
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    Paradoxical embolism (result of right-to-left shunt, high risk for embolism due to increased blood viscosity)

    
    
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    Endocarditis

    
    
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    Enlargement of the central pulmonary vessels

  
  
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  Hematological complications:

  
  
  
  
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    Increased erythropoiesis as a result of chronic hypoxemia

    
    
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    Hyperviscosity syndrome (as a result of high hematocrit and iron deficiency that adversely affects the deformability of the erythrocytes)

    
    
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    Iron deficiency (often as a result of bleeding or bloodletting)

    
    
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    Neutropenia and thrombocytopenia

    
    
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    Tendency to bleed (decreased synthesis of clotting factors, platelet dysfunction, thrombocytopenia)

  
  
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  Pulmonary complications:

  
  
  
  
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    Hemoptysis, intrapulmonary bleeding

    
    
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    Lung abscesses

  
  
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  Neurological complications:

  
  
  
  
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    Stroke, transient ischemic attacks (due to bleeding or thromboembolic events, promoted by atrial fibrillation)

    
    
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    Brain abscess

    
    
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    Tinnitus, vision disorders, paraesthesia, myalgia, headache (as a result of hyperviscosity, “hyperviscosity syndrome”)

  
  
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  Renal complications:

  
  
  
  
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    Proteinuria, hematuria

    
    
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    Progressive renal failure

  
  
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  Metabolic complications:

  
  
  
  
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    Hyperuricemia

    
    
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    Hyperbilirubinemia and gallstones

    
    
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    Nephrolithiasis

  
  
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  Orthopedic complications:

  
  
  
  
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    Joint pain (hypertrophic osteoarthropathy, localized cell proliferation with periostitis)