Definition

Pulmonary hypertension is present when the mean pulmonary artery pressure is greater than 25 mmHg at rest or greater than 30 mmHg during exercise.

Elevated pulmonary vascular resistance is defined as an increase in the pulmonary vascular resistance to 3 Wood units × m². It is a sign of pulmonary artery vasculopathy, which is initially reversible but is later irreversible (fixed).

Epidemiology

Idiopathic or familial pulmonary hypertension is extremely rare in childhood. It is assumed that their incidence is 2 patients per 1 million inhabitants.

Pathogenesis

The pulmonary artery pressure (PAP) is determined by three factors:

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  LAP = left atrial pressure

  
  
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  Q_P = pulmonary blood flow

  
  
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  R_P = pulmonary vascular resistance

Normally, the pulmonary artery pressure, which is increased at birth, drops rapidly within the first few weeks of life. After 6 to 8 weeks, it usually reaches the normal adult value of 1 to 3 Wood units × m². Later, the muscles of the pulmonary vessels become thin, the arteries increase in size, and new arteries and arterioles develop.

An increase in pulmonary artery pressure leads to changes in the pulmonary vascular bed with vasoconstriction, thrombosis in the small vessels, and remodeling including proliferation of smooth muscle and endothelial cells. These processes increase pulmonary hypertension, leading to pulmonary arterial vasculopathy and are sustained by an imbalance between protective and aggressive factors. Vasodilators (e.g., prostacyclin, NO) have a protective effect and vasoconstrictors (e.g., thromboxane, endothelin) have an aggressive effect. Prostacyclin and NO also have a very beneficial effect by inhibiting platelet aggregation and the proliferation of smooth muscle and endothelial cells. Hypoxia adversely affects pulmonary hypertension.

If pulmonary hypertension is due to an increased blood flow caused by a heart defect with a left-to-right shunt, the continuous overload on the pulmonary vessels leads to pulmonary arterial vasculopathy with an increase in pulmonary vascular resistance. If pulmonary vascular resistance exceeds the systemic resistance, shunt reversal develops with cyanosis (Eisenmenger reaction, Chapter 22). The time at which the Eisenmenger reaction occurs varies and depends not only on the shunt volume, but also on structural heart defects and other factors not yet fully understood. Patients with AV septal defects, TGA with a VSD, and with truncus arteriosus are at particularly high risk. For them, irreversible pulmonary hypertension may already occur in the first year of life if the heart defect is not corrected in time. In an ASD, however, pulmonary hypertension often does not develop for several decades. In children with trisomy 21 and a shunt defect, an Eisenmenger reaction often occurs earlier than in other children. The reason for this may be an obstruction of the upper airways that causes hypoxia and high endothelin levels.

Another cause of pulmonary artery hypertension is pulmonary venous congestion, for example, if there is increased pressure in the left atrium in left heart diseases (mitral stenosis, mitral regurgitation, cor triatrium, left ventricular dysfunction) or stenosis of the pulmonary veins.

The high pressure overload in pulmonary hypertension causes hypertrophy of the right ventricle. If the right ventricle becomes insufficient and cannot overcome the pulmonary resistance, there is insufficient filling of the left heart, and hypotension and cardiovascular shock occur. If there is a connection between the right and left heart (e.g., an ASD or VSD), this connection may function as an overflow valve and leads to sufficient filling of the left heart for maintaining adequate cardiac output. Because of the right-to-left shunt, however, cyanosis occurs. Since such an overflow valve in an Eisenmenger reaction is vital for maintaining adequate cardiac output, corrective surgery to close the shunt is contraindicated in such cases.

Etiology

Pulmonary hypertension in childhood occurs most often with the following disorders:

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  Congenital or acquired heart defects

  
  
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  Persistent pulmonary hypertension of the newborn

  
  
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  Idiopathic or familial pulmonary hypertension

  
  
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  Chronic lung diseases such as bronchopulmonary dysplasia, cystic fibrosis

Classification

Classification of pulmonary hypertension (from Simonneau et al. 2004)¹⁰⁰:

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  I. Pulmonary arterial hypertension:

  
  
  
  
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    Idiopathic

    
    
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    Familial

    
    
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    Associated with

    
    
    
    
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      Collagen diseases

      
      
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      Congenital shunt defects (ASD, VSD, PDA, AVSD, aortopulmonary window, truncus arteriosus communis, single ventricle with nonobstructive pulmonary blood flow)

      
      
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      Portal hypertension, HIV infection, pertussis

      
      
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      Drugs and toxins: e.g., amphetamines, cocaine, appetite suppressants, L-tryptophan, canola oil

      
      
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      Other diseases: e.g., thyroid disorders, storage diseases (glycogen storage diseases, Gaucher disease), congenital hemorrhagic telangiectasia, myeloproliferative disorders, splenectomy

  
  
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  II. Pulmonary arterial hypertension with relevant venous and capillary involvement:

  
  
  
  
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    Pulmonary veno-occlusive disease

    
    
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    Pulmonary capillary hemangiomatosis

  
  
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  III. Persistent pulmonary hypertension of the newborn (PPHN)

  
  
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  IV. Pulmonary hypertension in left heart diseases:

  
  
  
  
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    Left heart disease, pulmonary vein stenosis, cor triatrium

  
  
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  V. Pulmonary arterial hypertension in lung diseases and/or hypoxia

  
  
  
  
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    Chronic obstructive lung disease, interstitial lung disease

    
    
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    Bronchopulmonary dysplasia, congenital diaphragmatic hernia, hypoplastic lungs

    
    
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    Sleep apnea syndrome, chronic tonsillar hypertrophy, craniofacial anomalies, thoracic deformities, disorders of the respiratory muscles

    
    
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    Developmental disorders

    
    
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    Exposure to high altitudes

  
  
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  VI. Pulmonary arterial hypertension in chronic thrombotic or embolic disease:

  
  
  
  
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    Thrombotic occlusion of the proximal pulmonary arteries

    
    
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    Thrombotic occlusion of the distal pulmonary arteries

    
    
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    Sickle cell anemia

    
    
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    Nonthrombotic lung embolism (tumor, parasites, foreign body)

  
  
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  VII. Other diseases:

  
  
  
  
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    Sarcoidosis, histiocytosis X, lymphangiomatosis, scleroderma, compression of the pulmonary vessels (e.g., tumors)

Idiopathic hypertension and familial pulmonary hypertension were formerly known as primary pulmonary hypertensions, all others as secondary forms.

Symptoms

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  Rapid fatigue, deteriorating physical capacity

  
  
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  Exertional dyspnea, syncope: caused by the inability to adequately increase cardiac output during exercise

  
  
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  Headache

  
  
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  Angina pectoris symptoms: result of right ventricular ischemia (unfavorable ratio between right ventricular muscle mass, increased right ventricular pressure, and coronary supply)

  
  
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  Signs of right heart failure (edema, hepatomegaly, venous congestion, ascites)

  
  
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  Cyanosis at rest (blue lips disease): sign of mixed venous saturation and reduced cardiac output, another underlying disease (e.g., parenchymal lung disease), or a right-to-left shunt.

  
  
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  Bronchial obstruction: often associated with pulmonary hypertension

  
  
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  Hemoptysis: late symptom

The clinical severity of pulmonary hypertension is classified into four classes similar to those of heart failure (Table 21.1).