Pulmonary Hypertension - Causes and Classification

Causes and Classification

A 1973 meeting organized by the World Health Organization was the first to attempt classification of pulmonary hypertension. A distinction was made between primary and secondary PH, and primary PH was divided in the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms. A second conference in 1998 at Évian-les-Bains also addressed the causes of secondary PH (i.e. those due to other medical conditions), and in 2003, the 3rd World Symposium on Pulmonary Arterial Hypertension was convened in Venice to modify the classification based on new understandings of disease mechanisms. The revised system developed by this group provides the current framework for understanding pulmonary hypertension. The system includes several improvements over the former 1998 Evian Classification system. Risk factor descriptions were updated, and the classification of congenital systemic-to pulmonary shunts was revised. A new classification of genetic factors in PH was recommended, but not implemented because available data were judged to be inadequate.

The Venice 2003 Revised Classification system can be summarized as follows:

• WHO Group I - Pulmonary arterial hypertension (PAH)
  • Idiopathic (IPAH)
  • Familial (FPAH)
  • Associated with other diseases (APAH): collagen vascular disease (e.g. scleroderma), congenital shunts between the systemic and pulmonary circulation, portal hypertension, HIV infection, drugs, toxins, or other diseases or disorders
  • Associated with venous or capillary disease
• WHO Group II - Pulmonary hypertension associated with left heart disease
  • Atrial or ventricular disease
  • Valvular disease (e.g. mitral stenosis)
• WHO Group III - Pulmonary hypertension associated with lung diseases and/or hypoxemia
  • Chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD)
  • Sleep-disordered breathing, alveolar hypoventilation
  • Chronic exposure to high altitude
  • Developmental lung abnormalities
• WHO Group IV - Pulmonary hypertension due to chronic thrombotic and/or embolic disease
  • Pulmonary embolism in the proximal or distal pulmonary arteries
  • Embolization of other matter, such as tumor cells or parasites
• WHO Group V - Miscellaneous

The classification does not include sickle cell disease, Human herpesvirus 8, also associated with Kaposi's sarcoma, has been demonstrated in patients with PAH, suggesting that this virus may play a role in its development. Recent studies have been unable to find an association between human herpesvirus 8 and idiopathic pulmonary arterial hypertension.