Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling of pulmonary arterioles that leads to increased pulmonary vascular resistance, right heart failure, and death. It is associated with connective tissue diseases, including systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. PAH is characterized by dyspnea on exertion and fatigue. Syncopal events suggest severe disease. Patients may present with signs of right heart failure. One- and 3-year survival rates are approximately 81% and 52%, respectively. Given the high prevalence and mortality, algorithms for screening are currently under investigation and will hopefully lead to earlier diagnosis and improved survival.
Systemic sclerosis is the most common underlying disease associated with connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH), and has the poorest prognosis.
Patients with suspected PAH should undergo a complete evaluation, including right heart catheterization (RHC) and testing to rule out other possible causes of pulmonary hypertension.
Patients with RHC-confirmed PAH should be treated with PAH-specific therapies. However, the role of immunosuppression for the treatment of CTD-PAH is unclear.
The development of robust screening algorithms may lead to earlier diagnosis and improved survival in systemic sclerosis-PAH.
Pulmonary hypertension (PH) is a disease that is strictly defined by having a resting mean pulmonary artery pressure (mPAP) of 25 mm Hg or greater as measured by right heart catheterization (RHC). The causes of PH are diverse, but regardless of the cause, chronic elevation of pulmonary arterial pressures can lead to right ventricular strain, dilatation, dysfunction, and ultimately right heart failure. Historically, PH was classified as either primary or secondary PH. However, it was recognized that this classification scheme was insufficient for distinguishing between different types of PH. At the second World Symposium on PH in 1998, the causes of PH were categorized into 5 groups: group 1, pulmonary arterial hypertension (PAH); group 2, PH secondary to left heart disease; group 3, PH owing to chronic lung disease and/or hypoxia; group 4, chronic thromboembolic PH; and group 5, PH owing to unclear multifactorial mechanisms. Over the years, the classification scheme has been updated to reflect the growing understanding of the pathophysiology of different types of PH ( Box 1 ).
ALK-1, ENG, SMAD9, CAV1, KCNK3
Drug and toxin induced
Connective tissue disease
Human immunodeficiency virus
Congenital heart disease
1’. Pulmonary venoocclusive disease and/or pulmonary capillary hemangiomatosis
1’’. Persistent PH of the newborn (PPHN)
PH owing to left heart disease
Left ventricular systolic dysfunction
Left ventricular diastolic dysfunction
Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
PH owing to lung disease and/or hypoxia
Chronic obstructive pulmonary disease
Interstitial lung disease
Other pulmonary diseases with mixed restrictive and obstructive patterns
Alveolar hypoventilation disorders
Chronic exposure to high altitude
Developmental lung diseases
Chronic thromboembolic PH (CTEPH)
PH with unclear multifactorial mechanisms
Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy
Systemic disorders: sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis
Metabolic disorders: glycogen storage disorders, Gaucher disease, thyroid disorders
Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental PH
Abbreviations: PAH, pulmonary arterial hypertension; PH, pulmonary hypertension.
From Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;62:D36; with permission.