Etiology

• Pulmonary arterial hypertension (Group 1 PH)

• Left heart disease (Group 2 PH)

• Chronic lung diseases (Group 3 PH)

• Pulmonary artery obstruction (Group 4 PH)

• Unclear multifactorial mechanisms (Group 5 PH)

• Idiopathic

• Hereditary (e.g., BMPR2 loss-of-function mutation)

  • Encodes a set of inhibitors of vascular smooth muscle cell proliferation

  • Associated with a poor prognosis

• Drug-induced

  • Methamphetamine (and possibly amphetamines and cocaine)

  • Sympathomimetic appetite suppressants (e.g., diethylpropion, fenfluramine)

  • Chemotherapeutic agents, e.g., dasatinib

• Associated conditions

  • Connective tissue diseases, e.g., systemic sclerosis

  • Portopulmonary hypertension

  • Congenital heart disease (e.g., left-to-right shunt, Eisenmenger syndrome)

  • HIV infection

  • Schistosomiasis

• PPHN

• Congestive heart failure (CHF): e.g., HFrEF, HFpEF

• Valvular heart diseases, e.g., aortic valve stenosis, mitral valve stenosis

• Other acquired or congenital heart diseases causing postcapillary PH (e.g., hypoplastic left heart, aortic coarctation, HCM, LVOT obstruction)

• Obstructive lung diseases

  • COPD, emphysema

  • Obstructive sleep apnea

• Restrictive lung diseases: e.g., interstitial lung disease

• High altitude (e.g., high-altitude pulmonary hypertension)

• Others: e.g., developmental lung disorders, mixed obstructive and restrictive lung diseases

• Chronic thromboembolic pulmonary hypertension (CTEPH): Chronic thromboembolic occlusion of the pulmonary vessels

  • Recurrent microthrombi narrow the cross-sectional area of pulmonary vessels.

  • Affected individuals are at high risk for pulmonary embolism.

• Other causes of pulmonary artery (PA) obstruction: extrinsic compression by mediastinal tumors or masses, arteritis involving PAs, congenital PA stenoses, fibrosing mediastinitis

• Hematologic disorders (e.g., sickle cell disease, MPNs, chronic hemolytic anemias)

• Systemic disorders (e.g., sarcoidosis, neurofibromatosis, Langerhans cell histiocytosis)

• Metabolic disorders (e.g., metabolic syndrome, chronic kidney disease, Gaucher disease)

• Complex congenital heart disease

Periodic screening and monitoring for clinical features of PH is suggested for patients with any of the following:

• Family history of PAH

• Genetic screening positive in the patient or 1st-degree relative (e.g., for BMPR2)

• Exposure to drug or toxin known to cause PH (e.g., methamphetamine, fenfluramine)

• Scleroderma

• Mixed connective tissue diseases

• HIV

• Portal hypertension

• Recent (e.g., within the last 3–6 months) surgical repair of a congenital left-to-right shunt