What is the relationship between pulmonary hypertension and sarcoidosis?

From the Guidelines

Pulmonary hypertension (PH) is a significant complication of sarcoidosis that affects approximately 5-20% of patients with sarcoidosis and is associated with increased mortality, as reported in the 2020 American Thoracic Society clinical practice guideline 1. The relationship between pulmonary hypertension and sarcoidosis is complex, with PH typically developing due to multiple mechanisms including vascular compression by fibrosis or lymphadenopathy, vasculopathy from granulomatous inflammation, left heart dysfunction, and hypoxic vasoconstriction from parenchymal lung disease.

Key Points

• The prevalence of PH in sarcoidosis patients is estimated to be between 5-20% 1.
• Sarcoidosis-associated PH (SAPH) is an independent risk factor for increased mortality in sarcoidosis 1.
• Clinical manifestations such as exertional chest pain and/or syncope, exam findings of a prominent P2 or S4, reduced 6-minute walk distance, desaturation with exercise, reduced D LCO, increased pulmonary artery diameter relative to ascending aorta diameter, elevated brain natriuretic factor, and fibrotic lung disease are proposed as methods to identify patients at risk for SAPH 1.
• Transthoracic echocardiogram (TTE) is the most commonly recommended method to initially screen for the presence of PH 1.
• Right heart catheterization is suggested to definitively confirm or exclude PH in patients with suspected PH and a suggestive TTE 1.

Management

• Management of sarcoidosis-associated PH should begin with optimizing treatment of the underlying sarcoidosis, usually with corticosteroids like prednisone and steroid-sparing agents such as methotrexate or azathioprine in refractory cases.
• For PH-specific therapy, patients should be evaluated by a PH specialist for potential vasodilator therapy, with phosphodiesterase-5 inhibitors like sildenafil often being first-line, followed by endothelin receptor antagonists such as bosentan or ambrisentan 1.
• Oxygen therapy is essential for patients with hypoxemia, and diuretics like furosemide may help manage right heart failure symptoms.
• Regular echocardiographic monitoring every 6-12 months is recommended to assess disease progression, with right heart catheterization performed for definitive diagnosis and to guide therapy decisions 1.
• Lung transplantation may be considered in severe cases unresponsive to medical management.

From the Research

Relationship Between Pulmonary Hypertension and Sarcoidosis

• Pulmonary hypertension (PH) is a well-known complication of sarcoidosis, defined by a mean pulmonary artery pressure of ≥25 mm Hg 2.
• The estimated prevalence of sarcoidosis-associated PH (SAPH) ranges from 3% in patients referred to a tertiary center up to 79% in patients awaiting lung transplant 2.
• SAPH is most prevalent in patients with pulmonary fibrosis, though it can be independent of airflow obstruction or restriction 3.
• The mechanisms of sarcoidosis-PH are multifactorial, including specific vasculopathy, local increased vasoreactivity, extrinsic compression of pulmonary vessels, and portal hypertension 4.

Diagnosis and Treatment

• Diagnosis of PH in sarcoidosis is challenging since symptoms and signs overlap, and suspicion can be raised based on symptoms or tests, such as pulmonary function tests, laboratory findings, electrocardiography, or chest CT 2.
• PH screening mainly relies on transthoracic echocardiography, and right heart catheterization should be considered on a case-by-case basis in patients with clinical suspicion of PH 2.
• Treatment options are considered on a patient-level in a PH expert center and might include oxygen therapy, immunosuppressive, or PH-specific therapy 2.
• Targeted therapies, such as phosphodiesterase-5 inhibitors and endothelin receptor antagonists, have shown improvement in six-minute walk test, World Health Organisation functional class, and echocardiography in patients with SAPH 5.

Prognosis and Mortality

• SAPH is associated with high morbidity and mortality, with a significantly increased morbidity and mortality in sarcoidosis patients with PH compared to those without PH 2, 4.
• Mortality increases in patients with more advanced stages of sarcoidosis and/or PH 2.
• Lung transplantation can be considered in otherwise eligible patients with refractory SAPH 3, 4.