Clinical Features and Outcomes of Patients with Sarcoidosis-associated Pulmonary Hypertension

Abstract

The presence of pulmonary hypertension (PH) significantly worsens outcomes in patients with advanced sarcoidosis, but its optimal management is unknown. We aimed to characterize a large sarcoidosis-associated pulmonary hypertension (SAPH) cohort to better understand patient characteristics, clinical outcomes, and management strategies including treatment with PH therapies. Patients at Duke University Medical Center with biopsy-proven sarcoidosis and SAPH confirmed by right heart catheterization (RHC) were identified from 1990–2010. Subjects were followed for up to 11 years and assessed for differences by treatment strategy for their SAPH, including those who were not treated with PH-specific therapies. Our primary outcomes of interest were change in 6-minute walk distance (6MWD) and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) by after therapy. We included 95 patients (76% women, 86% African American) with SAPH. Overall, 70% of patients had stage IV pulmonary sarcoidosis, and 77% had functional class III/IV symptoms. Median NT-proBNP value was elevated (910 pg/mL), and right ventricular dysfunction was moderate/severe in 55% of patients. Median values for mean pulmonary artery pressure (49 mmHg) and pulmonary vascular resistance (8.5 Woods units) were consistent with severe pulmonary hypertension. The mortality rate over median 3-year follow-up was 32%. Those who experienced a clinical event and those who did not had similar overall echocardiographic findings, hemodynamics, 6MWD and NT-proBNP at baseline, and unadjusted analysis showed that only follow-up NT-proBNP was associated with all-cause hospitalization or mortality. A sign test to evaluate the difference between NT-Pro-BNP before and after PH therapy produced evidence that a significant difference existed between the median pre- and post-NT-Pro-BNP (−387.0 (IQR: −1373.0-109), p = 0.0495). Use of PH-specific therapy may be helpful in selected patients with SAPH and pre-capillary pulmonary vascular disease. Prospective trials are needed to characterize responses to PH-specific therapy in this subset of patients with SAPH.

Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline

“…Newer applications of PET are being developed, such as imaging based on deoxy-39-[18F]-fluorothymidine (178) Rationale for recommendation. Sarcoidosisassociated PH (SAPH) occurs in 5-20% of patients seen in sarcoidosis clinics (180)(181)(182)(183). Nearly half of patients with sarcoidosis with persistent dyspnea have been found to have SAPH (184,185), and SAPH is an independent risk factor for increased mortality in sarcoidosis (181,186).…”

“…Sarcoidosisassociated PH (SAPH) occurs in 5-20% of patients seen in sarcoidosis clinics (180)(181)(182)(183). Nearly half of patients with sarcoidosis with persistent dyspnea have been found to have SAPH (184,185), and SAPH is an independent risk factor for increased mortality in sarcoidosis (181,186). Other clinical manifestations, including exertional chest pain and/or syncope, exam findings of a prominent P2 or S4, reduced 6-minute walk distance, desaturation with exercise, reduced DL CO , increased pulmonary artery diameter relative to ascending aorta diameter (e.g., by CT scan), elevated brain natriuretic factor, and fibrotic lung disease, are proposed as methods to identify patients at risk for SAPH (182,184,(187)(188)(189), but these clinical parameters are unreliable.…”

Prevalence of sarcoidosis-associated pulmonary hypertension: cumulative analysis of two PULSAR studies

“…Treatment regimens were not assessed in both studies. Several drugs have been used to treat SAPH and have been investigated in different registries [3][4][5][6], showing that pulmonary arterial hypertension-specific treatment may be helpful in selected patients; however, controlled trials are rare. Next steps should be detailed phenotyping of SAPH patients and further studies that are needed to evaluate different treatment options in these selected SAPH phenotypes.…”

Advanced Pulmonary Sarcoidosis

“…87,95,103 One large series found significant improvement in BNP but no improvement in 6MWD or survival. 104 While some patients may have improvement of 6MWD after a year or more of therapy, it appears to be more likely to occur in those patients with only mild to moderate restriction (FVC of 55% predicted or greater). 103 Two recent large registries have reported on SAPH in France, the United States, Europe, and Middle East.…”