Sarcoidosis-Associated Pulmonary Hypertension: Outcome With Long-term Epoprostenol Treatment

doi:10.1378/chest.130.5.1481

Chest

Volume 130, Issue 5, November 2006, Pages 1481-1488

https://doi.org/10.1378/chest.130.5.1481 Get rights and content

Rationale

Pulmonary hypertension is a known complication of sarcoidosis and is associated with increased mortality. Little is known about the outcome of sarcoidosis-associated pulmonary hypertension, including response to treatment.

Objective

To determine the characteristics and outcome of patients with sarcoidosis-associated pulmonary hypertension treated with IV epoprostenol.

Design

Retrospective chart review of all cases of pulmonary hypertension with a concomitant diagnosis of sarcoidosis evaluated in the Boston University Pulmonary Hypertension Center from 2000 to 2004.

Measurements

Data collected included patient demographics, sarcoidosis stage, pulmonary function, echocardiography results, treatment, baseline and posttreatment hemodynamic measurements, and clinical outcome.

Results

Eight patients were identified; four of the patients had stage IV pulmonary sarcoidosis. Pulmonary function test results were notable for severe diffusion impairment (mean diffusion capacity of the lung for carbon monoxide, 30% of predicted), with only mild-to-moderate restrictive physiology (mean FVC, 59% of predicted). Seventy-five percent of patients required supplemental oxygen at the time of presentation. All patients had moderate or severe pulmonary hypertension and were New York Heart Association (NYHA)/World Health Organization (WHO) class III or IV. A vasodilator trial with epoprostenol was performed in seven of the eight patients; six of the seven patients had a significant hemodynamic response (> 25% reduction in pulmonary vascular resistance). All but one of the responders (five of six patients) continued on therapy. Average clinical improvement was one to two NYHA/WHO classes at a mean follow-up of 29 months (range, 15 to 49 months).

Conclusions

In patients with sarcoidosis-associated pulmonary hypertension, the severity of pulmonary vascular disease occurs out of proportion to lung function abnormalities. The majority of our patients responded to epoprostenol; survival may be improved in this group.

Section snippets

Design and Data Collection

In accordance with the protocol approved by the Institutional Review Board, we retrospectively reviewed all cases of pulmonary hypertension evaluated in the Boston University Pulmonary Hypertension Center between January 2000 and October 2004 and identified patients with a concurrent diagnosis of sarcoidosis. Data collected included patient demographics, sarcoidosis stage, treatment, pulmonary function, echocardiography results, baseline and posttreatment hemodynamics, complications of

Patients

Eight patients with sarcoidosis-associated pulmonary hypertension were identified (Table 1). In 75% of cases, sarcoidosis was diagnosed based on accepted clinical findings and biopsy results demonstrating noncaseating granulomas. Two patients were considered to have sarcoidosis based on typical clinical features (hilar lymphadenopathy, upper lobe fibrosis, typical eye involvement) in the absence of biopsy. Of the five patients reported who underwent long-term epoprostenol treatment, all had

Discussion

We report a series of patients with sarcoidosis-associated pulmonary hypertension, including their clinical characteristics and their outcome with both short-term and long-term IV epoprostenol treatment. In keeping with previous reports,1, 24, 8, 14 the majority of our patients had evidence of pulmonary fibrosis and required supplemental oxygen, suggesting that pulmonary parenchymal destruction and hypoxia account, at least in part, for the observed pulmonary hypertension in these patients.

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Unusual case of cerebral embolism after initiation of selexipag for sarcoidosis-related pulmonary hypertension: a case report
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Background: Pulmonary hypertension is a rare complication of sarcoidosis. The pathogenesis of sarcoidosis-related pulmonary hypertension is multifactorial, and patients with sarcoidosis-related pulmonary hypertension can have variable treatment responses and prognoses. While selexipag (Nippon Shinyaku / Kyoto / Japan) was recently approved in Japan for the treatment of pulmonary hypertension, the risk of cerebral infarction has not been clearly reported. Case report: A 63-year-old Asian female with a diagnosis of ocular and cutaneous sarcoidosis developed shortness of breath and was referred to our department to rule out cardiac sarcoidosis. Swan–Ganz catheterization was performed, and she was diagnosed with pulmonary arterial hypertension and started on selexipag. A few days after starting treatment, she presented with hemiplegia and was diagnosed with cardiogenic cerebral embolism by using magnetic resonance imaging. As there was no evidence of pre-existing intracardiac thrombosis, we suspected unusual cerebral embolism. Echocardiography revealed a deep venous thrombus and a bubble study revealed a right-left shunt through a patent foramen ovale. Conclusions: The initiation of selexipag improved pulmonary blood flow and caused cerebral embolism, which was an unusual and unexpected event. This report highlights the importance of confirming the presence of patent foramen ovale and a deep venous thrombus before starting treatment for pulmonary hypertension.
Characteristics and Outcomes of Pulmonary Angioplasty With or Without Stenting for Sarcoidosis-Associated Pulmonary Hypertension: Systematic Review and Individual Participant Data Meta-Analysis
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Background: Pulmonary angioplasty has been performed in patients with sarcoidosis-associated pulmonary hypertension (SAPH) but most evidence comes from case reports and small case series. Overall outcomes remain unclear. We conducted an individual participant data (IPD) meta-analysis of baseline, procedural, and outcome data of pulmonary angioplasty in patients with SAPH. Methods: We performed searches and systematically reviewed references from PubMed, Embase, Cochrane, ClinicalTrials.gov, and grey literature. We included IPD of patients who underwent pulmonary angioplasty for SAPH. Those without definitive diagnosis of sarcoidosis or with other causes of pulmonary vascular stenosis or compression were excluded. Results: Of 1293 screened references, 7 were included. IPD was obtained for 17 patients (mean age 58.6 (±9.1) years; 82.4% female); most of whom were Scadding stages III or IV and had NYHA FC III or IV. All patients with documented changes in 6-minute-walk distance (6MWD) had a significant improvement that ranged from 12.6 to 102.4% (P < 0.01). There were no deaths during a median follow-up of 6 (3-18) months. Conclusions: Pulmonary angioplasty with or without stenting of focal stenosis or compressions of pulmonary vessels may lead to significant improvement in 6MWD in patients with SAPH. However, this study had a small sample and some methodological limitations, such as analysis mostly of case reports and series. Randomized controlled clinical trials and/or large multicenter registry studies are needed to provide higher evidence in this topic.
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Pulmonary hypertension (PH) is a life-threatening disease with complex pathophysiology. The World Health Organization has classified PH in 5 groups according to etiology, the fifth of which corresponds to PH due to unknown or multiple mechanisms; including sarcoidosis-associated PH (SAPH). Although this system has been used to guide treatment recommendations according to each group, it does not provide much insight into the heterogeneous group 5. Furthermore, pulmonary vasodilators have been contraindicated for patients in this cluster which represents a challenge for the management of SAPH which can sometimes improve with these PH-directed drugs. In this review, we discuss the classification of SAPH; as well as the evidence behind the use of pulmonary vasodilator, invasive procedures, and lung transplantation for treating SAPH; and the little that is known about his disease in the setting of cardiac sarcoidosis.
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The most recent classification scheme put forth by the 6th World Symposium on Pulmonary Hypertension (WSPH) describes group 5 pulmonary hypertension (PH) as “pulmonary hypertension with unclear and/or multifactorial mechanisms.” Group 5 PH is subclassified into hematological disorders, systemic disorders, “other” disorders, and complex congenital heart disease. There are currently neither approved medications nor clear professional recommendations for the treatment of patients suffering from group 5 PH. This article discusses the nuances of the various diseases associated with group 5 PH organized by the WSPH subclassification system. Particular emphasis is spent on the maladies most likely encountered by the practicing clinician.
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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

The authors have no conflicts of interest to disclose.

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Chest

Original ResearchSarcoidosis-Associated Pulmonary Hypertension: Outcome With Long-term Epoprostenol Treatment

Rationale

Objective

Design

Measurements

Results

Conclusions

Section snippets

Design and Data Collection

Patients

Discussion

Chest

Chest

Chest

Chest

Chest

Chest

Chest

Chest

Chest

Chest

Chest

Chest

Right heart impairment in sarcoidosis: haemodynamic and echocardiographic study

Eur J Respir Dis

Pulmonary haemodynamics at rest and during exercise in patients with sarcoidosis

Respiration

Sarcoidosis and reactive pulmonary hypertension

Arch Intern Med

Sarcoidosis simulating pulmonary veno-occlusive disease

Am Rev Respir Dis

Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics

Eur Respir J

Original Research
Sarcoidosis-Associated Pulmonary Hypertension: Outcome With Long-term Epoprostenol Treatment