Sarcoidosis-associated pulmonary hypertension: Treatment and prognosis in adults

INTRODUCTION — Sarcoidosis is a multisystemic disease of unknown etiology that is characterized pathologically by nonnecrotizing granulomatous inflammation. Sarcoidosis-associated pulmonary hypertension (SAPH) is an increasingly recognized complication of sarcoidosis that is associated with a poor prognosis. Management varies depending on the predominant mechanism involved.

This topic will review the management of SAPH. The diagnosis of SAPH and management of other complications of sarcoidosis are discussed separately.

●(See "Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults".)

●(See "Clinical manifestations and diagnosis of sarcoidosis".)

●(See "Treatment of pulmonary sarcoidosis: Initial approach".)

●(See "Treatment of pulmonary sarcoidosis refractory to initial therapy".)

●(See "Overview of extrapulmonary manifestations of sarcoidosis".)

●(See "Gastrointestinal, hepatic, pancreatic, and peritoneal sarcoidosis".)

●(See "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

●(See "Management and prognosis of cardiac sarcoidosis".)

●(See "Sarcoid myopathy".)

●(See "Kidney disease in sarcoidosis".)

●(See "Neurologic sarcoidosis".)

●(See "Cutaneous manifestations of sarcoidosis".)

●(See "Sarcoidosis of bone".)

●(See "Cutaneous sarcoidosis: Management".)

Several societies have provided guidance on the evaluation and management of SAPH including recommendations from the 2020 American Thoracic Society Clinical Practice Guideline [1] and the 2022 World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) [2]. Our recommendations are mostly in keeping with this guidance.

REFERRAL TO EXPERT CENTER — We advocate for a multidisciplinary approach at a PH center that involves cardiologists, pulmonologists, and radiologists with experience in both PH and sarcoidosis. Multidisciplinary teams are necessary since the pathogenetic mechanism is often multifactorial and data in patients with SAPH are limited, rendering treatment decisions difficult.

All the information collected during the diagnostic evaluation and classification informs the therapeutic approach. These details are provided separately. (See "Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults" and "Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults", section on 'Postdiagnostic testing and phenotyping'.)

GENERAL MEASURES FOR ALL PATIENTS — For patients with SAPH, we follow the same basic principles of general management as for other patients with non-sarcoidosis-related PH. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)", section on 'General measures and supportive therapy'.)

Supportive care — Supportive care includes the following:

●Routine pulmonary and PH care – Patients with SAPH should exercise as tolerated, receive routine vaccinations (figure 1), be counselled against smoking (and vaping), and maintain a normal body mass index. When indicated, they should also be treated with oxygen and diuretics.(See "Long-term supplemental oxygen therapy".)

●Anticoagulation – We do not typically anticoagulate patients with SAPH unless another indication is present (eg, atrial fibrillation, chronic thromboembolic disease).

●Pregnancy – We counsel females of childbearing age about the risks of pregnancy.

●Rehabilitation – Cardiopulmonary rehabilitation is reasonable in those with indications (eg, severe dyspnea deconditioning). Rehabilitation has not been extensively studied in this population, but favorable responses have been noted in individual cases [3]. (See "Pulmonary rehabilitation".)

Optimizing therapy for comorbidities — We optimize therapies for any comorbidities known to be associated with or to worsen PH, particularly congestive heart failure, obstructive sleep apnea, obesity, and underlying lung disease, all of which are common in patients with SAPH [4]. We provide guidance on nutrition and weight loss, if needed. Fluid volume management is particularly important in those with group 2 and group 5 PH phenotypes (table 1). (See "Overview of the management of heart failure with reduced ejection fraction in adults" and "Obstructive sleep apnea: Overview of management in adults" and "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Optimized management of left heart disease'.)

SARCOIDOSIS-SPECIFIC THERAPIES — Sarcoidosis-specific therapies are targeted at treating granulomatous inflammation, which is presumed to be driving the development and progression of PH.

Anti-inflammatory therapy — We assess patients with SAPH to determine the likelihood of response to anti-inflammatory therapy. For potentially responsive patients with SAPH, we perform a trial of new or escalating anti-inflammatory therapy rather than maintaining current therapy. We do not alter anti-inflammatory treatment for SAPH in those who are unlikely to be responsive.

Assessing potential responsiveness — We consider patients potentially responsive to increased anti-inflammatory therapy if they have one or more of the following:

●Radiographic features suggesting active granulomatous inflammation

●Evidence of pulmonary vascular compression by granulomatous lesions

●Active inflammation (ie, uptake) on fluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET)

Patients who do not fulfill any of these criteria are considered unlikely to be responsive.

Agent selection — Anti-inflammatory agent selection varies among experts, but a trial of therapeutic escalation for 6 to 12 months is appropriate. Lack of response should prompt re-evaluation and likely de-escalation back to prior maintenance therapy.

●Treatment-naive patients – When anti-inflammatory therapy is deemed appropriate and the patient is treatment naive, we suggest use of a tumor necrosis factor alpha (TNF-alpha) inhibitor (eg, infliximab) or, if that is not feasible, low-dose glucocorticoids (eg, prednisone 0.1 to 0.2mg/kg/day) with methotrexate for 6 to 12 months. While some experts use larger doses of glucocorticoids in treatment-naive patients (eg, prednisone 0.3 to 0.6 mg/kg/day for one month then taper), we prefer to avoid overexposure to higher doses of glucocorticoids consistent with treatment guidelines due to their cumulative negative adverse effects. (See "Treatment of pulmonary sarcoidosis: Initial approach" and "Treatment of pulmonary sarcoidosis: Initial approach", section on 'Assessing disease severity and progression'.)

●Patients already receiving anti-inflammatory therapy – For patients already on anti-inflammatory therapy, we escalate immunosuppression (eg, add TNF-alfa inhibitor or add glucocorticoids to methotrexate). (See "Treatment of pulmonary sarcoidosis refractory to initial therapy".)

Once anti-inflammatory therapy is started or escalated, we initially follow these patients at 6 to 12 weeks to justify prolonged therapy for 6 to 12 months. Following-up with patients to determine the response to therapy is discussed below. (See 'Monitoring and follow-up' below.)

Our approach is based upon our experience and limited data that suggest a possible benefit from anti-inflammatory therapy [5-10]. As examples:

●In a study of 22 patients with SAPH and stage 2 or 3 sarcoidosis (table 2) on chest radiography, glucocorticoid therapy resulted in improvement in pulmonary hemodynamics at rest and during exercise [7]. Similarly, in a separate study, only patients who did not have stage 4 disease demonstrated improvement with a 20 percent reduction in systolic pulmonary artery pressure (PAP) at six months based on echocardiography [5].

●In the French Pulmonary Hypertension Registry, 11 patients with mixed mechanisms for SAPH were treated with high-dose glucocorticoids, either alone or in combination with a secondary immunosuppressive agent [10]. Compared with baseline, anti-inflammatory agents were associated with improvements in mean PAP (mPAP), peripheral vascular resistance, cardiac index, World Health Organization (WHO) functional class (table 3), and six-minute walk distance. The best response was seen in patients who had extrinsic pulmonary artery compression from lymph nodes that were associated with increased activity on FDG-PET scan.

Antifibrotic therapy — The effect of antifibrotic agents, such as pirfenidone and nintedanib, on the course of SAPH has not been well studied and is not typically started unless indicated for sarcoidosis-related lung disease. (See "Treatment of pulmonary sarcoidosis refractory to initial therapy".)

PH PHENOTYPE-TARGETED THERAPY

Assessing dominant phenotype — For patients with SAPH, we assess whether they have a dominant phenotype (table 1) and generally apply the same principles of management as for patients with that phenotype. This assessment is typically performed in the postdiagnostic setting using diagnostic investigations. Further details of this assessment are provided separately. (See "Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults", section on 'Postdiagnostic testing and phenotyping' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Postdiagnostic testing and classification'.)

While most patients with SAPH are classified as having group 5 PH, many patients have components of class 2 or 3 PH (or both) while a smaller proportion have class 4 disease. Patients with characteristics of group 1 pulmonary arterial hypertension (PAH) are rare [11]. Consequently, most patients with SAPH are not candidates for PH-specific therapy, but they may be eligible to participate in trials. Data that describe the prevalence of dominant phenotypes are discussed separately. (See "Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults", section on 'Epidemiology'.)

Avoidance of routine vasoreactivity testing — We do not routinely perform vasoreactivity testing unless the patient is thought to have a specific subtype of PAH (eg, idiopathic, heritable, or toxic-related PAH).

This approach is based upon the low prevalence of the vasoreactive PAH phenotype in SAPH. Data on vasoreactivity in SAPH are limited and variable. While older retrospective studies reported a high incidence of vasoresponsiveness (eg, 11 to 18 percent decrease in mean pulmonary artery pressure [mPAP] and 31 to 45 percent decrease in peripheral vascular resistance [12,13]), several newer studies reported acute vasoresponsiveness in less than 25 percent [14,15], and our experience suggests that it is considerably lower (eg, <5 percent). (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Vasoreactivity testing (select patients)'.)

PH without a dominant phenotype — There is no standard management strategy for patients who have mixed etiologies or patients without a dominant phenotype. Optimizing therapies for each potential phenotype contribution is reasonable. As examples, for patients with components of both cardiac- and pulmonary-related disease, we optimize therapy for left ventricular dysfunction and interstitial lung disease; patients with PAH-type physiology may be eligible for PAH-specific therapy in a clinical trial setting.

PH with dominant cardiac and/or pulmonary contributions — We manage patients who have PH with strong cardiac and/or pulmonary parenchymal phenotypes like patients with non-sarcoidosis-associated group 2 and 3 PH. Further details are provided in the following linked topics:

●(See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Management'.)

●(See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Treatment and prognosis".)

●(See "Management and prognosis of cardiac sarcoidosis".)

PH with vascular obstruction or thromboembolism — Some patients with SAPH have PH due to extrinsic pulmonary vascular compression by intrathoracic lymphadenopathy or fibrosing mediastinitis or, more rarely, PH due to chronic thromboembolic disease (CTEPH).

●Extrinsic pulmonary vascular compression – PH due to extrinsic sarcoid masses may respond to anti-inflammatory therapy. (See 'Anti-inflammatory therapy' above.)

As an adjunct, we evaluate candidacy for local therapies such as percutaneous balloon pulmonary angioplasty (BPA) and/or stenting of the pulmonary vascular tree. These interventions have improved the mPAP and six-minute walk distance in a few patients with SAPH [16-18]. (See "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy", section on 'Percutaneous balloon pulmonary angioplasty'.)

Patients with PH due to fibrosing mediastinitis may also respond to BPA/stenting, the details of which are provided separately. (See "Mediastinal granuloma and fibrosing mediastinitis", section on 'Symptomatic therapy'.)

●CTEPH – CTEPH is rare in SAPH. The management of CTEPH with anticoagulation and evaluation for pulmonary endarterectomy are discussed separately. (See "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy".)

PH with dominant primary pulmonary vasculopathy — Some patients with SAPH have PH that is not explained by any etiology (table 1) and may share hemodynamic characteristics similar to PAH. While patients with non-sarcoidosis-related PAH are candidates for PAH-specific therapy (ie, treatment that targets arterial vasoconstriction and arteriopathy), patients with SAPH are not generally candidates for such therapy. PAH-specific therapy should only be prescribed in a specialized center and (in general) only in a trial setting or a case-by-case basis due to the potential for harm in patients with sarcoidosis.

●Available PAH-specific therapies – The majority of the available PAH-specific therapies have been described in SAPH patients who are assessed to have a "PAH"-similar phenotype (table 4). PH-specific agents include prostacyclin pathway agonists (eg, epoprostenol, treprostinil, iloprost, selexipag), endothelin receptor antagonists (eg, bosentan, macitentan, ambrisentan), and nitric oxide-cyclic guanosine monophosphate enhancers (eg, phosphodiesterase [PDE] type 5 inhibitors sildenafil, tadalafil; soluble guanylate cyclase stimulator riociguat). Calcium channel blockers are not generally used in SAPH. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Vasoreactive patients'.)

If PAH-specific therapy is chosen outside of a trial setting on a case-by-case basis after discussion in a multidisciplinary meeting, sequential (eg, a PDE inhibitor, followed by a second oral agent one to two months later if initial therapy is tolerated) rather than upfront combination oral therapy is a safer approach. The treatment strategy is otherwise similar to that used in patients with non-sarcoidosis-related PAH, which is described separately. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy".)

●Efficacy – Only limited data describe the use of PAH-specific therapies in patients with SAPH. Studies generally consist of small cohorts or single-arm clinical trials or small randomized trials. In addition, in most studies, PAH specific therapy was combined with anti-inflammatory therapy, rendering it difficult to distinguish the contribution of each therapy to the overall response.

While bosentan is the most commonly studied therapy [15,19,20], other agents, including inhaled iloprost, inhaled nitric oxide, sildenafil, ambrisentan, macitentan, riociguat, or combination therapy, have shown improvements in functional capacity, quality of life, and hemodynamics [9,10,12,13,15,19-31]. However, data are not consistent. In addition, most studies suggest that the benefit is marginal and some even report rare cases of pulmonary edema and worsening of hypoxemia (likely due to the coexistence of pulmonary veno-occlusive disease [PVOD]) [32].

Patients with SAPH in whom decompensation is demonstrated following PAH-specific therapy (eg, worsening hypoxemia and/or pulmonary edema) should be re-evaluated for the possibility of PVOD/pulmonary capillary hemangiomatosis or for possible components of group 2/3 PH [13].

Special consideration may need to be given to a potential interaction between PAH-specific therapy and antifungals that may be used to treat fungal-related cavitary disease, which can be seen in patients with sarcoidosis.

MONITORING AND FOLLOW-UP — When left untreated, PH is progressive. Although there is no consensus, the following is our general approach to follow-up:

●For all patients with SAPH, every three to six months, we clinically monitor for worsening or improving symptoms of PH at every visit. This includes dyspnea, World Health Organization (WHO) functional class (table 3), exercise tolerance (eg, six-minute walk distance), and symptoms of right heart failure that may suggest progression (eg, leg edema, syncope). (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Clinical manifestations'.)

●For patients with SAPH on anti-inflammatory therapy, we additionally obtain N-terminal pro-brain natriuretic peptide. We also perform echocardiography after six months of therapy. There is no consensus or set criteria on what constitutes a response to therapy. We use clinical judgement and results of testing to inform management.

•For those with SAPH who have worsening symptoms, we assess for PH progression using repeat echocardiography.

We also assess the potential contribution of other etiologies to worsening symptoms in the context of the predominant phenotype. For example, for those with primarily a group 3 phenotype, we would assess lung parenchyma with computed tomographic imaging and pulmonary function tests. With a group 2 phenotype, we would begin with repeat echocardiography and consider cardiac fluorine-18-fluorodeoxyglucose-positron emission tomography or magnetic resonance imaging based on the results.

In some cases, right heart catheterization may also be needed to evaluate disease progression after excluding other causes of progressive symptoms (eg, deteriorating interstitial lung disease, newly developed cardiac disease, anemia, atrial fibrillation, pulmonary embolism). (See 'PH phenotype-targeted therapy' above and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Clinical manifestations' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Echocardiography' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Right heart catheterization'.)

•For those with SAPH who improve or are stable on anti-inflammatory therapy, we typically continue treatment at the lowest effective dose and obtain periodic echocardiograms, the frequency of which is based upon clinical judgment (eg, every one to two years in stable patients) to reassess heart size, function, and pulmonary hemodynamics, although the value of this approach is unproven.

●For those receiving PH-specific therapy, we follow up using the same protocol as that outlined in patients with non-sarcoidosis-related pulmonary arterial hypertension, the details of which are provided separately. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Follow-up'.)

REFRACTORY DISEASE

Organ transplant referral — For patients with SAPH who are refractory to therapy, lung or cardiac transplantation may be an option. PH does not influence candidacy for lung transplantation and outcomes appear to be no different than those in other patients undergoing lung transplantation. Further details regarding organ transplantation are provided separately. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Refractory patients' and "Treatment of pulmonary sarcoidosis refractory to initial therapy", section on 'Lung transplantation' and "Heart transplantation in adults: Indications and contraindications".)

Patients with SAPH may also be eligible for a right-to-left shunt as a temporizing measure (eg, bridge to transplantation). Further details on this procedure are provided separately. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Right-to-left shunt'.)

PROGNOSIS

Mortality — In patients with sarcoidosis, SAPH is an independent risk factor for mortality [10,33-36]. Multiple studies demonstrate a five-year mortality of approximately 35 to 45 percent [5,10,33,34,37-39]. The hazard ratio for mortality due to SAPH ranges from 7.4 to 8.2 when compared with patients who have sarcoidosis, but do not have PH [37,38].

As examples:

●An analysis of patients with SAPH using the United Network for Organ Sharing database in 2005 showed that 27 percent died awaiting lung transplantation [35]. In agreement, another study reported that among 43 patients with SAPH who were listed for lung transplantation, 53 percent died on the wait list [40]; the mortality rates at one, two, and three years were 34, 60, and 69 percent, respectively. However, estimates since then have reported lower mortality rates of approximately 18 percent while awaiting lung transplantation [41].

●In another retrospective cohort study, one-, two-, and five-year mortality rates in 22 patients with SAPH were 15, 26, and 41 percent, respectively [5].

●In a two-year follow-up study of 130 patients with SAPH, the mortality rate of SAPH without left ventricular dysfunction was 36 percent [37], 10-fold higher than the mortality rate for patients with sarcoidosis without PH [37].

●The multinational SAPH registry, which includes only patients with precapillary PH, described a one-, three-, and five-year transplant-free survival rate of 89, 71, and 62 percent, respectively [39]. The French SAPH registry, which included patients with severe precapillary PH (mean pulmonary artery pressure [mPAP] >35 mmHg or mPAP 25 to 35 mmHg with cardiac index <2.5 L/min/m²) reported similar rates of survival at one year (93 percent), three years (74 percent), and five years (55 percent) [10].

The impact of pulmonary arterial hypertension-specific or other therapies on quality of life, longevity, and mortality in SAPH is unknown.

Other outcomes — The presence of SAPH is associated with reduced exercise tolerance, increased supplemental oxygen requirement, increased need for help in activities of daily living, poorer quality of life, and higher likelihood of unemployment compared with sarcoidosis alone [33,42]. Patients are seven times more likely to require supplemental oxygen if they develop SAPH [42].

Prognostic factors — Prognostic factors that have been associated with reduced survival in SAPH include the following:

●World Health Organization (WHO) functional class IV (table 3) [5]

●Chest radiograph stage 4 (table 2) [37,38]

●Reduced diffusing capacity for carbon monoxide <35 percent predicted [10,22,39]

●Six-minute walk distance <300 m [10,39]

●mPAP >35 mmHg without evidence of left ventricular dysfunction [37,43]

●Increased pulmonary vascular resistance (>3 Wood units) [22,37,43]

●Evidence of right ventricular failure (eg, right atrial pressure >15 mmHg) [22,34,40]

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sarcoidosis" and "Society guideline links: Pulmonary hypertension in adults".)

SUMMARY AND RECOMMENDATIONS

●Multidisciplinary approach – Treatment of sarcoidosis-associated pulmonary hypertension (SAPH) warrants a multidisciplinary approach at PH centers with experience in both PH and sarcoidosis. (See 'Referral to expert center' above.)

●Assess the potential for anti-inflammatory therapy – We initially determine the likelihood of PH response to anti-inflammatory therapy. For potentially responsive SAPH patients, we perform a trial of new or escalating anti-inflammatory therapy rather than no therapy or maintaining current therapy (Grade 2C). Our approach is based upon our experience and limited data that suggest a possible benefit from anti-inflammatory therapy in this population. (See 'Anti-inflammatory therapy' above.)

•A potential response to anti-inflammatory therapy includes one or more of the following:

-Radiographic features suggesting active granulomatous inflammation

-Evidence of pulmonary vascular compression by granulomatous lesions

-Active inflammation on fluorine-18-fluorodeoxyglucose-positron emission tomography

•When anti-inflammatory therapy is chosen, we suggest addition of tumor necrosis factor alpha (TNF-alpha) inhibitor (eg, infliximab) rather than other agents (Grade 2C). Low-dose glucocorticoids (eg, 0.1 to 0.2 mg/kg/day of oral prednisone) with methotrexate is a reasonable alternative. These options minimize cumulative negative adverse effects of high-dose glucocorticoids.

●PH-phenotype-targeted therapy – For patients with SAPH, we assess whether a dominant phenotype is present (table 1). Further details of this assessment are provided separately. (See 'PH phenotype-targeted therapy' above and "Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults", section on 'Postdiagnostic testing and phenotyping' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Postdiagnostic testing and classification'.)

We generally apply the same principles of management as for patients with that phenotype with the following SAPH-specific issues:

•Avoidance of vasoreactivity testing – We do not routinely perform vasoreactivity testing since vasoreactive pulmonary arterial hypertension (PAH) is a rare occurrence in SAPH. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Vasoreactivity testing (select patients)'.)

•No dominant phenotype – There is no standard management strategy for patients who have mixed etiologies or no dominant etiology for their SAPH. Optimizing therapies for each contribution is reasonable. (See 'PH without a dominant phenotype' above.)

•Contributions from concomitant cardiac and/or pulmonary parenchymal disease – We optimize therapy for contributing cardiopulmonary disease, which is discussed separately:

-(See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Management'.)

-(See "Management and prognosis of cardiac sarcoidosis".)

-(See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Treatment and prognosis".)

-(See "Treatment of pulmonary sarcoidosis: Initial approach" and "Treatment of pulmonary sarcoidosis refractory to initial therapy".)

•Vascular obstruction or chronic venous thromboembolism – Patients with pulmonary vascular obstruction may respond to anti-inflammatory therapy and, in some cases, local interventions such as balloon pulmonary angioplasty and/or stenting. Patients with evidence of chronic thromboembolic disease may be evaluated for anticoagulation and/or pulmonary endarterectomy.

-(See "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy", section on 'Percutaneous balloon pulmonary angioplasty'.)

-(See "Mediastinal granuloma and fibrosing mediastinitis", section on 'Symptomatic therapy'.)

-(See "Chronic thromboembolic pulmonary hypertension: Initial management and evaluation for pulmonary artery thromboendarterectomy".)

•Dominant primary pulmonary vasculopathy – For most patients with hemodynamic findings consistent with group 1 PAH, we suggest not prescribing PAH-specific therapy (Grade 2C). Limited data in this population suggest possible harms including hypoxemia and pulmonary edema. However, on a case-by-case basis under the supervision of experts in a specialized center or in the context of a trial, PAH-specific therapy is sometimes administered; in such cases, sequential therapy (eg, a phosphodiesterase inhibitor, followed by a second oral agent in one to two months if initial therapy is tolerated) rather than upfront combination oral therapy is a safer approach. (See 'PH with dominant primary pulmonary vasculopathy' above and "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy".)

●Monitoring and follow-up – For all patients with SAPH, every three to six months we clinically assess symptoms, World Health Organization (WHO) functional class (table 3), and exercise tolerance (eg, six-minute walk distance).

•For patients with SAPH on anti-inflammatory therapy, we additionally obtain N-terminal pro-brain natriuretic peptide levels and also perform echocardiography after six months of therapy. We use clinical judgement and results of testing to inform the decision to manage therapy. For those who respond or stabilize with anti-inflammatory therapy, we typically continue treatment at the lowest effective dose while in those with worsening symptoms, we assess for PH progression and the potential contribution of other etiologies (See 'Monitoring and follow-up' above.)

•For those receiving PH-specific therapy, we follow up using the same protocol as that outlined in patients with non-sarcoidosis-related PAH, the details of which are provided separately. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Follow-up'.)

•For patients with SAPH who are refractory to therapy, lung or cardiac transplantation may be an option. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy", section on 'Refractory patients' and "Treatment of pulmonary sarcoidosis refractory to initial therapy", section on 'Lung transplantation'.)

●Prognosis – The prognosis of SAPH is poor. In patients with sarcoidosis, SAPH is an independent risk factor for mortality. Five-year mortality rates are approximately 35 to 45 percent, with the highest rates in those awaiting lung transplantation. The impact of therapy on quality of life, longevity, and mortality is unknown. (See 'Prognosis' above.)