Pulmonary Hypertension In Sarcoidosis Research Articles

Echocardiographic estimate of pulmonary artery pressure in sarcoidosis patients - real world data from a multi-national study.

Introduction:Echocardiographic measurement of the right ventricular systolic pressure (RVSP) is commonly used for estimating systolic pulmonary artery pressure (PASP) measured during right heart catheterization (RHC) in patients suspected for pulmonary hypertension (PH). Generally, there seems to be a strong correlation. However, this has been reported as less robust in sarcoidosis. We aim to investigate the correlation between RVSP and RHC measurements using real world data and analyzed factors influencing the relationship between RVSP and PASP in sarcoidosis.Methods & Results:Data of patients with and without sarcoidosis associated PH who had both a measurable echocardiographic RVSP and invasive PASP were collected from the RESAPH registry, PULSAR study and Cincinnati Sarcoidosis Clinic database (n=173, 60.1% female, mean age 56.0±9.5 years). Among them, 124 had PH confirmed by RHC. There was a strong correlation between RVSP and PASP (r=0.640). This correlation was significant in both male and female, white or non-white, forced vital capacity (FVC) >60%, and presence of fibrosis (p<0.001). However, it was less robust in patients with FVC of 50% or less. RVSP was considered inaccurate if the difference with PASP was > 10mmHg. Inaccurate echocardiographic estimation of the invasive PASP occurred in 50.8%, with overestimation mostly in patients without PH, and underestimation in patients with severe PH. An RVSP>50mmHg was associated with worse survival.Conclusions:In this real world multicenter cohort of sarcoidosis patients, we found a significant correlation between RVSP as determined by echocardiography and invasive PASP. Over- or underestimation of PASP occurred frequently. Therefore, echocardiographic RVSP measurement alone to screen for PH in sarcoidosis should be used with caution.

Pulmonary Artery 18F-Fluorodeoxyglucose Uptake by PET/CMR as a Marker of Pulmonary Hypertension in Sarcoidosis

ObjectivesThis study investigated whether pulmonary artery (PA) 18F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures. Background18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH). MethodsIn a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, 18F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE). ResultsThirty-three subjects demonstrated clear 18F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA 18F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA 18F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P < 0.05). In the subgroup that underwent TTE, signs of PH were present in a significantly higher number of patients with PA 18F-FDG uptake (14 [51.9%] vs 37 [29.8%]; P < 0.05). Qualitative assessment of 18F-FDG uptake in the PA wall showed a sensitivity of 33% and specificity of 96% for separating patients with PH based on RHC-derived PA pressures. SUVmax and TBR in the PA wall correlated with PA pressure derived from RHC and/or TTE. ConclusionsWe demonstrate that 18F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.

An update on sarcoidosis-associated pulmonary hypertension.

Pulmonary hypertension in sarcoidosis is a well known entity. Sarcoidosis-associated pulmonary hypertension (SAPH) incurs substantial morbidity and mortality. This review examines recent literatures published on epidemiology, prognosis and therapeutic management in SAPH. Several registries have been published between 2017 and 2020. The consensus conclusion - SAPH is a harbinger for poor prognosis. Several factors were noted for predicting adverse outcome in SAPH like reduced 6-min walk distance and diffusing capacity for carbon monoxide. Given its adverse outcome, experts have now focused on methods for early screening of SAPH in sarcoid patients. The exploration of pulmonary vasodilator drugs in SAPH is ongoing. In recent times, trials have been published utilizing Macitentan and parenteral prostacyclin in severe SAPH. Although these trials show encouraging results, the evidence from these studies are limited to approve these agents as preferred drugs for treating SAPH. A large multicentric trial of drugs used for pulmonary arterial hypertension with meaningful, yet feasible, event driven endpoint is still lacking. Lately, interventional treatment by pulmonary artery balloon pulmonary angioplasty and stenting has gained traction for treating pulmonary artery stenosis and chronic thromboembolic pulmonary hypertension. However, the conclusion is still based on small cohorts or case series. Several registries have highlighted SAPH portends an unfavorable consequence. On the contrary, no published guideline exists to treat SAPH. The precise role of immunosuppressive agents is unclear. The limited evidence favoring use of pulmonary vasodilators arise from small retrospective case series and/or single-center nonrandomized observational studies. Further multicenter randomized research is warranted to better define patient population to treat and how best to treat them.

Predicting pulmonary hypertension in sarcoidosis; value of PH probability on echocardiography.

Pulmonary hypertension (PH) is a well-recognised complication of sarcoidosis. Non-invasive diagnosis is challenging due to limited accuracy of echocardiography in interstitial lung disease. This study evaluates the value of echocardiographic PH probability for diagnosing PH in pulmonary sarcoidosis. All consecutive patients between August 2015 and November 2018 were prospectively screened for PH, and classified as low, intermediate or high PH probability. Patients with intermediate or high PH probability were referred for right heart catheterisation. PH was defined as a mean pulmonary artery pressure of ≥ 25mm Hg. Additional data on pulmonary function and chest-CT was collected. Of all 479 patients, PH was present in 17 and absent in 19 patients. Six patients refused right heart catheterisation. PH was present in 33% and 75% of patients with intermediate and high PH probability respectively (n = 36). TRV max was measurable in 46% of all patients. Measurability did not correlate with FVC% predicted or presence of significant fibrosis. In intermediate and high PH probability, TRV max < 2.9m/s successfully ruled out PH whereas a TRV max > 3.4 confirmed PH in all patients. If TRV max was absent or in between 2.9 and 3.4, secondary echocardiographic signs were not able to improve the diagnostic accuracy. PH is unlikely in patients with a TRV max < 2.9m/s on echocardiography, whereas PH is highly suspected in a TRV max > 3.4m/s. Discrimination is challenging if the TRV max is between 2.9-3.4m/s or absent. Additional secondary signs do not improve discrimination. Decision making for further investigations should be made by an expert team.

Pulmonary hypertension in patients with sarcoidosis: A single-center experience.

Sarcoidosis is a systemic granulomatous disease rarely complicated by pulmonary hypertension (PH). The prevalence of PH in sarcoidosis is unclear and has differences between ethnic groups. This study aimed to investigate the prevalence and predictors of PH in a Turkish cohort. The study included 55 patients with biopsy-proven sarcoidosis in a single center. All patients underwent detailed transthoracic echocardiography (TTE) to assess the probability of PH as recommended. Right heart catheterization (RHC) was performed for patients with intermediate-high risk of PH. Patients with mean pulmonary artery pressure >20 mm Hg by RHC were defined as PH. Demographic and clinical characteristics, laboratory data, spirometry, 6-min walk test, and TTE were compared between low and intermediate-high risk PH groups. The probability of PH was low with 47 patients. Eight patients had intermediate-high probability of PH, and two of them refused to undergo RHC. Of six intermediate-high probability patients, three had PH, and all of them had post-precapillary PH. The prevalence of PH in sarcoidosis was 5.5% (3/55). Six-minute walk distance (6 MWD) and diastolic parameters (E/A ratio, E' wave, and left atrial volume) were significantly lower, and New York Heart association class and N-terminal probrain natriuretic peptide (NT-proBNP) level were higher in intermediate-high risk PH patients compared with low-risk PH patients. The frequency of PH in sarcoidosis was 5.5% in a Turkish cohort. NT-proBNP, 6 MWD, diastolic function parameters, and myocardial strain parameters can be useful predictors of PH in patients with sarcoidosis, besides known echocardiographic parameters.

Sarcoidosis Associated Pulmonary Hypertension: Correlation of Cascular Morphologic Changes with Hemodynamic Data in Explanted Lungs

Purpose Sarcoidosis associated pulmonary hypertension (PH) is classified as WHO Group V according to the 2018 WHO classification system. Previous case series have demonstrated efficacy of pulmonary vasodilators in treating severe PH in sarcoidosis. We present a series of patients with sarcoidosis associated PH and describe correlation between the pre-transplant hemodynamic data from a right heart catheterization (RHC) and vascular morphologic changes in the native explanted lungs. Methods Patients with sarcoidosis who underwent lung transplantation at Loyola University Medical Center were analyzed from 2014-2018. We collected demographic data, RHC data, NYHA functional class data, and echocardiogram. Pathology was reviewed to assess for presence and severity of fibrosis, presence or absence of granulomas in lung parenchyma and lymph nodes, and vascular morphologic changes using Heath Edwards PH classification. We evaluated PH changes in arterioles, muscular arteries of 1mm and 3mm caliber, and elastic arteries. These findings were correlated to RHC data. Results Seven patients who had a RHC prior to lung transplantation were identified and had a mean pulmonary artery pressure greater than 25 mmHg. All of the patients had well-formed granulomas except two cases that showed ill formed granulomas. 5 of 7 cases had lymph nodes involved and 5 of 7 had fibrosis. Medial hypertrophy of 1 and 3mm arteries was observed in all cases. 3 of 4 patients with severe PH (NYHA Class IV) and RV dysfunction on echocardiogram were on parenteral prostacyclin therapy at the time of transplant and had grade 3 changes in the 1 mm arteries and grade 2 changes in the 3 mm arteries. Only 2 of 7 cases showed arteriolar changes, which correlated with higher pressures. No plexiform lesions were seen in any of the patients. Conclusion In our series of sarcoidosis patients with PH who underwent lung transplant or transplantation, vascular morphologic changes at the level of the 1 mm and arterioles correlated with the presence of severe PH (NYHA Class IV) and RV dysfunction on echocardiogram. These patients lack the plexiform lesions typically seen in idiopathic pulmonary arterial hypertension. Our study may identify a subset of sarcoid patients who have significant vascular remodeling and possibly explains the recently observed favorable response to vasodilator therapy.

Intracardiac hemodynamic abnormalities in patients with sarcoidosis

The aim of this study was to evaluate intracardiac hemodynamic abnormalities in patients with pulmonary sarcoidosis and to investigate relevant factors. Methods. The study involved 42 patients with chronic pulmonary sarcoidosis. Chest computed tomography (CT), echocardiography, body plethysmography, spirometry, 6-minute walking test, and measurements of lung diffusing capacity (DLCO), blood gases and blood C-reactive protein (CRP) were performed in all patients. Results. Chronic cor pulmonale was detected in 26.2% of patients. The right heart diastolic dysfunction was found in 14.3% of patients, the left heart diastolic dysfunction was found in 23.8% of patients, the mean pulmonary artery pressure (mPAP) was increased in 19% of patients. The right ventricular diameter was found to be related to the inspiratory bronchial resistance (Rin) (R = 0.480; p = 0.02), the intrathoracic gas volume (ITGV) (R = –0.670; p = 0.001), DLCO(R = 0.438; p = 0.013), and pulmonary fibrosis. The right heart systolic function (TAPSE) was related to DLCO(R = 0.518; p = 0.006), the total lung capacity (TLC) (R = 0.639; p = 0.001) and pulmonary fibrosis. The increased mPAP was related to the extension of disseminated lung lesions (R = 0.716; p = 0.018), blood oxygen partial pressure (R = 0.486; p = 0.017) and CRP level. The 6-min distance was related to Rin, the right ventricular diameter, parameters of the right heart diastolic function (tricuspid E / A ratio) (R = 0.486; p = 0.01), and ITGV (R = 0.494; p = 0.006). Conclusion. The development of cor pulmonale in patients with pulmonary sarcoidosis was related to DLCO, Rin and pulmonary fibrosis. The extension of disseminated lung lesions, hypoxemia and increased CRP were related to pulmonary hypertension. Different factors associated with cor pulmonale and pulmonary hypertension in sarcoidosis could prompt further investigation of different phenotypes of this disease with the intrinsic central hemodynamic abnormalities.

Predictive value of pulmonary function testing in the evaluation of pulmonary hypertension in sarcoidosis.

Background: In sarcoidosis patients, pulmonary hypertension (PH) is associated with significant morbidity and mortality. Early identification of sarcoidosis-associated pulmonary hypertension (SAPH) has substantial clinical implications. While a number of pulmonary function testing (PFT) variables have been associated with SAPH, the optimal use of PFT’s in screening for SAPH is unknown. Objectives: To examine the predictive value of PFT’s for echocardiographic PH in a cohort of sarcoidosis patients. Methods: We conducted a retrospective cohort study of patients with sarcoidosis from a single center over a period of five years. All consecutive adult patients with a diagnosis of biopsy-proven sarcoidosis (determined by review of the medical chart) who underwent PFT and echocardiographic testing were included. Echocardiographic risk of PH (either intermediate or high) was determined by the presence of echocardiographic PH signs and tricuspid regurgitant jet velocity. Data analysis was performed using multivariate logistic regression analysis with least absolute shrinkage and selection operator. Results: Of the 156 patients included in the study, 42 (27%) met the criteria for echocardiographic PH. Roughly equal proportions met the criteria for intermediate risk (45%) as did for high risk of PH (55%). The percent predicted of diffusion capacity for carbon monoxide (%DLCO) and forced vital capacity (%FVC) were predictive of echocardiographic PH. No other PFT variables outperformed these two markers, and the incorporation of additional PFT variables failed to significantly enhance the model. Conclusions: The %FVC and %DLCO emerged as being predictive of echocardiographic PH in this cohort of biopsy-proven sarcoidosis patients. Potentially reflecting the multifactorial pathogenesis of PH in sarcoidosis, incorporation of other PFT variables failed to enhance screening for PH in this population. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 308-316)

Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension.

Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited.Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25-35 mmHg with cardiac index <2.5 L·min-1·m-2) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126 patients with severe S-APH were analysed (mean±sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis.

Pulmonary hypertension in sarcoidosis

Pulmonary hypertension (PH) is a relatively common complication of sarcoidosis. In different studies, prevalence of PH in sarcoidosis varies from 6% to 74%. PH associated with sarcoidosis (PHAS) is typically associated with poor prognosis. Though PHAS is diagnosed more often in patients with advanced sarcoidosis, it could occasionally occur without pulmonary parenchymal lesions. Pathophysiology of PHAS is quite complex and includes several mechanisms including pulmonary fibrosis, hypoxic vasoconstriction, pulmonary vascular granulomatous obliteration and / or angiitis, extrinsic pulmonary vascular compression, pulmonary venoocclusive disease, and left heart disease. Management of PHAS is based on treatment of hypoxemia, active sarcoidosis and comorbidities. A role of systemic steroids in therapy of PHAS remains controversial. Pulmonary arterial hypertension (PAH) specific therapy has not been yet recommended in PHAS, but prostanoids, endothelin receptor antagonists and phosphodi esterase5 inhibitors were effective in some patients with PHAS in several small trials. Additional welldesigned randomized placebocontrolled studies are needed to investigate a role of PAHspecific therapy in certain cohorts of patients with PHAS.

Expression profiling elucidates a molecular gene signature for pulmonary hypertension in sarcoidosis.

Pulmonary hypertension (PH), when it complicates sarcoidosis, carries a poor prognosis, in part because it is difficult to detect early in patients with worsening respiratory symptoms. Pathogenesis of sarcoidosis occurs via incompletely characterized mechanisms that are distinct from the mechanisms of pulmonary vascular remodeling well known to occur in conjunction with other chronic lung diseases. To address the need for a biomarker to aid in early detection as well as the gap in knowledge regarding the mechanisms of PH in sarcoidosis, we used genome-wide peripheral blood gene expression analysis and identified an 18-gene signature capable of distinguishing sarcoidosis patients with PH (n = 8), sarcoidosis patients without PH (n = 17), and healthy controls (n = 45). The discriminative accuracy of this 18-gene signature was 100% in separating sarcoidosis patients with PH from those without it. If validated in a large replicate cohort, this signature could potentially be used as a diagnostic molecular biomarker for sarcoidosis-associated PH.

Pulmonary hypertension complicating pulmonary sarcoidosis.

Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis.

Pulmonary artery diameter to predict pulmonary hypertension in pulmonary sarcoidosis

Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis with a prevalence ranging from 5% to 74% [1]. The aetiology of PH in sarcoidosis is not fully understood. Usually, it is attributed to the destruction of the distal capillary bed by lung fibrosis and/or chronic hypoxaemia. However, the severity of PH does not correlate consistently with the degree of pulmonary fibrosis, and PH exists in sarcoidosis patients without fibrosis, suggesting a multifactorial mechanism. The presence of PH is associated with a poor prognosis, and early diagnosis and treatment might improve outcome [1]. Echocardiography should always be performed when PH is suspected [2]. However, the accuracy of echocardiography in patients with interstitial lung diseases is often limited due to poor image quality and unreliable tricuspid regurgitation signal to measure the right ventricular systolic pressure (RVSP) [3]. Further invasive investigation with the gold standard, right heart catheterisation (RHC), is often required. In order to optimise the noninvasive diagnostic approach, there is a need for more accurate predictors of PH. Computed tomography (CT) may raise suspicion of PH in symptomatic patients or those examined for unrelated indications by showing an increased pulmonary artery (PA) diameter (≥29 mm) and PA diameter/ascending aorta diameter (AAD) ratio (≥1.0) [2]. Similarly, PA diameter indexed to body surface area (BSA) has been suggested as possible predictor of PH. However, these parameters have never been investigated in pulmonary sarcoidosis specifically. Pulmonary artery indexed for body surface area is the most accurate predictor for PH on CT in pulmonary sarcoidosis

Pulmonary hypertension in sarcoidosis of the respiratory organs

Pulmonary hypertension in sarcoidosis of the respiratory organs

Sarcoidosis-associated pulmonary hypertension and lung transplantation for sarcoidosis.

Pulmonary hypertension (PH) is a significant complication of sarcoidosis, occurring in approximately 6 to > 20% of cases, and markedly increases mortality among these patients. The clinician should exercise a high index of suspicion for sarcoidosis-associated PH (SAPH) given the nonspecific symptomatology and the limitations of echocardiography in this patient population. The pathophysiology of PH in sarcoidosis is complex and multifactorial. Importantly, there are inherent differences in the pathogenesis of SAPH compared with idiopathic pulmonary arterial hypertension, making the optimal management of SAPH controversial. In this article, we review the epidemiology, diagnosis, prognosis, and treatment considerations for SAPH. Lung transplantation (LT) is a viable therapeutic option for sarcoid patients with severe pulmonary fibrocystic sarcoidosis or SAPH refractory to medical therapy. We discuss the role for LT in patients with sarcoidosis, review the global experience with LT in this population, and discuss indications and contraindications to LT.

Clinical Characteristics, Haemodynamics and Treatment of Pulmonary Hypertension in Sarcoidosis in a Single Centre, and Meta-Analysis of the Published Data

Pulmonary hypertension (PH) in sarcoidosis is associated with bad outcomes. Although there is interest in using pulmonary vasodilators (PVs) for PH in sarcoidosis, there are few data to support their use. In this study, a retrospective review of a cohort of patients with PH and sarcoidosis was conducted, focusing on those treated with PVs, and a meta-analysis of published reports indexed in MEDLINE was performed. Twenty-four patients were found. The rate of mortality or transplantation rate was 41.2%. Median survival without transplantation was 5.3 years. More patients who died or underwent transplantation during follow-up had moderate or severe lung fibrosis (66.7% vs 15.4%), had right ventricular dysfunction (80% vs 7.7%), and were in World Health Organization class IV (66.7% vs 30.8%). Body surface areas were lower in patients with events, as was cardiac output. Mortality was not different between patients treated with PVs and those not treated (54.5% vs 38.5%, p= 0.44) despite the treated patients' having more right ventricular dysfunction and worse hemodynamics. In a Cox regression survival model, lower body surface area, right ventricular dysfunction, and the presence of moderate or severe lung fibrosis were predictors of worse outcomes, but not treatment with PVs. PV-treated patients (n= 11) showed improved 6-minute walk distances and decreased N-terminal pro-B-type natriuretic peptide levels during follow-up. There was a trend toward improvement in hemodynamic profile. Four studies plus the data from this study were included in the meta-analysis. Six-minute walk distance improved by 30.64 m after treatment. Hemodynamics improved, with a reduction in mean pulmonary arterial pressure of 8.03 mm Hg and a decrease in pulmonary vascular resistance of 4.23 Wood units. In conclusion, PH in sarcoidosis is associated with adverse outcomes, particularly when accompanied by right ventricular dysfunction and/or moderate or severe lung fibrosis. Treating selected patients can improve hemodynamics and functional parameters.

Pulmonary hypertension in sarcoidosis, caused by extrinsic compression of major pulmonary vessels

Pulmonary hypertension is an increasingly recognised complication of sarcoidosis that arises from a variety of physiological mechanisms, including pulmonary fibrosis, granulomatous vasculitis, and circulating vasoactive mediators. We present the case of a young man with sarcoidosis complicated by fatal pulmonary hypertension due to extrinsic compression of the major pulmonary vessels by mediastinal granulomatous inflammation and lymphadenopathy.

Treatment of Sarcoidosis-Associated Pulmonary Hypertension: A Two-Center Experience

Pulmonary hypertension (PH) is a common complication of sarcoidosis that is associated with increased mortality. The pathogenesis of PH in sarcoidosis is uncertain, and the role of pulmonary arterial hypertension (PAH)-specific therapies remains to be determined.We conducted a retrospective study of patients with sarcoidosis and PH at two referral centers. New York Heart Association (NYHA) functional class, exercise capacity, hemodynamic data, pulmonary function tests, and survival were collected and analyzed.Twenty-two sarcoidosis patients treated with PAH-specific therapies were identified. After a median of 11 months of follow-up, NYHA class was improved in nine subjects. Mean 6-min walk distance (n = 18) increased by 59 m (p = 0.032). Patients with a higher FVC experienced a greater increment in exercise capacity. Among 12 patients with follow-up hemodynamic data, mean pulmonary artery pressure was reduced from 48.5 +/- 4.3 to 39.4 +/- 2.8 mm Hg (p = 0.008). The 1- and 3-year transplant-free survival rates were 90% and 74%, respectively.PAH-specific therapy may improve functional class, exercise capacity, and hemodynamics in PH associated with sarcoidosis. Prospective, controlled trials of PAH therapies for sarcoidosis are warranted to verify this apparent benefit. Mortality among the study population was high, highlighting the need for urgent evaluation at a lung transplant center.

Pulmonary hypertension and granulomatous vasculitis in sarcoidosis

To examine the recent advancements of the epidemiology, pathophysiology, clinical characteristics, radiographic studies, diagnostic modalities, treatment, and prognosis of pulmonary hypertension in sarcoidosis. A large retrospective study found 73.8% of patients with sarcoidosis listed for transplant had pulmonary hypertension. Several other studies found pulmonary hypertension to be associated mostly with advanced sarcoidosis, although frequencies in nonfibrotic disease were not uncommon. Destruction of vasculature due to fibrotic lung disease is most likely the common cause; however, other mechanisms have been proposed. In a small study, pulmonary venous occlusive disease was observed in the explanted lungs. Several studies have found an association with pulmonary function and the incidence of pulmonary hypertension. Right heart failure was seen in 21-23% of patients. In one study, high-resolution computer tomography findings, such as presence of lymphadenopathy, opacities, and thickened bronchovascular bundles, were not significantly different. Septal lines and ground-glass opacities were found at higher frequency in sarcoidosis-associated pulmonary hypertension. Corticosteroids were effective in treating some patients with sarcoidosis-associated pulmonary hypertension. Inhaled nitric oxide, epoprostenol, and bosentan have been shown to be efficacious in a small number of patients. Pulmonary hypertension is not infrequently observed in sarcoidosis. Further studies are needed to elucidate the epidemiology, mechanisms, treatment, and significance of sarcoidosis-associated pulmonary hypertension.

Incidence of Pulmonary Hypertension and Its Clinical Relevance in Patients With Sarcoidosis

To investigate the frequency of pulmonary hypertension (PH) and clinical parameters associated with PH in sarcoidosis patients. A prospective, observational study was performed on 246 consecutive Japanese sarcoidosis patients followed up at the outpatient sarcoidosis clinic in the Central Clinic of Kyoto. The patients were evaluated for PH by Doppler echocardiography. Among these patients, 192 underwent pulmonary function tests. In addition, high-resolution CT of the lung was evaluated for the presence of lymph node enlargement, lung opacity, and thickening of bronchovascular bundles in 122 patients. PH was defined as estimated systolic pulmonary artery pressure (sPAP) > or = 40 mm Hg. The frequency of PH was evaluated, and clinical parameters were compared between patients with PH and those without PH. Among 212 patients who were successfully evaluated for sPAP, 12 patients (5.7%) had PH. Patients with PH had the following clinical characteristics: advanced chest radiographic stage, decreased oxygen saturation, predominantly male gender, and decreased percentage of predicted vital capacity, percentage of predicted FVC, percentage of predicted FEV1, percentage of predicted functional residual capacity, and percentage of predicted total lung capacity (%TLC). Multivariate logistic regression analysis showed that decreased %TLC was independently associated with PH. There was a weak negative correlation between sPAP and %TLC (p < 0.05). The frequency of PH in Japanese sarcoidosis patients was 5.7% evaluated with Doppler echocardiography. Decreased lung volume increases the risk of PH developing in patients with sarcoidosis.