Pulmonary Arterial Hypertension In Systemic Sclerosis Patients Research Articles

An Overview of Different Techniques for Improving the Treatment of Pulmonary Hypertension Secondary in Systemic Sclerosis Patients.

In systemic sclerosis (SSc) mortality is mainly linked to lung involvement which is characterized by interstitial lung disease (ILD) and pulmonary hypertension (PH). In SSc, PH may be due to different etiologies, including ILD, chronic thromboembolic disease, pulmonary veno-occlusive disease, and pulmonary arterial hypertension (PAH). The main tool to screen PAH is transthoracic echocardiography (TTE), which has a sensitivity of 90%, even if definitive diagnosis should be confirmed by right heart catheterization (RHC). The radiological evaluation (i.e., HRTC) plays an important role in defining the possible causes and in monitoring the evolution of lung damage. For PAH, identifying individuals who have borderline elevation of pulmonary arterial pressure needs to be appropriately managed and followed. In the past few years, the strategy for the management of PAH has significantly evolved and new trials are underway to test other therapies. This review provides an overview of the tools to evaluate PAH in SSc patients and on treatment options for these patients.

Impact of routine screening on detection, severity and outcome of pulmonary arterial hypertension in systemic sclerosis

Abstract Introduction It has been reported that up to 20% of systemic sclerosis (SSc) patients can be asymptomatic at the time of pulmonary arterial hypertension (PAH) diagnosis. The significant prevalence rate, lack of symptoms and high morbidity and mortality from SSc-PAH as well as the potential benefit from early intervention with the more widely available therapeutic options provide a strong rationale for active screening programs. The DETECT algorithm was developed in 2013 from a large prospective and multicentre study in SSc patients with higher risk of PAH. The objective of this study was to examine the impact of a screening program on the early detection of SSc-PAH. We looked at serial patients diagnosed with SSc associated PAH (SSC-PAH) in a large national pulmonary hypertension referral centre. Patients and methods All newly diagnosed adult patients with SSc-PAH prospectively enrolled in a large national pulmonary hypertension referral centre. The current study included newly diagnosed patients between January 2006 and January 2018. Results Three-hundred and five patients were diagnosed with SSc-PAH in our centre between 2006 and 2018. Of these, 164 patients were diagnosed before 2013 (January 2006 - December 2012) and 141 after 2013 (January 2013 - January 2018). Demographics were similar at presentation between the two groups. The non-invasive (WHO-FC, 6-MWD and NT-proBNP) and haemodynamic measurements (RAP, CI and SvO2) were used to calculate the ESC guidelines risk score. It was noted that higher proportion of patients in the post-2013 were in the higher risk categories than the pre 213 group (84.4% vs. 78%) but this was not found to be statistically significant (p value 0.356). There was no statistically significant difference in survival between the two groups (Post 2013 group, 1-, 3- year and 5-year survival was 87.9%, 60.4% and 52.1%, respectively and pre-2013 group 1-, 3- year and 5-year survival 89.6%, 65.2% and 49%, respectively) with a log rank p value of 0.869. Applying Cox regression analysis of proportional hazard and adjusting for ESC risk score at baseline, predicted survival was not found to be statistically different between the two groups. The ESC risk category at baseline was a highly significant predictor of survival as expected. Conclusion There remains a strong rationale for active screening for PAH in SSc patients which has a poor prognosis despite advances in therapeutic strategies. However, the current screening programme does not seem to have resulted in significantly earlier detection in this cohort. It would be important to analyse other patient populations in order to understand the impact of screening programmes. The current screening programs limitations may explain why we have not been able to detect more patients in the lower risk categories. Further development of these programs in order to overcome their shortfalls is direly needed. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Health ServiceRoyal Free NHS Trust Survival analysis

The Relationship between Pulmonary Damage and Peripheral Vascular Manifestations in Systemic Sclerosis Patients.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by the presence of generalized vasculopathy and tissue fibrosis. Collagen vascular disorder in SSc is due to fibroblast and endothelial cell dysfunctions. This leads to collagen overproduction, vascular impairment and immune system abnormalities and, in the last stage, multi-organ damage. Thus, to avoid organ damage, which has a poor prognosis, all patients should be carefully evaluated and followed. This is particularly important in the initial disease phase, so as to facilitate early identification of any organ involvement and to allow for appropriate therapy. Pulmonary disease in SSc mainly involves interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). High-resolution computed tomography (HRCT) and pulmonary function tests (PFT) have been proposed to monitor parenchymal damage. Although transthoracic echocardiography is the most commonly used screening tool for PAH in SSc patients, definitive diagnosis necessitates confirmation by right heart catheterization (RHC). Moreover, some studies have demonstrated that nailfold videocapillaroscopy (NVC) provides an accurate evaluation of the microvascular damage in SSc and is able to predict internal organ involvement, such as lung impairment. This review provides an overview of the correlation between lung damage and microvascular involvement in SSc patients.

Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with and without PAH using a machine learning approach and to validate the findings in an external cohort.Serum samples from patients with SSc and PAH (n=77) and SSc without pulmonary hypertension (non-PH) (n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the Myriad RBM Discovery platform consisting of 313 proteins. Samples from an independent validation SSc cohort (PAH n=22 and non-PH n=22) were obtained from the University of Sheffield (Sheffield, UK).Random forest analysis identified a novel panel of eight proteins, comprising collagen IV, endostatin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-7, matrix metallopeptidase-2, neuropilin-1, N-terminal pro-brain natriuretic peptide and RAGE (receptor for advanced glycation end products), that discriminated PAH from non-PH in SSc patients in the DETECT Discovery Cohort (average area under the receiver operating characteristic curve 0.741, 65.1% sensitivity/69.0% specificity), which was reproduced in the Sheffield Confirmatory Cohort (81.1% accuracy, 77.3% sensitivity/86.5% specificity).This novel eight-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.

P167 Pulmonary hypertension in patients with systemic sclerosis: an audit of screening practices, incidence and cost over 10 years

Abstract Background Patients with systemic sclerosis (SSc) are at risk of developing pulmonary arterial hypertension (PAH), a subtype of pulmonary hypertension (PH) which is not due to left-heart disease, chronic hypoxia or pulmonary arterial thrombus. The European Society of Cardiology recommends annual screening of patients with SSc due to the insidious presentation of PAH, poor outcomes, and the availability of effective treatments. Transthoracic echocardiography is the standard screening investigation, but NT pro-BNP, a biochemical marker of ventricular stretch, may be a cost-effective initial test with echocardiography reserved for patients with new or worsening symptoms or increasing NT pro-BNP. Our centre introduced NT pro-BNP as an adjunct to echocardiography in 2014. Methods We audited our SSc-PAH screening programme from 2009-2018 against the standard that every SSc patient should be screened annually with echocardiography or NT pro-BNP. Patients seen by the regional PH service prior to the first rheumatology clinic were excluded. We used our centre’s database of SSc patients and electronic patient records to determine if a patient had undergone PH screening. We calculated cost estimates from our hospital’s biochemistry and echocardiography departments. Results From 2009 to 2018, the number of SSc patients requiring annual screening rose from 81 to 215. In 2009, 65% of patients were screened - all with echocardiography. In 2018, 88% of patients were screened - 25% had an echocardiogram and 83% had a NT pro-BNP. 63% of patients were screened only through NT pro-BNP. Across the 1476 patient-years studied, only 6 new cases of PH were identified. PH was secondary to ILD in two cases, and true PAH in three cases (one patient refused diagnostic right-heart catheterisation). All three PAH diagnoses came from echocardiograms requested for worsening dyspnoea, so are not attributable to the screening programme. On 31 December 2018, 55% of these patients were taking phosphodiesterase 5 inhibitors (PDE-5i) for severe Raynaud’s phenomenon (50% on sildenafil and 5% on tadalafil). 4% of patients were prescribed bosentan and 3% of patients were prescribed dual therapy with a PDE5i and bosentan. This may explain our centre’s low incidence of PAH. The annual cost of screening per patient has dropped from £82 in 2014 to £59 in 2018, and the total annual cost has plateaued since 2014, despite rising patient numbers and improved screening rates. Conclusion Since introducing NT pro-BNP alongside echocardiography as a screening tool for PAH in SSc patients, we spend less on our screening programme per patient and achieve higher screening rates. However, in 10 years, our screening programme has not detected any asymptomatic cases of PAH, raising questions about the necessity of screening asymptomatic SSc patients. Widespread PDE-5i use may contribute to the low incidence of PAH in our cohort. Disclosures L. Spray None. J. Vila None. B. Griffiths None.

Whole blood viscosity in systemic sclerosis: a potential biomarker of pulmonary hypertension?

Our goal was to determine if whole blood viscosity (WBV) can be used to predict the risk of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). Patients with SSc were analyzed. Out of 107 patients, 26 patients, found to have confirmed diagnosis of PAH, were classified as those with (n= 26, PAH group) and without PAH (n= 81, non-PAH group). We calculated estimated WBV at both high (HSR) and low shear rates (LSR) from hematocrit and total serum protein levels. Total protein levels were significantly higher and the anti-centromere antibody (ACA) was more frequent in the PAH group. Furthermore, anti-topoisomerase antibody (anti-scl-70) was significantly less frequent in the PAH group. The WBV values were significantly higher at HSR (16.68 ± 0.38 vs. 16.24 ± 0.58; p< 0.001) and at LSR (51.81 ± 7.21 vs. 42.97 ± 11.76; p< 0.001) in PAH group. The multivariate analysis revealed that the WBV at both shear rates independently designated the presence of PAH in SSc patients. The ROC curve showed that the sensitivity and specificity of LSR and HSR were 92.3% and 61.7% (AUC 0.759, p< 0.001), and 88.5% and 65.4% (AUC 0.770, p< 0.001) with a cutoff value of 43.56 and 16.32 for WBV, respectively. Higher WBV levels in SSc patients were an independent indicator for PAH development in this cohort. WBV-LSR and WBV-HSR values might help exclude the PAH possibility in patients diagnosed with SSc and remain as an independently associated biomarker for follow-up of these patients for future risk of PAH development. Findings remain to be confirmed by other cohorts.Key Points• The most important cause of morbidity and mortality in systemic sclerosis patients is considered to be pulmonary arterial hypertension.• When the symptoms of PAH are not recognized earlier in the course of the SSc, the prognosis might be worse.• Higher whole blood viscosity levels in scleroderma patients with PAH was an independent indicator for PAH development.

Validating Alinity immuno- and clinical chemistry assays for routine use

The autoantibody profile, which varies between races, has rarely been reported in Chinese Han systemic sclerosis (SSc) patients. The present study aims to investigate the autoantibody profile of Chinese Han SSc patients using a commercial line immunoassay.The prevalence of autoantibodies to Ro-52, PDGFR, Ku, PM75, PM100, Th/To, NOR90, Fib, RP155, RP11, CENP-B, CENP-A and Scl-70 were analyzed in serum samples obtained from healthy controls (n = 30), SSc patients (n = 320) and non-SSc connective-tissue disease patients (n = 100) using an Euroline Systemic Sclerosis Profile kit.SSc patients had increased prevalence of anti-RP11 (P = 0.032), anti-CENPB (P < 0.001), anti-CENPA (P = 0.001) and anti-Scl-70 (P < 0.001), but had decreased prevalence of anti-Ro-52 (P = 0.004), when compared to non-SSc CTDs. Furthermore, SSc patients had increased prevalence of anti-Ro-52 (P = 0.003), anti-CENPB (P = 0.034), anti-CENPA (P = 0.034) and anti-Scl-70 (P < 0.001), when compared to HCs. In addition, SSc patients with interstitial lung disease (ILD) had increased prevalence of anti-Ro-52 (P = 0.046) and anti-Scl-70 (P = 0.035), but had decreased prevalence of anti-CENPB (P < 0.001) and anti-CENPA (P < 0.001). Moreover, SSc patients with pulmonary arterial hypertension (PAH) had increased prevalence of anti-Ro-52 (P = 0.013) and decreased prevalence of anti-Scl-70 (P = 0.001). Anti-Ro-52 and anti-Scl-70 had increased values for predicting ILD in SSc patients, while anti-Ro-52 had increased values for predicting PAH in SSc patients.A commercial line immunoassay was used to evaluate the diagnostic value of autoantibodies in Chinese Han SSc patients. The results clearly indicate that the immunoblot assay has good diagnostic utility for SSc. Anti-Ro-52, anti-RP11, anti-CENPB, anti-CENPA and anti-Scl-70 are useful for diagnosing SSc in the Chinese Han population. Anti-Ro-52, anti-CENPB, anti-CENPA and anti-Scl-70 have a potential value for diagnosing ILD in SSc patients. Furthermore, anti-Ro-52 and anti-Scl-70 may be used to diagnose PAH in SSc patients.

Harmonization protocols for Lp-PLA2 activity reagents: An initial attempt in China

The autoantibody profile, which varies between races, has rarely been reported in Chinese Han systemic sclerosis (SSc) patients. The present study aims to investigate the autoantibody profile of Chinese Han SSc patients using a commercial line immunoassay.The prevalence of autoantibodies to Ro-52, PDGFR, Ku, PM75, PM100, Th/To, NOR90, Fib, RP155, RP11, CENP-B, CENP-A and Scl-70 were analyzed in serum samples obtained from healthy controls (n = 30), SSc patients (n = 320) and non-SSc connective-tissue disease patients (n = 100) using an Euroline Systemic Sclerosis Profile kit.SSc patients had increased prevalence of anti-RP11 (P = 0.032), anti-CENPB (P < 0.001), anti-CENPA (P = 0.001) and anti-Scl-70 (P < 0.001), but had decreased prevalence of anti-Ro-52 (P = 0.004), when compared to non-SSc CTDs. Furthermore, SSc patients had increased prevalence of anti-Ro-52 (P = 0.003), anti-CENPB (P = 0.034), anti-CENPA (P = 0.034) and anti-Scl-70 (P < 0.001), when compared to HCs. In addition, SSc patients with interstitial lung disease (ILD) had increased prevalence of anti-Ro-52 (P = 0.046) and anti-Scl-70 (P = 0.035), but had decreased prevalence of anti-CENPB (P < 0.001) and anti-CENPA (P < 0.001). Moreover, SSc patients with pulmonary arterial hypertension (PAH) had increased prevalence of anti-Ro-52 (P = 0.013) and decreased prevalence of anti-Scl-70 (P = 0.001). Anti-Ro-52 and anti-Scl-70 had increased values for predicting ILD in SSc patients, while anti-Ro-52 had increased values for predicting PAH in SSc patients.A commercial line immunoassay was used to evaluate the diagnostic value of autoantibodies in Chinese Han SSc patients. The results clearly indicate that the immunoblot assay has good diagnostic utility for SSc. Anti-Ro-52, anti-RP11, anti-CENPB, anti-CENPA and anti-Scl-70 are useful for diagnosing SSc in the Chinese Han population. Anti-Ro-52, anti-CENPB, anti-CENPA and anti-Scl-70 have a potential value for diagnosing ILD in SSc patients. Furthermore, anti-Ro-52 and anti-Scl-70 may be used to diagnose PAH in SSc patients.

Abnormal pulmonary artery systolic pressure response after exercise in systemic sclerosis patients: A PRISMA-compliant meta-analysis.

Background:Pulmonary artery systolic pressure (PASP) is an important parameter for detecting pulmonary arterial hypertension (PAH). The difference between rest PASP and post-exercise PASP (ΔPASP) may play a role in predicting and screening resting PAH. The aim of this study is to analyze ΔPASP in systemic sclerosis (SSc) patients with PAH or non-PAH and suggest a cutoff value of ΔPASP for detection of PAH.Methods:PubMed, Embase, and Web of Science were searched for relevant publications up to July 7, 2018. Characteristics of control, no PAH, exercise-induced PAH (EIPH) and PAH subgroups in SSc patients were extracted. R 3.5.0 with the “meta” package was used to conduct this meta-analysis.Results:Twelve articles involving 1279 patients were included in this study. The subgroups meta-analysis showed pooled mean ΔPASP in different subgroups: control group (8.6 mmHg, 95% CI: 6.9–10.5), no PAH group (12.2 mmHg, 95% CI: 11.2–13.2), EIPH group (26.0 mmHg, 95% CI: 24.2–27.7) and PAH group (36.2 mmHg, 95% CI: 29.7–42.7).Conclusion:Combining the results of our study with the previous studies, an abnormal increase in PASP after exercise could indicate the development of PAH in SSc patients. In addition, if ΔPASP>29 mmHg, a high suspicion of PAH should be raised.

Evaluation of a commercial immunoassay for autoantibodies in Chinese Han systemic sclerosis population

ObjectiveThe autoantibody profile, which varies between races, has rarely been reported in Chinese Han systemic sclerosis (SSc) patients. The present study aims to investigate the autoantibody profile of Chinese Han SSc patients using a commercial line immunoassay. MethodsThe prevalence of autoantibodies to Ro-52, PDGFR, Ku, PM75, PM100, Th/To, NOR90, Fib, RP155, RP11, CENP-B, CENP-A and Scl-70 were analyzed in serum samples obtained from healthy controls (n = 30), SSc patients (n = 320) and non-SSc connective-tissue disease patients (n = 100) using an Euroline Systemic Sclerosis Profile kit. ResultsSSc patients had increased prevalence of anti-RP11 (P = 0.032), anti-CENPB (P < 0.001), anti-CENPA (P = 0.001) and anti-Scl-70 (P < 0.001), but had decreased prevalence of anti-Ro-52 (P = 0.004), when compared to non-SSc CTDs. Furthermore, SSc patients had increased prevalence of anti-Ro-52 (P = 0.003), anti-CENPB (P = 0.034), anti-CENPA (P = 0.034) and anti-Scl-70 (P < 0.001), when compared to HCs. In addition, SSc patients with interstitial lung disease (ILD) had increased prevalence of anti-Ro-52 (P = 0.046) and anti-Scl-70 (P = 0.035), but had decreased prevalence of anti-CENPB (P < 0.001) and anti-CENPA (P < 0.001). Moreover, SSc patients with pulmonary arterial hypertension (PAH) had increased prevalence of anti-Ro-52 (P = 0.013) and decreased prevalence of anti-Scl-70 (P = 0.001). Anti-Ro-52 and anti-Scl-70 had increased values for predicting ILD in SSc patients, while anti-Ro-52 had increased values for predicting PAH in SSc patients. ConclusionA commercial line immunoassay was used to evaluate the diagnostic value of autoantibodies in Chinese Han SSc patients. The results clearly indicate that the immunoblot assay has good diagnostic utility for SSc. Anti-Ro-52, anti-RP11, anti-CENPB, anti-CENPA and anti-Scl-70 are useful for diagnosing SSc in the Chinese Han population. Anti-Ro-52, anti-CENPB, anti-CENPA and anti-Scl-70 have a potential value for diagnosing ILD in SSc patients. Furthermore, anti-Ro-52 and anti-Scl-70 may be used to diagnose PAH in SSc patients.

An Update on Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: a Review of the Current Literature.

This review will summarize the most current literature on the clinical impact, epidemiology, risk factors, screening recommendations, predictors of outcomes, and treatment options in patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). PAH continues to be a major cause of morbidity and mortality in SSc. Many risk factors and predictors of outcomes have been identified in patients with SSc including clinical, hemodynamic, and laboratory parameters. Screening for PAH in SSc patients is important and screening algorithms have been developed. Despite many available treatment options for PAH, prognosis remains poor. Awareness of risk factors, early detection, and up-front combination treatment are important considerations in SSc-PAH and may lead to improved outcomes. Further research to develop better biomarkers and therapies is needed to continue to improve survival and outcomes in patients with SSc-PAH.

Echocardiographic assessment of regional right ventricular systolic function using two-dimensional strain echocardiography and evaluation of the predictive ability of longitudinal 2D-strain imaging for pulmonary arterial hypertension in systemic sclerosis patients.

Systemic sclerosis (SSc) is a generalized connective tissue disorder, and SSc patients are at risk of developing pulmonary arterial hypertension (PAH). The aims of this study are to evaluate the right ventricular regional systolic function using two-dimensional speckle-tracking echocardiography (2D STE) and to determine the predictive ability of peak longitudinal systolic strain (PLSS) at the RV lateral wall for PAH in SSc patients. 80 SSc patients (mean age 51 ± 12years) were included in the study. Echocardiography and 2D STE were performed at baseline and after 12months. RHC was performed only in SSc patients with clinical indications. PLSS at the apical segment of the RV free wall was significantly impaired in PAH patients compared with non-PH patients (-14.6 ± 5.9 vs. - 22.2 ± 7.5%, p = 0.034). PLSS at the basal, mid, and apical segments of the RV free wall was lower in both groups at follow-up compared to baseline, but the drop in strain values was statistically significant only in the non-PH group (p < 0.05). Right atrial area (OR 1.758; p = 0.023), peak tricuspid regurgitation velocity (OR 24.23; p = 0.011) and PLSS at the apical segment of the RV lateral wall (OR 2.47; p = 0.005) were independent predictors of PAH. A cut-off value of - 14.48% PLSS at the apical segment of the RV lateral wall resulted in 100% specificity for predicting PAH in SSc patients. RV pressure overload affects RV systolic function as manifested by impaired RV longitudinal deformation. Evaluating RV regional systolic function with 2D STE could be useful as an additional echocardiographic parameter for screening PAH in SSc patients.

OP0036 An Evidence-Based Tool for Detection of Pulmonary Arterial Hypertension in Systemic Sclerosis: The Detect Study

BackgroundDiagnosis of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) requires right heart catheterisation (RHC). Current screening recommendations are consensus-based and focus on echocardiography and symptoms. While false positives are...

AB0818 Nitric oxide diffusion and pulmonary capillary blood volume measurement in scleroderma patients

BackgroundCarbon monoxide diffusing capacity test (DLCO) is a non invasive diagnostic method for interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), frequent and severe complications of systemic sclerosis (SSc)....

FRI0397 Baseline characteristics of systemic sclerosis patients with borderline mean pulmonary artery pressure: post-hoc analysis from the detect study

BackgroundPatients with mean pulmonary artery pressures (mPAP) of 21–24 mmHg have ‘borderline’ pulmonary arterial hypertension (PAH) and may represent an early, milder stage of pulmonary vasculopathy in those at high...

Non-invasive diagnostic and functional evaluation of cardiac involvement in patients with systemic sclerosis

Elevated serum brain natriuretic peptide (BNP) released from myocytes of ventricles upon stretch have been found in patients with isolated right ventricular (RV) pressure overload. However, limited data suggest that serum BNP may be elevated in systemic sclerosis (SSc) patients, especially with RV dysfunction. We assessed serum N-terminal proBNP (NT-proBNP) in SSc and evaluated whether it reflects the severity of RV overload. We prospectively studied 51 consecutive patients (47F, mean age 53.3 +/- 15.2 years) with SSc (mean disease duration 9 +/- 12.4 years). The control group formed 31 healthy subjects (27F, mean age 52.6 +/- 12.1 years). NT-proBNP level, 6-minute walking test (6MWT), and transthoracic echocardiography (TTE) for the assessment of RV overload were performed. Serum NT-proBNP exceeded the reference value of 125 pg/mL in 31 (61%) SSc patients. The mean serum log NT-proBNP concentration in SSc was higher than in controls (2.138 +/- 0.527 vs. 1.634 +/- 0.420 pg/mL, p < 0.001). 13 (25%) SSc patients have tricuspid regurgitation peak gradient (TRPG) exceeding 31 mmHg reflecting pulmonary arterial hypertension (PAH). The SSc presented other echocardiographic signs of RV overload. Mean 6MWT distance was shorter in SSc than in controls (528 +/- 100 vs. 617 +/- 80 m, p < 0.001). NT-proBNP level correlated positively with TRPG, RV diameter, RV Tei index and negatively with 6MWT distance. ROC analysis identified >115 pg/ml as the best NT-proBNP threshold predicting PAH for SSc patients (sensitivity 92%, specificity 44%). Results of our study suggest that NT-proBNP measurement is a useful screening method for PAH in SSc patients. Since elevated plasma NT-proBNP level reflects the degree of right ventricular overload and limitation of exercise capacity, abnormal NT-proBNP levels should imply further evaluation including echocardiography.

Pulmonary Involvement in Systemic Sclerosis

Scleroderma, also known as progressive systemic sclerosis (SSc), is a multisystem autoimmune disorder characterized by inflammation and fibrosis involving the skin as well as internal organs such as the vasculature, esophagus, and the respiratory tract. Pulmonary involvement consists most often of interstitial fibrosis and pulmonary vascular disease leading to pulmonary arterial hypertension (PAH). Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis. Pulmonary hemorrhage with acute renal failure and diffuse alveolar hemorrhage in the absence of a history of renal involvement or penicillamine intake have rarely been reported in patients with systemic sclerosis.On high resolution CT, evidence of interstitial disease is seen in approximately 90% of patients, the main findings being a fine reticular pattern involving the subpleural regions of the lower lobe. Other common findings include ground-glass opacities, honeycombing, and parenchymal micronodules. The most distinctive pulmonary histologic findings in patients with scleroderma are the vascular changes found in PAH in the absence of significant interstitial fibrosis.There is no strong evidence that any drug alters the course of the two main types of lung disease in systemic sclerosis. This apparent failure of therapy may reflect the fact that pulmonary involvement is usually identified at an established or late stage. It has been suggested that, for fibrosing alveolitis, corticosteroids are most effective if given in combination with cyclophosphamide. In some patients with SSc, PAH has been considered as a major cause of morbidity and mortality. Centrally infused prostacyclin (epoprostenol) and its subcutaneously infused analog treprostinil improve hemodynamics, as well as the quality of life and survival in these patients. Iloprost has also shown a positive effect on PAH in SSc patients. More recently, bosentan, an endothelin receptor antagonist, has proved effective in controlling PAH after 6 months' treatment. Sildenafil has been used as a selective pulmonary vasodilator in SSc patients with isolated PAH. This drug decreased mean pulmonary artery pressure and pulmonary vascular resistance, and increased cardiac output, with much improvement of the physical condition of the patients. Lung transplant can be considered as a last option.Clinicians must be aware of the possibility of lung disease in patients with SSc so that it can be treated as early as possible.

Successful treatment with sildenafil in systemic sclerosis patients with isolated pulmonary arterial hypertension: two case reports

We describe two systemic sclerosis (SSc) patients with isolated pulmonary arterial hypertension (PAH) who were given treatment with 50 mg oral sildenafil per day. We evaluated the efficacy of oral sildenafil for isolated PAH in SSc patients by direct assessment with cardiac catheterization before and 6 months after the initiation of sildenafil. Right-heart catheterization demonstrated decreased mean pulmonary artery pressure, decreased pulmonary vascular resistance, and increased cardiac output after treatment with sildenafil. Brain natriuretic peptide levels were gradually decreased. The 6-min walking distance was greatly extended. Moreover, the physical conditions of both patients were much improved. We recognized no adverse events. We propose that oral sildenafil may be beneficial as a selective pulmonary vasodilator and as long-term treatment in SSc patients with isolated PAH.