Pulmonary Hypertension In Systemic Sclerosis Research Articles

Pulmonary Hypertension in Systemic Sclerosis.

Systemic sclerosis is a multisystem connective tissue disease that is associated with substantial morbidity and mortality. Visceral organ involvement is common in patients with systemic sclerosis and occurs independently of skin manifestations. Pulmonary hypertension (PH) is an important and prevalent complication of systemic sclerosis. The clinical classification of PH cohorts conditions with similar pathophysiological mechanisms into one of five groups. While patients with systemic sclerosis can manifest with a spectrum of pulmonary vascular disease, notable clinical groups include group 1 pulmonary arterial hypertension (PAH) associated with connective tissues disease, PAH with features of capillary/venous involvement, group 2 PH associated with left heart disease, and group 3 PH associated with interstitial lung disease. Considerable efforts have been made to advance screening methods for PH in systemic sclerosis including the DETECT and ASIG (Australian Scleroderma Interest Group) composite algorithms. Current guidelines recommend annual assessment of the risk of PAH as early recognition may result in attenuated hemodynamic impairment and improved survival. The treatment of PAH associated with systemic sclerosis requires a multidisciplinary team including a PH specialist and a rheumatologist to optimize immunomodulatory and PAH-specific therapies. Several potential biomarkers have been identified and there are several promising PAH therapies on the horizon such as the novel fusion protein sotatercept. This chapter provides an overview of PH in systemic sclerosis, with a specific focus on group 1 PAH.

Nailfold capillaroscopy and candidate-biomarker levels in systemic sclerosis-associated pulmonary hypertension: A cross-sectional study.

Pulmonary hypertension is one of the leading causes of death in systemic sclerosis. Early detection and treatment of pulmonary hypertension in systemic sclerosis is crucial. Nailfold capillaroscopy microscopy, vascular autoantibodies AT1R and ETAR, and several candidate-biomarkers have the potential to serve as noninvasive tools to identify systemic sclerosis patients at risk for developing pulmonary hypertension. Here, we explore the classifying potential of nailfold capillaroscopy microscopy characteristics and serum levels of selected candidate-biomarkers in a sample of systemic sclerosis patients with and without different forms of pulmonary hypertension. A total of 81 consecutive systemic sclerosis patients were included, 40 with systemic sclerosis pulmonary hypertension and 41 with no pulmonary hypertension. In each group, quantitative and qualitative nailfold capillaroscopy microscopy characteristics, vascular autoantibodies AT1R and ETAR, and serum levels of 24 soluble serum factors were determined. For evaluation of the nailfold capillaroscopy microscopy characteristics, linear regression analysis accounting for age, sex, and diffusing capacity of the lungs for carbon monoxide percentage predicted was used. Autoantibodies and soluble serum factor levels were compared using two-sample t test with equal variances. No statistically significant differences were observed in quantitative or qualitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibody ETAR and AT1R titer between systemic sclerosis-pulmonary hypertension and systemic sclerosis-no pulmonary hypertension. In contrast, several serum levels of soluble factors differed between groups: Endostatin, sVCAM, and VEGFD were increased, and CXCL4, sVEGFR2, and PDGF-AB/BB were decreased in systemic sclerosis-pulmonary hypertension. Random forest classification identified Endostatin and CXCL4 as the most predictive classifiers to distinguish systemic sclerosispulmonary hypertension from systemic sclerosis-no pulmonary hypertension. This study shows the potential for several soluble serum factors to distinguish systemic sclerosis-pulmonary hypertension from systemic sclerosis-no pulmonary hypertension. We found no classifying potential for qualitative or quantitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibodies.

Pulmonary hypertension in systemic sclerosis with usual interstitial pneumonia

Retrospective study comparing pulmonary hypertension risk in systemic sclerosis (SSc) and non-SSc interstitial lung disease patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Retrospective analysis of 144 interstitial lung disease patients, 53 SSc (32 UIP and 21 NSIP) and 91 non-SSc (47 UIP and 44 NSIP). Pulmonary hypertension was diagnosed as pulmonary systolic artery pressure (PAPs) > 25mmHg. All SSc and non-SSc patients with pulmonary hypertension were classified WHO Group 3. Pulmonary hypertension was identified in 21/32 (65.6%), 9/21 (42.8%), 14/47 (29.7%), and 28/44 (45.4%) SSc-UIP, SSc-NSIP, control-UIP, and control-NSIP groups, respectively. PAPs mean of SSc-UIP group was higher than control-UIP group (32.6 ± 9.8 vs 28.5 ± 6.6, p-value = 0.02). PAPs mean of SSc-NSIP group was lower than control-NSIP group (27.0 ± 7.1 vs 33.9 ± 8.8, p = 0.002). Frequency of patients with PAP > 25mmHg in SSc-UIP group was 60% higher in comparison to control-UIP (OR = 1.62, 95% CI 0.51-5.16) and SSc-NSIP (OR = 1.60, 95% CI 0.45-5.70) groups. Logistic regression analysis estimating the linear trend per ten-unit increase in PAPs levels demonstrated an increment for the SSc-UIP group compared to the control-UIP (OR = 2.64, 95% CI 1.25-5.58, p = 0.01) and the control-NSIP (OR = 6.34, 95% CI 2.82-14.3, p < 0.001) groups. The case-control study confirms that pulmonary hypertension is frequently found in SSc patients and demonstrates, for the first time, a significant increased risk of pulmonary hypertension among SSc-UIP patients.

Dynamic Prediction of Pulmonary Hypertension in Systemic Sclerosis Using Landmark Analysis.

Pulmonary hypertension (PH) is a serious complication of systemic sclerosis (SSc). In this study, we explored the prediction of short-term risk for PH using serial pulmonary function tests (PFTs) and other disease features. SSc patients in whom disease onset occurred ≥10 years prior to data retrieval and for whom autoantibody specificity and PFT data were available were included in this study. Mixed-effects modeling was used to describe changes in PFTs over time. Landmarking was utilized to include serial assessments and stratified Cox proportional hazards regression analysis with landmarks as strata was used to develop the PH prediction models. We analyzed data from 1,247 SSc patients, 16.3% of whom were male and 35.8% of whom had diffuse cutaneous SSc. Anticentromere, antitopoisomerase, and anti-RNA polymerase antibodies were observed in 29.8%, 22.0%, and 11.4% of patients, respectively, and PH developed in 13.6% of patients. Over time, diffusing capacity for carbon monoxide (DLco) and carbon monoxide transfer coefficient (Kco) declined in all SSc patients (up to 1.5% per year) but demonstrated much greater annual decline (up to 4.5% and 4.8%, respectively) in the 5-7 years preceding PH diagnosis. Comparisons between multivariable models including either DLco, Kco, or forced vital capacity (FVC)/DLco ratio, demonstrated that both absolute values and change over the preceding year in those measurements were strongly associated with the risk of PH (hazard ratio [HR] 0.93 and 0.76 for Kco and its change; HR 0.90 and 0.96 for DLco and its change; and HR 1.08 and 2.01 for FVC/DLco ratio and its change; P < 0.001 for all). The Kco-based model had the greatest discriminating ability (Harrell's C-statistic 0.903). Our findings strongly support the importance of PFT trends over time in identifying patients at risk of developing PH.

A Multimodal Prediction Model for Diagnosing Pulmonary Hypertension in Systemic Sclerosis.

Diagnosis of pulmonary hypertension (PH) in systemic sclerosis (SSc) requires an invasive right heart catheterization (RHC), often based on an elevated estimated pulmonary artery systolic pressure on screening echocardiography. However, because of the poor specificity of echocardiography, a greater number of patients undergo RHC than necessary, exposing patients to potentially avoidable complication risks. The development of improved prediction models for PH in SSc may inform decision-making for RHC in these patients. We conducted a retrospective study of 130 patients with SSc; 66 (50.8%) were diagnosed with PH by RHC. We used data from pulmonary function testing, electrocardiography, echocardiography, and computed tomography to identify and compare the performance characteristics of 3 models predicting the presence of PH: 1) random forest, 2) classification and regression tree, and 3) logistic regression. For each model, we generated receiver operating curves and calculated sensitivity and specificity. We internally validated models using a train-test split of the data. The random forest model performed best with an area under the curve of 0.92 (95% confidence interval [95% CI] 0.83-1.00), sensitivity of 0.95 (95% CI 0.75-1.00), and specificity of 0.80 (95% CI 0.56-0.94). The 2 most important variables in our random forest model were pulmonary artery diameter on chest computed tomography and diffusing capacity for carbon monoxide on pulmonary function testing. In patients with SSc, a random forest model can aid in the detection of PH with high sensitivity and specificity and may allow for better patient selection for RHC, thereby minimizing patient risk.

Combined cardiopulmonary test and exercise Doppler echocardiography in systemic sclerosis

Abstract Background Cardiopulmonary exercise test (CPET) and exercise Doppler echocardiography (EDE) may be useful for the early detection of pulmonary hypertension in systemic sclerosis (SSc) Aim To assess the feasibility of CPET and EDE in detecting early changes in gas exchange and/or pulmonary hemodynamics in SSc Methods From 2016 to 2021, we evaluated 19 SSc patients (Group 1, age = 52.58±11.27, women 17 (89.5%)), and age 32.10±6.67, men 17 (89.4%) matched healthy controls (Group 2). Simultaneous CPET and EDE were performed. With CPET, we assessed peak oxygen uptake (VO2), peak respiratory quotient (RQ), respiratory equivalent ratio for carbonic gas (VE/VCO2), and maximal respiratory equivalent divided by maximal ventilatory ventilation (V̇E Max/VVM). With EDE, we assessed tricuspid regurgitant velocity (TRV) jet and pulmonary flow acceleration time (ACT) to derive systolic pulmonary arterial pressure (SPAP). Results Exercise duration was similar in the 2 groups (Group 1 = 9.2±2.93 vs Group 2 = 10.14±1.78 minutes). Among CPET parameters, SSc patients showed lower peak VO2 (Group 1 = 1.23±0.55 vs Group 2 = 2.45±0.7, p&amp;lt;0.001), similar RQ (1.10±0.10 vs 1.17±0.09;. p=0.036), VE/VCO2 (Group 1 = 31.90±3.65 vs Group 2 = 23.79±2.64, p&amp;lt;0.001) and V̇E Max/VVM (Group 1 = 1.93±0.60 vs Group 2 = 1.76±0.36, p=NS). With EDE, feasibility at peak stress was low for TRV (Group 1 = 42% vs Group 2 = 58%, p=NS), moderate for ACT (Group 1 = 53% vs Group 2 = 78%, p=NS) and high when at least one was technically adequate (Group 1 = 73% vs Group 2 = 100%, p&amp;lt;0.001). Rest TRV (Group 1 = 2.48±0.14 vs Group 2 = 2.08±0.12 m/s, p=0.033) and ACT (Group 1 = 100.14±10.63 vs Group 2 = 108.86±6.38 ms, p=0.482) showed similar values in the 2 groups (será que ficou similar?). During stress, TRV increased more markedly in SSc (Group 1 = 3.33±0.32 vs Group 2 = 2.34±0.09 m/s, p=0.004) and ACT decreased (Group 1 = 81.9±6.54 vs 73.39±5.18 ms, p=0.304), with estimated peak SPAP higher in SSc (Group 1 = 53.34±7.88 vs Group 2 = 43.33±5.49, p&amp;lt;0.001): see figure. Conclusion CPET and EDE offer complementary information on gas exchange and pulmonary hemodynamics in SSc and can detect early alterations missed by resting assessment. The success rate of EDE increases significantly with the combination of TRV and ACT. Funding Acknowledgement Type of funding sources: None.

Prevalence and clinical correlates of pulmonary hypertension in systemic sclerosis

Development of pulmonary artery hypertension (PAH) worsens prognosis of systemic sclerosis (SSc) and can be either isolated precapillary PAH or secondary to interstitial lung disease (ILD). Early diagnosis is of crucial importance. There is scarcity of data on PAH in patients with SSc in Bangladesh. The objective if the study is to determine the Prevalence and clinical correlates of pulmonary hypertension in systemic sclerosis. Clinical and functional characteristics of 100 patients of systemic sclerosis were studied and they were evaluated by echocardiography to detect pulmonary artery hypertension. Our objective was to study the prevalence and the clinical correlation of PAH in SSc. PAH was found in 29% patients on echocardiography. Prevalence tend to increase with age of onset and duration of disease. However, it did not differ significantly between patients with limited cutaneous SSc (lcSSc) and patients with diffuse cutaneous SSc (dcSSc). On binary logistic regression analysis, none of the studied variables had any independent influence on development of PAH. PAH in SSc occurs in a remarkable proportion (29%) of patients without any ominous signs in early stages. Non-invasive screening of patients with SSc for PAH will help in early diagnosis and appropriate timely therapeutic intervention before significant end-organ damage occurs.

C15. Biventricular Heart Failure and Pulmonary Hypertension in Systemic Sclerosis: a rare and unusual case report

Abstract Backgrounds Systemic sclerosis (SSc), chronic multisystem autoimmune disease, characterized by excessive fibrosis and vascular endothelial dysfunction. Cardiovascular involvement may be induced by various pathways, either primary or secondary to pulmonary hypertension or renal involvement. Case Summary A 46 years old woman presented to emergency department with cold, dark purplish ulcers in fingertips with progressive worsening pain in upper extremities, claudication intermitten, and dyspneu since 4 months ago. She had a mask-like facial, shiny skin, microstomia, restricted mouth opening, calcinosis cutis, Raynauds phenomenon, and sclerodactyly. There were pansystolic murmur grade III/6 in tricuspid area, and rales in basal lungs. ECG showed sinus rhythm with fragmented QRS, poor R-wave progression. Chest X-Ray revealed pancardiomegaly with pleural effusion and HRCT thorax revealed interstitial lungs disease. The laboratory revealed leucocytosis, increase D-dimer (870 ug/L), negative ANA and ds-DNA test, positive anti SCl test. Echocardiography showed biventricular dysfunction with decreased LVEF 37% (Teichz) and TAPSE 10 mm, RA RV dilatation, severe TR with high probability for PH. Extremities Doppler showed normal arteries and veins system. These findings indicates that primary and secondary cardiac involvement in SSc. Heart failure, pulmonary hypertension, and cyclophosphamide medication were administered Discussion Primary cardiac involvement, a direct consequence of SSc, may manifest as fibrosis of the myocardial, conduction system, pericardial and, valvular disease. Furthermore, a secondary phenomenon due to pulmonary arterial hypertension (PAH), and kidney pathology. Though the burden remains low, it may worsen the outcome, consequently, all patients with SSc should undergo screening.

C15. Biventricular Heart Failure and Pulmonary Hypertension in Systemic Sclerosis: a rare and unusual case report

Abstract Backgrounds Systemic sclerosis (SSc), chronic multisystem autoimmune disease, characterized by excessive fibrosis and vascular endothelial dysfunction. Cardiovascular involvement may be induced by various pathways, either primary or secondary to pulmonary hypertension or renal involvement. Case Summary A 46 years old woman presented to emergency department with cold, dark purplish ulcers in fingertips with progressive worsening pain in upper extremities, claudication intermitten, and dyspneu since 4 months ago. She had a mask-like facial, shiny skin, microstomia, restricted mouth opening, calcinosis cutis, Raynauds phenomenon, and sclerodactyly. There were pansystolic murmur grade III/6 in tricuspid area, and rales in basal lungs. ECG showed sinus rhythm with fragmented QRS, poor R-wave progression. Chest X-Ray revealed pancardiomegaly with pleural effusion and HRCT thorax revealed interstitial lungs disease. The laboratory revealed leucocytosis, increase D-dimer (870 ug/L), negative ANA and ds-DNA test, positive anti SCl test. Echocardiography showed biventricular dysfunction with decreased LVEF 37% (Teichz) and TAPSE 10 mm, RA RV dilatation, severe TR with high probability for PH. Extremities Doppler showed normal arteries and veins system. These findings indicates that primary and secondary cardiac involvement in SSc. Heart failure, pulmonary hypertension, and cyclophosphamide medication were administered Discussion Primary cardiac involvement, a direct consequence of SSc, may manifest as fibrosis of the myocardial, conduction system, pericardial and, valvular disease. Furthermore, a secondary phenomenon due to pulmonary arterial hypertension (PAH), and kidney pathology. Though the burden remains low, it may worsen the outcome, consequently, all patients with SSc should undergo screening.

Pulmonary hypertension in systemic sclerosis: diagnosis by systematic screening and prognosis after three years follow-up

BackgroundSystemic sclerosis (SSc) is a rare disease, and the presence of pulmonary hypertension can be a determining factor in prognosis. The aim of this study was to evaluate the diagnosis, profile, and prognosis of systemic sclerosis pulmonary hypertension (SSc-PH) diagnosed by systematic screening in a Brazilian population.MethodsA cohort of SSc patients underwent systematic screening for SSc-PH. Patients were referred for right heart catheterization (RHC) according to transthoracic echocardiogram or a combination of diagnostic tools. The clinical, immunological, and hemodynamic features and prognosis after 3 years were evaluated.ResultsTwenty patients underwent RHC. SSc pulmonary arterial hypertension (SSc-PAH) was the most common group of SSc-PH. These patients had long disease duration, high urate levels and highly elevated mean pulmonary arterial pressure (mPAP) and peripheral vascular resistance (PVR) on hemodynamics. Patients with mPAP > 20– < 25 mmHg had hemodynamic features of intermediate disease. Patients with SSc-PH associated to interstitial lung disease (SSc-ILD-PH) had signs of vasculopathy on hemodynamics. In patients with no-SSc-PH, the survival at 1, 2, and 3 years was 96%, 92% and 92%, respectively and in patients with SSc-PH it was 86.7%, 60% and 53.3%, respectively.ConclusionsPatients identified with SSc-PAH and SSc-ILD-PH in our screening had severe clinical and hemodynamic features. Mortality remains high in SSc-PH but was more related to Bo-PAH and SSc-ILD-PH, while in SSc-PAH, the prognosis was better. Trial registration: Current Controlled Trials ISRCTN 72968188, July 8th, 2021. Retrospectively registered.

Significance of asymptomatic hyperuricemia in ankylosing spondylitis

Over the past decades, there has been an increase in the incidence of asymptomatic hyperuricemia (AHU), which includes an increased level (&gt;360 μmol/L) of uric acid (UA) in the blood serum of patients with no clinical manifestations of gout. AHU is reported in various rheumatic diseases, mainly in osteoarthritis, in which AHU is one of the manifestations of the metabolic syndrome. There is relationship between AHU and pulmonary hypertension in systemic sclerosis, arterial hypertension (AH) in men with seronegative rheumatoid arthritis, extensive cutaneous psoriasis and metabolic disorders in psoriatic arthritis. There are almost no data on AHU in ankylosing spondylitis (AS), which served objective for this work.Objective: to assess the association of AHU with AS duration and activity and the presence of comorbid diseases.Patients and methods. A retrospective analysis of 48 medical histories of patients with diagnosed AS, who were treated in V.A. Nasonova Research Institute of Rheumatology from 2015 to 2019 years, whose serum UA level was &gt;360 μmol/L.Results and discussion. More than half of patients with AS and AHU were overweight, 21% were obese. AH was diagnosed in 43.7% of patients. Stage II–III chronic kidney disease was detected in 16.7% of patients, urolithiasis – in 18.8%. 4 (8.3%) patients had diabetes mellitus. The serum UA level in patients with AS was 422.0 ± 61.6 μmol/L. In patients with AS, an association between AHU and age, duration and disease activity was noted. There was no statistically significant rela- tionship between HG and blood glucose, cholesterol, creatinine levels, body mass index. Correlation analysis revealed a statistically significant relationship between the glomerular filtration rate (GFR) and the age of patients (r=-0.54, p&lt;0.001), the duration of the disease (r=-0.40, p&lt;0.05), cholesterol level (r=-0.48, p=0.01), UA level (r=-0.45, p=0.03) and blood pressure (r=-0.54, p&lt;0.001). There was no association between disease activity and GFR (p&gt;0.05).Conclusion. In AS, an association between an increased level of UA in the blood serum and the duration and activity of the disease, and patient's age, was established.

Pulmonary Hypertension Phenotypes in Systemic Sclerosis: The Right Diagnosis for the Right Treatment.

Systemic sclerosis is an auto-immune disease characterized by skin involvement that often affects multiple organ systems. Pulmonary hypertension is a common finding that can significantly impact prognosis. Molecular pathophysiological mechanisms underlying pulmonary hypertension in systemic sclerosis can be extremely heterogeneous, leading to distinct clinical phenotypes. In addition, different causes of pulmonary hypertension may overlap within the same patient. Since pulmonary hypertension treatment is very different for each phenotype, it is fundamental to perform an adequate diagnostic work-up to properly and promptly identify the prevalent mechanism underlying pulmonary hypertension in order to start the right therapies. When pulmonary hypertension is caused by a primary vasculopathy of the small pulmonary arteries, treatment with pulmonary vasodilators, often in an initial double-combination regimen, is indicated, aimed at reducing the mortality risk profile. In this review, we describe the different clinical phenotypes of pulmonary hypertension in the scleroderma population and discuss the utility of clinical tools to identify the presence of pulmonary vascular disease. Furthermore, we focus on systemic sclerosis-associated pulmonary arterial hypertension, highlighting the advances in the knowledge of right ventricular dysfunction in this setting and the latest updates in terms of treatment with pulmonary vasodilator drugs.

Drug repurposing in Raynaud's phenomenon through adverse event signature matching in the World Health Organization pharmacovigilance database.

Several pharmacological treatments are recommended for Raynaud's phenomenon (RP) secondary to systemic sclerosis, but they only have modest efficacy. A way to efficiently identify new drugs is drug repurposing, which can be based on signature matching. The signature could be derived from chemical structures, pharmacological affinity or adverse event profiles. We propose to use the World Health Organization (WHO) pharmacovigilance database to generate repositioning hypotheses for treatments of RP through adverse event signature matching. We first screened all drugs associated with at least 1 case of erythromelalgia, an adverse effect opposite to RP. In parallel, to define the adverse event signature of drugs recommended in secondary RP from the WHO pharmacovigilance database, we selected the 14 most representative adverse drug reactions (ADRs). Lastly, we performed a hierarchical cluster analysis to identify drugs with similar ADR signature to vasodilatory drugs used in RP. In total, 179 drugs were associated with erythromelalgia; they were related to 860 334 adverse events representative of RP drugs in the WHO pharmacovigilance database. Hierarchical cluster analysis allowed identification of 6 clusters. The most stable cluster contained 7 drugs, among which 5 are recommended in secondary RP, or pertain to the same drug class: epoprostenol, nifedipine, nicardipine, lacidipine and israpidine. The 2 remaining drugs were alemtuzumab and fumaric acid. Our ADR signature matching approach suggests that alemtuzumab and fumaric acid could be effective treatments of secondary RP. The latter is currently being investigated as a treatment of pulmonary hypertension in systemic sclerosis.

Management of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare and complex immune-mediated connective tissue disease characterized by multi-organ fibrosis and dysfunction. Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a leading cause of death in this population. Pulmonary arterial hypertension (PAH) can coexist with other forms of pulmonary hypertension in SSc, including pulmonary hypertension related to left heart disease, interstitial lung disease, chronic thromboembolism and pulmonary venous occlusive disease, which further complicates diagnosis and management. Available pulmonary arterial hypertension therapies target the nitric oxide, endothelin and prostacyclin pathways. These therapies have been studied in SSc-PAH in addition to idiopathic PAH, often with different treatment responses. In this article, we discuss the management as well as the treatment options for patients with SSc-PAH.

A review of exercise pulmonary hypertension in systemic sclerosis.

In general, pulmonary vascular disease has important negative prognostic implications, regardless of the associated condition or underlying mechanism. In this regard, systemic sclerosis is of particular interest as it is the most common connective tissue disease associated with pulmonary hypertension, and a well-recognized at-risk population. In the setting of systemic sclerosis and unexplained dyspnea, the concept of using exercise to probe for underlying pulmonary vascular disease has acquired significant interest. In theory, a diagnosis of systemic sclerosis-associated exercise pulmonary hypertension may allow for earlier therapeutic intervention and a favorable alteration in the natural history of the pulmonary vascular disease. In the context of underlying systemic sclerosis, the purpose of this article is to provide a comprehensive review of the evolving definition of exercise pulmonary hypertension, the current role and methodologies for non-invasive and invasive exercise testing, and the importance of the right ventricle.

Pulmonary arterial hypertension in systemic sclerosis: Diagnosis and treatment according to the European Society of Cardiology and European Respiratory Society 2015 guidelines.

Scleroderma (systemic sclerosis) is an autoimmune connective tissue disease which presents endothelial dysfunction and fibroblast dysregulation, resulting in vascular and fibrotic disorders. Pulmonary hypertension is frequent in patients with systemic sclerosis: the natural evolution of the disease can induce the development of different forms of pulmonary hypertension, representing one of the main causes of death. Among the different forms of pulmonary hypertension in systemic sclerosis, pulmonary arterial hypertension is the most frequent one (rate of occurrence is estimated between 7% and 12%). This pulmonary vascular complication should be treated with a combination of drugs that is able to counteract endothelial dysfunction, antagonizing the endothelin-1 system and replacing prostaglandin I2 and nitric oxide activity. A correct diagnosis is mandatory, because it is possible only for pulmonary arterial hypertension to use specific drugs that are able to control the symptomatic condition and the evolution of the disease. According to the most recent guidelines, for the patients with systemic sclerosis, also without pulmonary hypertension symptoms, echocardiography screening for the detection of pulmonary hypertension is recommended. Pulmonary arterial hypertension screening programs in systemic sclerosis patients is able to identify milder forms of the disease, allowing earlier management and better long-term outcome.

Risk Factors for Mortality and Cardiopulmonary Hospitalization in Systemic Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry.

We sought to identify predictors of mortality and cardiopulmonary hospitalizations in patients at risk for pulmonary hypertension (PH) and enrolled in PHAROS, a prospective cohort study to investigate the natural history of PH in systemic sclerosis (SSc). The at-risk population for PH was defined by the following entry criteria: echocardiogram systolic pulmonary arterial pressure > 40 mmHg, or DLCO < 55% predicted or ratio of % forced vital capacity/%DLCO > 1.6, measured by pulmonary function testing. Baseline clinical measures were evaluated as predictors of hospitalization and death between 2005 and 2014. Cox proportional hazards models were censored at date of PH onset or latest study visit and adjusted for age, sex, race, and disease duration. Of the 236 at-risk subjects who were followed for a median of 4 years (range 0.4-8.5 yrs), 35 developed PH after entering PHAROS (reclassified as PH group). In the at-risk group, higher mortality was strongly associated with male sex, low %DLCO, exercise oxygen desaturation, anemia, abnormal dyspnea scores, and baseline pericardial effusion. Risks for cardiopulmonary hospitalization were associated with increased dyspnea and pericardial effusions, although PH patients with DLCO < 50% had the highest risk of cardiopulmonary hospitalizations. Risk factors for poor outcome in patients with SSc who are at risk for PH were similar to others with SSc-PH and SSc-pulmonary arterial hypertension, including male sex, DLCO < 50%, exercise oxygen desaturation, and pericardial effusions. This group should undergo right heart catheterization and receive appropriate intervention if PH is confirmed.

Phenotyping pulmonary hypertension in systemic sclerosis: a moving target.

Phenotyping pulmonary hypertension in systemic sclerosis: a moving target.

New insights into the recognition, classification and management of systemic sclerosis-associated pulmonary hypertension.

Pulmonary hypertension is a common complication of systemic sclerosis (SSc), and remains a leading cause of morbidity and mortality. We will review recent developments in the recognition, classification and treatment of pulmonary hypertension in SSc. Advances in screening for pulmonary arterial hypertension (PAH) and use of exercise haemodynamics may help to identify pulmonary vascular disease earlier in SSc. Recent studies have led to changes in recommendations for adjunct therapy and selection of pulmonary vasodilators for the treatment of SSc-associated PAH. Recent advances in the diagnosis, classification and management of pulmonary hypertension in SSc have continued to improve our understanding of this challenging disease. Ongoing investigation in the pathogenesis of this disease will afford the opportunity to develop targeted therapies to improve outcomes for SSc patients with pulmonary hypertension.

Lung Density and Pulmonary Artery Diameter are Predictors of Pulmonary Hypertension in Systemic Sclerosis.

The aim was to evaluate computed tomography (CT)-measured pulmonary artery diameter (PAD) and lung density as predictors of pulmonary hypertension (PH) in subjects with systemic sclerosis (SSc). We compared these PAD values with normal values and between SSc subgroups with PH and/or interstitial lung disease (ILD). We investigated whether PAD predicts PH and whether lung densitometry, by using the 85th percentile density value (Perc85) as a measure for ILD, can predict PH. PAD and Perc85 were measured in axial CT scans and compared between 54 SSc and 76 control subjects. Four SSc subgroups were defined on the basis of PH (systolic PA pressure ≥35 mm Hg) and/or ILD (fibrosis score ≥7): PH-/ILD-, PH-/ILD+, PH+/ILD-, and PH+/ILD+. The association of PAD with age, body mass index, Perc85, lung function, and hemodynamic measures was investigated using univariate correlation along with the predictive value of these measures with respect to PH. PAD in SSc was larger than that in controls (30.1±4.9 vs. 26.9±2.7 mm, P<0.001). PH+ patients showed increased PAD compared with PH- patients (34.2±4.2 vs. 28.6±4.3 mm, P<0.001), where PH+/ILD+ subjects showed the widest diameter (34.6±4.1 mm). In SSc patients, hemodynamic measures, age, body mass index, Perc85, and lung function correlated with PAD. PAD was best explained by Perc85, together with age (R=0.358). PAD best predicted PH (AUC, 0.877; P<0.001), and PAD≥30.7 mm showed 80% sensitivity and 87% specificity. Perc85 also predicted PH (AUC, 0.733; P=0.024). In subjects with SSc, lung density and PAD are CT markers, each with predictive value for PH.