Systemic Sclerosis-related Pulmonary Arterial Hypertension Research Articles

Towards a Better Prognosis in Patients with Systemic Sclerosis-Related Pulmonary Arterial Hypertension: Recent Developments and Perspectives.

Precapillary pulmonary hypertension (PH) is a significant complication of systemic sclerosis (SSc). It represents one of the leading causes of morbidity and mortality, correlating with a significantly dismal prognosis and quality of life. Despite advancements in the management of patients with pulmonary arterial hypertension associated with SSc (SSc-PAH), no significant improvement has been reported in survival of patients with precapillary SSc-PH associated with extensive lung parenchyma disease. International expert consensus and guidelines for the management of PH recommend annual screening of SSc patients for early detection of pre-capillary PH. The implementation of screening algorithms capable of identifying patients with a high likelihood of developing PH could help limit unnecessary right-heart catheterization procedures and prevent significant delay in diagnosis. Furthermore, early initiation of up-front combination targeted therapy in patients with PAH has shown increase in survival rates, indicating that timely and aggressive medical therapy is key for stabilizing and even improving functional class, hemodynamic parameters and 6 min walking distance (6MWD) in this population. Further research is warranted into the benefit of PAH-targeted therapies in patients with PH associated with lung disease. Lastly, we discuss the potential role of immunosuppression using biologic agents in the therapeutic management of precapillary PH in SSc patients.

Peripheral microvascular function is linked to cardiac involvement on cardiovascular magnetic resonance in systemic sclerosis-related pulmonary arterial hypertension.

Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation, and fibrosis, and carries one of the worst prognoses if patients also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, patients with SSc-PAH demonstrate disproportionately high mortality, presumably due to cardiac involvement. In this cross-sectional study, the relationship between cardiac involvement revealed by cardiovascular magnetic resonance (CMR) and systemic microvascular disease severity measured with nailfold capillaromicroscopy (NCM) in patients with SSc-PAH is evaluated and compared with patients with idiopathic PAH (IPAH). Patients with SSc-PAH and IPAH underwent CMR, echocardiography, and NCM with post-occlusive reactivity hyperaemia (PORH) testing on the same day. CMR imaging included T2 (oedema), native, and post-contrast T1 mapping to measure the extracellular volume fraction (ECV, fibrosis) and adenosine-stress-perfusion imaging measuring the relative myocardial upslope (microvascular coronary perfusion). Measures of peripheral microvascular function were related to CMR indices of oedema, fibrosis, and myocardial perfusion. SSc-PAH patients (n = 20) had higher T2 values and a trend towards a higher ECV, compared with IPAH patients (n = 5), and a lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH. NCD correlated with ECV and T2 (r = -0.443 and -0.464, respectively, P < 0.05 for both) and with markers of diastolic dysfunction on echocardiography. PORH testing, but not NCD, correlated with the relative myocardial upslope (r = 0.421, P < 0.05). SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared with IPAH patients. These markers correlated well with peripheral microvascular dysfunction, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may contribute to the disproportionate high mortality in SSc-PAH.

Kiosk 3R-FA-03 - Peripheral Microvascular Function Is Linked to Cardiac Involvement on CMR in Systemic Sclerosis-related Pulmonary Arterial Hypertension

Kiosk 3R-FA-03 - Peripheral Microvascular Function Is Linked to Cardiac Involvement on CMR in Systemic Sclerosis-related Pulmonary Arterial Hypertension

Peripheral microvascular function is linked to cardiac involvement on CMR in systemic sclerosis-related pulmonary arterial hypertension patients

Abstract Background Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation and fibrosis, and carries one of the worst prognosis in patients who also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, SSc-PAH patients demonstrate disproportionately high morbidity and mortality, presumably due to cardiac involvement. Purpose To determine the pathophysiology of cardiac involvement in SSc, cardiovascular magnetic resonance (CMR) measures of perfusion, inflammation and fibrosis were compared between SSc-PAH and idiopathic PAH (IPAH) patients. In addition, the correlation between myocardial involvement on CMR and known markers of peripheral microvascular function was assessed. Methods Consecutive patients with SSc-PAH and IPAH of similar age and gender, consecutively underwent CMR imaging, and nailfold capillaroscopy (NC) with post-occlusive reactivity hyperaemia-test (PORH-test). CMR imaging included T2 mapping (inflammation), pre- and postcontrast T1 mapping to calculate the extracellular volume fraction (ECV, fibrosis), and adenosine-stress perfusion imaging to measure the relative myocardial upslope (microvascular perfusion), all measurements were performed on the left ventricle. These CMR markers were related to peripheral microvascular function by NC and PORH-test. Results Twenty SSc-PAH patients (71 [62–77] years, 14% male) and 5 IPAH patients (69 [47–77] years, 20% male) were included. SSc-PAH patients had higher ECV and T2 values than IPAH patients. NC showed lower average capillary density and reduced recruitment of capillaries after PORH in SSc-PAH patients, corresponding to impaired microvascular structure and function. Both higher ECV and T2 values correlated with lower average capillary density (r=−0.454 and −0.583, respectively, p&amp;lt;0.05 for both). Additionally, higher T2 values and lower relative myocardial upslope correlated with worse peripheral microvascular function measured by PORH-test (r=−0.471 and r=0.421, respectively, p&amp;lt;0.05 for both). Conclusion SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared to IPAH patients. These markers correlated well with worse peripheral microvascular function, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may have important therapeutic implications, for which future studies are warranted evaluating the role of anti-inflammatory/anti-fibrotic therapy. Funding Acknowledgement Type of funding sources: None.

Combination therapy in systemic sclerosis-related pulmonary arterial hypertension: survival benefits at high cost

Combination therapy in systemic sclerosis-related pulmonary arterial hypertension: survival benefits at high cost

Cost-Effectiveness of Combination Therapy for Patients With Systemic Sclerosis-Related Pulmonary Arterial Hypertension.

BackgroundTo evaluate the cost‐effectiveness of combination pulmonary arterial hypertension specific therapy in systemic sclerosis–related PAH.Methods and ResultsHealth outcomes and costs were captured through data linkage. Health utility was derived from Medical Outcomes Study Short Form‐36 scores. A probabilistic discrete‐time model was developed to simulate lifetime changes in costs and health utility. Mortality was predicted using a Gompertz parametric survival model. For both treatment arms, the simulations were started using the same cohort of 10 000 patients. Probabilistic sensitivity analysis was performed using the Monte Carlo simulation with 1000 sets of sampled parameter values. Of 143 patients with systemic sclerosis–related pulmonary arterial hypertension, 89 were on monotherapy and 54 on combination therapy. Mean simulated costs per patient per year in monotherapy and combination therapy groups were AU$23 411 (US$16 080) and AU$29 129 (US$19 982), respectively. Mean life years and quality‐adjusted life years from pulmonary arterial hypertension diagnosis to death of patients receiving monotherapy were 7.1 and 3.0, respectively, and of those receiving combination therapy were 9.2 and 3.9, respectively. Incremental costs per life year and quality‐adjusted life year gained of combination therapy compared with monotherapy were AU$47 989 (US$32 920) and AU$113 823 (US$78 082), respectively. At a willingness‐to‐pay threshold of AU$102 000 (US$69 972) per life year gained, and of AU$177 222 (US$121 574) per quality‐adjusted life year gained, the probability of combination therapy being cost‐effective was 0.95.ConclusionsThe incremental cost per quality‐adjusted life year gained of combination therapy compared with monotherapy was substantial in the base case analysis. Given the fatal prognosis of systemic sclerosis–related pulmonary arterial hypertension and the incremental cost per life year of AU$47 989 (US$32 920), combination therapy could be considered cost‐effective in systemic sclerosis–related pulmonary arterial hypertension.

Candidate Genes Identified in Systemic Sclerosis-Related Pulmonary Arterial Hypertension Were Associated with Immunity, Inflammation, and Cytokines.

Background Pulmonary complications of systemic sclerosis (SSc), including pulmonary arterial hypertension (PAH), are the leading causes of patient death. However, the precise molecular mechanisms of its etiology are unclear. This study's objective was to identify the candidate genes involved in the progression of SSc-PAH and investigate the genes' function. Methods The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers. Then, gene ontology analysis was performed. A second dataset was used, GSE19617, to validate the hub genes. The verified hub genes' potential function was further explored using gene set enrichment analysis (GSEA). Results Through average link-level clustering, a total of seven modules were classified. A total of 938 hub genes were identified in the key module, and the key module's function mainly enriched was related to chemokine activities. Subsequently, four candidate genes, BTG3, CCR2, RAB10, and TMEM60, were filtered. The expression levels of these four hub genes were consistent in the GSE19617 and GSE33463 datasets. We plotted the ROC curve of the hub genes (all AUC > 0.70). Furthermore, the results of the GSEA for hub genes were correlated with complement and inflammatory responses. Conclusions The hub genes (BTG3, CCR2, RAB10, and TMEM60) performed well in distinguishing the SSc-PAH patients from controls, and some biological functions, related to immunity, inflammation, and cytokines, might pave the way for follow-up studies on the diagnosis and treatment of SSc-PAH.

Trends in systemic sclerosis and systemic sclerosis-related pulmonary arterial hypertension mortality in the USA.

There are limited data nationwide on the burden of systemic sclerosis (SSc)-related mortality. We aimed to determine recent trends in SSc and SSc-related pulmonary arterial hypertension (PAH) mortality overall and across population subgroups.Using death certificate data from the National Center for Health Statistics, we computed the age-adjusted mortality rates of SSc and SSc-SSc−PAH, a lethal prevailing complication, across demographic groups, geographic regions and comorbid cardiorespiratory conditions, and used Joinpoint regression analysis to calculate the average annual percentage change (APC) in mortality.From 2003 to 2016, 25 175 death records contained a code for SSc. Decedents were predominantly female (81%) and white (73%), with an average age of 66±14 years. The age-adjusted mortality rate decreased by 3% per year from 6.6 in 2003 to 4.3 per 1 000 000 population in 2016. Also, a decreasing trend was found when SSc was stratified by age, sex, race and geographic region. The prevalence of PAH was 23%. The odds of PAH were highest in female and black decedents, and in decedents with concomitant pulmonary embolism, cardiomyopathy and interstitial lung disease (ILD). SSc−PAH mortality remained stable from 2003 to 2008 then decreased by 3% per year from 2008 to 2016. In decedents with SSc−PAH, among all concomitant comorbidities, the mortality rate associated with ILD had the highest increase (average APC 6%, 95% CI 2%−10%).The mortality rate from SSc decreased from 2003 to 2016. Decreases in mortality rates were similar across demographic groups and geographic regions. SSc−PAH-related mortality remained stable. The death rate for SSc−ILD and concomitant PAH increased during this period.

Pulmonary arterial hypertension and atrial arrhythmias: incidence, risk factors, and clinical impact.

Atrial arrhythmia (AA) occurrence in pulmonary arterial hypertension (PAH) may determine clinical deterioration and affect prognosis. In this study we assessed AA incidence in idiopathic (IPAH) and systemic sclerosis related PAH (SSc-PAH) and evaluated risk factors, management, and impact on mortality. We collected baseline data from consecutive IPAH or SSc-PAH patients prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and July 2016. During follow-up AA onset, treatment, and outcome were recorded. Among 317 patients (201 SSc-PAH, 116 IPAH), 42 developed AA (19 atrial fibrillation, 10 flutter-fibrillation, 9 atrial flutter, and 4 atrial ectopic tachycardia) with a 13.2% cumulative incidence. Most events were associated with hospitalization (90.5%). Electrical or pharmacological cardioversion was attempted in most cases. Patients with AA had higher right atrial pressure, pulmonary wedge pressure (P < 0.005), NT-proBNP (P < 0.05), and thyroid disease prevalence (P < 0.005). Higher mortality was observed in patients with AA, though not statistically significant (LogRank P = 0.323). Similar long-term mortality between IPAH with AA and SSc-PAH without AA was observed (LogRank P = 0.098). SSc-PAH with AA had the worst prognosis. In PAH patients AA occurrence is a matter of significant concern. Therapeutic strategies aimed at restoring sinus rhythm may represent an important goal.

Abstract 21027: Prognostic Evaluation and Risk Assessment in Scleroderma Patients With Newly Diagnosed Pulmonary Arterial Hypertension

Introduction: Systemic sclerosis related pulmonary arterial hypertension (SScPAH) is characterized by a worse prognosis in comparison to idiopathic pulmonary arterial hypertension (IPAH). The estimated mortality risk reported in the current European guidelines for pulmonary hypertension has been evaluated mostly in IPAH patients. The aim of this study was to explore the ability of the risk assessment proposed in the guidelines to predict long-term mortality in SScPAH patients. Methods: The study population constituted patients diagnosed with SScPAH and prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Program from 2000-2016. Patients with assessment of WHO functional class, 6-minute walking distance (6MWD), and right heart catheterization measurements at diagnosis were included in the analysis. A Cox proportional hazards model was used to examine the adjusted hazard ratio (HR) of mortality for each of the following four low-risk criteria: WHO functional class I-II, 6MWD &gt;440m, right atrial pressure &lt;8mmHg, and cardiac index ≥2.5L/min/m 2 . A Kaplan-Meier curve was plotted to describe overall survival at 5 years. Results: 151 patients (mean age 61.2, 84.8% female) were included in the analysis. Over a mean follow-up period of 4.9 years, 87 patients (57.6%) died. In Cox proportional hazards multivariate analysis, the HR (95%CI) of mortality compared to the presence of no low-risk criteria was 0.65 for one criterion (0.37-1.15), 0.34 for two (0.17-0.68), 0.16 for three (0.06-0.44), and 0.10 for four (0.01-0.78). Figure 1 describes the 5-year survival according to the number of criteria. Conclusion: Our study highlights that only a small proportion of SScPAH patients are diagnosed at an early stage of PAH disease, suggesting the need of more intense PAH screening programs for this population. Current guidelines for risk assessment in IPAH patients can also be helpful in SScPAH patients, particularly in identifying patients at higher risk of mortality.

Nailfold capillaroscopic changes in patients with idiopathic pulmonary arterial hypertension and systemic sclerosis-related pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in systemic sclerosis (SSc). Lung microvascular changes can play a role in the pathogenesis of idiopathic PAH (IPAH) also. The aim of this study is to investigate the presence of capillaroscopic abnormalities in patients with IPAH and to evaluate the differences in capillary nailfold changes between patients with IPAH and patients with SSc with and without PAH. Methods39 SSc patients (19 with PAH – SSc-PAH and 20 without – SSc-noPAH), 21 subjects with IPAH and 20 healthy subjects were recruited. PAH was diagnosed by right heart catheterization. Nailfold videocapillaroscopy was performed (NVC) in all recruited subjects; capillary quantitative parameters (loops length and width, capillary density, neoangiogenesis) were evaluated and a semiquantitative scoring was used (normal, minor or major abnormalities for healthy controls and IPAH subjects and specific patterns – early, active and late – for SSc subjects) to define microvascular alterations. ResultsThe presence of capillaroscopic abnormalities was detected in 38,1% subjects with IPAH; particularly, compared to healthy controls, capillary density was significantly lower (7,5±1,65loops/mm vs 9±1,37loops/mm p<0,05) and mean capillary width was significantly higher (21±13μm vs 17±3μm p<0,05). A more severe NVC pattern (active/late) was described. SSc-PAH patients compared to SSc-noPAH patients (73,2% vs 50% respectively, p<0,05), with a significantly lower capillary density (5,64±1,9loops/mm vs 6,5±1,3loops/mm p<0,05) and a significantly higher capillary width (55±7μm vs 35±8μm - p<0,05) and mean number of neoangiogenesis (N/mm) (1±0,33 vs 0,2±0,22 respectively p<0,05). ConclusionsThese data, beyond to confirm the role of microvascular damage in SSc-related PAH, support the hypothesis of systemic microvascular involvement in IPAH also, which can be detected by NVC, although further studies are needed to establish whether the changes in the systemic microcirculation are causal or consequential to PAH.

Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). We sought to determine survival, predictors of mortality, and health-related quality of life (HRQoL) related to PAH in a large SSc cohort with PAH.MethodsWe studied consecutive SSc patients with newly diagnosed (incident) World Health Organization (WHO) Group 1 PAH enrolled in a prospective cohort between 2009 and 2015. Survival methods were used to determine age and sex-adjusted standardised mortality ratio (SMR) and years of life lost (YLL), and to identify predictors of mortality. HRQoL was measured using the Short form 36 (SF-36) instrument.ResultsAmong 132 SSc-PAH patients (112 female (85%); mean age 62 ± 11 years), 60 (45.5%) died, with a median (±IQR) survival time from PAH diagnosis of 4.0 (2.2–6.2) years. Median (±IQR) follow up from study enrolment was 3.8 (1.6–5.8) years. The SMR for patients with SSc-PAH was 5.8 (95% CI 4.3–7.8), with YLL of 15.2 years (95% CI 12.3–18.1). Combination PAH therapy had a survival advantage (p < 0.001) compared with monotherapy, as did anticoagulation compared with no anticoagulation (p < 0.003). Furthermore, combination PAH therapy together with anticoagulation had a survival benefit compared with monotherapy with or without anticoagulation and combination therapy without anticoagulation (hazard ratio 0.28, 95% CI 0.1–0.7). Older age at PAH diagnosis (p = 0.03), mild co-existent interstitial lung disease (ILD) (p = 0.01), worse WHO functional class (p = 0.03) and higher mean pulmonary arterial pressure at PAH diagnosis (p = 0.001), and digital ulcers (p = 0.01) were independent predictors of mortality.ConclusionsDespite the significant benefits conferred by advanced PAH therapies suggested in this study, the median survival in SSc PAH remains short at only 4 years.

Epidemiology and disease characteristics of systemic sclerosis-related pulmonary arterial hypertension: results from a real-life screening programme

BackgroundPulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc). Annual screening with echocardiogram (ECHO) is recommended. We present the methodological aspects of a PAH screening programme in a large Australian SSc cohort, the epidemiology of SSc-PAH in this cohort, and an evaluation of factors influencing physician adherence to PAH screening guidelines.MethodsPatient characteristics and results of PAH screening were determined in all patients enrolled in a SSc longitudinal cohort study. Adherence to PAH screening guidelines was assessed by a survey of Australian rheumatologists. Summary statistics, chi-square tests, univariate and multivariable logistic regression were used to determine the associations of risk factors with PAH.ResultsAmong 1636 patients with SSc, 194 (11.9%) had PAH proven by right-heart catheter. Of these, 160 were detected by screening. The annual incidence of PAH was 1.4%. Patients with PAH diagnosed on subsequent screens, compared with patients in whom PAH was diagnosed on first screen, were more likely to have diffuse SSc (p = 0.03), be in a better World Health Organisation (WHO) Functional Class at PAH diagnosis (p = 0.01) and have less advanced PAH evidenced by higher mean six-minute walk distance (p = 0.03), lower mean pulmonary arterial pressure (p = 0.009), lower mean pulmonary vascular resistance (p = 0.006) and fewer non-trivial pericardial effusions (p = 0.03). Adherence to annual PAH screening using an ECHO-based algorithm was poor among Australian rheumatologists, with less than half screening their patients with SSc of more than ten years disease duration.ConclusionPAH is a common complication of SSc. Physician adherence to PAH screening recommendations remains poor. Identifying modifiable barriers to screening may improve adherence and ultimately patient outcomes.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

IntroductionSystemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension...

Towards early detection of pulmonary hypertension: a call to arms

The more powerful the obstacle, the more glory we have in overcoming it – Mascarille, Moliere, L’Etourdi ou Les Contretemps , Act V, Scene XI Emerging evidence demonstrates that early detection alters outcomes in systemic sclerosis-related pulmonary arterial hypertension (PAH) [1]. The endeavours of the pulmonary hypertension community over the last 20 years have improved survival with modern treatment strategies but prognosis remains poor [2]. On average, even in the current era, patients have been symptomatic for >2 years by the time the diagnosis of pulmonary hypertension is made [3, 4]. If our understanding of the pathobiology of PAH is correct, then by the time of diagnosis, there will have been extensive remodelling and/or obliteration of a very significant proportion of the small muscular pulmonary arteries in our patients. The imperative over the coming decade for those of us treating pulmonary hypertension is to improve our ability to diagnose it early, when permanent damage to the pulmonary circulation is limited, leading to improved outcomes and, potentially, a normal quality of life with modern therapy. In response to these facts, patient-led support groups in Europe, North America and Australia have instigated campaigns not only to raise awareness of the existence of PAH but also to encourage individuals with unexplained breathlessness or fatigue to pursue a diagnosis with their doctors. This will inevitably lead to increasing referrals to pulmonary vascular clinics of patients with unexplained dyspnoea, syncope or fatigue. In some of these individuals, investigation will confirm a diagnosis of established PAH and, in others, alternative causes of their symptoms will be diagnosed. However, clinicians will be faced with symptomatic patients who have a moderate-to-high pre-test probability of pulmonary vascular disease based on clinical history or examination in whom echocardiography and other assessments at rest …

Performance of screening algorithms in systemic sclerosis-related pulmonary arterial hypertension: a systematic review

Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). There is emerging evidence that screening may enable the earlier detection and treatment of SSc-PAH, and thereby improve survival. We undertook a systematic review to evaluate the performance of current screening algorithms in SSc-PAH. We searched the Medline and EMBASE databases to 31 March 2012. We selected studies if they applied a screening algorithm to consecutively enrolled SSc patients not known to have PAH; SSc-PAH had to be confirmed on right heart catheterisation (RHC). The performance of each screening algorithm and the methodological quality of each study was evaluated. Nine studies met the inclusion criteria with a total intent-to-screen population of 3504 participants. In studies of patients with prevalent disease, the positive predictive value (PPV) of screening for PAH was 20.4-87.0%. In studies of patients with incident disease, the PPV of screening for PAH was 20.0-30.7%. The PPV of algorithms using echocardiography alone, or in combination with other tests, was comparable. No study enabled an accurate determination of negative predictive value, sensitivity or specificity of the screening algorithm as only patients who screened positive underwent confirmatory testing with RHC. The optimal timing and frequency of repeat screening is unknown. The low to moderate PPV of current screening algorithms, coupled with the inability to determine accurately the negative predictive value, sensitivity and specificity, suggests that there is a need to validate further these algorithms before making recommendations regarding screening for SSc-PAH.

THU0258 N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis

BackgroundPulmonary Arterial Hypertension (PAH) is a major cause of mortality in SSc. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of...

Should patients with systemic sclerosis‐related pulmonary arterial hypertension be anticoagulated?

Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial.

The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study

IntroductionPulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH.MethodsWe evaluated our proposed algorithm (PFT with NT-proBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).ResultsOverall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8%, respectively.ConclusionsThe combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies.

TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients

IntroductionSystemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial...