Are troponin and B-type natriuretic peptides useful biomarkers for the diagnosis of systemic sclerosis heart involvement? A systematic literature review.

BACKGROUND: Systemic sclerosis (SSc) heart involvement (SHI) is a leading cause of SSc-associated mortality and once clinically overt, carries a very poor prognosis. There remain no established diagnostic criteria for SHI. This study aimed to systematically review the literature regarding the role of cardiac troponin (cTn) and B-type natriuretic peptide (BNP) or N-terminal B-type natriuretic peptide (NT-proBNP) in the diagnosis of SHI. METHODS: A comprehensive search of the MEDLINE (Ovid), EMBASE and Pubmed databases was performed to identify adult human studies of at least 10 SSc patients with a primary focus of SHI that included data on cTn and BNP or NT-proBNP results. Only cohort studies and case-controlled studies were identified and the quality of the evidence presented in each study was assessed according to the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Of the 2742 studies identified by the database search, 12 articles fulfilled the study inclusion criteria. Three out of four studies evaluating SHI using cardiac magnetic resonance imaging found no association between cardiac biomarkers and imaging changes. By comparison echocardiographic abnormalities, cardiac arrhythmias and congestive cardiac failure were more likely to be associated with elevated cardiac biomarkers. Comparison of results between studies was limited by the highly heterogenous definitions of SHI and inclusion criteria employed across studies. CONCLUSION: There are insufficient data to draw definitive conclusions about the role of cTn and BNP / NT-proBNP in the diagnosis of SHI. Currently available literature suggests that cardiac biomarkers may have some role, in conjunction with other diagnostic modalities, in identifying SHI; however, this remains a much-needed area of clinical research.

Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis.

BACKGROUND: Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality. METHODS: Clinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models. RESULTS: Of 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex. CONCLUSIONS: ANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.