Elevated sST2 associates with cardiac involvement and declines after treatment in newly diagnosed patients with idiopathic inflammatory myopathies

POS0865 REDUCED BONE MINERAL DENSITY IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: A CASE CONTROL STUDY

Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

Patients with idiopathic inflammatory myopathies (IIMs) are at risk of reduced bone mineral density (BMD). To compare the prevalence of reduced BMD between patients with IIMs and controls and to determine its risk factors. This was a single-center case-control study. BMD was assessed by dual-energy X-ray absorptiometry. The prevalence of reduced BMD in IIM patients and age-and sex-matched non-rheumatological controls was compared. The BMD results of female IIM were also compared to age-matched female rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Independent factors associated with reduced BMD in IIM patients were identified by multivariate analyses. A total of 230 patients (IIM: 65, non-rheumatological controls: 65, RA: 50, SLE: 50) were recruited. The mean age of IIM patients was 58.6 ± 11.0 years and 76.9% were females. Significantly, more IIM patients had reduced BMD (73.8% versus 43.1%, p = 0.043) and osteoporosis (29.2% versus 13.8%, p = 0.033) than non-rheumatological controls. Multivariate analysis confirmed that IIM was independently associated with reduced BMD (OR: 2.12, p = 0.048, 95% CI: 1.01-4.46). The prevalence of reduced BMD was not significantly different between IIM, RA, and SLE patients but the mean hip BMD was the lowest in the IIM group (0.641 ± 0.152 g/cm2versus 0.663 ± 0.102g/cm2 in the RA group versus 0.708 ± 0.132 g/cm2 in the SLE group, p = 0.035). Lower body mass index and more advanced age were independently associated with lower BMD in IIM patients. Reduced BMD was more prevalent in IIM patients than in non-rheumatological controls. Hip BMD was lower in patients with IIMs than RA or SLE. Close monitoring and early treatment are encouraged especially in patients with risk factors.

Idiopathic inflammatory myopathies (IIM) can affect multiple organs, including the heart, potentially leading to arrhythmia, heart failure, and thereby a poor prognosis. We hypothesised that cardiac and skeletal muscle involvement in patients with IIM share pathological mechanisms, and that severe skeletal muscle involvement may be associated with cardiac involvement. The aim of this study was to identify disease-related parameters that indicate cardiac involvement in newly diagnosed patients with IIM. In this prospective study, 34 newly diagnosed patients with IIM and 9 age- and gender-matched healthy controls underwent cardiac magnetic resonance imaging, blood analyses for skeletal muscle markers, and assessments of IIM-specific disease features. Cardiac involvement was detected by cardiac magnetic resonance imaging in 47% of patients with newly diagnosed IIM, presenting as ongoing myocarditis/perimyocarditis (44%), ongoing pericarditis (25%) or previous myocarditis (31%). IIM patients with cardiac involvement had significantly more prevalent myositis (p=0.018) and higher levels of serum markers of muscle inflammation (myoglobin, p=0.039; alanine aminotransferase, p=0.045 and aspartate aminotransferase p=0.005) compared to IIM without cardiac involvement. IIM with ongoing myocarditis/peri-myocarditis displayed significantly elevated cardiac troponin I (cTnI) levels than IIM with ongoing pericarditis (p=0.015) or previous myocarditis (p=0.015). Additionally, cTnI levels were strongly correlated to myositis (as clinical manifestation, p=0.011), creatin kinase (p=0.001), myoglobin (p=0.001), lactate dehydrogenase (p=0.008) and aspartate aminotransferase (p=0.0.001). Cardiac involvement as detected by cardiac magnetic resonance imaging is common at time of diagnosis in patients with IIM and is closely linked to the severity of skeletal muscle involvement.

Objective We aimed to investigate the cardiovascular profile, including risk factors and cardiovascular abnormalities, in patients with idiopathic inflammatory myopathies (IIMs). Method In this cross-sectional study, 109 IIM patients and 20 age- and gender-matched healthy controls were enrolled and underwent electrocardiographic and transthoracic echocardiographic examinations. We analysed blood levels of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP), assessed IIM disease-specific features, and evaluated the medical history of cardiovascular risk factors. IIM patients were stratified into two groups: those with previous cardiac involvement and those without. Results IIM patients had a higher body mass index (BMI) and a greater prevalence of diabetes mellitus and dyslipidaemia than healthy controls (p = 0.023, p = 0.024, and p = 0.042, respectively). They also showed significantly higher rates of arrhythmia, cardiac axis deviation, negative T-waves, and suspected pulmonary hypertension, along with elevated NT-proBNP levels (p = 0.041, p = 0.004, p = 0.041, p = 0.012, and p = 0.034, respectively). A significantly higher proportion (p = 0.037) of immune-mediated necrotizing myopathy (IMNM) subtype (50%) was found among IIM with previous cardiac involvement compared to those without (20%). cTnI levels were significantly higher in IIM with cardiac involvement than in IIM without cardiac involvement (p = 0.009). Conclusions Cardiovascular complications in patients with IIM may result from an increased prevalence of traditional cardiovascular risk factors, such as higher BMI, diabetes mellitus, and dyslipidaemia, and/or from direct cardiac involvement, such as previous myocarditis. Cardiac involvement in IIM is notably associated with the IMNM subtype.

Background:Psychiatric comorbidity is frequent in autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. However, the risk of psychiatric comorbidity in idiopathic inflammatory myopathies (IIM) patients is less...

Soluble suppression of tumorigenesis-2 (sST2), a member of the interleukin-1 receptor family, is a novel biomarker of mechanical stress that is measurable in serum. It has been shown in humans and animals to be physiologically related to cardiac hypertrophy, fibrosis, and ventricular dysfunction. This study aimed to evaluate sST2 levels in cats with cardiomyopathy. In addition, serum sST2 and other cardiac biomarker levels were compared. Twenty-four client-owned cats with hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) were investigated. The cats included in the study were divided into four groups (I, II, III, and IV) according to the American College of Veterinary Internal Medicine (ACVIM) classification. Class B1 cats were included in group I (n=7), class B2 cats were included in group II (n=6), class C cats were included in group III (n=6), and healthy control-group cats in group IV (n=5). Measurement of cardiac troponin I (cTnI), cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), sST2 levels, and echocardiographic examinations were performed in all groups, and correlations were investigated. We observed positive correlations among sST2 levels and CK-MB and LA diameter (p=0.05). There was no correlation between sST2, NT-proBNP, Troponin I, Troponin T, AST, and LDH levels. We confirmed positive correlations between NT-proBNP levels and LA diameter (p&lt;0.05), CK-MB, IVSd, LVFWd, and LA/Ao ratio (p&lt;0.01). Cardiac biomarkers have diagnostic significance for feline cardiomyopathies. There was no statistically significant difference in sST2 levels between the groups. However, further research is needed to investigate the relationship between the severity of cardiomyopathies and sST2 levels in cats.

To measure creatine distribution in idiopathic inflammatory myopathy (IIM) patients' myocardial segments and investigate whether cardiovascular magnetic resonance (CMR) chemical exchange saturation transfer (CEST) creatine mapping can detect subclinical myocardial changes, CEST's ability was further compared with other conventional CMR mapping sequences. Forty IIM patients (53.5 ± 10.5 years, 26 males) and eight healthy controls (35.4 ± 6 years, 5 males) underwent CMR scans on a 3.0-T MR scanner. Patients with IIM were further classified into two subgroups according to cardiac troponin T (cTn-T) values: the elevated cTn-T subgroup (n = 14) and the normal cTn-T subgroup (n = 26). Cine imaging, T2 SPAIR, LGE imaging, T1 mapping, T2 mapping, and Cr (creatine) CEST were performed. Cr mapping showed significantly reduced creatine in IIM patients among global myocardium (IIM: 0.109 ± 0.063, controls: 0.121 ± 0.021, p < 0.05), and decreased creatine signals were detected in all 16 cardiac segments (p < 0.05). Patients also had significantly prolonged native T1 and decreased enhanced T1 values in each cardiac segment (p < 0.05). There was no significant difference of LVEF and T2 values between IIM patients and controls. Between the two subgroups, elevated cTn-T was linked with creatine and extracellular volume fraction (ECV) values, providing a global average creatine signal of 0.107 vs 0.112 (p < 0.05) and 24.7 vs 32.4 (p < 0.05). Creatine CEST mapping can detect early-stage heart involvement with negative LGE findings in IIM. Compared with T1 mapping, CEST provides increased sensitivity to ECV measurement, making it significantly better than T1, and a promising CMR sequence for screening subclinical myocardial damage. • IIM patients with potential or ongoing heart involvement, elevated ECV, and reduced Cr CEST values could provide valuable information. • ECV and Cr CEST values were closely related to elevated cTn-T.

The aim of this study was to assess left ventricular (LV) myocardial strain in patients with connective tissue disease (CTD) and compare LV deformation between subgroups of idiopathic inflammatory myopathy (IIM) and non-IIM. Ninety-eight patients with CTD, comprising 56 with IIM and 42 with non-IIM, and 30 healthy subjects were enrolled and underwent 3.0T cardiac magnetic resonance imaging (MRI) scanning. The LV function and strain parameters were measured and assessed. Our result revealed that CTD patients had preserved LV ejection fraction (60.85%) and had significantly decreased global and regional peak strain (PS) in radial, circumferential, and longitudinal directions (all p < 0.05). IIM patients showed significantly reduced global longitudinal PS (GLPS) and longitudinal PS at apical slice, whereas all strain parameters decreased in non-IIM patients. Except GLPS and longitudinal PS at apical slice, all strain parameters in non-IIM patients were lower than those in IIM patients. By Pearson’s correlation analysis, the LV global radial and circumferential PS were correlated to N-terminal pro-brain natriuretic peptide level and LV ejection fraction in both IIM and non-IIM patients. This study indicated that CTD patients showed abnormal LV deformation despite with preserved LVEF. The impairment of LV deformation differed between IIM and non-IIM patients.

AB0652 QTC INTERVAL PROLONGATION IN A SCANDINAVIAN COHORT OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES AND SYSTEMIC SCLEROSIS: CORRELATIONS WITH CLINICAL VARIABLES

To compare the performance of magnetic resonance (MR) relaxometry parameters to discriminate myocardial and skeletal muscle inflammation in idiopathic inflammatory myopathy (IIM) patients from healthy controls. For this retrospective case-control study, 20 consecutive IIM patients (54 ± 18years, 11 females) with cardiac involvement (troponin level > 50ng/l) and 20 healthy controls (47 ± 12years, 9 females) were included. All patients without cardiac MR imaging < 2weeks prior to the laboratory testings were excluded. T1/T2 relaxation times, as well as T1-derived extracellular volume (ECV), relative tissue T1 shortening ΔT1 = (native T1tissue-post contrast T1tissue)/native T1tissue), and enhancement fraction EHF = (native T1tissue-post contrast T1tissue)/(native T1blood-post contrast T1blood), were compared using Mann-Whitney U test and ROC analysis. All measured MR relaxometry parameters significantly discriminated IIM patients and healthy controls, except T2 in skeletal muscles and ECV in the myocardium. In skeletal muscles, post contrast T1 and T1-derived parameters showed the best performance to discriminate IIM patients from healthy controls (AUC = 0.98 for post contrast T1 and AUC 0.94-0.97 for T1-derived parameters). Inversely, in the myocardium, native T1 and T2 showed better diagnostic performance (AUC = 0.89) than post contrast T1 (AUC = 0.76), ECV (AUC = 0.58), ΔT1 (AUC = 0.80) and EHF (0.82). MR relaxometry parameters applied to the myocardium and skeletal muscles might be useful to separate IIM patients from healthy controls. However, different tissue composition and vascularization should be taken into account for their interpretation. ΔT1 and EHF may be simple alternatives to ECV in highly vascularized tissues such as the myocardium. • MR relaxometry parameters applied to the myocardium and skeletal muscles are highly useful to separate IIM patients from healthy controls. • Different tissue composition and vascularization should be taken into account for T1 and T2 mapping parameter interpretation. • ΔT1 and EHF may be simple alternatives to ECV in highly vascularized tissues such as the myocardium.

Cardiac involvement is common in idiopathic inflammatory myopathy (IIM) but often subclinical. Cardiac magnetic resonance (CMR) is a promising tool in detecting cardiac involvement in patients with IIM. The aim of this study was to assess cardiac involvement in IIM patients by CMR feature tracking (CMR-FT). Thirty-seven IIM patients and 25 controls were enrolled in this retrospective study. The left ventricular (LV) functional parameters such as volume and ejection fraction were measured. Global and regional LV peak strain (PS) in radial, circumferential and longitudinal directions were derived from cine images. Left atrial (LA) volume, longitudinal strain and strain rate (SR) parameters and LA reservoir function, conduit function and booster pump function were assessed, respectively. IIM patients with preserved LVEF showed significantly reduced global and regional LV PS in longitudinal direction (all p < 0.05). Compared with controls, LA reservoir and conduit function were significantly impaired in IIM patients (all p < 0.05). The global LV longitudinal PS, LAVpre-ac and SRe were independent predictors of IIM. By Pearson's correlation analysis, the LV global radial, circumferential and longitudinal PS were all correlated to LVEF in IIM patients (r = 0.526, p < 0.001 vs. r = -0.514, p < 0.001 vs. r = - 0.288, p = 0.023). CMR-FT based LV and LA deformation performance could early detect cardiac involvement in IIM patients with preserved LVEF.

Cardiac involvement in patients with idiopathic inflammatory myopathies (IIM) is often subclinical but associated with poor prognosis. This study aimed to evaluate the diagnostic utility of cardiac troponin T (cTnT) for identifying myocardial involvement in IIM, using cardiac magnetic resonance (CMR) imaging. One hundred and sixteen IIM patients underwent clinical evaluation, laboratory tests, electrocardiogram (ECG), and CMR. The diagnostic performance of cTnT was assessed using receiver-operating characteristic (ROC) curves, while linear regression was used to explore associations between cTnT and myocardial involvement markers. Myocardial involvement, detected by late gadolinium enhancement (LGE) on CMR, was present in 63.8% of patients. Those with cardiac involvement exhibited significantly elevated cTnT levels (> 157.85ng/L), which correlated with native T1, native T2, and extracellular volume (ECV) values. The cTnT threshold of 157.85ng/L demonstrated sensitivity and specificity of 62.2% and 92.9%, respectively. Elevated cTnT levels (> 157.85ng/L) are associated with cardiac involvement in IIM patients and could serve as a valuable non-invasive biomarker for early detection, particularly in subclinical cases. Further investigations are warranted to refine its clinical applicability. Key Points •A specific cTnT threshold (> 157.85ng/L) demonstrates high sensitivity (62.2%) and specificity (92.9%) for identifying cardiac involvement. • Utilization of cardiac magnetic resonance imaging (CMR) as a reference standard enhances diagnostic accuracy for subclinical myocardial injury. • Findings support cTnT as a practical, non-invasive screening tool, guiding early detection and management of cardiac involvement in IIM.

BackgroundHeat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features.MethodsHsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay.ResultsHsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3–40.1] vs 9.8 [7.5–13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations.ConclusionsHsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM.

We aim to explore the prevalence of coronary artery calcification (CAC) and ascending/descending thoracic aorta (AA/DA) dilation in idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) patients, and to assess associations between cardiovascular disease (CVD) risk factors and these imaging signatures. This study recruited 151 IIM patients, 140 SLE patients, and 195 controls. The CAC and AA/DA diameters were quantified using non-gated chest CT images. The independent samples t-test or Mann-Whitney test was chosen for comparisons of continuous variables between patients and healthy controls. For categorical data, comparisons were made using the chi-square test or Fisher's exact test. Multivariate regression or Spearman's correlation analysis was employed to probe the associations between CVD risk factors and Framingham risk score (FRS) with imaging signatures. The IIM and SLE patients showed significantly higher prevalence of CAC and AA/DA dilatation (P < 0.01). Age was a risk factor for both CAC and AA/DA dilatation in all cohorts (P < 0.01). In IIM patients, the AA/DA dilatation was associated with BMI (P = 0.05). In SLE patients, CAC was associated with the elevated CRP level (P = 0.05). Without CAC, both IIM and SLE patients showed significant correlations between AA/DA diameters and FRS (P < 0.01, P < 0.01). Only in SLE patients, the interleukin-6 (IL-6) level correlated with AA/DA diameters. The IIM and SLE patients more commonly exhibit CAC and AA/DA dilation. These subclinical atherosclerosis signs are associated with traditional CVD risk factors. For AID patients without CAC, AA/DA diameters could serve as a potential biomarker for early CVD risk. Key Points • The study characterized the manifestation of subclinical atherosclerosis imaging biomarkers (CAC, AA/DA dilation) in IIM and SLE patients. • AA/DA diameters could serve as an early imaging biomarker in clinical management for IIM and SLE patients with early-onset and no CAC present.