Heart involvement in systemic sclerosis: emerging concepts.

PURPOSE OF REVIEW: Systemic sclerosis (SSc)-associated heart involvement (SHI) is a significant cause of both morbidity and mortality in individuals with SSc. SHI can take many different forms, and likely is a spectrum of fibroinflammatory cardiac disease. Presenting features include arrhythmia, ventricular systolic or diastolic dysfunction, pericardial disease, and exercise intolerance. Risk of sudden cardiac death in SSc is likely 10-30-fold greater than general population estimates. In this review, we explore what is known about the pathogenesis of SHI, its prevention and management, and discuss available strategies for screening for SHI in light of new recommendations for the routine screening of SHI in all SSc patients. RECENT FINDINGS: We describe the spectrum, clinical features, and pathogenesis of SHI. Furthermore, we review the new recommendations for screening for SHI in individuals with SSc. SUMMARY: There is a large, under-recognized burden of SHI in people living with SSc, which likely contributes to the significant increase in sudden cardiac death observed in SSc. However, a broad-based screening approach, including asymptomatic, low-risk patients should be viewed with caution given the lack of evidence-based treatments and interventions for SHI particularly in this group.

Investigating the trajectory of functional disability in systemic sclerosis: group-based trajectory modelling of the Health Assessment Questionnaire-Disability Index.

OBJECTIVES: To identify the trajectories and clinical associations of functional disability in systemic sclerosis (SSc). METHODS: Australian Scleroderma Cohort Study (ASCS) participants meeting ACR/EULAR criteria for SSc recruited within 5 years of disease onset, with ≥2 Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were included. Group based trajectory modelling (GBTM) was used to identify the number and shape of HAQ-DI trajectories. Between group comparisons were made using the chi-squared test, two-sample t-test or Wilcoxon rank-sum test as appropriate. Multiple logistic regression was used to identify features associated with trajectory group membership. Survival analyses were performed using Kaplan Meier and Cox proportional hazard modelling. RESULTS: We identified two HAQ-DI trajectory groups within 426 ASCS participants with incident SSc: low-stable disability (n=221, 52%), and high-increasing disability (n=205, 48%). Participants with high-increasing disability were older at disease onset, more likely to have diffuse SSc (dcSSc), cardiopulmonary disease, multimorbidity, digital ulcers, and gastrointestinal involvement (all p≤0.01), as was use of immunosuppression (p<0.01). Multimorbidity was associated with high-increasing trajectory group membership (OR3.1, 95%CI1.1-8.8, p=0.04); independently, multiple SSc features were also strongly associated including dcSSc (OR2.3, 95%CI1.3-4.2, p<0.01), proximal weakness (OR7.3, 95%CI2.0-27.1, p<0.01) and joint contractures (OR2.7, 95%CI1.3-5.3, p<0.01). High-increasing physical disability was associated with an almost two-fold increased risk of mortality (HR1.9, 95%CI1.0-3.8, p=0.05), and higher symptom burden. CONCLUSIONS: Two trajectories of functional disability in SSc were identified. Those with high-increasing functional disability had a distinct clinical phenotype and worse survival compared to those with low-stable functional disability. These data highlight the pervasive nature of physical disability in SSc, and its prognostic importance.

The burden and determinants of fatigue in incident and prevalent systemic sclerosis.

OBJECTIVES: To investigate the burden and clinical associations of fatigue in systemic sclerosis (SSc) as measured by FACIT-Fatigue scores. METHODS: Australian Scleroderma Cohort Study participants with ≥1 FACIT-Fatigue score were included. Participants were divided into those with incident SSc (≤5 years SSc duration at recruitment and FACIT-Fatigue score recorded within 5 years of disease onset) or prevalent SSc (first FACIT-Fatigue score recorded >5 years after SSc onset). Generalised estimating equations were used to model change in FACIT-Fatigue scores over time, expressed as an increasing (improving) or decreasing (worsening) score. RESULTS: Of 859 participants, 215 had incident SSc and 644 prevalent SSc. First-recorded FACIT-Fatigue scores were similar in those with incident (37 units, IQR 25-45.5) and prevalent SSc (36 units, IQR 23-44; p=0.17), as were lowest-ever recorded FACIT-Fatigue scores (incident 23 units; prevalent 22 units, p=0.75). In incident SSc, higher skin scores (regression coefficient (RC) -1.5 units, 95%CI -2.3 to -0.8), PAH (RC -8.2, 95%CI -16.5 to 0.1) and reduced left ventricular function (RC -10.6, 95%CI -18.3 to -2.8) were associated with more severe fatigue. In prevalent SSc, higher skin scores (RC -0.6, 95%CI -1.3 to 0), gastrointestinal symptoms (RC -6.6, 95%CI -9.0 to -4.2), hypoalbuminaemia (RC -2.8, 95%CI -5.0 to -0.7), BMI<18.5kg/m2 (RC -6.3, 95%CI -10.3 to -2.2), raised CRP (RC -3.1, 95%CI -4.7 to -1.5), and anaemia (RC -1.7, 95%CI -3.5 to 0.1) were associated with more severe fatigue. CONCLUSIONS: The burden of fatigue is substantial in both incident and prevalent SSc. Cardiopulmonary and gastrointestinal involvement are associated with worse fatigue.

Patient experiences of muscle biopsy in idiopathic inflammatory myopathies: a cross-sectional survey.

INTRODUCTION: Muscle biopsy plays an important role in the diagnostic evaluation of individuals with suspected idiopathic inflammatory myopathies (IIM). However, variability in biopsy practices may result in a heterogenous patient experience. The existing literature offers limited insights into the experiences and perspectives of patients undergoing muscle biopsy. METHODS: This study employed a 27-item online survey to comprehensively characterise the experience of muscle biopsy among Australian patients, including their concerns, beliefs about procedure utility, information sources, physical sensations, perceived complications and recovery. RESULTS: A total of 111 Australian individuals who reported a diagnosis of IIM completed the survey, with data collected from March to June 2023. Most participants had inclusion body myositis (76/111, 68.5%) and had undergone one biopsy procedure (87/111, 78.4%) as part of their IIM work-up. Nine of the 111 respondents did not undergo a muscle biopsy. The procedure was well-tolerated by many respondents, however, a notable number of respondents experienced post-procedural pain lasting > 72 h (27/102, 26.5%), increasing weakness post-biopsy (13.7%), numbness at the biopsy site (18/102, 17.6%) and a recovery time beyond 3 days (36/102, 35.3%). A substantial minority (30/111, 27%) felt they were inadequately informed about the risks and benefits of the procedure. CONCLUSIONS: This survey highlights that although muscle biopsy is often well-tolerated, there are considerable patient concerns that are often inadequately addressed. Our findings underscore the need for improved patient-doctor communication and support throughout the biopsy process.

Muscle biopsy practices in the evaluation of idiopathic inflammatory myopathies: An international survey of expert clinicians.

BACKGROUND: Muscle biopsy is an important test in the evaluation of individuals with suspected myopathy, including those with suspected idiopathic inflammatory myopathy (IIM). Various approaches, including open surgical biopsy, needle biopsy and conchotome forceps, have been reported. However the real-world utilisation of these approaches remains unclear. There are no established guidelines for the use of muscle biopsy, or selection of biopsy technique, in investigating IIM and international practices are not well-documented. This study describes current approaches to muscle biopsy amongst clinicians with expertise in IIM. METHODS: A survey regarding muscle biopsy practices was disseminated among members of the International Myositis Assessment and Clinical Studies (IMACS) group. Data were analysed using descriptive statistics. RESULTS: One-hundred and sixteen clinicians completed the survey, primarily rheumatologists. Open surgical biopsy was the most commonly employed technique (74.5 %), followed by needle (11.3 %) and conchotome (9.4 %) approaches. Clinical examination was the most common method of muscle selection, with 85.2 % of respondents reporting they 'always or almost always' relied on it. MRI and electromyography were also frequently utilised for muscle selection (51.9 %, 45.4 % respectively). There was variability in the perceived utility of muscle biopsy in certain clinical contexts, such as presence of myositis specific antibodies or cutaneous manifestations of dermatomyositis. While respondents generally reported low complication rates following muscle biopsy, non-diagnostic histopathology was commonly reported, regardless of procedural approach. CONCLUSION: Clinicians managing IIM report muscle biopsy to be well tolerated however, non-diagnostic results are common. Substantial heterogeneity regarding perceived indications for biopsy, procedural approaches, and muscle selection strategies were observed within this expert group. Future research is needed to establish best practice and determine the role of muscle biopsy in the context of continued advancements in serological profiling of IIM.

Examining the Case for Palliative Care in Patients With Systemic Sclerosis.

Systemic sclerosis (SSc) is a complex, multiorgan disease that causes substantial and progressive symptoms and impairs quality of life. International guidelines recommend early, integrated palliative care for patients with advanced cardiopulmonary disease, such as heart failure and interstitial lung disease, as this care can improve patient, caregiver, and healthcare outcomes. In this article, we examine the potential need and role for palliative care in SSc. We propose that early, integrated palliative care could improve symptom control and quality of life and recommend a research agenda for palliative care in SSc to address the lack of evidence in this area.

Development and Initial Validation of the Novel Scleroderma Clinical Trials Consortium Activity Index.

OBJECTIVE: Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant clinical challenge. The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index Working Group (WG) to develop a novel measure of disease activity (SCTC-AI). METHODS: Using consensus methodology, we developed a conceptual definition of disease activity. Literature review and expert consensus generated provisional SCTC-AI items, which were reduced by Delphi survey. Provisional items were weighted against a combined endpoint of morbidity and mortality, using time-dependent Cox proportional hazards regression analysis of the Australian Scleroderma Cohort Study (ASCS) (n=1,254). External validation of the SCTC-AI was performed using data collected from 1,103 Canadian Scleroderma Research Group Study participants. RESULTS: Disease activity in SSc was defined using consensus methodology as 'aspects of disease that are reversible, or can be arrested, with time and, or effective therapy'. One-hundred and forty-one provisional SCTC-AI items were generated and reduced using 3 rounds of Delphi survey and statistical reduction and weighting, against mortality and quality of life measures, yielding a final 24-item index with a maximum possible score of 140. Survival analysis in an external cohort showed a graded relationship between disease activity scores and survival (p<0.01). CONCLUSION: We present a novel instrument to quantify the burden of disease activity in SSc. We have employed a rigorous consensus-based process in combination with data-driven methods, to develop an instrument that has face, content and criterion validity. Further work is required to fully validate and confirm the construct and discriminative validity of the SCTC-AI.

Lack of paternal silencing and ecotype-specific expression in head and body lice hybrids.

Paternal genome elimination (PGE) is a non-Mendelian inheritance system, described in numerous arthropod species, in which males develop from fertilized eggs, but their paternally inherited chromosomes are eliminated before or during spermatogenesis. Therefore, PGE males only transmit their maternally inherited set of chromosomes to their offspring. In addition to the elimination of paternal chromosomes, diverse PGE species have also repeatedly evolved the transcriptional silencing of the paternal genome, making males effectively haploid. However, it is unclear if this paternal chromosome silencing is mechanistically linked to the chromosome elimination or has evolved at a later stage, and if so, what drives the haploidization of males under PGE. In order to understand these questions, here we study the human louse, Pediculus humanus, which represents an ideal model system, as it appears to be the only instance of PGE where males eliminate, but not silence their paternal chromosomes, although the latter remains to be shown conclusively. In this study, we analyzed parent-of-origin allele-specific expression patterns in male offspring of crosses between head and body lice ecotypes. We show that hybrid adult males of P. humanus display biparental gene expression, which constitutes the first case of a species with PGE in which genetic activity of paternal chromosomes in the soma is not affected by embryonic silencing or (partial or complete) elimination. We did however also identify a small number of maternally biased genes (potentially imprinted genes), which may be involved in the elimination of paternal chromosomes during spermatogenesis. Finally, we have identified genes that show ecotype-specific expression bias. Given the low genetic diversity between ecotypes, this is suggestive for a role of epigenetic processes in ecotype differences.

Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.

OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.

Outcomes of Patients With Diffuse Systemic Sclerosis Eligible for Autologous Stem Cell Transplantation Treated With Conventional Therapy.

OBJECTIVE: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT. METHODS: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed. ASCS patients who had already undergone transplantation were excluded from analysis. RESULTS: Of the 492 patients with dcSSc in the ASCS, 56 met ASTIS inclusion criteria for ASCT (56 of 492 [11.4%]) and 30 met SCOT inclusion criteria (30 of 492 [6.1%]). An additional 11 patients met ASTIS or SCOT inclusion criteria, but they were excluded due to severe organ manifestations. EFS at 4 years in ASCS patients meeting ASTIS inclusion criteria was 83.3% and in ASCS patients meeting SCOT inclusion criteria was 81.2%. EFS at 4 years in ASCS patients who met ASTIS and SCOT inclusion but also exclusion criteria was 46.7% and 45.7%, respectively. CONCLUSION: ASCS patients meeting ASTIS and/or SCOT inclusion criteria who were not treated with ASCT have similar EFS at 4 years as patients receiving ASCT and better EFS than those receiving cyclophosphamide in the ASTIS and SCOT trials. This may reflect confounders unable to be controlled for, including survivor bias, but may also reflect improved standard of care for dcSSc over time.

Retention of an Endosymbiont for the Production of a Single Molecule.

Sap-feeding insects often maintain two or more nutritional endosymbionts that act in concert to produce compounds essential for insect survival. Many mealybugs have endosymbionts in a nested configuration: one or two bacterial species reside within the cytoplasm of another bacterium, and together, these bacteria have genomes that encode interdependent sets of genes needed to produce key nutritional molecules. Here, we show that the mealybug Pseudococcus viburni has three endosymbionts, one of which contributes only two unique genes that produce the host nutrition-related molecule chorismate. All three bacterial endosymbionts have tiny genomes, suggesting that they have been coevolving inside their insect host for millions of years.

Toward trustworthy COVID-19 interventions: Building vaccine trust through community-university partnerships.

Prior research identifies trust as critical to increase vaccine acceptance and uptake. However, few intervention studies have sought to develop or test strategies for bolstering vaccine-related trust. To address this gap, this exploratory study identifies features of COVID-19 vaccine hesitancy interventions that can promote or undermine trust across three interconnected domains: institutional, interpersonal, and product (the vaccine itself). We draw on focus groups (N = 27 participants) with community and university partners involved with hosting COVID-19 testing and vaccine events in underserved Oklahoma communities. Focus groups explored participants' experiences serving community health needs and elicited feedback on proposed vaccine hesitancy interventions. Proposed interventions included two technology-based strategies (text message reminders and tablet-based testimonials and education) and one dialogue-based strategy (anti-body test interpretation). We find that community partners perceived local universities as trustworthy institutions because of their association with popular sports programs, academic credentials, and proximity, creating opportunities to address vaccine-related distrust through community-university partnerships. The most promising intervention strategies for building interpersonal trust included engaging in one-on-one dialogue and using autonomy enhancing approaches. Finally, interventions that successfully encouraged vaccine trust did so by incorporating personalized health information about individuals' potential level of protection and susceptibility to the COVID-19 virus. These findings can inform future public health efforts to create trustworthy vaccine hesitancy interventions.

Frequency and implications of malnutrition in systemic sclerosis.

OBJECTIVES: To quantify the frequency and impact of malnutrition in systemic sclerosis (SSc), as diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria, based on weight loss, body mass index (BMI) and muscle atrophy. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 concurrent weight and height measurement were included. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Multivariable logistic regression models were used to establish the determinants of malnutrition diagnosis. Kaplan-Meier and Cox proportional hazard models were used for survival analyses, based on malnutrition diagnosis, and individual GLIM criteria (% weight loss, BMI thresholds and presence of muscle atrophy). RESULTS: In this study of 1903 participants, 43% were diagnosed with malnutrition according to GLIM criteria, of whom 33% had severe malnutrition. Participants diagnosed with malnutrition were older, and more likely to have dcSSc, higher SSc severity scores and RNA polymerase-3 positivity. Gastrointestinal (GI) involvement, multimorbidity, cardiopulmonary disease, raised inflammatory markers, hypoalbuminaemia and anaemia were more common in malnourished participants (p< 0.01). Multimorbidity (OR1.6, 95%CI1.2-2.0, p< 0.01), pulmonary arterial hypertension (OR2.1, 95%CI1.4-2.0, p< 0.01) and upper GI symptoms (OR1.6, 95%CI1.3-2.0, p< 0.01) were all associated with malnutrition.Health-related quality-of-life (HRQoL) and physical function were poorer in malnourished participants. Survival was worse in those with malnutrition after adjusting for age, sex and dcSSc (HR 1.4, 95%CI1.1-1.7, p< 0.01). CONCLUSIONS: Malnutrition is common in SSc and confers poorer survival, HRQoL and physical function.

Predictors and prognosis of pulmonary hypertension complicating interstitial lung disease in systemic sclerosis.

OBJECTIVE: To identify those with concurrent pulmonary hypertension (PH) and interstitial lung disease (ILD) in systemic sclerosis (SSc) and determine their disease severity, therapeutic approach, and survival. METHODS: Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study (ASCS) who were diagnosed on right heart catherisation with pulmonary hypertension were included. Logistic regression was used to determine the associations of ILD with PH hemodynamic parameters and therapeutic approach. Kaplan-Meier survival curves were used to estimate survival. RESULTS: Of 1,883 SSc patients, 164 (8.7%) developed incident PH over a median follow up of 4.3 (1.7-7.9) years. Of these, 43.9% had concurrent ILD at PH diagnosis (PH-ILD) and 56.1% had Group 1 PAH. Extensive ILD was present at PH diagnosis in 40.3%. Despite these distinct PH cohorts, a similar frequency of each PH cohort was treated with vasodilatory therapy at PH diagnosis, regardless of the presence or severity of ILD. The majority (87.5%) of those with extensive ILD and PH received upfront vasodilatory therapy at PH diagnosis with no difference in its tolerability or therapy cessation compared with Group 1 PAH. Although vasodilator therapy was not associated with a survival advantage in those with extensive ILD, its use was associated with an improvement in symptoms, physical function, and quality of life (QoL). CONCLUSION: Despite vasodilator therapy, survival in SSc-PH is poor, with the presence of concurrent ILD associated with worse survival. Although vasodilator therapy commenced at PH diagnosis does not portray an improved survival in PH with extensive ILD, it appears well tolerated and may improve symptoms, physical function, and QoL.

Quantifying the Need for Specialist Palliative Care Management in Patients With Systemic Sclerosis.

OBJECTIVE: The importance of early integration of palliative care in the management of complex multisystem diseases has been recognized. In this study, we aimed to quantify the need for specialist palliative care in patients with systemic sclerosis (SSc). METHODS: Using data from 875 patients enrolled in the Australian Scleroderma Cohort Study, we defined the need for palliative care as a high symptom burden at two or more consecutive study visits, at ≥50% of overall study visits, or at the study visit immediately before death. Symptoms of interest included breathlessness, fatigue, pain, depression, anxiety, constipation, and diarrhea. Logistic regression analyses evaluated the association between individual symptoms and SSc manifestations. Linear regression analysis evaluated the relationship between palliative care needs and quality of life (QoL) and function. RESULTS: Almost three-quarters of patients (72.69%) met the threshold for specialist palliative care needs. Severe fatigue (54.17%) was most common, followed by breathlessness (23.66%) and severe constipation (21.14%). Concurrent severe symptoms were frequently observed. Severe breathlessness (coefficient [coef] -7.95, P < 0.01) and pain (coef -7.70, P < 0.01) were associated with the largest reductions in physical QoL. Severe mood symptoms were associated with the greatest reduction in mental QoL (coef -12.91, P < 0.01). Severe pain (coef 0.56, P < 0.01), breathlessness (coef 0.49, P < 0.01), and mood symptoms (coef 0.40, P < 0.01) had a significant impact on function. CONCLUSION: SSc is frequently associated with multiple severe symptoms that may be amenable to palliative care intervention. Given the strong association between symptom burden and impaired QoL targeted, effective symptom management in parallel with standard-of-care treatments may improve overall patient outcomes.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. METHODS: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. RESULTS: At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. CONCLUSION: The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.

Proximal weakness and creatine kinase elevation in systemic sclerosis: Clinical correlates, prognosis and functional implications.

OBJECTIVES: To determine the frequency, clinical correlates and implications of clinical evidence of muscle disease in systemic sclerosis (SSc). METHODS: Australian Scleroderma Cohort Study participants with ≥1 creatine kinase (CK) and proximal power assessment were subdivided according to presence of proximal weakness (PW: proximal muscle power<5/5) and CK elevation(≥140IU/L). Participants were assigned to one of four groups: concurrent PW&CK elevation, PW alone, CK elevation alone or neither. Between-group comparisons were made with chi-squared, ANOVA or Kruskal-Wallis tests. Survival analysis was performed using time-varying-covariate Cox regression modelling. Longitudinal data were modelled using multinomial logistic and linear regression. RESULTS: Of 1786 participants, 4 % had concurrent PW&CK elevation, 15 % PW alone, 24 % CK elevation and 57 % neither. Participants with PW&CK elevation displayed a severe, inflammatory SSc phenotype, with more frequent dcSSc(p < 0.01), tendon friction rubs(p < 0.01), synovitis(p < 0.01) and digital ulceration(p = 0.03). Multimorbidity(p < 0.01) and cardiopulmonary disease, including ischaemic heart disease(p < 0.01) and pulmonary arterial hypertension(p < 0.01), were most common in those with PW, with and without CK elevation. Men with anti-Scl70 positivity most frequently had CK elevation alone, without other significant clinical differences. Multivariable modelling demonstrated 3.6-fold increased mortality in those with PW&CK elevation (95 %CI 1.9-6.6, p < 0.01) and 2.1-fold increased mortality in PW alone (95 %CI 1.4-3.0, p < 0.01) compared to those without PW or CK elevation. CK elevation alone conferred better survival (HR 0.7, 95 %CI 0.4-1.1, p = 0.09) compared to those with no PW or CK elevation. PW regardless of CK elevation was associated with impaired physical function, with reduced six-minute-walk-distance (p < 0.01), higher HAQ-DI scores (p < 0.01) and increased patient-reported dyspnoea (p = 0.04). CONCLUSION: Clinical features of myopathy are highly prevalent in SSc, affecting almost half of our study cohort. Detection of PW and elevated CK alone, even without imaging or histopathological identification of SSc-myopathy, identified important clinical associations and are associated with poorer function and overall prognosis.

Inflammatory Arthritis in Systemic Sclerosis: Its Epidemiology, Associations, and Morbidity.

OBJECTIVE: To describe the epidemiology, associations, and impact of inflammatory arthritis (IA) in systemic sclerosis (SSc). METHODS: Patients with SSc prospectively enrolled in the Australian Scleroderma Cohort Study were included. IA was defined clinically as the presence of synovitis on examination. Logistic regression was used to determine the associations of IA with SSc manifestations and serological parameters. Patient-reported outcome measures were used to capture physical function and health-related quality of life (HRQoL). RESULTS: IA was a common SSc manifestation affecting one-third (33.3%) of patients over a median follow-up of 4.3 (1.7-8.4) years. Associations of IA included diffuse SSc (odds ratio [OR] 1.33, 95% confidence interval [95% CI] 1.01-1.74, P = 0.042), concurrent musculoskeletal manifestations (joint contractures and tendon friction rubs, OR 1.70, 95% CI 1.34-2.15, P < 0.001); myositis (OR 2.11, 95% CI 1.39-3.20, P < 0.001), and sicca symptoms (OR 1.57, 95% CI 1.14-2.16, P = 0.006), whereas IA was negatively associated with pulmonary arterial hypertension (OR 0.52, 95% CI 0.35-0.78, P = 0.002). Neither the presence of rheumatoid factor nor U1 small nuclear RNP were associated with IA (OR 1.13, 95% CI 0.88-1.44, P = 0.331, OR 1.46, 95% CI 0.89-2.39, P = 0.129 respectively). Positive anticyclic citrullinated protein antibodies, although at low frequency, were more common in those with IA compared with those without IA (7.5% vs 1.5%, P < 0.001). IA was associated with significantly lower HRQoL score (P < 0.001) and more physical disability than in those without IA (P < 0.001). CONCLUSION: IA is a common disease manifestation that is more frquently seen in diffuse disease. IA is associated with poor HRQoL and physical disability. Further research is needed into the effective management of IA in SSc.

Are there more acute cardiac hospitalizations in winter in patients with systemic sclerosis? An analysis from the National Inpatient Sample.

Objective: Cold-induced transient myocardial ischemia has been described in patients with systemic sclerosis. The clinical impact of cold exposure in systemic sclerosis patients with acute cardiac conditions is unknown. We compared the seasonal variation of acute cardiac hospitalizations in patients with and without systemic sclerosis. Methods: We performed a retrospective cross-sectional study using the National Inpatient Sample from 2016 to 2019. The primary outcome was acute cardiac hospitalization primarily due to heart failure, acute myocardial infarction, or cardiac arrhythmias. We compared the proportion of acute cardiac hospitalizations in each season in patients with and without systemic sclerosis. We also performed a subgroup analysis by US geographic region (Northeast, Midwest, South, West). Results: There were a total of 10,118,002 acute cardiac hospitalizations over the 4-year study period. Compared to those without systemic sclerosis, patients with systemic sclerosis who were hospitalized for acute cardiac care were younger (mean age 67 ± 13 vs 70 ± 14 years, p < 0.01), a greater proportion were female (82% vs 45%, p < 0.01), and a smaller proportion were Caucasian (68% vs 71%, p < 0.01). There was a lesser proportion of traditional cardiovascular risk factors in systemic sclerosis compared to non-systemic sclerosis patients. There was no significant difference in the proportion of winter admissions between systemic sclerosis and non-systemic sclerosis patients for total acute cardiac hospitalizations (26.4% vs 25.9%, p = 0.51), heart failure (27.0% vs 26.5%, p = 0.64), acute myocardial infarction (26.9% vs 25.5%, p = 0.50), or arrhythmias (24.3% vs 25.0%, p = 0.68). The results were consistent across all four US geographic regions. Conclusion: Our study did not support that patients with systemic sclerosis had a disproportionally higher risk of acute cardiac hospitalization in winter compared to the general population. We found that systemic sclerosis patients hospitalized for acute cardiac care had a lower burden of traditional cardiovascular risk factors than their non-systemic sclerosis counterparts.