Involvement In Systemic Sclerosis Research Articles

Scleroderma renal crisis and renal involvement in systemic sclerosis.

Scleroderma renal crisis (SRC) is a rare, potentially life-threatening complication that affects 2-15% of patients with systemic sclerosis (SSc, also known as scleroderma). SRC typically presents in patients with early, rapidly progressive, diffuse cutaneous SSc within the first 3-5 years after the onset of a non-Raynaud sign or symptom. SRC is characterized by an acute, usually symptomatic increase in blood pressure, a rise in serum creatinine levels, oliguria and thrombotic microangiopathy in about 50% of patients. The prognosis of SRC substantially improved in the 1980s with the introduction of angiotensin-converting-enzyme inhibitors for rapid blood pressure control, with additional antihypertensive agents as required. However, the survival of patients with SRC can still be improved. Current patient survival is 70-82% at 1 year, but decreases to 50-60% at 5 years despite dialysis support. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for transplantation. In this Review, we discuss progress made in the identification and proactive management of patients at risk of SRC and make recommendations aimed at optimizing management for those who progress to chronic kidney failure.

Comparative study of left ventricular function in a group of asymptomatic patients with systemic sclerosis and a controls group

Introduction. Cardiac involvement in systemic sclerosis (SSc) represents a major cause of morbidity and mortality and constitutes a turning point in this disease. The aim of this study was to describe echocardiographic data in asymptomatic patients with SSc and compare them to results obtained in a control population in order to unmask subclinical cardiac involvement during systemic sclerosis. Material and methods. A prospective study was conducted between 2012 and 2017 including two groups: group A included 25 asymptomatic scleroderma patients without other comorbidities, while group B consisted of 25 control and healthy subjects. The two groups were examined by echocardiography coupled with tissue Doppler and 2D strain. Results. The mean age of our patients was 45 ± 7 years. The sex ratio was 0.8. The control population was epidemiologically similar to the group of patients. The anatomical data of the left ventricle and the ejection fraction were normal and comparable between the two groups, but the Tei index was significantly higher in group A (0.8 ± 0.04 vs. 0.28 ± 0.07, p < 0.01). Tissue Doppler velocity S peak measurement was reduced in group A compared to group B (5.6 ± 0.5 vs. 9.30 ± 0.5, p < 0.01), and global longitudinal strain was also altered in scleroderma patients (–11 ± 0.4 vs. –18 ± 0.3, p < 0.01). There was no significant difference in E/A ratio, however early left ventricular diastolic dysfunction was revealed by a higher E/Ea and E/Vp ratio in group A compared to group B with respectively (13 ± 1.8 vs. 6 ± 1.6, p < 0.01) and (2.2 ± 0.6 vs. 1.5 ± 0.6, p < 0.01), a longer Ap–Am duration (≥ 20 ms), and a higher volume of the left atrium was noted in group A. The mean value of the pulmonary pressions was 37.9 ± 9 mm Hg in patients with scleroderma versus 25 ± 3 mm Hg for the control group (p < 0.01). There was no right ventricular dysfunction. Conclusions. Cardiac involvement during systemic sclerosis precedes clinical expression. Echocardiography coupled with tissue Doppler and 2D strain are useful to detect these abnormalities at a subclinical stage of the disease.

A New Era in the Treatment of Scleroderma-associated Interstitial Lung Disease?

Pulmonary involvement in systemic sclerosis or scleroderma (SSc) is mainly represented by SSc-associated interstitial lung disease (SSc-ILD) and pulmonary hypertension1,2. SSc-ILD is a major challenge: It is both a very frequent and a very severe complication of SSc. According to the literature, SSc-ILD is or will be present in around one-half of patients with diffuse SSc, and one-third of patients with limited cutaneous SSc3. SSc-ILD is now one of the leading causes of death in SSc4. This explains why much effort has been expended to understand and better know the characteristics of patients with SSc-ILD as well as to manage them properly. However, despite decades of observational studies and a few randomized ones, the optimal management of patients with SSc-ILD is still a matter of debate. From an historic point of view, the cornerstone of SSc-ILD treatment has mainly been immunosuppressants. This can be explained by the fact that SSc is a connective tissue disease in which inflammation and immune abnormalities play a central role5. The immune system, especially in regards to B and T lymphocytes, is fully involved in fibroblast activation and fibrogenesis by secreting proinflammatory and profibrotic cytokines and growth factors6. The most common immunosuppressant, cyclophosphamide (CYC), has been tested in many open-label studies and a few randomized control trials (RCT), as well as being recommended in the European League Against Rheumatism Scleroderma Trials and Research group guidelines7. However, the results of those RCT are still dividing the medical community. In the FAST study, there was no significant … Address correspondence to Prof. D. Launay, Service de Medecine Interne, Hopital Claude-Huriez, CHRU Lille, rue Michel Polonovski, F-59037 LILLE Cedex, France. E-mail: david.launay{at}univ-lille2.fr

Pulmonary involvement in systemic sclerosis.

Systemic sclerosis (SSc) is a multi-systemic autoimmune disease that mainly affects the skin, lungs, gastrointestinal tract, heart and kidneys. Pulmonary disease in patients with SSc is strongly associated with mortality. The mechanisms involved into its pathophysiology include the activation of autoimmune cells and hyperplasia of fibroblasts with an increased capacity to produce collagen and diminished collagen breakdown. Although pulmonary biopsy is the gold standard for the diagnosis of interstitial lung disease in SSc, the most commonly used method is high-resolution computed tomography due to its high sensitivity and specificity. Herein, a comprehensive review on the pulmonary involvement in SSc is presented highlighting the radiologic-pathologic correlations.

Unique Abnormalities in Right Ventricular Longitudinal Strain in Systemic Sclerosis Patients.

Cardiac involvement in systemic sclerosis (scleroderma [SSc]) adversely affects long-term prognosis, often remaining undetectable despite close clinical examination and 2-dimensional echocardiographic monitoring. Speckle-derived strain of the right ventricle (RV) was utilized to detect occult abnormalities in regional and global contractility in SSc patients. A total of 138 SSc patients with technically adequate echocardiograms was studied and compared with 40 age- and sex-matched healthy non-SSc controls. Standard assessment of RV chamber function included tricuspid annular plane systolic excursion and fractional area change. RV longitudinal systolic speckle-derived strain was assessed in the basal, mid, and apical free wall. Tricuspid annular plane systolic excursion was not different between groups (P=0.307). Although fractional area change was lower in SSc patients than in controls (mean, 48.9 versus 55; P=0.002), the mean fractional area change was still within the normal range (>35). In contrast, RV longitudinal systolic speckle-derived strain measures were significantly different between groups, both globally (-20.4% versus -17.7%; P=0.005) and regionally: they were decreased in the apex (-8.5% versus -17.1%; P<0.0001) and mid segments (-12.4% versus -20.9%; P<0.0001), and increased in the base (-32.2% versus -23.3%; P=0.0001) for the SSc group. The regional difference in the base compared with the apex was significantly greater for SSc than for controls (P<0.0001 for interaction). The differences observed in regional strain between SSc and control were unchanged after adjusting for RV systolic pressure. Speckle-derived strain reveals a heterogenous pattern of regional heart strain in SSc that is not detected by conventional measures of function, suggestive of occult RV myocardial disease.

Erratum to: Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival.

Cardiac involvement (CI) is a known complication of SSc associated with increased mortality. Our objective was to describe a cohort of patients with SSc and CI and to assess the differences between cutaneous subsets regarding their presentation and survival. Three hundred and ninety-three Spanish patients from a single center, diagnosed with SSc, were retrospectively studied for evidence of CI using noninvasive and invasive tests from 1976 to 2011. Clinical, epidemiological, immunological and therapeutic features of patients with CI were compared to those without it and within the different cutaneous subsets of SSc. CI was present in 173 (44 %) patients. Mitral regurgitation (67 %), conduction alterations (45 %) and left ventricle diastolic dysfunction (40 %) were the most common findings. Pericardial involvement and heart failure were more frequent in diffuse SSc (dcSSc) than in limited or sine scleroderma SSc. CI accounted for 20 % of deaths, and it was an independent mortality risk factor (HR 2.1, P = 0.02), but once CI was established, classical dcSSc mortality risk factors determined mortality. Patients with dcSSc developed CI faster than limited (HR 1.9, P = 0.003) or sine SSc patients (HR 2.5, P = 0.002), specially during the first year after SSc onset. We found statistically significant differences between the 3 SSc subsets in the presentation of pericardial involvement and heart failure. CI increased the mortality and appeared at a higher rate, especially during the first year after SSc onset. Screening for heart involvement should be performed at diagnosis and during follow-up.

Management of Musculoskeletal Involvement in Systemic Sclerosis.

Musculoskeletal (MSK) pain is a frequent complaint (between 40–80 % of SSc patients) of patients with systemic sclerosis (SSc) and is most problematic in patients with early diffuse SSc. There are several MSK pain syndromes that can be seen in SSc: seronegative polyarthritis, rheumatoid arthritis, tendonitis, fibromyalgia and other MSK pain syndromes. There are, however, few systemically performed studies that show us the best ways to evaluate or to treat these syndromes. This article presents an expert’s opinion about how to evaluate these pain syndromes and how best to treat them, given the limited amount of scientific data that are available.

Pulmonary involvement in systemic sclerosis: A clinical profile.

Background:Systemic sclerosis is a generalized disorder of connective tissue affecting skin and internal organs. Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients.Objectives:This study intends to study the frequency of occurrence of pulmonary involvement in progressive systemic sclerosis (PSS) and to describe the clinical and radiological picture of pulmonary involvement in PSS.Materials and Methods:This was a descriptive cross-sectional study. A detailed history, modified Rodnan score, clinical examination, routine investigation, antinuclear antibody, immuno biot, chest X-ray (CXR), pulmonary function test (PFT), and 6 min walk test (6MWT) were performed on all patients. High resolution computed tomography was done on those who consented.Results:Hundred subjects with PSS were included in the study; 90 were females and 10 were males. Common presenting complaints were skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in 92%. Chest wall thickening was seen in 40 subjects (40%). 90 (90%) of the studied subjects had pulmonary involvement, longer duration of disease was significantly associated with pulmonary involvement (P < 0.05). Dyspnea, cough, bilateral crepitations, CXR, Borg score, and Rodnan score was found to be significantly associated with severe pulmonary involvement (P < 0.05).Conclusion:The prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3rd of patients, that is 29 (29%) were detected to have pulmonary involvement despite being asymptomatic for respiratory complaints, hence early screening and evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and easily available screening tests which can be used in resource-limited settings.

Cardiovascular magnetic resonance patterns of biopsy proven cardiac involvement in systemic sclerosis

BackgroundTo determine morphological and functional cardiovascular magnetic resonance (CMR) patterns in histopathologically confirmed myocardial involvement in patients with systemic sclerosis (SSc).MethodsTwenty patients (6 females; mean age 41 ± 11 years) with histopathologically proven cardiac involvement in SSc in the years 2008–2016 were retrospectively evaluated. Morphological, functional and late gadolinium enhancement (LGE) images were acquired in standard angulations at 1.5 T CMR. Pathologies were categorized: 1) Pericardial effusion; 2) pathologic left (LV) or right ventricular (RV) contractility (hypokinesia, dyssynchrony, and diastolic restriction); 3) reduced left (LV-EF) and right ventricular ejection fraction (RV-EF); 4) fibrosis and/or inflammation (positive LGE); 5) RV dilatation. 95 % confidence intervals (CI) were calculated for appearance of pathologic EF and RV dilatation.ResultsSeven patients (35 %) had positive CMR findings in three categories, 9 patients (45 %) in four categories and 4 patients (20 %) in five categories. The distribution of pathologic findings was: minimal pericardial effusion in 7 patients (35 %), moderate pericardial effusion >5 mm in nine patients (45 %); abnormal LV or RV contractility in 19 patients (95 %), reduced LV or RV function in 14 patients (70 %; 95 % CI: 51–88 %), pathologic LGE in all patients, RV dilatation in 6 patients (30 %; 95 % CI: 15–54 %).ConclusionsCMR diagnosis of myocardial involvement in SSc requires increased attention to subtle findings. Pathologic findings in at least three of five categories indicate myocardial involvement in SSc.

0244: Prognostic value of heart rhythmic events in systemic sclerosis

Systemic sclerosis (SSc) is a multi-systemic disease, responsible for the occurrence of fibrosis interesting skin and some organs such as the heart. The rhythm and conduction disturbances are probably one of the main prognostic factors for heart involvement in systemic sclerosis. Conduction disorders are common and generally not serious, and arrhythmias, especially ventricular ones are more threatening. Performing Holter ECG. Shows significant abnormal Heart rhythm disturbances percentage. Make a descriptive analysis of various rhythm disorder and conduction defects in a population of patients with SSc. From December 2010 to June 2014, 234 patients including 205 women and 29 men with systemic sclerosis were included. Each patient underwent a baseline ECG, cardiac echo Doppler looking for heart damages. A cardiac MRI was performed to search a myocardial fibrosis when segmental wall motion abnormalities were found by echo. 50 Holter ECG has been performed. All patients were in sinus rhythm. Supra ventricular, ventricular premature beats or a combination of both were found in 12.8%. Conduction disorders (first degree AV block, Mobitz 1 AVB, ILBBB, LBBB, RBBB, LAHB) were found in 11.5%. There have been 3 ventricular tachycardia and one sudden death among patients treated for ventricular hyperexcitability with myocardial fibrosis. Of the 50 Holter ECG performed, we recorded an episode of paroxysmal ACFA, supra ventricular hyperexcitability in 39 patients (78%), ventricular hyperexcitability in 44 patients (88%), very important in more than half the cases and often associated with myocardial fibrosis. There was no high degree conduction disturbances. Rhythm and conduction disorders are frequently encountered in systemic sclerosis and constitute one of cardiac manifestations affecting the vital prognosis.

Macrophage Involvement in Systemic Sclerosis: Do We Need More Evidence?

The pathogenesis of systemic sclerosis is still unknown, although immune cells, mainly macrophages/monocytes, may have an important role in initiating and/or perpetuating the disease. Macrophages and monocytes are often classified as pro-inflammatory M1 phenotype or classic activation and pro-fibrotic/anti-inflammatory M2 phenotype or alternative activation. In this review, we highlighted the most relevant research regarding the involvement of macrophages/monocytes in the pathogenesis of this complex disease.

Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis.

The aim of this study was to evaluate in systemic sclerosis (SSc) retrospectively the effect of Bosentan and Sildenafil and their combination on Raynaud's phenomenon (RP), function, and capillaroscopic patterns. One hundred and twenty-three SSc patients (mean age ± sd, 57.69 ± 14.07 years) were retrospectively evaluated and divided into two groups according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification score: group 1 score < 10, group 2 score > 10. Each group was divided into three subgroups according to treatment: Bosentan, Sildenafil, and Bosentan + Sildenafil. Nailfold videocapillaroscopy (NVC), Scleroderma Health Assessment Questionnaire (SHAQ) and Raynaud Condition Score (RCS) were performed at baseline and after 3 and 6 months. In Bosentan (29 patients: 12, group 1; 17, group 2), NVC changed significantly in both groups, after 3 and 6 months (p = 0.00439, group 1; p = 0.00035, group 2). In group 1, the "active" and the "late" patterns reduced, and the "aspecific" increased. In group 2, there was a reduction of late patterns, a worsening of SHAQ (p < 0.005) and an improvement of RCS (p = 0.00014). In Sildenafil (63 patients: 35, group 1; 28, group 2), after 3 months, NVC patterns changed significantly in both groups(p = 0.042 group 1, p = 0.00089 group 2). In group 1, the late and early patterns increased, and the aspecific decreased. In group 2, a significant change of NVC pattern was observed also after 6 months (p = 0.00089): the late pattern increased while the active one reduced. After 6 months, SHAQ was significantly reduced in group 1 (p = 0.00027) and in group 2 (p = 0.0043). RCS improved in both groups (p = 0.0042, group 1; p = 0.0016, group 2). Combination therapy (Bosentan + Sildenafil) (31 patients: 14, group 1; 17, group 2) induced significant changes on NVC only in group 1 after 3 (p = 0.00256) and 6 months (p = 0.000349) with a reduction of the late and active patterns and an increase of the early pattern. In both groups, after 6 months, SHAQ (p < 0.05, group 1; p = 0.00049, group 2) and RCS significantly reduced (group 1, p = 0.00024; group 2, p = 0.0021). Patients treated with Bosentan + Sildenafil show a significant improvement of RCS and NVC. This combination therapy may exert a vascular activity achieving an amelioration of the structure of microvasculature in SSc.

High frequency ultrasound of skin involvement in systemic sclerosis – a follow-up study

IntroductionHigh-frequency ultrasound offers a potential for objective and quantitative assessment of skin thickness and skin echogenicity in systemic sclerosis (SSc). Few studies have however assessed the longitudinal changes of skin involvement using ultrasound. The aim of the study was to investigate changes in skin thickness in early SSc using high frequency ultrasound during one year of follow-up in comparison to other measurements of skin fibrosis.MethodsThis retrospective study comprised 75 consecutive patients with disease duration shorter than 3 years, in whom ultrasound examination of skin thickness was performed at baseline and at the one year follow-up at five predefined sites.ResultsRepeated ultrasound examination identified significant changes in a majority of patients. In 21 patients, the total sum of skin thickness (TST) increased, while TST decreased in 37 patients. On a group level there were significant decreases in skin thickness of the chest (p = 0.024) and in the TST (p = 0.011) during the observation time. Both baseline and follow-up TST correlated to serum-COMP (rS: 0.41; p = 0.001; rS: 0.49; p < 0.001), modified Rodnan skin score (mRSS; rS: 0.48; p < 0.001; rS: 0.48; p < 0.001) and hand mobility in scleroderma (HAMIS; rS: 0.30; p = 0.043; rS: 0.64; p < 0.001). Changes in TST correlated with changes in serum-COMP (rS: 0.30; p = 0.034), changes in mRSS (rS: 0.43; p < 0.001) and changes in HAMIS (rS: 0.53; p = 0.001) during follow-up.ConclusionsIn early SSc, skin thickness measured by high frequency ultrasound develops in parallel with serum-COMP, mRSS and the HAMIS test. Ultrasound examination of the skin allows for objective assessment of one facet of the complex process of skin fibrosis in early SSc.

Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival.

Cardiac involvement (CI) is a known complication of SSc associated with increased mortality. Our objective was to describe a cohort of patients with SSc and CI and to assess the differences between cutaneous subsets regarding their presentation and survival. Three hundred and ninety-three Spanish patients from a single center, diagnosed with SSc, were retrospectively studied for evidence of CI using noninvasive and invasive tests from 1976 to 2011. Clinical, epidemiological, immunological and therapeutic features of patients with CI were compared to those without it and within the different cutaneous subsets of SSc. CI was present in 173 (44%) patients. Mitral regurgitation (67%), conduction alterations (45%) and left ventricle diastolic dysfunction (40%) were the most common findings. Pericardial involvement and heart failure were more frequent in diffuse SSc (dcSSc) than in limited or sine scleroderma SSc. CI accounted for 20% of deaths, and it was an independent mortality risk factor (HR 2.1, P=0.02), but once CI was established, classical dcSSc mortality risk factors determined mortality. Patients with dcSSc developed CI faster than limited (HR 1.9, P=0.003) or sine SSc patients (HR 2.5, P=0.002), specially during the first year after SSc onset. We found statistically significant differences between the 3 SSc subsets in the presentation of pericardial involvement and heart failure. CI increased the mortality and appeared at a higher rate, especially during the first year after SSc onset. Screening for heart involvement should be performed at diagnosis and during follow-up.

Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis.

IVIG is known to confer significant benefit in rheumatologic conditions, including inflammatory myopathy. This study aimed to assess the efficacy of IVIG across different aspects of internal organ involvement in refractory active SSc, particularly the gastrointestinal (GI) system. SSc patients with overlap polymyositis who remained active and unresponsive to conventional disease-modifying agents and who subsequently received IVIG were identified. GI symptoms were assessed using validated questionnaires. The Medical Research Council Sum Score for muscle strength and modified Rodnan skin score (mRSS) were assessed. Serial measurements were undertaken at baseline prior to the first IVIG treatment and post-treatment in the most recent assessment. Fifteen SSc patients were consecutively recruited into this observational study. The mean duration of IVIG treatment was 2.3 years, with treatment frequency ranging from every 6 weeks to 4 months. Compared with baseline, there was a significant reduction in gastro-oesophageal reflux frequency and intensity mean scores (P = 0.006 and P = 0.013, respectively). Significant improvement in the Gastrointestinal Tract (GIT) 2.0 score from a baseline mean score of 1.07 (s.d. 0.67) to 0.60 (0.46) (P = 0.002) was observed. There was regression in the markers of muscle disease with a reduction in the mean (s.d.) Medical Research Council sum score and the median creatine kinase level (P = 0.001 and P = 0.025, respectively). Significant amelioration of the mean basal modified Rodnan skin score from 21.5 (s.d. 13.8) to 10 (10.6) (P = 0.005) was observed. IVIG may be a helpful adjunctive therapy in the amelioration of some key clinical aspects in refractory SSc. Sustained benefit from IVIG suggests a specific immunomodulatory effect on those with established SSc GI complications.

Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis.

BackgroundEndothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ involvements or cutaneous subgroups of SSc patients.MethodMPs in platelet-poor plasma from 121 patients with SSc, 79 and 42 with limited and diffuse cutaneous disease, respectively, were characterized by flow cytometry for their capacity to bind annexin V in combination with surface markers of either platelets (PMPs), leukocytes (LMPs) or endothelial cells (EMPs). Soluble E- and P-selectin levels were determined in plasma. By correlation analyses, this was held against involvement of skin, lung function, lung fibrosis, pulmonary artery hypertension, and serology.ResultsNone of the markers were associated with cutaneous subgroups of SSc. Concentrations of annexin V non-binding EMPs and annexin V non-binding LMPs were negatively correlated to pulmonary diffusing capacity (DLCO) (r = -0.28; p = 0.003; r = -0.26; p = 0.005) and forced vital capacity (FVC) (r = -0.24; p = 0.009; r = -0.29; p = 0.002), driven by patients with limited and diffuse cutaneous disease, respectively. Soluble E-selectin levels correlated negatively to DLCO (r = -0.21, p = 0.03) and FVC (r = -0.25; p = 0.007); and soluble P-selectin correlated negatively to DLCO (r = -0.23, p = 0.01).ConclusionNegative correlations between annexin V non-binding EMP and LMP concentrations with lung function parameters (DLCO and FVC) differed between limited and diffuse cutaneous subsets of SSc, indicative of various pathogeneses of lung involvement in SSc, possibly with a differential role of MPs.

Right ventricular thickness as predictor of global myocardial performance in systemic sclerosis: A Doppler tissue imaging study

BackgroundCardiopulmonary involvement in systemic sclerosis (SSc) is a poor prognostic factor, due to pulmonary hypertension and right ventricular dysfunction. We assessed the echocardiographic parameters of right ventricular (RV) function in SSc and correlated echocardiographic findings to clinical features of the disease. MethodsThirty patients with SSc (cases) and 30 healthy, age-matched subjects (controls) were studied. Echocardiography, including tissue Doppler imaging, was used to evaluate cardiac function. ResultsPulmonary hypertension could be documented in only 5 cases by Doppler echo, using Bernoulli principle. RV diastolic function was significantly deranged in cases. RV systolic function and left ventricle (LV) diastolic function were also significantly deranged in the cases. RV thickness was increased in patients with SSc. There were no significant differences in the echocardiographic variables between diffuse and limited subtypes of SSc. Myocardial performance index (MPI) of both ventricles were increased in cases. We could demonstrate RV thickness as the single most important predictor of MPI of both ventricles with sensitivity of 82% and specificity of 72% for RV-MPI and 63% for LV-MPI. Diastolic function was not found to be affected by disease duration or Rodnan skin score. ConclusionPatients with SSc exhibit abnormal RV and LV diastolic functions as well as abnormal RV systolic function. RV wall thickness was found to be simple and the single best predictor of global myocardial performance. RV dysfunction may be a response to intermittent pulmonary arterial hypertension, lung parenchymal involvement, or secondary to LV diastolic dysfunction in SSc.

A right ventricular diastolic impairment is common in systemic sclerosis and is associated with other target-organ damage

Heart involvement in systemic sclerosis (SSc) is a strong prognostic factor. Our aim was to examine left ventricle (LV) and right ventricle (RV) involvement. We examined LV and RV, systolic and diastolic functions, using echocardiography and Tissue-Doppler echocardiography (TDE) indexes, in a cohort of 212 consecutive SSc patients seen during a 9-month period at 2 institutions (Paris, France and Los Angeles, USA). They were compared to 50 healthy controls. When compared to controls, SSc patients had consistently impaired RV indices that include reduced RV contractility (p < 0.001), larger right atrial area (p = 0.027) and overall RV diastolic dysfunction (25% of SSc patients versus 0% of controls; p < 0.001). Patients also exhibited alterations in LV contractility and diastolic function (p < 0.001 each). In multivariate analysis, RV contractility as expressed by the TDE S(T) parameter was associated with TDE LV contractility S(M) (p = 0.030), DLCO (p = 0.013) whereas RV diastolic impairment was associated with systolic pulmonary artery pressure (p = 0.015). A subgroup of 27 patients had proven pulmonary arterial hypertension (PAH); comparison between SSc-PAH versus SSc free of PAH patients revealed reduced LV diastolic function (transmitral E/A ratio, p = 0.045 and E(A) < 10 cm/s, p = 0.029), reduced overall RV contractility (21.5% versus 4.5%; p = 0.03) and reduced RV diastolic function (transtricuspid E/A ratio; p = 0.014 and 68% versus 29% with impaired function; p = 0.001). Our data show that RV is commonly affected in SSc with predominant impaired diastolic function. Several factors, including primary heart, lung vascular disease and pulmonary hypertension, contribute to such impairment.

Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study.

Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 ± 2.6 to 11.53 ± 3.4 mmHg (p = 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p = 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( + 2.11 ± 2.0 versus -0.45 ± 2.3 mmHg, p = 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted.

Clinical and histopathological features of patients with systemic sclerosis undergoing endomyocardial biopsy.

BackgroundCardiac involvement in systemic sclerosis (SSc) is associated with a variable phenotype including heart failure, arrhythmias and pulmonary hypertension. The aim of the present study was to evaluate clinical characteristics, histopathological findings and outcome of patients with SSc and a clinical phenotype suggesting cardiac involvement.Methods and Results25 patients with SSc and clinical signs of cardiac involvement were included between June 2007 and December 2010. They underwent routine clinical work-up including laboratory testing, echocardiography, left and right heart catheterization, holter recordings and endomyocardial biopsy. Primary endpoint (EP) was defined as the combination of cardiovascular death, arrhythmic endpoints (defined as appropriate discharge of implantable cardioverter defibrillator (ICD)) or rehospitalization due to heart failure. The majority of patients presented with slightly impaired left ventricular function (mean LVEF 54.1±9.0%, determined by echocardiography). Endomyocardial biopsies detected cardiac fibrosis in all patients with a variable area percentage of 8% to 32%. Cardiac inflammation was diagnosed as follows: No inflammation in 3.8%, isolated inflammatory cells in 38.5%, a few foci of inflammation in 30.8%, several foci of inflammation in 15.4%, and pronounced inflammation in 7.7% of patients. During follow up (FU) (22.5 months), seven (28%) patients reached the primary EP. Patients with subsequent events showed a higher degree of fibrosis and inflammation in the myocardium by trend. While patients with an inflammation grade 0 or 1 showed an event rate of 18.2%, the subgroup of patients with an inflammation grade 2 presented with an event rate of 25% versus an event rate of 50% in the subgroup of patients with an inflammation grade 3 and 4, respectively (p=0.193). Furthermore, the subgroup of patients with fibrosis grade 1 showed an event rate of 11%, patients with fibrosis grade 2 and 3 presented with an event rate of 33% and 42% respectively (p = 0.160).ConclusionsPatients with SSc and clinical signs of cardiac involvement presented with mildly impaired LVEF. Prognosis was poor with an event rate of 28% within 22.5 months FU and was associated with the degree of cardiac inflammation and fibrosis.