Heart Involvement In Systemic Sclerosis Research Articles

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. >125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p<0.001). A 3D LACI of >2 associated with NTproBNP of >125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p<0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.

Heart involvement in systemic sclerosis: emerging concepts.

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. We describe the spectrum, clinical features, and pathogenesis of SHI. Furthermore, we review the new recommendations for screening for SHI in individuals with SSc. 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.

Cardiac magnetic resonance imaging in systemic sclerosis: Heart involvement in high-resolution.

Cardiac magnetic resonance imaging (CMR) is the gold-standard non-invasive method of assessing cardiac structure and function, including tissue characterisation. In systemic sclerosis (SSc), heart involvement (SHI) is a leading cause of mortality yet remains poorly understood. SHI is underestimated by conventional echocardiography, and CMR provides an important opportunity to better identify and quantify subtle myocardial changes including oedema and fibrosis. This review summarises current CMR techniques, the role of CMR in SSc and SHI, and the opportunities to further our understanding of its pathogenesis and management.

Therapeutic strategies for primary heart involvement in systemic sclerosis.

Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), even though often underdiagnosed. SSc-pHI has been recently defined as cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications. SSc-pHI represents a major determinant of mortality in SSc, accounting alone for about 12% of disease-related deaths; its early recognition and promptly therapeutic interventions are therefore crucial. Both perfusion defects and myocardial inflammation contribute to the occurrence of myocardial fibrosis that precipitates myocardial remodeling, potentially leading to heart failure and arrhythmic complications. To date, clear evidence and guidelines for effectively managing SSc pHI are not established yet, resulting in a lack of a defined therapeutic algorithm. In this review we summarize the most recent scientific literature on the prevailing therapeutic strategies and interventions to manage SSc-pHI, with particular focus on therapeutic strategies to counteract the 3 major pathogenic events of the disease, i.e. microvascular damage, myocardial inflammation and myocardial fibrosis.

Speckle-tracking global longitudinal strain predicts death and cardiovascular events in patients with systemic sclerosis.

Albeit often asymptomatic, heart involvement in systemic sclerosis (SSc) represents a negative prognostic factor, accounting for nearly one-fourth of all deaths. Global longitudinal strain (GLS) is accurate in detecting heart involvement in patients with SSc and no overt cardiac disease and allows early detection and longitudinal monitoring, but its association with clinical endpoints has not been tested so far. The primary outcome was the association between left and right GLS and mortality for all causes. The secondary outcome was the association between left and right GLS and hospitalizations. A prospective longitudinal study enrolling all consecutive patients with SSc without structural heart disease or previous cardiovascular event.A total of 164 patients were enrolled, of whom 19 (11.5%) died during follow-up and 48 (29.3%) were hospitalized. Both left (LV) and right ventricle (RV) GLS at enrolment were independently associated with an increased risk of death for all causes and hospitalizations. Patients with biventricular GLS impairment, respectively, had a 4.2-, 4.9-, and 13.9-fold increased risk of death when compared with patients with only LV, only RV, or no impairment (P < 0.001). The incidence of hospitalization in patients with biventricular GLS impairment was nearly four times higher when compared with patients with only LV or only RV impairment, and nine times higher when compared with normal biventricular GLS (P < 0.001). Biventricular GLS is associated with an increased risk of death and hospitalization in patients with SSc during a median of 3-year follow-up, acting as a reliable and accurate prognostic tool in everyday practice.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

The Involvement of Smooth Muscle, Striated Muscle, and the Myocardium in Scleroderma: A Review.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by heterogeneous changes involving numerous organs and systems. The currently available data indicate that muscle injury (both smooth and striated muscles) is widespread and leads to significant morbidity, either directly or indirectly. From the consequences of smooth muscle involvement in the tunica media of blood vessels or at the level of the digestive tract, to skeletal myopathy (which may be interpreted strictly in the context of SSc, or as an overlap with idiopathic inflammatory myopathies), muscular injury in scleroderma translates to a number of notable clinical manifestations. Heart involvement in SSc is heterogenous depending on the definition used in the various studies. The majority of SSc patients experience a silent form of cardiac disease. The present review summarizes certain important features of myocardial, as well as smooth and skeletal muscle involvement in SSc. Further research is needed to fully describe and understand the pathogenic pathways and the implications of muscle involvement in scleroderma.

Primary heart involvement in systemic sclerosis, from conventional to innovative targeted therapeutic strategies.

Primary heart involvement is frequent in systemic sclerosis, even though often sub-clinical, and includes cardiac abnormalities that are predominantly attributable to systemic sclerosis rather than other causes and/or complications. A timely diagnosis is crucial to promptly start the appropriate therapy and to prevent the potential life-threatening early and late complications. There is little evidence on how to best manage systemic sclerosis-primary heart involvement as no specific treatment recommendations for heart disease are available, and a shared treatment approach is still lacking. The objective of this review is to summarize the state of the art of current literature and the overall management strategies and therapeutic approaches for systemic sclerosis-primary heart involvement. Novel insights into pathogenic mechanisms of systemic sclerosis-primary heart involvement are presented to facilitate the comprehension of therapeutic targets and novel treatment strategies.

Heart Involvement in Systemic Sclerosis: the Role of Magnetic Resonance Imaging.

Systemic sclerosis (SSc) is a severe connective tissue disease characterized by diffuse vascular damage and aberrant activation of immune system, resulting in inflammation and fibrosis of skin and internal organs, including the heart. Cardiac involvement is frequent in SSc, even though often unrecognized due to the occult nature at early stages and to the lack of a defined diagnostic algorithm. Once clinically evident, heart involvement is associated with a poor prognosis, representing the leading cause of death in about one third of SSc patients. Thus, its early recognition and monitoring are of crucial importance to allow a prompt therapeutic intervention and to improve patients' outcomes. Cardiac Magnetic Resonance (CMR) is a non-invasive, non-radiating imaging technique of great importance for the assessment of cardiovascular system, and represents the modality of choice for the morpho-functional and structural characterization of the heart. In SSc, CMR allows a precise definition of biventricular and biatrial size and function, and a detailed tissue characterization. CMR has been therefore extensively proposed in SSc as a non-invasive diagnostic tool to characterize heart involvement, particularly myocardial involvement. In this review, we summarize the most recent evidences to support the use of CMR in SSc as an important tool to recognize and characterize scleroderma heart disease. Furthermore, the unmet needs and the future perspectives of a CMR-based approach for the early detection of SSc heart involvement are discussed.

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition.

Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5-300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46-1.00) for the first round and 0.55 (0.44-1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47-1.00)). Criterion validity showed a 78 (73-84)% correctness versus gold standard. A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.

Interleukin-1 and Systemic Sclerosis: Getting to the Heart of Cardiac Involvement.

Systemic sclerosis (SSc) is rare, severe connective tissue disease characterized by endothelial and vascular damage, immune activation, and resulting in inflammation and fibrosis of skin and internal organs, including the heart. SSc is associated with high morbidity and mortality. Cardiac involvement is frequent in SSc patients, even though often asymptomatic at early stages, and represents one of the major causes of SSc-related mortality. Heart involvement has a variable clinical presentation, and its pathogenesis is not completely understood. Myocardial fibrosis is traditionally considered the immunopathologic hallmark of heart involvement in SSc. This unique histological feature is paralleled by distinctive clinical and prognostic features. The so-called “vascular hypothesis” represents the most credited hypothesis to explain myocardial fibrosis. More recently, the prominent role of an inflammatory myocardial process has been identified as a cardinal event in the evolution to fibrosis, thus also delineating an “inflammation-driven pathway to fibrosis”. The pro-inflammatory cytokine interleukin (IL)-1 has an apical and cardinal role in the myocardial inflammatory cascade and in cardiac dysfunction. The primary aim of this perspective article is: to present the emerging evidence on the role of IL-1 and inflammasome in both SSc and heart inflammation, to review the complex interplay between cellular metabolism and inflammasome activation, and to discuss the rationale for targeted inhibition of IL-1 for the treatment of SSc-heart involvement, providing preliminary experimental and clinical data to support this hypothesis.

Significant and Early Cardiac Involvement in Systemic Sclerosis Detected by Cardiac Magnetic Resonance

Heart involvement in systemic sclerosis (SSc) is common and often diagnosed late in the disease course. It may involve the myocardium, pericardium and conducting system, though there is heterogeneity in presentation. We sought to characterise cardiac involvement in SSc using cardiac Magnetic Resonance imaging (CMR).

Effect of rituximab on heart involvement in systemic sclerosis

As of now, there has been a great body of data on the use of rituximab (RTM) in systemic sclerosis (SS), mainly on its positive effect on skin fibrosis and lung injury. However, information is still scarce about the effect of RTM on other organs and systems, namely the heart affected by SS.Objective: to assess the time course of changes in the signs of heart involvement in SS patients one year after initiation of RTM therapy.Subjects and methods. The paper gives data on changes in cardiac disorders in 71 patients with SS one year after the prescription of RTM.Results and discussion. The rate of cardiac rhythm and conduction disorders and diastolic dysfunction was unchanged. At the same time, a significant increase in left ventricular ejection fraction (EF) and a reduction in the severity of dyspnea was achieved, which correlated with improved lung function (a significant rise in forced vital capacity). The results of treatment in three patients with predominant heart involvement associated with SS (coronary heart disease and hypertension were ruled out) were considered in detail. These patients displayed pronounced positive changes as increased EF, less severe cardiac arrhythmias, reduced chronic heart failure, better quality of life, as well as the synchronicity of lower disease activity, less skin induction, improved lung function, and stabilized pulmonary artery systolic pressure.Conclusion. RTM in combination with traditional therapy can be considered as a potentially effective drug for the treatment of heart involvement in SS.

P3489Bidimensional speckle-tracking detects subclinical heart involvement in systemic sclerosis

P3489Bidimensional speckle-tracking detects subclinical heart involvement in systemic sclerosis

Value of cardiac magnetic resonance imaging in systemic sclerosis.

ObjectivesTo assess the prevalence and patterns of cardiac abnormalities as detected by cardiac magnetic resonance imaging (MRI) in systemic sclerosis.Material and methodsTwenty-six consecutive patients with systemic sclerosis underwent cardiac MRI to determine morphological, functional, perfusion at rest, and delayed enhancement abnormalities.ResultsAt least one abnormality on cardiac MRI was observed in 19/26 (73%) patients. Increased myocardial signal intensity in T2 was observed in 10 patients (38.5%), thinning of the left ventricular myocardium in 1 patient (3.5%), and pericardial effusion in 12 patients (46%). Left and right ventricular ejection fractions were altered in 10 patients (38.5%) and 11 patients (42%), respectively. Myocardial delayed contrast enhancement was found in 11 (42%) patients. No perfusion defects at rest were found. Patients with limited systemic sclerosis had similar cardiac MRI abnormalities to patients with diffuse systemic sclerosis. Four out of 11 patients (36.4%) without pulmonary arterial hypertension had right ventricular dilatation.ConclusionsThe present study shows that cardiac MRI is an accurate and reliable technique to diagnose cardiac involvement in systemic sclerosis and to analyze precisely its mechanisms, including inflammatory, microvascular and fibrotic components. As it is non-invasive, quantitative and highly sensitive, cardiac MRI appears to be a method of choice to determine the natural history of untreated patients or to accurately monitor the effects of treatment. Moreover, it could provide powerful prognostic factors in both groups. Compared to echocardiography, cardiac MRI appears to provide additional information by visualizing myocardial fibrosis and inflammation. Finally, the present study has shown that RV dilatation is not specific for pulmonary arterial hypertension and could correspond to a specific heart involvement in systemic sclerosis.

Sclérodermie systémique : efficacité des immunoglobulines intraveineuses pour l’atteinte cardiaque sévère ?

BackgroundThe heart involvement in systemic sclerosis is frequent and can touch various sites. The prognosis in the presence of heart disease is poor, but few data are available about its management. CaseWe report the case of 48 years old woman with systemic sclerosis which presented severe heart involvement. She has severe heart failure, supraventricular arrhythmias and symptomatic pericarditis, which required surgical intervention and immunosuppressive drugs (steroids with rituximab). Despite this treatment, she has persistent severe heart impaired function and intravenous immunoglobulins have been initiated. She experienced progressively the improvement of dyspnea, of heart systolic ejection fraction and decrease of Rodnan scale. ConclusionOur case illustrates a severe heart involvement in systemic sclerosis which have been improved by intravenous immunoglobulins.

Retraction: Value of cardiac magnetic resonance imaging in systemic sclerosis.

[This retracts the article DOI: 10.5114/reum.2018.75520.].

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.

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.

Heart involvement in systemic sclerosis: a combined echocardiographic and scintigraphic study.

The aim of this study is to investigate systemic sclerosis (SSc) patients without clinically evident heart disease for cardiac abnormalities. SSc patients and age- and sex-matched healthy controls from the hospital staff underwent transthoracic echocardiography for the assessment of the left ventricle (LV) morphology and function and estimation of the pulmonary artery systolic pressure (PASP). Patients further underwent stress-rest myocardial perfusion imaging (MPI) scintigraphy by single-photon emission computed tomography (SPECT). Thirty-seven patients were included (33 women, 19 with diffuse, and 18 with limited SSc). LV hypertrophy was more common in SSc patients than controls (24.3 vs 0%, p = 0.001). Impaired LV relaxation was found in 45.9% of patients and 40.5% controls (p = 0.639). Excluding patients with arterial hypertension, LV hypertrophy was still found in 23.1% and LV relaxation impairment in 38.5%. PASP over 30mmHg was found in 13 patients (35.1%), 11 of whom had no history of pulmonary arterial hypertension (PAH). Of 35 patients who underwent SPECT, 21 patients (60%) exhibited reversible LV perfusion defects. Their mean age was 51.8years; four patients were younger than 40years old and eight patients younger than 50years. In all cases, ischemia was graded as mild or moderate and in a single case, graded as significant. Subclinical heart involvement is common in SSc patients even in the younger age groups. LV hypertrophy and impaired relaxation, raised PASP, and ischemia on MPI with SPECT are found in a significant proportion of SSc patients. Careful screening of SSc patients for potential heart involvement and consultation by a cardiologist may be of value.