Heart Involvement in Systemic Sclerosis Underappreciated

Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts of AHA and AIDA in SSc. Methods: The study included consecutive SSc patients (n = 116, aged 53 ± 13 years, 83.6% females, median disease duration 7 years) with clinically suspected heart involvement (symptoms, abnormal ECG, abnormal troponin I or natriuretic peptides, and abnormal echocardiography). All SSc patients underwent CMR. Serum AHA and AIDA were measured by indirect immunofluorescence in SSc and in control groups of non-inflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141), and normal blood donors (NBD) (n = 270). AHA and AIDA status in SSc was correlated with baseline clinical, diagnostic features, and outcome. Results: The frequency of AHA was higher in SSc (57/116, 49%, p < 0.00001) than in NICD (2/160, 1%), IHF (2/141, 1%), or NBD (7/270, 2.5%). The frequency of AIDA was higher (65/116, 56%, p < 0.00001) in SSc than in NICD (6/160, 3.75%), IHF (3/141, 2%), or NBD (1/270, 0.37%). AHAs were associated with interstitial lung disease (p = 0.04), history of chest pain (p = 0.026), abnormal troponin (p = 0.006), AIDA (p = 0.000), and current immunosuppression (p = 0.01). AHAs were associated with death (p = 0.02) and overall cardiac events during follow-up (p = 0.017). Conclusions: The high frequencies of AHA and AIDA suggest a high burden of underdiagnosed autoimmune HInv in SSc. In keeping with the negative prognostic impact of HInv in SSc, AHAs were associated with dismal prognosis.

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Effect of rituximab on heart involvement in systemic sclerosis

Rheumatology Science and Practice ◽

10.14412/1995-4484-2018-709-715 ◽

2019 ◽

Vol 56 (6) ◽

pp. 709-715 ◽

Cited By ~ 1

Author(s):

L. A. Garzanova ◽

L. P. Ananyeva ◽

O. A. Koneva ◽

O. B. Ovsyannikova

Keyword(s):

Systemic Sclerosis ◽

Lung Function ◽

Time Course ◽

Systolic Pressure ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Pulmonary Artery Systolic Pressure ◽

Ventricular Ejection Fraction ◽

Heart Involvement ◽

One Year

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.

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Subclinical progression of systemic sclerosis-related cardiomyopathy

European Journal of Preventive Cardiology ◽

10.1177/2047487320916591 ◽

2020 ◽

Vol 27 (17) ◽

pp. 1876-1886

Author(s):

Giulia Stronati ◽

Lucia Manfredi ◽

Alessia Ferrarini ◽

Lucia Zuliani ◽

Marco Fogante ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Speckle Tracking ◽

Cardiac Involvement ◽

Global Longitudinal Strain ◽

Prospective Longitudinal Study ◽

Heart Involvement ◽

Increased Risk ◽

Prospective Longitudinal

Aims Cardiac involvement in patients with systemic sclerosis (SSc) is frequent and represents a negative prognostic factor. Recent studies have described subclinical heart involvement of both the right ventricle (RV) and left ventricle (LV) via speckle-tracking-derived global longitudinal strain (GLS). It is currently unknown if SSc-related cardiomyopathy progresses through time. Our aim was to assess the progression of subclinical cardiac involvement in patients with SSc via speckle-tracking-derived GLS. Methods This was a prospective longitudinal study enrolling 72 consecutive patients with a diagnosis of SSc and no structural heart disease nor pulmonary hypertension. A standard echocardiographic exam and GLS calculations were performed at baseline and at follow-up. Results Traditional echocardiographic parameters did not differ from baseline to 20-month follow-up. LV GLS, despite being already impaired at baseline, worsened significantly during follow-up (from –19.8 ± 3.5% to –18.7 ± 3.5%, p = .034). RV GLS impairment progressed through the follow-up period (from –20.9 ± 6.1% to –18.7 ± 5.4%, p = .013). The impairment was more pronounced for the endocardial layers of both LV (from –22.5 ± 3.9% to –21.4 ± 3.9%, p = .041) and RV (–24.2 ± 6.2% to –20.6 ± 5.9%, p = .001). A 1% worsening in RV GLS was associated with an 18% increased risk of all-cause death or major cardiovascular event ( p = .03) and with a 55% increased risk of pulmonary hypertension ( p = .043). Conclusion SSC-related cardiomyopathy progresses over time and can be detected by speckle-tracking GLS. The highest progression towards reduced deformation was registered for the endocardial layers, which supports the hypothesis that microvascular dysfunction is the main determinant of heart involvement in SSc patients and starts well before overt pulmonary hypertension.

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Heart involvement in systemic sclerosis involves the right heart not the left heart

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2006.10.965 ◽

2007 ◽

Vol 56 (2) ◽

pp. AB65

Keyword(s):

Systemic Sclerosis ◽

Left Heart ◽

Right Heart ◽

Heart Involvement ◽

The Right

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

Clinical Rheumatology ◽

10.1007/s10067-014-2666-3 ◽

2014 ◽

Vol 33 (8) ◽

pp. 1105-1111 ◽

Cited By ~ 10

Author(s):

Charalampos Papagoras ◽

Kerstin Achenbach ◽

Niki Tsifetaki ◽

Spyridon Tsiouris ◽

Andreas Fotopoulos ◽

...

Keyword(s):

Systemic Sclerosis ◽

Heart Involvement ◽

Scintigraphic Study

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

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211053246 ◽

2021 ◽

pp. 239719832110532

Author(s):

Cosimo Bruni ◽

Maya H Buch ◽

Daniel E Furst ◽

Giacomo De Luca ◽

Aleksandra Djokovic ◽

...

Keyword(s):

Systemic Sclerosis ◽

Literature Review ◽

Clinical Research ◽

Systematic Literature Review ◽

Nominal Group Technique ◽

Face Validity ◽

Nominal Group ◽

Rater Agreement ◽

Consensus Definition ◽

Heart Involvement

Introduction: 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. Methods: 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. Results: 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. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.

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

Frontiers in Immunology ◽

10.3389/fimmu.2021.653950 ◽

2021 ◽

Vol 12 ◽

Author(s):

Giacomo De Luca ◽

Giulio Cavalli ◽

Corrado Campochiaro ◽

Cosimo Bruni ◽

Alessandro Tomelleri ◽

...

Keyword(s):

Systemic Sclerosis ◽

Myocardial Fibrosis ◽

Cardiac Involvement ◽

Interleukin 1 ◽

Inflammasome Activation ◽

High Morbidity ◽

Prognostic Features ◽

Heart Involvement ◽

Targeted Inhibition

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.

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