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Oliveira MI, Bragança B, Gomes JR, Santos M. Cardiac Involvement and Heart Failure Staging in Patients with Systemic Sclerosis Without Pulmonary Arterial Hypertension. J Clin Med 2025; 14:2211. [PMID: 40217662 PMCID: PMC11989942 DOI: 10.3390/jcm14072211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/17/2025] [Accepted: 03/19/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by fibrosis and vascular damage, significantly increasing the risk of heart failure (HF). Methods: This cross-sectional study included 61 SSc patients (92% female, mean age 63 ± 13 years), excluding those with pulmonary arterial hypertension, referred to a tertiary pulmonary hypertension center. HF stages were classified according to updated guidelines. Clinical, echocardiographic, hemodynamic, and functional capacity data were analyzed in relation to HF stages. Results: A total of 48% of patients had pre-symptomatic HF (5% stage A, 43% stage B), while 38% had symptomatic HF (stage C). Advanced HF stages were significantly associated with older age (p = 0.02) and multiorgan involvement (p = 0.045) but not with SSc subtype or autoantibodies. Structural and functional echocardiographic abnormalities were prevalent (77% and 10%, respectively). Markers of elevated ventricular filling pressure such as left atrial volume (p = 0.011) and E/e' ratio (p = 0.03) correlated with HF severity. Functional impairment was observed with lower 6 min walk test (6MWT) distance (p = 0.017), reduced VO2 peak (p = 0.015), and increased VE/VCO2 slope (p = 0.002). Resting pulmonary artery wedge pressure did not correlate with HF stage (p = 0.93). VE/VCO2 slope and 6MWT were independently associated with HF severity. Conclusions: Preclinical and symptomatic HF are highly prevalent in SSc patients. HF staging was linked to disease severity, age, and cardiovascular risk factors. Functional capacity tests (6MWT and CPET) serve as valuable tools for HF risk stratification. These findings highlight the critical need for comprehensive cardiovascular assessment and targeted management strategies to mitigate HF progression in SSc patients.
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Affiliation(s)
- Maria Isilda Oliveira
- Pulmonary Vascular Disease Unit, Department of Cardiology, Unidade Local de Saúde de Santo António, 4099-001 Porto, Portugal;
- Department of Immuno-Physiology and Pharmacology, Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal
- Physical Activity, Health and Leisure Research Centre (CIAFEL), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal
| | - Bruno Bragança
- Department of Cardiology, Unidade Local de Saúde Tâmega e Sousa, 4564-007 Penafiel, Portugal;
- Department of Immuno-Physiology and Pharmacology, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), RISE-Health, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
| | - José Rodrigues Gomes
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
| | - Mário Santos
- Pulmonary Vascular Disease Unit, Department of Cardiology, Unidade Local de Saúde de Santo António, 4099-001 Porto, Portugal;
- Department of Immuno-Physiology and Pharmacology, Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal
- ITR—Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
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Cecere A, Perazzolo Marra M, Zanatta E, Civieri G, Iliceto S, Tona F. Coronary microvascular dysfunction in autoimmune rheumatic diseases: beyond coronary flow velocity reserve. Front Cardiovasc Med 2024; 11:1372703. [PMID: 39234606 PMCID: PMC11371758 DOI: 10.3389/fcvm.2024.1372703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 07/31/2024] [Indexed: 09/06/2024] Open
Abstract
Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of disorders characterized by an inappropriate immune reactivity against different body tissues. Patients affected by ARDs present increased cardiovascular morbidity and mortality, which significantly impacts long-term prognosis. Endothelial dysfunction, inflammation, oxidative stress, and autoimmunity are strictly involved in atherosclerosis progression and coronary microvascular dysfunction (CMD), both of which contribute to increased cardiovascular risk. CMD represents the inability of the coronary microvasculature to respond with vasodilation to increased cardiac metabolic demands and can be assessed by non-invasive and invasive imaging tests. Coronary flow velocity reserve assessed by echocardiography has been demonstrated to accurately identify ARDs patients with CMD. However, stress cardiac magnetic resonance (CMR) accurately assesses myocardial ischemia, perfusion, and viability in ARDs patients. The myocardial perfusion reserve index (MPRI) is a robust semiquantitative imaging marker that represents the vasodilatory capacity of the coronary microcirculation in response to a vasodilator stress. In the absence of significant coronary stenosis, ARDs patients revealed a reduced MPRI in comparison with the general population, regardless of the presence of myocardial fibrosis. Identification of CMD in asymptomatic patients could be crucial to precociously start targeted medical therapy, avoiding major adverse cardiac events in this clinical setting. This review aims to summarize the current evidence regarding CMD in ARDs patients, focusing on the role of stress CMR and the promising myocardial perfusion analysis.
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Affiliation(s)
- Annagrazia Cecere
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Martina Perazzolo Marra
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Elisabetta Zanatta
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
- Department of Medicine, University of Padova, Padova, Italy
| | - Giovanni Civieri
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Sabino Iliceto
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Francesco Tona
- Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University of Padova, Padova, Italy
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Fairley JL, O’Rourke R, Puranik R, Nikpour M. Cardiac magnetic resonance imaging in systemic sclerosis: Heart involvement in high-resolution. RHEUMATOLOGY AND IMMUNOLOGY RESEARCH 2024; 5:83-92. [PMID: 39015845 PMCID: PMC11248552 DOI: 10.1515/rir-2024-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/12/2024] [Indexed: 07/18/2024]
Abstract
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.
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Affiliation(s)
- Jessica L Fairley
- The University of Melbourne, Melbourne, Victoria, Australia
- St. Vincent’s Hospital Melbourne, Melbourne, Victoria, Australia
| | - Rachael O’Rourke
- The Prince Charles Hospital, Brisbane, Queensland, Australia
- The University of Queensland, Brisbane, Queensland, Australia
| | - Rajesh Puranik
- The University of Sydney, Sydney, New South Wales, Australia
- Royal Prince Alfred HospitalSydney, New South Wales, Australia
| | - Mandana Nikpour
- The University of Melbourne, Melbourne, Victoria, Australia
- St. Vincent’s Hospital Melbourne, Melbourne, Victoria, Australia
- The University of Sydney, Sydney, New South Wales, Australia
- Royal Prince Alfred HospitalSydney, New South Wales, Australia
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4
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Fairley JL, Hansen D, Proudman S, Sahhar J, Ngian GS, Walker J, Host LV, La Gerche A, Prior D, Burns A, Morrisroe K, Stevens W, Nikpour M, Ross L. Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis. Semin Arthritis Rheum 2024; 66:152443. [PMID: 38631275 DOI: 10.1016/j.semarthrit.2024.152443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 03/13/2024] [Accepted: 03/22/2024] [Indexed: 04/19/2024]
Abstract
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.
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Affiliation(s)
- Jessica L Fairley
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
| | - Dylan Hansen
- Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Susanna Proudman
- Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia; Department of Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Joanne Sahhar
- Department of Rheumatology, Monash Health, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Gene-Siew Ngian
- Department of Rheumatology, Monash Health, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Jenny Walker
- Department of Rheumatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Lauren V Host
- Fiona Stanley Hospital, Perth, Western Australia, Australia
| | - André La Gerche
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; Department of Cardiology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia; The Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - David Prior
- Department of Cardiology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Andrew Burns
- Department of Cardiology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Kathleen Morrisroe
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Wendy Stevens
- Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Mandana Nikpour
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia; The University of Sydney School of Public Health, Sydney, New South Wales, Australia; Royal Prince Alfred Hospital Sydney, New South Wales, Australia
| | - Laura Ross
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
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5
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Fairley JL, Hansen D, Burns A, Prior D, La Gerche A, Morrisroe K, Stevens W, Nikpour M, Ross LJ. Contribution of Left Ventricular Diastolic Dysfunction to Survival and Breathlessness in Systemic Sclerosis-Associated Interstitial Lung Disease. J Rheumatol 2024; 51:495-504. [PMID: 38224991 DOI: 10.3899/jrheum.2023-0801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2023] [Indexed: 01/17/2024]
Abstract
OBJECTIVE To explore the effect of left ventricular (LV) diastolic dysfunction (LVDD) in systemic sclerosis (SSc)-associated interstitial lung disease (ILD), and to investigate SSc-specific associations and clinical correlates of LVDD. METHODS There were 102 Australian Scleroderma Cohort Study participants with definite SSc and radiographic ILD included. Diastolic function was classified as normal, indeterminate, or abnormal according to 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines for assessment of LV diastolic function. Associations between clinical features and patient- and physician-reported dyspnea were evaluated using logistic regression. Survival analyses were performed using Kaplan-Meier survival estimates and Cox regression modeling. RESULTS LVDD was identified in 26% of participants, whereas 19% had indeterminate and 55% had normal diastolic function. Those with ILD and LVDD had increased mortality (hazard ratio 2.4, 95% CI 1.0-5.7; P = 0.05). After adjusting for age and sex, those with ILD and LVDD were more likely to have severe dyspnea on the Borg Dyspnoea Scale (odds ratio [OR] 2.6, 95% CI 1.0-6.6; P = 0.05) and numerically more likely to record World Health Organization Function Class II or higher dyspnea (OR 4.2, 95% CI 0.9-20.0; P = 0.08). Older age (95% CI 1.0-6.4; P = 0.05), hypertension (OR 5.0, 95% CI 1.8-13.8; P < 0.01), and ischemic heart disease (OR 4.8, 95% CI 1.5-15.7; P < 0.01) were all associated with LVDD, as was proximal muscle atrophy (OR 5.0, 95% CI 1.9-13.6; P < 0.01) and multimorbidity (Charlson Comorbidity Index scores ≥ 4, OR 3.0, 95% CI 1.1-8.7; P = 0.04). CONCLUSION LVDD in SSc-ILD is more strongly associated with traditional LVDD risk factors than SSc-specific factors. LVDD is associated with worse dyspnea and survival in those with SSc-ILD.
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MESH Headings
- Humans
- Female
- Dyspnea/etiology
- Dyspnea/physiopathology
- Scleroderma, Systemic/complications
- Scleroderma, Systemic/mortality
- Scleroderma, Systemic/physiopathology
- Lung Diseases, Interstitial/mortality
- Lung Diseases, Interstitial/physiopathology
- Lung Diseases, Interstitial/etiology
- Lung Diseases, Interstitial/complications
- Male
- Middle Aged
- Ventricular Dysfunction, Left/physiopathology
- Ventricular Dysfunction, Left/diagnostic imaging
- Ventricular Dysfunction, Left/mortality
- Aged
- Australia/epidemiology
- Adult
- Echocardiography
- Diastole
- Cohort Studies
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Affiliation(s)
- Jessica L Fairley
- J.L. Fairley, MBBS, A. Burns, PhD, D. Prior, PhD, K. Morrisroe, PhD, M. Nikpour, PhD, L.J. Ross, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne
| | - Dylan Hansen
- D. Hansen, MBiostat, W. Stevens, MBBS, St. Vincent's Hospital Melbourne
| | - Andrew Burns
- J.L. Fairley, MBBS, A. Burns, PhD, D. Prior, PhD, K. Morrisroe, PhD, M. Nikpour, PhD, L.J. Ross, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne
| | - David Prior
- J.L. Fairley, MBBS, A. Burns, PhD, D. Prior, PhD, K. Morrisroe, PhD, M. Nikpour, PhD, L.J. Ross, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne
| | - André La Gerche
- A. La Gerche, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne, and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. M. Nikpour and L. Ross contributed equally to this work
| | - Kathleen Morrisroe
- J.L. Fairley, MBBS, A. Burns, PhD, D. Prior, PhD, K. Morrisroe, PhD, M. Nikpour, PhD, L.J. Ross, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne
| | - Wendy Stevens
- D. Hansen, MBiostat, W. Stevens, MBBS, St. Vincent's Hospital Melbourne
| | - Mandana Nikpour
- J.L. Fairley, MBBS, A. Burns, PhD, D. Prior, PhD, K. Morrisroe, PhD, M. Nikpour, PhD, L.J. Ross, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne;
| | - Laura J Ross
- J.L. Fairley, MBBS, A. Burns, PhD, D. Prior, PhD, K. Morrisroe, PhD, M. Nikpour, PhD, L.J. Ross, PhD, The University of Melbourne, and St. Vincent's Hospital Melbourne
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De Luca G, Matucci-Cerinic M, Mavrogeni SI. Diagnosis and management of primary heart involvement in systemic sclerosis. Curr Opin Rheumatol 2024; 36:76-93. [PMID: 37962165 DOI: 10.1097/bor.0000000000000990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
PURPOSE OF REVIEW In systemic sclerosis (SSc) primary heart involvement (pHI) is frequent, even though often unrecognized due to its occult nature and to the lack of a specific diagnostic algorithm. The purpose of this review is to report the state of the art of the evidence in the current literature, as well as the overall diagnostic modalities and therapeutic strategies for primary heart involvement in SSc. RECENT FINDINGS SSc-pHI is defined by the presence of cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications; it may be sub-clinical and must be confirmed through diagnostic investigations. Novel electrocardiographic analysis and cardiac magnetic resonance (CMR) with mapping techniques have been recently proposed, showing a great utility in the early identification of SSc-pHI and in the noninvasive characterization of myocardial tissue. Immunosuppressive therapy emerged as fundamental to curb myocardial inflammation, and recent preclinical and clinical data support the role of antifibrotic drugs to treat SSc-pHI. SUMMARY our review will help clinicians to properly integrate the available diagnostic modalities for the assessment of SSc-pHI. The ultimate goal is to propose a feasible diagnostic algorithm for the early identification of patients with SSc-pHI, and a schematic therapeutic approach to manage SSc-pHI.
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Affiliation(s)
- Giacomo De Luca
- Vita-Salute San Raffaele University
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Sophie I Mavrogeni
- Onassis Cardiac Surgery Center
- University Research Institute of Maternal and Child Health and Precision Medicine and UNESCO Chair in Adolescent Healthcare, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece
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Gargani L, Bruni C, Todiere G, Pugliese NR, Bandini G, Bellando-Randone S, Guiducci S, D’Angelo G, Campochiaro C, De Luca G, Stagnaro C, Lombardi M, Dagna L, Pepe A, Allanore Y, Moggi-Pignone A, Matucci-Cerinic M. Digital Ulcers and Ventricular Arrhythmias as Red Flags to Predict Replacement Myocardial Fibrosis in Systemic Sclerosis. J Clin Med 2023; 13:89. [PMID: 38202095 PMCID: PMC10779804 DOI: 10.3390/jcm13010089] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Cardiac involvement in systemic sclerosis (SSc) affects the prognosis of the disease. Echocardiography is the first line imaging tool to detect cardiac involvement, but it is not able to routinely detect myocardial fibrosis. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is the gold standard for replacement myocardial fibrosis assessment, but its availability is currently limited. AIM We aimed to assess the clinical and instrumental parameters that would be useful for predicting the presence of LGE-CMR, to achieve a better selection of patients with SSc that could benefit from third-level CMR imaging. METHODS 344 SSc patients underwent a comprehensive echocardiogram and LGE-CMR on the same day; for 189 patients, a 24 h ECG Holter monitoring was available. RESULTS CMR showed non-junctional replacement myocardial fibrosis via LGE in 25.1% patients. A history of digital ulcers (OR 2.188; 95% C.I. 1.069-4.481) and ventricular arrhythmias at ECG Holter monitoring (OR 3.086; 95% C.I. 1.191-7.998) were independent predictors of replacement myocardial fibrosis. CONCLUSIONS CMR can detect patterns of clinical and subclinical cardiac involvement, which are frequent in SSc. A history of digital ulcers and evidence of ventricular arrhythmias at ECG Holter monitoring are red flags for the presence of replacement myocardial fibrosis in CMR. The association between digital ulcers and myocardial fibrosis suggests that a similar pathological substrate of abnormal vascular function may underlie peripheral vascular and cardiac complications.
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Affiliation(s)
- Luna Gargani
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy
| | - Cosimo Bruni
- Division of Rheumatology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, 50121 Florence, Italy
| | - Giancarlo Todiere
- U.O.C. Risonanza Magnetica Specialistica, Fondazione Toscana G. Monasterio, 56124 Pisa, Italy
| | | | - Giulia Bandini
- Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Florence, 50121 Florence, Italy
| | - Silvia Bellando-Randone
- Division of Rheumatology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, 50121 Florence, Italy
| | - Serena Guiducci
- Division of Rheumatology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, 50121 Florence, Italy
| | - Gennaro D’Angelo
- U.O.C. Risonanza Magnetica Specialistica, Fondazione Toscana G. Monasterio, 56124 Pisa, Italy
| | - Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, 20132 Milan, Italy
| | - Giacomo De Luca
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, 20132 Milan, Italy
| | - Chiara Stagnaro
- Department of Rheumatology, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Massimo Lombardi
- Multimodality Cardiac Imaging Section, Policlinico San Donato, 20097 Milan, Italy
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, 20132 Milan, Italy
| | - Alessia Pepe
- Institute of Radiology, Department of Medicine, University of Padua, 35122 Padua, Italy
| | - Yannick Allanore
- French National Institute of Health and Medical Research (INSERM) U1016, Université de Paris, Hôpital Cochin, 75014 Paris, France
| | - Alberto Moggi-Pignone
- Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Florence, 50121 Florence, Italy
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, 20132 Milan, Italy
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8
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Azzam M, Awad A, Abugharbyeh A, Kahaleh B. Myocarditis in connective tissue diseases: an often-overlooked clinical manifestation. Rheumatol Int 2023; 43:1983-1992. [PMID: 37587233 DOI: 10.1007/s00296-023-05428-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 08/08/2023] [Indexed: 08/18/2023]
Abstract
To discuss what is currently known about myocarditis in the context of major connective tissue diseases, including Systemic lupus erythematosus, Rheumatoid Arthritis, Sjogren, Dermato-myositis and Polymyositis, Systemic Sclerosis, and Mixed connective tissue disease. Variability exists between studies regarding the incidence of myocarditis in connective tissue diseases, which is hypothesized to be the result of its subclinical course in most cases. Extensive gaps of knowledge exist in the field of pathophysiology. Although endomyocardial biopsy remains to be the gold standard for diagnosis, the advancement in non-invasive modalities such as cardiac MRI, echocardiography, and nuclear medicine has allowed for earlier and more frequent detection of myocarditis. A lack of treatment guidelines was found across the different connective tissue diseases. Most of the literature available revolved around myocarditis in the context of Systemic lupus erythematosus. Numerous recent studies were published that contributed to advancements in diagnosis and treatment however, there remains a lack of diagnostic and treatment guidelines.
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Affiliation(s)
- Muayad Azzam
- Faculty of Medicine, The University of Jordan, Amman, 11942, Jordan.
| | - Amro Awad
- Faculty of Medicine, The University of Jordan, Amman, 11942, Jordan
| | - Aya Abugharbyeh
- Division of Rheumatology and Immunology, University of Toledo Medical Center, Toledo, USA
| | - Bashar Kahaleh
- Division of Rheumatology and Immunology, University of Toledo Medical Center, Toledo, USA
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9
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Fairley JL, Ross L, Quinlivan A, Hansen D, Paratz E, Stevens W, Kistler PM, McLellan A, La Gerche A, Nikpour M. Sudden cardiac death, arrhythmias and abnormal electrocardiography in systemic sclerosis: A systematic review and meta-analysis. Semin Arthritis Rheum 2023; 62:152229. [PMID: 37354723 DOI: 10.1016/j.semarthrit.2023.152229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/15/2023] [Accepted: 05/17/2023] [Indexed: 06/26/2023]
Abstract
OBJECTIVE To calculate the frequency of sudden cardiac death(SCD), arrhythmia and conduction defects in SSc. METHODS MEDLINE/EMBASE were searched to January 2023. English-language studies reporting the incidence/frequency of SCD, arrhythmia and electrocardiography(ECG) abnormalities in SSc were included. Odds ratios(OR), estimations of annual incidence or pooled frequencies were calculated. RESULTS Seventy-nine studies(n = 13,609 participants with SSc) were included in the meta-analysis. Methodology and outcomes were heterogeneous. Ten studies included cohorts with known/suspected SSc-associated heart involvement(SHI), generally defined as clinically-manifest cardiac disease/abnormal cardiac investigations. The incidence of SCD in SHI was estimated to be 3.3% annually(n = 4 studies, 301PY follow-up). On ambulatory ECG, 18% of SHI cohorts had non-sustained ventricular tachycardia(NSVT; n = 4, 95%CI3.2-39.3%), 70% frequent premature ventricular complexes (PVCs; n = 1, 95%CI34.8-93.3%), and 8% atrial fibrillation (AF; n = 1, 95%CI4.2-13.6%). Nineteen studies included participants without SHI, defined as normal cardiac investigations/absence of cardiac disease. The estimated incidence of SCD was approximately 2.9% annually (n = 1, 67.5PY). Compared to healthy controls, individuals without SHI demonstrated NSVT 13.3-times more frequently (n = 2, 95%CI2-102), and paroxysmal supraventricular tachycardia 7-times more frequently (n = 4, 95%CI3-15). Other ambulatory ECG abnormalities included NSVT in 9% (n = 7, 95%CI6-14%), >1000 PVCs/24 h in 6% (n = 2, 95%CI1-13%), and AF in 7% (n = 5, 0-21%). Fifty studies included general SSc cohorts unselected for cardiac disease. The incidence of SCD was estimated to be 2.0% annually(n = 4 studies, 1646PY). Unselected SSc cohorts were 10.5-times more likely to demonstrate frequent PVCs (n = 2, 95%CI 2-59) and 2.5-times more likely to have an abnormal electrocardiography (n = 2, 95%CI1-4). CONCLUSIONS The incidence of SCD in SSc is estimated to be 1.0-3.3% annually, at least 10-fold higher than general population estimates. Arrhythmias including NSVT and frequent PVCs appear common, including amongst those without known/suspected SHI.
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Affiliation(s)
- Jessica L Fairley
- The University of Melbourne, Melbourne, Victoria, Australia; St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Laura Ross
- The University of Melbourne, Melbourne, Victoria, Australia; St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Alannah Quinlivan
- The University of Melbourne, Melbourne, Victoria, Australia; St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Dylan Hansen
- St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Elizabeth Paratz
- St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia; The Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Wendy Stevens
- The University of Melbourne, Melbourne, Victoria, Australia; St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Peter M Kistler
- The University of Melbourne, Melbourne, Victoria, Australia; The Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; The Alfred Hospital, Melbourne, Victoria, Australia; Monash University, Melbourne, Australia
| | - Alex McLellan
- St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Andre La Gerche
- The University of Melbourne, Melbourne, Victoria, Australia; St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia; The Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Mandana Nikpour
- The University of Melbourne, Melbourne, Victoria, Australia; St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
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Penglase R, Girgis L, Englert H, Brennan X, Jabbour A, Kotlyar E, Ma D, Moore J. Cardiotoxicity in autologous haematopoietic stem cell transplantation for systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2023; 8:87-100. [PMID: 37287946 PMCID: PMC10242691 DOI: 10.1177/23971983221145639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 11/15/2022] [Indexed: 09/20/2023]
Abstract
Autologous haematopoietic stem cell transplantation is now well-established as an effective treatment for severe systemic sclerosis with clear demonstration of favourable end-organ and survival outcomes. Treatment-related cardiotoxicity remains the predominant safety concern and contraindicates autologous haematopoietic stem cell transplantation in patients with severe cardiopulmonary disease. In this review, we describe the cardiovascular outcomes of autologous haematopoietic stem cell transplantation recipients, discuss the potential mechanisms of cardiotoxicity and propose future mitigating strategies.
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Affiliation(s)
- Ross Penglase
- Department of Rheumatology, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
- University of New South Wales, Sydney, NSW, Australia
- St. Vincent’s Centre for Applied Medical Research, Darlinghurst, NSW, Australia
| | - Laila Girgis
- Department of Rheumatology, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
- University of New South Wales, Sydney, NSW, Australia
- St. Vincent’s Centre for Applied Medical Research, Darlinghurst, NSW, Australia
| | - Helen Englert
- Department of Haematology and BM Transplantation, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
| | - Xavier Brennan
- Department of Cardiology and Heart and Lung Transplantation, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
| | - Andrew Jabbour
- University of New South Wales, Sydney, NSW, Australia
- Department of Cardiology and Heart and Lung Transplantation, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
| | - Eugene Kotlyar
- University of New South Wales, Sydney, NSW, Australia
- Department of Cardiology and Heart and Lung Transplantation, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
| | - David Ma
- University of New South Wales, Sydney, NSW, Australia
- St. Vincent’s Centre for Applied Medical Research, Darlinghurst, NSW, Australia
- Department of Haematology and BM Transplantation, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
| | - John Moore
- University of New South Wales, Sydney, NSW, Australia
- St. Vincent’s Centre for Applied Medical Research, Darlinghurst, NSW, Australia
- Department of Haematology and BM Transplantation, St. Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia
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Ali AM, Yakupoglu HY, Fuchs TA, Larsen TH, Aukrust P, Gunnarsson R, Saeed S. Cardiac involvement in systemic and local vasculitides: The value of non-invasive multimodality imaging. Curr Probl Cardiol 2023; 48:101718. [PMID: 37003450 DOI: 10.1016/j.cpcardiol.2023.101718] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 03/21/2023] [Indexed: 04/03/2023]
Abstract
Despite significant advances in managing systemic vasculitides, cardiovascular morbidity and mortality are still of primary concern. Advances in non-invasive imaging have broadened our understanding of the clinical heterogeneity of cardiac involvement in vasculitides. Common cardiovascular complications in primary or secondary vasculitides are; coronary artery aneurysms, acute coronary syndromes, myocarditis, pericarditis, endocarditis, and valvular dysfunction. Echocardiography, cardiac magnetic resonance (CMR), positron emission tomography (PET), and CT angiography are essential in identifying cardiac involvement and guiding treatment. Here, we present our experiences of cardiac involvement in systemic vasculitides, covering most aspects of common cardiac complications based on a multi-modality approach to challenging (real-world) cases. As many cardiac manifestations are clinically silent, heart function should be systemically assessed by a multi-modality imaging-based approach, including ECG, serial echocardiograms with strain imaging and 3D, and CMR to detect early signs of cardiac manifestations. This enables timely intervention and optimal medical treatment, which is essential for a better prognosis. There is a need for better and closer collaboration in clinical practice and research fields between Cardiologists and Rheumatologists.
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Affiliation(s)
- Abukar Mohamed Ali
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - H Yakup Yakupoglu
- Medical University Clinic, Division of Cardiology, Kantonsspital Aarau, Aarau, Switzerland
| | - Tobias A Fuchs
- Medical University Clinic, Division of Cardiology, Kantonsspital Aarau, Aarau, Switzerland
| | - Terje H Larsen
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.; Department of Biomedicine, University of Bergen, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital - Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital - Rikshospitalet, Oslo
| | | | - Sahrai Saeed
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway..
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12
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Grimaldi MC, Rosato E, D’Angelo A, Cristiano E, Marchitti S, Volpe M, Rubattu S, Romaniello A. The prognostic role of the echocardiographic tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/sPAP) ratio and its relationship with NT-proANP plasma level in systemic sclerosis. Front Cardiovasc Med 2023; 9:1021048. [PMID: 36733829 PMCID: PMC9887033 DOI: 10.3389/fcvm.2022.1021048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 12/20/2022] [Indexed: 01/18/2023] Open
Abstract
Background The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/sPAP) ratio is an echocardiographic estimation of the right ventricle to pulmonary artery (RV/PA) coupling, with a validated prognostic role in different clinical settings. Systemic sclerosis (SSc) patients without evident cardiovascular involvement frequently display subtle RV impairment. The amino-terminal atrial natriuretic peptide (NT-proANP) plasma level relates to SSc disease progression and mortality. We aimed to assess the prognostic value of the TAPSE/sPAP ratio and its relationship with NT-proANP plasma level in SSc patients without overt cardiovascular involvement. Methods We retrospectively analysed 70 SSc consecutive patients, with no clinical evidence of cardiovascular involvement or pulmonary hypertension (PH), and 30 healthy controls (HC) in a retrospective, single-centre study. All SSc patients underwent recurrent clinical and echocardiographic assessments and NT-proANP plasma level was assessed at baseline. SSc-related cardiovascular events and deaths were extracted during a 6-year follow-up. The complete work-up for the diagnosis, treatment and management of PH performed along the 6 years of follow-up referred to the 2015 European Society of Cardiology guidelines. Results Systemic sclerosis patients showed lower TAPSE/sPAP ratio at baseline compared to HC [SSc median value = 0.71 mm/mmHg, (IQR 0.62-0.88) vs. HC median value = 1.00 mm/mmHg, (IQR 0.96-1.05); p < 0.001]. Multivariable Cox analysis revealed TAPSE/sPAP ratio as an independent predictor for SSc-related cardiovascular events [HR = 3.436 (95% CI 1.577-7.448); p = 0.002] and mortality [HR = 3.653 (95% CI 1.712-8.892); p = 0.014]. The value of TAPSE/sPAP ratio < 0.7 mm/mmHg was identified as an optimal cut-off for predicting adverse outcomes (p < 0.001) by receiver operating characteristic (ROC) analyses. NT-proANP level significantly related to TAPSE/sPAP ratio (r = 0.52, p < 0.001). TAPSE/sPAP ratio combined with NT-proANP showed an overall significant prognostic role in this SSc population, confirmed by Kaplan-Meier analysis (Log rank p < 0.001). Conclusion The TAPSE/sPAP ratio, as an index of RV/PA coupling, is an affordable predictor of cardiovascular events and mortality in SSc and, combined with NT-proANP level, may improve the clinical phenotyping and prognostic stratification of SSc patients.
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Affiliation(s)
- Maria Chiara Grimaldi
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy,Department of Cardiovascular and Pneumological Sciences, Catholic University of Sacred Heart, Rome, Italy,Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy,*Correspondence: Maria Chiara Grimaldi,
| | - Edoardo Rosato
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Adriano D’Angelo
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Ernesto Cristiano
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Simona Marchitti
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy
| | - Massimo Volpe
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy,San Raffaele Pisana Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Speranza Rubattu
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy,Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy
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Sclerodermic Cardiomyopathy—A State-of-the-Art Review. Diagnostics (Basel) 2022; 12:diagnostics12030669. [PMID: 35328222 PMCID: PMC8947572 DOI: 10.3390/diagnostics12030669] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 02/27/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and complex pathophysiologic links which lead to fibrosis of skin and internal organs, including the heart, lungs, and gut. However, more than 100 years after the first description of cardiac disease in SSc, sclerodermic cardiomyopathy (SScCmp) is an underrecognized, occult disease with important adverse long-term prognosis. Laboratory tests, electrocardiography (ECG) and cardiovascular multimodality imaging techniques (transthoracic 2D and 3D echocardiography, cardiac magnetic resonance (CMR), and novel imaging techniques, including myocardial deformation analysis) provide new insights into the cardiac abnormalities in patients with SSc. This state-of-the-art review aims to stratify all the cardiac investigations needed to diagnose and follow-up the SScCmp, and discusses the epidemiology, risk factors and pathophysiology of this important cause of morbidity of the SSc patient.
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14
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Kumar K, Seetharam K, Poonam F, Gulati A, Sadiq A, Shetty V. The Role of Cardiac Imaging in the Evaluation of Cardiac Involvement in Systemic Diseases. Cureus 2021; 13:e20708. [PMID: 35106243 PMCID: PMC8788898 DOI: 10.7759/cureus.20708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2021] [Indexed: 11/05/2022] Open
Abstract
For systemic diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis, systemic vasculitis, myopathies, and mixed connective tissue diseases, cardiac disease is a major contributing factor for morbidity and mortality. The cardiovascular manifestations are the result of various pathophysiological components, which complicate management. Furthermore, the signs and symptoms can be subtle and missed due to the complex nature of the underlying condition. As a result, various imaging approaches play an imperative role in diagnosis and prognosis. The evolving role of these modalities could lead to risk stratification and improved therapies in the future. In conclusion, our review article will highlight the role of cardiac imaging in the evaluation of cardiac involvement for systemic diseases.
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15
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Repolarization in systemic sclerosis: a meta-analysis. Clin Rheumatol 2021; 41:1131-1137. [PMID: 34843000 DOI: 10.1007/s10067-021-05996-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/08/2021] [Accepted: 11/13/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVES Systemic sclerosis (SSc) is a rare connective tissue disease characterized by immune dysregulation, vascular damage, and increased deposition of extracellular matrix. In SSc, cardiac manifestations are common and account for 14% of deaths. Numerous studies have examined electrocardiographic findings in SSc patients yielding conflicting reports regarding QTc duration. We conducted a systematic review and meta-analysis of existing studies to investigate whether QTc duration may aid in diagnosis and risk stratification of SSc patients. METHODS Two electronic databases (PubMed and Embase) were searched for case-control and cohort studies assessing QTc duration in SSc patients published before March 1, 2021. A random-effects model was used to meta-analyze the results, and included studies were tested for heterogeneity. Linear regression was performed to determine correlations between comorbidities, and QTc duration. RESULTS Ninety-six studies, abstracts, and posters were identified. After abstract review and duplicate removal, 23 manuscripts remained. After application of the inclusion and exclusion criteria, 10 studies remained which were quantitatively analyzed. The weighted mean QTc was found to be 422.21 ms for SSc patients and 411.43 ms for control subjects. A significant increase in QTc duration among SSc patients was found, with a standardized mean difference of 0.59 (p < 0.01, 95% CI 0.27-0.92). No significant correlation was found between underlying traits and QTc values. Substantial heterogeneity was found between the studies (I2 = 83%, p < 0.01). CONCLUSION A significant increase in QTc duration is observed in SSc patients, though the absolute prolongation is not extreme. Therefore, the clinical utility of this finding is unclear and merits large prospective observations. Key Points • A statistically significant prolongation of the QTc interval exists in patients with systemic sclerosis. • Absolute QTc differences between healthy controls and scleroderma patients are not extreme, and, as such, may be of limited clinical utility. • When assessing the underlying traits of systemic sclerosis patients, no statistically significant correlations were found between underlying parameters and QTc duration.
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Abstract
PURPOSE OF REVIEW Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis. RECENT FINDINGS The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation.
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Abstract
Primary systemic sclerosis heart involvement (pSHI) is an important disease manifestation that accounts for a significant proportion of systemic sclerosis (SSc)-associated mortality. A broad clinical spectrum of pSHI exists, which ranges from asymptomatic perfusion abnormalities to diastolic dysfunction or acute myocarditis and congestive heart failure. With improving sensitivity of cardiac investigations, it is increasingly recognized that there is a large burden of subclinical cardiac disease in patients with SSc. Early signs of pSHI can be subtle and determining the etiology of cardiac abnormalities from other causes of cardiomyopathy such as hypertension, ischemic heart disease (IHD), and pulmonary vascular disease remain challenging. Early identification of pSHI potentially provides clinicians with a window of opportunity for intervention to avert progression to heart failure. However, optimal screening and treatment guidelines are lacking, and it is an area of much needed further clinical research.
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Galea N, Rosato E, Gigante A, Borrazzo C, Fiorelli A, Barchetti G, Trombetta AC, Digiulio MA, Francone M, Catalano C, Carbone I. Early myocardial damage and microvascular dysfunction in asymptomatic patients with systemic sclerosis: A cardiovascular magnetic resonance study with cold pressor test. PLoS One 2020; 15:e0244282. [PMID: 33351821 PMCID: PMC7755221 DOI: 10.1371/journal.pone.0244282] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 12/05/2020] [Indexed: 01/25/2023] Open
Abstract
PURPOSE Cardiac involvement in Systemic Sclerosis (SSc) is increasingly recognized as a mayor cause of morbidity and mortality. The aim of present study is to investigate the early stages of cardiac involvement in SSc by Cardiovascular magnetic resonance (CMR), combining the non-invasive detection of myocardial inflammation and fibrosis using T2 and T1 mapping techniques and the assessment of microcirculatory impairment through perfusion response to cold pressor test (CPT). METHODS 40 SSc patients (30 females, mean age: 42.1 years) without cardiac symptoms and 10 controls underwent CMR at 1.5 T unit. CMR protocol included: native and contrast-enhanced T1 mapping, T2 mapping, T2-weighted, cineMR and late gadolinium enhancement (LGE) imaging. Microvascular function was evaluated by comparing myocardial blood flow (MBF) on perfusion imaging acquired at rest and after CPT. Native myocardial T1 and T2 relaxation times, extracellular volume fraction (ECV), T2 signal intensity ratio, biventricular volumes and LGE were assessed in each patient. RESULTS SSc patients had significantly higher mean myocardial T1 (1029±32ms vs. 985±18ms, p<0.01), ECV (30.1±4.3% vs. 26.7±2.4%, p<0.05) and T2 (50.1±2.8ms vs. 47±1.5ms, p<0.01) values compared with controls. No significant differences were found between absolute MBF values at rest and after CPT; whereas lower MBF variation after CPT was observed in SSc patients (+33 ± 14% vs. +44 ± 12%, p<0.01). MBF variation had inverse correlation with native T1 values (r: -0.32, p<0.05), but not with ECV. CONCLUSIONS Myocardial involvement in SSc at preclinical stage increases native T1, T2 and ECV values, reflecting inflammation and fibrosis, and reduces vasodilatory response to CPT, as expression of microvascular dysfunction.
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Affiliation(s)
- Nicola Galea
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Edoardo Rosato
- Department of Clinical Medicine, Clinical Immunology Unit- Scleroderma Center, Sapienza University of Rome, Rome, Italy
| | - Antonietta Gigante
- Department of Clinical Medicine, Clinical Immunology Unit- Scleroderma Center, Sapienza University of Rome, Rome, Italy
| | - Cristian Borrazzo
- Statistical Unit, Department of Public Health and Infectious Disease, Sapienza University of Rome, Rome, Italy
- Radiotherapy Unit, Ospedale San Pietro Fatebenefratelli, Rome, Italy
| | - Andrea Fiorelli
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Giovanni Barchetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Amelia Chiara Trombetta
- Department of Clinical Medicine, Clinical Immunology Unit- Scleroderma Center, Sapienza University of Rome, Rome, Italy
| | - Maria Anna Digiulio
- Department of Clinical Medicine, Clinical Immunology Unit- Scleroderma Center, Sapienza University of Rome, Rome, Italy
| | - Marco Francone
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Carlo Catalano
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Iacopo Carbone
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
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Cen X, Feng S, Wei S, Yan L, Sun L. Systemic sclerosis and risk of cardiovascular disease: A PRISMA-compliant systemic review and meta-analysis of cohort studies. Medicine (Baltimore) 2020; 99:e23009. [PMID: 33217802 PMCID: PMC7676589 DOI: 10.1097/md.0000000000023009] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Systemic sclerosis (SSc) is an autoimmune disorder leading to extensive fibrosis and microvascular injury. Macrovascular disease is well documented in other autoimmune rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the link is unclear between SSc and macrovascular disease, particularly atherosclerotic cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between SSc and CVD. METHODS A thorough literature search was conducted in the Cochrane, Embase, Medline, and PubMed to identify all cohort studies comparing the risk of CVD with and without SSc. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular end points were calculated. The risk of bias of included studies was assessed by the Newcastle-Ottawa scale. RESULTS Seven cohort studies with a total of 14,813 study participants were included. In a comparison of SSc patients versus non-SSc controls, the pooled HR for cardiovascular disease was 2.36 (95% CI 1.97-2.81); for peripheral vascular disease was 5.27 (95%CI 4.27-6.51); for myocardial infarction was 2.36 (95% CI 1.71-3.25); and for stroke was 1.52 (95% CI 1.18-1.96). CONCLUSION This meta-analysis revealed that SSc was associated with an increased risk of CVD. Clinicians who manage patients with SSc should be aware of the increased cardiovascular burden and undertake preventive measures.
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Affiliation(s)
- Xintao Cen
- Department of Dermatology, Zhujiang Hospital, Southern Medical University
| | - Sining Feng
- Department of Dermatology, Zhujiang Hospital, Southern Medical University
| | - Shanshan Wei
- Department of Dermatology, Zhujiang Hospital, Southern Medical University
| | - Lu Yan
- Department of Dermatology, Zhujiang Hospital, Southern Medical University
| | - Ledong Sun
- Department of Dermatology, Zhujiang Hospital, Southern Medical University
- Department of Dermatology, the Fifth Affiliated Hospital of Southern Medical University, Guangzhou, China
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Bordonaro V, Bivort D, Dresselaers T, De Langhe E, Bogaert J, Symons R. Myocardial T1 mapping and extracellular volume quantification as novel biomarkers in risk stratification of patients with systemic sclerosis. Clin Radiol 2020; 76:162.e1-162.e8. [PMID: 33109349 DOI: 10.1016/j.crad.2020.09.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 09/30/2020] [Indexed: 11/29/2022]
Abstract
AIM To study the prognostic value of myocardial native T1 and extracellular volume (ECV), measured by cardiovascular magnetic resonance (CMR), in patients with systemic sclerosis (SSc). MATERIALS AND METHODS Thirty-three SSc patients (16/33 male, 48.5%) were studied using multiparametric CMR including native T1 mapping with ECV calculation, T2 mapping, and late gadolinium enhancement (LGE). Patients were followed-up for cardiac death, haemodynamically significant arrhythmia, or heart failure. Results were compared with 33 age- and gender-matched healthy controls. RESULTS When compared with controls, SSc patients had higher myocardial native T1 (1,058.9±71 versus 989.4±21.4 ms, p<0.001), higher T2 (54.9±5.7 versus 50±2.5 ms, p<0.001), and ECV values (27.9±5.4% versus 24.8±2%, p<0.004). LGE was present in eight patients (24%), two subendocardial, five midwall, and four subepicardial. LGE, native T1, and ECV were significantly associated with adverse events during follow-up in multivariate Cox regression analysis. Kaplan-Meier analysis demonstrated significant divergence of the survival curves based on the presence of elevated native T1 (≥1,069 ms) or ECV (≥31.4%) values. CONCLUSION Cardiac involvement is frequent in SSc. Both native T1 mapping and ECV represent novel non-invasive markers of myocardial fibrosis and could be used in the risk stratification of patients with SSc. CMR mapping may provide a novel biomarker for disease monitoring and study of therapies aiming to reduce myocardial fibrosis in SSc.
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Affiliation(s)
- V Bordonaro
- Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium
| | - D Bivort
- Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
| | - T Dresselaers
- Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium
| | - E De Langhe
- Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
| | - J Bogaert
- Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium
| | - R Symons
- Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium.
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21
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Tipparot T, Foocharoen C, Mahakkanukrauh A, Suwannaroj S, Nanagara R, Pussadhamma B, Chaosuwannakit N. Clinical and laboratory predictions of myocardial inflammation as detected by cardiac magnetic resonance imaging in patients with systemic sclerosis: A pilot study. Int J Rheum Dis 2019; 22:2125-2133. [PMID: 31659856 DOI: 10.1111/1756-185x.13727] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 09/25/2019] [Accepted: 09/26/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cardiac magnetic resonance imaging (cardiac MRI) has high sensitivity and specificity for differentiating cardiac fibrosis from inflammation. There is no data on the clinical and laboratory association or prediction of myocardial inflammation in systemic sclerosis-a major organ involvement in systemic sclerosis (SSc). OBJECTIVES Our aim was to ascertain the clinical and laboratory associations with myocardial inflammation in SSc patients as detected by cardiac MRI. METHODS A cross-sectional study was conducted among Thai adult SSc patients who had: disease onset <4 years; a New York Heart Association functional class ≥ II; and followed up at the Scleroderma Clinic, Khon Kaen University, between June 2018 and January 2019. We excluded patients who were taking steroids and/or immunosuppressants or had a diagnosed heart disease before being diagnosed with SSc. All enrolled patients underwent cardiac MRI, and clinical and laboratory assessments the same date. Myocardial inflammation was defined by cardiac MRI per the Lake Louise Criteria. RESULTS A total of 30 SSc patients were enrolled. The female-to-male ratio was 1.8:1. The majority (73%) had diffuse cutaneous SSc. The respective mean age and median duration of disease was 57 ± 8 and 2.0 years (interquartile range 1.5-2.7). Myocardial inflammation was detected in 22 patients (73.3%). The multivariate analysis revealed that every 5 years of increased age at onset and every 5-point increase in the modified Rodnan skin score (mRSS) at onset was significantly associated with myocardial inflammation (odds ratio 0.47, 95% CI 0.22-0.98; and 2.64 95% CI 1.04-6.74, respectively). Neither the SSc subset, internal organ involvement, inflammatory markers, nor cardiac and muscle enzymes were associated with myocardial inflammation in SSc. CONCLUSION Myocardial inflammation is common in early-onset SSc. An increased risk of myocardial inflammation was associated with young age and high mRSS at onset. Cardiac MRI is the suggested evaluation for high-risk SSc patients experiencing dyspnea on exertion.
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Affiliation(s)
- Thapanee Tipparot
- Division of Rheumatology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chingching Foocharoen
- Division of Rheumatology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Ajanee Mahakkanukrauh
- Division of Rheumatology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Siraphop Suwannaroj
- Division of Rheumatology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Ratanavadee Nanagara
- Division of Rheumatology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Burabha Pussadhamma
- Division of Cardiology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
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22
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Rodrigues GD, Tobaldini E, Bellocchi C, Santaniello A, Caronni M, Severino A, Froldi M, Beretta L, da Silva Soares PP, Montano N. Cardiac autonomic modulation at rest and during orthostatic stress among different systemic sclerosis subsets. Eur J Intern Med 2019; 66:75-80. [PMID: 31202484 DOI: 10.1016/j.ejim.2019.06.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 05/28/2019] [Accepted: 06/05/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVE To compare autonomic heart rate variability (HRV) parameters at rest and during active stand in a population of SSc patients, taking into account SSc subsets age-matched to healthy control subjects. METHODS Sixty-nine consecutive SSc patients were enrolled in study; these included 12 subjects with early SSc, 39 with limited cutaneous (lcSSc) and 18 with diffuse cutaneous SSc (dcSSc) along with 36 age- and sex-matched healthy controls (HC). ECG and respiration were recorded in supine position and in orthostatism (ORT). HRV analysis was performed on samples of 300 beats. Spectral analysis identified two oscillatory components, low frequency (LFnu, sympathetic) and high frequency (HFnu, vagal). Symbolic analysis identified three patterns, 0 V%, (sympathetic) and 2UV% and 2LV%, (vagal). The %∆ORT was calculated from the differences between HRV in ORT and SUP, normalized (%) by the HRV values at rest. RESULTS SSc as a whole had higher markers of sympathetic (LF, 0 V%) and lower markers of vagal modulation (HR, 2UV%, 2LV%) compared to HCs. In addition, %∆LFnu, %∆HFnu, %∆0 V, %∆2UV and %∆2LV were lower in SSc than HC. dcSSc and lcSSc were dissimilar to HC as far as rest indexes were concerned (↑LF/HF, ↑LFnu, ↓HFnu, ↑0 V% and ↓2UV%) while no differences could be detected between HC and EaSSc. CONCLUSION SSc showed a reduced vagal and increased sympathetic modulation at rest and a blunted autonomic response to ORT in comparison to HC. These alterations were mostly detectable in the advanced and fibrotic forms of SSc (dcSSc and lcSSc), while EaSSc were similar to HC.
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Affiliation(s)
- Gabriel Dias Rodrigues
- Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niterói, Brazil; National Institute for Science & Technology - INCT (In)activity & Exercise, CNPq, Niterói, (RJ) Rio de Janeiro, Brazil
| | - Eleonora Tobaldini
- Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Chiara Bellocchi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Alessandro Santaniello
- Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Monica Caronni
- Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Adriana Severino
- Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Marco Froldi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Lorenzo Beretta
- Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Pedro Paulo da Silva Soares
- Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niterói, Brazil; National Institute for Science & Technology - INCT (In)activity & Exercise, CNPq, Niterói, (RJ) Rio de Janeiro, Brazil
| | - Nicola Montano
- Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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23
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Yang X, Qu L, Li Y, Li X. Complete atrioventricular block in a patient with systemic sclerosis. Scand J Rheumatol 2019; 48:422-423. [PMID: 31220990 DOI: 10.1080/03009742.2019.1572221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- X Yang
- Department of Rheumatology, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China
| | - L Qu
- Department of Rheumatology, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China
| | - Y Li
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China
| | - X Li
- Department of Rheumatology, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China
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24
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Buleu F, Sirbu E, Caraba A, Dragan S. Heart Involvement in Inflammatory Rheumatic Diseases: A Systematic Literature Review. ACTA ACUST UNITED AC 2019; 55:medicina55060249. [PMID: 31174287 PMCID: PMC6632037 DOI: 10.3390/medicina55060249] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/29/2019] [Accepted: 05/31/2019] [Indexed: 12/31/2022]
Abstract
Introduction: Patients with inflammatory rheumatic diseases have an increased risk of developing cardiovascular manifestations. The high risk of cardiovascular pathology in these patients is not only due to traditional cardiovascular risk factors (age, gender, family history, smoking, sedentary lifestyle, cholesterol), but also to chronic inflammation and autoimmunity. Aim: In this review, we present the mechanisms of cardiovascular comorbidities associated with inflammatory rheumatic diseases, as they have recently been reported by different authors, grouped in electrical abnormalities, valvular, myocardial and pericardial modifications and vascular involvement. Methods: We conducted a systematic search of published literature on the following online databases: EBSCO, ScienceDirect, Scopus and PubMed. Searches were limited to full-text English-language journal articles published between 2010 and 2017 using the following key words: heart, systemic inflammation, autoimmunity, rheumatic diseases and disease activity. After the primary analysis we included 50 scientific articles in this review. Results: The results showed that cardiac manifestations of systemic inflammation can occur frequently with different prevalence in rheumatoid arthritis (RA), systemic lupus erythematosus(SLE), systemic sclerosis(SSc) and ankylosing spondylitis(AS). Rheumatologic diseases can affect the myocardium, cardiac valves, pericardium, conduction system and arterial vasculature. Conclusions: Early detection, adequate management and therapy of specific cardiac involvement are essential in rheumatic disease. Electrocardiographic and echocardiographic evaluation should be performed as routine investigations in patients with inflammatory rheumatic diseases.
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Affiliation(s)
- Florina Buleu
- Departament of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy "Victor Babeș", Timișoara 300041, Romania.
| | - Elena Sirbu
- Department of Physical Therapy and Special Motricity, West University of Timișoara, Timișoara 300223, Romania.
| | - Alexandru Caraba
- Departament of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy "Victor Babeș", Timișoara 300041, Romania.
| | - Simona Dragan
- Departament of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy "Victor Babeș", Timișoara 300041, Romania.
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25
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Ross L, Prior D, Proudman S, Vacca A, Baron M, Nikpour M. Defining primary systemic sclerosis heart involvement: A scoping literature review. Semin Arthritis Rheum 2019; 48:874-887. [PMID: 30170705 DOI: 10.1016/j.semarthrit.2018.07.008] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 07/09/2018] [Accepted: 07/20/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Clinically evident primary heart involvement due to systemic sclerosis (SHI) is considered a poor prognostic factor and is a leading cause of systemic sclerosis (SSc) related death. Yet, there remains no consensus definition of SHI and poor understanding of the natural history and risk factors for the development of SHI. METHODS We performed a scoping literature review of published articles with a primary focus of SHI to capture previously used definitions of SHI and items used to measure SHI. Any factors reported to be associated with an increased risk of SHI were recorded. RESULTS Of the 2436 records identified in a search of MEDLINE, EMBASE and PubMed databases, 295 were included in the final scoping review. Analysis of the literature revealed studies of variable quality, generally low patient numbers and highly heterogeneous definitions of SHI within studies. There is no clear consensus from the literature as to the scope of SHI and the prognostic significance of sub-clinical investigation abnormalities commonly detected. CONCLUSION The lack of a standardised definition of SHI remains a significant unmet need in SSc. The results of this review will assist in the development of consensus classification criteria to enable more accurate quantification of the burden of SHI, identification of factors associated with increased risk of developing SHI, and evaluation of the efficacy of any novel therapeutic strategies.
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Affiliation(s)
- Laura Ross
- Department of Medicine at St Vincent's Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065, Australia; Department of Rheumatology, St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia.
| | - David Prior
- Department of Medicine at St Vincent's Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065, Australia; Department of Cardiology, St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia.
| | - Susanna Proudman
- Rheumatology Unit, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
| | - Alessandra Vacca
- Unit of Rheumatology, University Hospital of Cagliari, S.S. 554, bivio per Sestu, 09042 Monserrato (CA), Italy..
| | - Murray Baron
- Division of Rheumatology, Jewish General Hospital, McGill University, 5750 Côtes-des-Neiges Rd, Montreal, QC H3S 1Y9, Canada.
| | - Mandana Nikpour
- Department of Medicine at St Vincent's Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065, Australia; Department of Rheumatology, St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia.
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26
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Abnormalities of heart rate turbulence and heart rate variability as indicators of increased cardiovascular risk in patients with systemic sclerosis. Postepy Dermatol Alergol 2019; 36:707-713. [PMID: 31997999 PMCID: PMC6986290 DOI: 10.5114/ada.2019.83134] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 07/15/2018] [Indexed: 01/16/2023] Open
Abstract
Introduction Systemic sclerosis (SSc) is a connective tissue disease manifested by progressive fibrosis of many internal organs including the cardiovascular system and development of autonomic disorders with sympathetic predominance. These abnormalities can increase cardiovascular mortality. Aim To evaluate heart rate turbulence (HRT) and variability (HRV) parameters (indicator of autonomic imbalance) obtained from 24-hour ECG Holter monitoring, as predictors of the increased cardiovascular risk in patients with scleroderma. Material and methods Thirty-twoscleroderma patients and 30 healthy people were included. After clinical examination, ECG, routine laboratory tests and echocardiography, participants performed 24-hour Holter-ECG at home. For HRT assessment, turbulence onset (To) and turbulence slope (Ts) parameters were used. Both time and frequency domain analysis of HRV was used. The HRV circadian rhythm was also evaluated. Results Time domain: SDNN, SDNN-ix, SDANN and frequency domain: LF, VLF, ULF, NHF, NLF, parameters were lower, while p50NN was higher in SSc as compared to the control group. There was also a loss of the circadian rhythm for r-MSSD and p50NN present in the control group. Abnormal HRT parameters To and/or Ts occurred in the SSc group only. The median value of To = –1.24% and Ts = 11.13 ms/RR did not differ significantly as compared to the control group. Conclusions The study confirmed the presence of HRV disturbances, including HRV circadian rhythm, as it may seem at an early stage of SSc. The HRT disorders may be characterized by the increasing changes with advancing disease. This indicates the presence of autonomic imbalance and an increased cardiovascular risk.
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27
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Rodríguez-Reyna TS, Rosales-Uvera SG, Kimura-Hayama E, Hernández-Reyes P, Mercado-Velázquez P, Benavides-Suárez SA, Esquinca-González A, Núñez-Álvarez CA. Myocardial fibrosis detected by magnetic resonance imaging, elevated U-CRP and higher mRSS are predictors of cardiovascular complications in systemic sclerosis (SSc) patients. Semin Arthritis Rheum 2019; 49:273-278. [PMID: 30853116 DOI: 10.1016/j.semarthrit.2019.02.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 01/10/2019] [Accepted: 02/04/2019] [Indexed: 11/27/2022]
Abstract
INTRODUCTION In previous studies we showed that prevalence of myocardial fibrosis as assessed by late enhancement on cardiac MRI in SSc patients is 45% and is associated to diffuse disease (dcSSc) and lower left ventricle ejection fraction; microvascular damage defined as decreased perfusion on cardiac MRI after adenosine infusion, was also very frequent (79%). Our aim was to identify baseline characteristics associated to the development of cardiovascular outcomes (heart failure, coronary artery disease, arrhythmias, vasculopathy, elevated systolic pulmonary artery pressure and death) in SSc patients with previously documented myocardial fibrosis and microvascular damage. PATIENTS AND METHODS We included 62 SSc patients who participated in the study of prevalence of myocardial fibrosis (2008-2010) and in our local SSc cohort. We performed baseline clinical evaluation, cardiac MRI, coronary CT angiography, transthoracic echocardiogram, and yearly clinical and cardiovascular evaluation that included Medsger's severity scale items, electrocardiogram, echocardiogram, chest X-ray or HRCT and spirometry; we registered presence and severity of internal organ involvement and cardiovascular outcomes. Ordinal variables were analyzed using Chi square test and Fisher test when appropriate, numeric variables were compared using Student's t-test or Mann Whitney U when appropriate, logistic regression and Cox proportional hazard ratio were used to perform multivariable analysis. RESULTS We obtained follow-up information from 62 patients (29 dcSSc, 33 lcSSc), mean follow-up was 43.5 months. Multivariable analysis showed that elevated basal ultrasensitive CRP was associated to mortality (p = 0.004, OR: 11.9, 95% CI 2.1-65.7) and recurrent digital tip ischemic ulcers (p = 0.001, OR 26.8, 95% CI 3,9-181.3) on follow-up. Myocardial fibrosis, particularly in the middle segments (p = 0.01, OR: 11.49, 95% CI 1.6-83), and older age (p = 0.02, OR: 1.11, 95% CI 1.01-1.22) were associated to heart failure on follow-up. Higher maximum mRSS was associated to coronary artery disease (p = 0.02, OR: 1.2, 95% CI 1.02-1.38), while insertion point fibrosis (p = 0.001, OR: 12.5 95% CI 2.7-56.6) was associated to recurrent digital tip ischemic ulcers. CONCLUSIONS This study shows that myocardial fibrosis, elevated ultrasensitive CRP, and higher maximum mRSS are independent predictors of cardiovascular outcomes in SSc patients. Future studies should focus on early preventive and therapeutic strategies for this group of patients.
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Affiliation(s)
- Tatiana S Rodríguez-Reyna
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. Col. Belisario Dominguez Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Sandra G Rosales-Uvera
- Radiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
| | | | - Pablo Hernández-Reyes
- Cardiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
| | - Pamela Mercado-Velázquez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. Col. Belisario Dominguez Sección XVI, Tlalpan, Mexico City 14080, Mexico
| | - Sergio A Benavides-Suárez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. Col. Belisario Dominguez Sección XVI, Tlalpan, Mexico City 14080, Mexico
| | - Alexia Esquinca-González
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. Col. Belisario Dominguez Sección XVI, Tlalpan, Mexico City 14080, Mexico
| | - Carlos A Núñez-Álvarez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. Col. Belisario Dominguez Sección XVI, Tlalpan, Mexico City 14080, Mexico
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28
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Habib G, Bucciarelli-Ducci C, Caforio ALP, Cardim N, Charron P, Cosyns B, Dehaene A, Derumeaux G, Donal E, Dweck MR, Edvardsen T, Erba PA, Ernande L, Gaemperli O, Galderisi M, Grapsa J, Jacquier A, Klingel K, Lancellotti P, Neglia D, Pepe A, Perrone-Filardi P, Petersen SE, Plein S, Popescu BA, Reant P, Sade LE, Salaun E, Slart RHJA, Tribouilloy C, Zamorano J. Multimodality Imaging in Restrictive Cardiomyopathies: An EACVI expert consensus document In collaboration with the "Working Group on myocardial and pericardial diseases" of the European Society of Cardiology Endorsed by The Indian Academy of Echocardiography. Eur Heart J Cardiovasc Imaging 2018; 18:1090-1121. [PMID: 28510718 DOI: 10.1093/ehjci/jex034] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 02/14/2017] [Indexed: 12/11/2022] Open
Abstract
Restrictive cardiomyopathies (RCMs) are a diverse group of myocardial diseases with a wide range of aetiologies, including familial, genetic and acquired diseases and ranging from very rare to relatively frequent cardiac disorders. In all these diseases, imaging techniques play a central role. Advanced imaging techniques provide important novel data on the diagnostic and prognostic assessment of RCMs. This EACVI consensus document provides comprehensive information for the appropriateness of all non-invasive imaging techniques for the diagnosis, prognostic evaluation, and management of patients with RCM.
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Affiliation(s)
- Gilbert Habib
- Aix- Aix-Marseille Univ, URMITE, Aix Marseille Université-UM63, CNRS 7278, IRD 198, INSERM 1095.,Cardiology Department, APHM, La Timone Hospital, Boulevard Jean Moulin, 13005 Marseille, France
| | - Chiara Bucciarelli-Ducci
- Bristol Heart Institute, National Institute of Health Research (NIHR) Bristol Cardiovascular Biomedical Research Unit (BRU), University of Bristol, Bristol, UK
| | - Alida L P Caforio
- Cardiology, Department of Cardiological Thoracic and Vascular Sciences, University of Padova, Italy
| | - Nuno Cardim
- Multimodality Cardiac Imaging Department, Sports Cardiology and Cardiomyopathies Centre-Hospital da Luz; Lisbon, Portugal
| | - Philippe Charron
- Université Versailles Saint Quentin, INSERM U1018, Hôpital Ambroise Paré, Boulogne-Billancourt, France.,Centre de référence pour les maladies cardiaques héréditaires, APHP, ICAN, Hôpital de la Pitié Salpêtrière, Paris, France
| | | | - Aurélie Dehaene
- Department of Radiology and Cardiovascular Imaging, APHM, Hôpitaux de la Timone, Pôle d'imagerie Médicale, 13005 Marseille, France
| | - Genevieve Derumeaux
- Department of Physiology, INSERM U955, Université Paris-Est Creteil, Henri Mondor Hospital, DHU-ATVB, AP-HP, Créteil, France
| | - Erwan Donal
- Cardiologie-CHU Rennes & CIC-IT 1414 & LTSI INSERM 1099 - Université Rennes-1
| | - Marc R Dweck
- Centre for Cardiovascular Science, University of Edinburgh
| | - Thor Edvardsen
- Department of Cardiology, Center for Cardiological Innovation and Institute for Surgical Research, Oslo University Hospital, Oslo, Norway.,University of Oslo, Oslo, Norway
| | - Paola Anna Erba
- Regional Center of Nuclear Medicine, Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy
| | - Laura Ernande
- Department of Physiology, INSERM U955, Université Paris-Est Creteil, Henri Mondor Hospital, DHU-ATVB, AP-HP, Créteil, France
| | - Oliver Gaemperli
- University Heart Center Zurich, Interventional Cardiology and Cardiac Imaging 19, Zurich
| | - Maurizio Galderisi
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Julia Grapsa
- Department of Cardiovascular Sciences, Imperial College of London, London, UK
| | - Alexis Jacquier
- Department of Radiology and Cardiovascular Imaging, APHM, Hôpitaux de la Timone, Pôle d'imagerie Médicale, Aix-Marseille Université, CNRS, CRMBM UMR 7339, 13385 Marseille, France
| | - Karin Klingel
- Department of Molecular Pathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany
| | - Patrizio Lancellotti
- Departments of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium.,Gruppo Villa Maria Care and Research, Anthea Hospital, Bari, Italy
| | - Danilo Neglia
- Cardiovascular Department, Fondazione Toscana G. Monasterio, CNR Institute of Clinical Physiology, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Alessia Pepe
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio C.N.R.-Regione Toscana Pisa, Italy
| | | | - Steffen E Petersen
- Department of Advanced Cardiovascular Imaging, William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts, London, UK
| | - Sven Plein
- Division of Biomedical Imaging, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine LIGHT Laboratories, University of Leeds, UK
| | - Bogdan A Popescu
- University of Medicine and Pharmacy 'Carol Davila'-Euroecolab, Institute of Cardiovascular Diseases, Bucharest, Romania
| | | | | | - Erwan Salaun
- Cardiology Department, La Timone Hospital, Marseille France
| | - Riemer H J A Slart
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands.,Department of Biomedical Photonic Imaging, University of Twente, PO Box 217, 7500 AEEnschede, The Netherlands
| | - Christophe Tribouilloy
- Department of Cardiology, University Hospital Amiens, Amiens, France and INSERM U-1088, Jules Verne University of Picardie, Amiens, France
| | - Jose Zamorano
- University Hospital Ramon y Cajal Carretera de Colmenar Km 9,100, 28034 Madrid, Spain
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Asano Y, Jinnin M, Kawaguchi Y, Kuwana M, Goto D, Sato S, Takehara K, Hatano M, Fujimoto M, Mugii N, Ihn H. Diagnostic criteria, severity classification and guidelines of systemic sclerosis. J Dermatol 2018; 45:633-691. [PMID: 29687465 DOI: 10.1111/1346-8138.14162] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 11/06/2017] [Indexed: 01/17/2023]
Abstract
Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc.
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Affiliation(s)
- Yoshihide Asano
- Department of Dermatology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Jinnin
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasushi Kawaguchi
- Institute of Rheumatology, Tokyo Woman's Medical University, Tokyo, Japan
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Daisuke Goto
- Department of Rheumatology, Faculty of Medicine, Univertity of Tsukuba, Ibaraki, Japan
| | - Shinichi Sato
- Department of Dermatology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Takehara
- Department of Molecular Pathology of Skin, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
| | - Masaru Hatano
- Graduate School of Medicine Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan
| | - Manabu Fujimoto
- Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Naoki Mugii
- Section of Rehabilitation, Kanazawa University Hospital, Ishikawa, Japan
| | - Hironobu Ihn
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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30
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Guo J, Miller RG, Costacou T, Follansbee WP, Orchard TJ. Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes. J Diabetes Complications 2018; 32:298-304. [PMID: 29366734 PMCID: PMC5820228 DOI: 10.1016/j.jdiacomp.2017.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 12/01/2017] [Accepted: 12/15/2017] [Indexed: 11/22/2022]
Abstract
OBJECTIVES We aimed to assess association between abnormal LVEF, in the absence of coronary artery disease (CAD), and 25-year incidence of major outcomes of diabetes (MOD) in a cardiology substudy of the Pittsburgh Epidemiology of Diabetes Complications cohort of childhood-onset type 1 diabetes. METHODS 115 normotensive type 1 diabetes individuals without known CAD, underwent a baseline exercise radionuclide ventriculography. Abnormal LVEF was defined as a resting ejection fraction <50% or a failure to increase ejection fraction with exercise by >5% (men) or a fall in ejection fraction with exercise (women). Cox proportional hazards models were used to predict the composite endpoint of MOD (first instance of major CAD, stroke, end-stage renal disease, blindness, amputation or diabetes-related death). RESULTS Mean baseline age was 28 and diabetes duration 19 years. In a mean follow-up of 19 years, 50 MOD events were identified. Allowing for established risk factors at baseline, abnormal LVEF (n = 22) independently predicted MOD incidence (HR = 2.12, 95% CI: 1.12-4.00, p = 0.022) but not major CAD (HR = 1.33, 95% CI: 0.53-3.33, p = 0.539). CONCLUSIONS An abnormal LVEF may identify diabetic cardiomyopathy and predict long term risk of MOD (but not CAD alone) in type 1 diabetes individuals, consistent with it reflecting microvascular disease.
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Affiliation(s)
- Jingchuan Guo
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Rachel G Miller
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Tina Costacou
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States
| | - William P Follansbee
- Department of Cardiology, University of Pittsburgh Medical, Center, Pittsburgh, PA, United States
| | - Trevor J Orchard
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States.
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31
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Frantz S, Falcao-Pires I, Balligand JL, Bauersachs J, Brutsaert D, Ciccarelli M, Dawson D, de Windt LJ, Giacca M, Hamdani N, Hilfiker-Kleiner D, Hirsch E, Leite-Moreira A, Mayr M, Thum T, Tocchetti CG, van der Velden J, Varricchi G, Heymans S. The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC. Eur J Heart Fail 2018; 20:445-459. [PMID: 29333691 PMCID: PMC5993315 DOI: 10.1002/ejhf.1138] [Citation(s) in RCA: 135] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Revised: 12/03/2017] [Accepted: 12/18/2017] [Indexed: 12/11/2022] Open
Abstract
Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies.
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Affiliation(s)
- Stefan Frantz
- Department of Internal Medicine I, University Hospital Würzburg, Germany; Department of Internal Medicine III, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Ines Falcao-Pires
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Jean-Luc Balligand
- Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et Clinique (IREC), and Clinique Universitaire Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Medizinische Hochschule, Hannover, Germany
| | | | - Michele Ciccarelli
- Department of Medicine and Surgery, University of Salerno, Baronissi, Italy
| | - Dana Dawson
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland
| | - Leon J de Windt
- Department of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Mauro Giacca
- International Centre for Genetic Engineering and Biotechnology (ICGEB) and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Nazha Hamdani
- Department of Cardiovascular Physiology, Ruhr University Bochum, Bochum, Germany
| | - Denise Hilfiker-Kleiner
- Molecular Cardiology, Department of Cardiology and Angiology, Medizinische Hochschule, Hannover, Germany
| | - Emilio Hirsch
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
| | - Adelino Leite-Moreira
- Department of Physiology and Cardiothoracic Surgery and Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Manuel Mayr
- The James Black Centre and King's British Heart Foundation Centre, King's College, University of London, London, UK
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, and REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany
| | - Carlo G Tocchetti
- Department of Translational Medical Sciences, Federico II University, Naples, Italy
| | - Jolanda van der Velden
- Department of Physiology, VU University Medical Center, Amsterdam Cardiovascular Sciences Institute, Amsterdam, The Netherlands.,Netherlands Heart Institute, Utrecht, The Netherlands
| | - Gilda Varricchi
- Department of Translational Medical Sciences, Federico II University, Naples, Italy.,Center for Basic and Clinical Immunology Research (CISI), Federico II University, Naples, Italy
| | - Stephane Heymans
- Department of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.,Netherlands Heart Institute, Utrecht, The Netherlands.,Department of Cardiovascular Sciences, Leuven University, Leuven, Belgium
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32
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Hromádka M, Seidlerová J, Suchý D, Rajdl D, Lhotský J, Ludvík J, Rokyta R, Baxa J. Myocardial fibrosis detected by magnetic resonance in systemic sclerosis patients – Relationship with biochemical and echocardiography parameters. Int J Cardiol 2017; 249:448-453. [DOI: 10.1016/j.ijcard.2017.08.072] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 07/13/2017] [Accepted: 08/29/2017] [Indexed: 01/06/2023]
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Nevskaya T, Baron M, Pope JE. Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort. Rheumatology (Oxford) 2017; 56:1111-1122. [PMID: 28340090 DOI: 10.1093/rheumatology/kex015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2016] [Indexed: 11/13/2022] Open
Abstract
Objective To estimate the effect of disease activity, as measured by the European Scleroderma Research Group Activity Index (EScSG-AI), on the risk of subsequent organ damage in a large systemic sclerosis (SSc) cohort. Methods Of 421 SSc patients from the Canadian Scleroderma Research Group database with disease duration of ⩽ 3 years, 197 who had no evidence of end-stage organ damage initially and available 3 year follow-up were included. Disease activity was assessed by the EScSG-AI with two variability measures: the adjusted mean EScSG-AI (the area under the curve of the EScSG-AI over the observation period) and persistently active disease/flare. Outcomes were based on the Medsger severity scale and included accrual of a new severity score (Δ ⩾ 1) overall and within organ systems or reaching a significant level of deterioration in health status. Results After adjustment for covariates, the adjusted mean EScSG-AI was the most consistent predictor of risk across the study outcomes over 3 years in dcSSc: disease progression defined as Δ ⩾ 1 in any major internal organ, significant decline in forced vital capacity and diffusing capacity of carbon monoxide, severity of visceral disease and HAQ Disability Index worsening. In multivariate analysis, progression of lung disease was predicted solely by adjusted mean EScSG-AI, while the severity of lung disease was predicted the adjusted mean EScSG-AI, older age, modified Rodnan skin score (mRSS) and initial severity. The EScSG-AI was associated with patient- and physician-assessed measures of health status and overpowered the mRSS in predicting disease outcomes. Conclusion Disease activity burden quantified with the adjusted mean EScSG-AI predicted the risk of deterioration in health status and severe organ involvement in dcSSc. The EScSG-AI is more responsive when done repeatedly and averaged.
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Affiliation(s)
- Tatiana Nevskaya
- Division of Rheumatology, St. Joseph's Health Care, University of Western Ontario, London, ON
| | - Murray Baron
- Division of Rheumatology, Jewish General Hospital, McGill University, Montreal, QC, Canada
| | - Janet E Pope
- Division of Rheumatology, St. Joseph's Health Care, University of Western Ontario, London, ON
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34
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Mavrogeni S, Koutsogeorgopoulou L, Karabela G, Stavropoulos E, Katsifis G, Raftakis J, Plastiras S, Noutsias M, Markousis-Mavrogenis G, Kolovou G. Silent myocarditis in systemic sclerosis detected by cardiovascular magnetic resonance using Lake Louise criteria. BMC Cardiovasc Disord 2017; 17:187. [PMID: 28716007 PMCID: PMC5513128 DOI: 10.1186/s12872-017-0619-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 07/05/2017] [Indexed: 12/12/2022] Open
Abstract
Background Systemic sclerosis (SSc) is an autoimmune disease characterized by microvascular abnormalities, inflammation and fibrosis. We hypothesized that myocarditis may be diagnosed in asymptomatic SSc, undergoing routine cardio-vascular magnetic resonance (CMR) for fibrosis assessment, using the Lake Louise criteria: T2 ratio, early (EGE) and late gadolinium enhanced (LGE) images. Methods Eighty-two asymptomatic SSc, diagnosed according to American College of Rheumatology criteria, aged 43 ± 5 yrs., 62 with diffuse (dSSc) and 20 with localized (lSSc) systemic sclerosis were evaluated by CMR, performed at 1.5 T scanner, according to Lake Louise criteria. Results CMR documented normal biventricular function in all SSc. However, 7/62 (11.2%) with dSSc and 2/20 (10%) with lSSc, had CMR signs of myocarditis according to Lake Louise criteria, without any clinical cardiac symptom. In these 9 patients, T2 ratio, EGE ratio and LGE (positive in all 9 SSc) were 2.8 ± 0.5%, 8 ± 3% and 5 ± 3% of LV mass, respectively. No correlation between CMR and blood inflammatory indices (C-reactive protein and erythrocyte sedimentation rate), cardiac troponin T, disease characteristics or type of SSc was identified. A repeat CMR at 6 months, after treatment with prednisone and azathioprine, showed normalisation of the acute inflammation CMR indices. Conclusions Silent myocarditis may be diagnosed using the Lake Louise paper criteria in SSc patients without cardiac symptoms, has no correlation with blood inflammatory indices, cardiac troponin or disease characteristics. CMR is a promising tool to diagnose silent myocarditis in SSc and monitor the response to immunosuppressive treatment.
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Affiliation(s)
- Sophie Mavrogeni
- Onassis Cardiac Surgery Center, 50 Esperou Street, 175-61 P.Faliro, Athens, Greece.
| | | | | | | | | | | | | | - Michel Noutsias
- Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle, Ernst-Grube-Straße 40, D-06120, Halle (Saale), Germany
| | | | - Genovefa Kolovou
- Onassis Cardiac Surgery Center, 50 Esperou Street, 175-61 P.Faliro, Athens, Greece
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35
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Giacomelli R, Di Cesare E, Cipriani P, Ruscitti P, Di Sibio A, Liakouli V, Gennarelli A, Carubbi F, Splendiani A, Berardicurti O, Di Benedetto P, Ciccia F, Guggino G, Radchenko G, Triolo G, Masciocchi C. Pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance identifies very early cardiac involvement in systemic sclerosis patients of recent onset. Int J Rheum Dis 2017; 20:1247-1260. [DOI: 10.1111/1756-185x.13107] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Roberto Giacomelli
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Ernesto Di Cesare
- Department of Biotechnological and Applied Clinical Sciences; Division of Cardiac Radiology; Laboratory of Radiobiology; University of L'Aquila; L'Aquila Italy
| | - Paola Cipriani
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Piero Ruscitti
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Alessandra Di Sibio
- Department of Biotechnological and Applied Clinical Sciences; Division of Radiology; Laboratory of Radiobiology; University of L'Aquila; L'Aquila Italy
| | - Vasiliki Liakouli
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Antonio Gennarelli
- Department of Biotechnological and Applied Clinical Sciences; Division of Radiology; Laboratory of Radiobiology; University of L'Aquila; L'Aquila Italy
| | - Francesco Carubbi
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Alessandra Splendiani
- Department of Biotechnological and Applied Clinical Sciences; Division of Radiology; Laboratory of Radiobiology; University of L'Aquila; L'Aquila Italy
| | - Onorina Berardicurti
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Paola Di Benedetto
- Division of Rheumatology; Department of Biotechnological and Applied Clinical Science; School of Medicine; University of L'Aquila; L'Aquila Italy
| | - Francesco Ciccia
- Division of Rheumatology; Department of Internal Medicine; University of Palermo; Palermo Italy
| | - Giuliana Guggino
- Division of Rheumatology; Department of Internal Medicine; University of Palermo; Palermo Italy
| | - Ganna Radchenko
- Institute of Cardiology of Ukrainian National Academy of Medical Science; Kyiv Ukraine
| | - Giovanni Triolo
- Division of Rheumatology; Department of Internal Medicine; University of Palermo; Palermo Italy
| | - Carlo Masciocchi
- Department of Biotechnological and Applied Clinical Sciences; Division of Radiology; Laboratory of Radiobiology; University of L'Aquila; L'Aquila Italy
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36
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Mavrogeni SI, Schwitter J, Gargani L, Pepe A, Monti L, Allanore Y, Matucci-Cerinic M. Cardiovascular magnetic resonance in systemic sclerosis: "Pearls and pitfalls". Semin Arthritis Rheum 2017; 47:79-85. [PMID: 28522072 DOI: 10.1016/j.semarthrit.2017.03.020] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 02/17/2017] [Accepted: 03/29/2017] [Indexed: 10/19/2022]
Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular dysfunction and excessive fibrosis, involving internal organs including the heart. The estimated prevalence of cardiac involvement in SSc is high and remains subclinical until the late stages. It is either primary, related to myocardial inflammation and fibrosis, or secondary, due to pulmonary arterial hypertension (SSc-PAH) or systemic hypertension, in those patients with renal involvement. Cardiovascular magnetic resonance (CMR) is a useful tool for the early assessment of cardiac involvement in SSc. It is the gold standard technique to assess ventricular volumes,ejection fraction, and in particular is very useful to reliably and non-invasively detect myocardial inflammation, early perfusion defects, and myocardial fibrosis. However, the CMR evaluation in SSc may be problematic, because of cardiac and respiratory artefacts, commonly found in these patients. Therefore, a high level of expertise is necessary for both acquisition and interpretation of CMR images in SSc.
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Affiliation(s)
- Sophie I Mavrogeni
- Cardiology Department, Onassis Cardiac Surgery Center, 50 Esperou St, 175-61, P. Faliro, Athens, Greece.
| | - Juerg Schwitter
- Cardiovascular Department, Cardiac MR Center of the CHUV, Centre Hospitalier Universitaire Vaudois-CHUV, Lausanne, Switzerland
| | - Luna Gargani
- National Research Council, Institute of Clinical Physiology, Pisa, Italy
| | - Alessia Pepe
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio C.N.R., Pisa, Italy
| | - Lorenzo Monti
- Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Yannick Allanore
- Rheumatology A Department, Cochin Hospital, Paris Descartes University, Paris, France
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Geriatric Medicine, AOUC, Florence, Italy
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37
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Mayr A, Kitterer D, Latus J, Steubing H, Henes J, Vecchio F, Kaesemann P, Patrascu A, Greiser A, Groeninger S, Braun N, Alscher MD, Sechtem U, Mahrholdt H, Greulich S. Evaluation of myocardial involvement in patients with connective tissue disorders: a multi-parametric cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2016; 18:67. [PMID: 27733210 PMCID: PMC5062828 DOI: 10.1186/s12968-016-0288-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Severe arrhythmias or heart failure may be surrogates of myocardial involvement in patients with connective tissue disorders (CTD). However, most patients present with unspecific symptoms, normal ECG, and preserved left ventricular ejection fraction (LV-EF). Therefore, timely diagnosis by an accurate technique is crucial. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has proven value for the detection of focal processes, but due to the often diffuse character of fibrosis/inflammation in CTD patients, CMR mapping techniques might be of incremental value for the assessment of myocardial involvement. Purpose of this study was to evaluate a multi-parametric CMR protocol as a screening tool for myocardial involvement in CTD patients. METHODS Forty CTD patients were prospectively enrolled and underwent CMR, twenty healthy volunteers served as control group. RESULTS Mean LV-EF was 62 %; LGE prevalence was low (18 %). CTD patients had higher native T1 (1008 vs. 962 ms, p = 0.001), lower post contrast T1 (494 vs. 526 ms, p = 0.008), expanded extracellular volume (ECV) (28 vs. 25 %, p = 0.001), and higher T2 values (53 vs. 49 ms, p < 0.001) compared to controls. Among patients with values higher than the 95 % percentile of healthy controls, native T1 and T2 values seem to be the most promising discriminators. CONCLUSION CTD patients showed higher T1, ECV, and T2 values compared to controls, with most significant differences for native T1 and T2, which seem to be independent of the presence of LGE. Our data suggest that CMR mapping techniques are of incremental value in the detection of myocardial involvement in CTD patients.
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Affiliation(s)
- Agnes Mayr
- Division of Radiology, University Hospital Innsbruck, Innsbruck, Austria
| | - Daniel Kitterer
- Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Medical Center Stuttgart, Stuttgart, Germany
| | - Joerg Latus
- Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Medical Center Stuttgart, Stuttgart, Germany
| | - Hannah Steubing
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
| | - Joerg Henes
- Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II (Oncology, Haematology, Immunology, Rheumatology, Pulmology), University Hospital Tuebingen, Tuebingen, Germany
| | - Francesco Vecchio
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
| | - Philipp Kaesemann
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
| | - Alexandru Patrascu
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
| | | | | | - Niko Braun
- Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Medical Center Stuttgart, Stuttgart, Germany
| | - M. Dominik Alscher
- Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Medical Center Stuttgart, Stuttgart, Germany
| | - Udo Sechtem
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
| | - Heiko Mahrholdt
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
| | - Simon Greulich
- Division of Cardiology, Robert-Bosch-Medical Center Stuttgart, Auerbachstrasse 110, 70376 Stuttgart, Germany
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Emrani Z, Karbalaie A, Fatemi A, Etehadtavakol M, Erlandsson BE. Capillary density: An important parameter in nailfold capillaroscopy. Microvasc Res 2016; 109:7-18. [PMID: 27614146 DOI: 10.1016/j.mvr.2016.09.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 09/03/2016] [Accepted: 09/03/2016] [Indexed: 10/21/2022]
Abstract
Nailfold capillaroscopy is one of the various noninvasive bioengineering methods used to investigate skin microcirculation. It is an effective examination for assessing microvascular changes in the peripheral circulation; hence it has a significant role for the diagnosis of Systemic sclerosis with the classic changes of giant capillaries as well as the decline in capillary density with capillary dropout. The decline in capillary density is one of microangiopathic features existing in connective tissue disease. It is detectable with nailfold capillaroscopy. This parameter is assessed by applying quantitative measurement. In this article, we reviewed a common method for calculating the capillary density and the relation between the number of capillaries as well as the existence of digital ulcers, pulmonary arterial hypertension, autoantibodies, scleroderma patterns and different scoring system.
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Affiliation(s)
- Zahra Emrani
- Medical Image and Signal Processing Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Abdolamir Karbalaie
- Royal Institute of Technology (KTH), School of Technology and Health, SE-100 44 Stockholm, Sweden.
| | - Alimohammad Fatemi
- Department of Rheumatology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Mahnaz Etehadtavakol
- Medical Image and Signal Processing Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Björn-Erik Erlandsson
- Royal Institute of Technology (KTH), School of Technology and Health, SE-100 44 Stockholm, Sweden.
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39
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A critical view on cardiovascular risk in systemic sclerosis. Rheumatol Int 2016; 37:85-95. [PMID: 27405985 DOI: 10.1007/s00296-016-3530-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 07/05/2016] [Indexed: 12/22/2022]
Abstract
Systemic Sclerosis (SSc) is an autoimmune disorder characterized by microvascular injury and diffuse fibrosis of the skin and internal organs. While macrovascular disease and higher risk for cardiovascular events are well documented in other systemic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, the presence and extent of atherosclerosis among patients with SSc is yet to be established. Primary cardiac involvement, due to impairment of coronary microvascular circulation and myocardial fibrosis, considerably affects prognosis and life expectancy of individuals with SSc, representing one of the leading causes of death in this population. On the other hand the existence and prevalence of atherosclerotic coronary disease remains an issue of debate as studies comparing structural and morphological markers of atherosclerosis and cardiovascular events between SSc patients and the general population have yielded controversial results. The aim of this review is to summarize recent literature about the prevalence of cardiovascular disease in SSc, review the surrogate markers of CVD that have been evaluated and examine whether common pathogenic mechanisms exist between SSc and macrovascular disease.
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40
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Becker MO, Riemekasten G. Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course. Expert Rev Clin Immunol 2015; 12:115-35. [PMID: 26558747 DOI: 10.1586/1744666x.2016.1115717] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Systemic sclerosis (SSc, or scleroderma) is a rheumatic disease with distinct features that encompass autoimmunity, vascular lesions (vasculopathy) and tissue fibrosis. The disease has a high morbidity and mortality compared with other rheumatic diseases. This review discusses risk factors and markers that predict the disease course and the occurrence of disease manifestations, with an emphasis on major organ involvement. In addition, risk factors will be described that are associated with mortality in SSc patients. The review addresses the impact of recent developments on screening, diagnosis and risk stratification as well as the need for further research where data are lacking.
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Affiliation(s)
- Mike O Becker
- a Department of Rheumatology and Clinical Immunology , University Hospital Charité Berlin , Berlin , Germany
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41
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González-Cambeiro MC, Abu-Assi E, Abumuaileq RRY, Raposeiras-Roubín S, Rigueiro-Veloso P, Virgós-Lamela A, Díaz-Castro O, González-Juanatey JR. Systemic sclerosis: A rare cause of heart failure? Rev Port Cardiol 2015; 34:617.e1-5. [DOI: 10.1016/j.repc.2015.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 02/21/2015] [Accepted: 02/25/2015] [Indexed: 10/23/2022] Open
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González-Cambeiro MC, Abu-Assi E, Abumuaileq RRY, Raposeiras-Roubín S, Rigueiro-Veloso P, Virgós-Lamela A, Díaz-Castro O, González-Juanatey JR. Systemic sclerosis: A rare cause of heart failure? REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2015. [DOI: 10.1016/j.repce.2015.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Topuzoglu S, Knobler R, Movadat O, Petkov V, Foedinger D, Just U, Pehamberger H, Jantschitsch C. Incidence of lung cancer in patients with systemic sclerosis treated with extracorporeal photopheresis. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2015; 31:175-83. [PMID: 25495608 DOI: 10.1111/phpp.12155] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/07/2014] [Indexed: 01/29/2023]
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) improves skin sclerosis in systemic sclerosis (SSc) patients. SSc is associated with an increased risk of lung cancer. As ECP is supposed to exert immunomodulatory effects, a possible impact of ECP on the incidence of lung cancer in SSc patients was evaluated. METHODS Seventy-one SSc patients treated with ECP at the Photopheresis Unit of the Department of Dermatology at the Medical University of Vienna between 1991 and 2013 were analyzed retrospectively. RESULTS We calculated a standardized incidence ratio (SIR) for lung cancer in ECP-treated SSc patients of 2.34 [95% confidence interval (CI) 1.63-2.49]. This is in accordance with recent meta-analyses demonstrating a significantly enhanced risk of lung carcinoma in SSc patients. Comparison of the lung cancer risks of these patients with our ECP-treated patients revealed that ECP has no influence. Each patient with lung carcinoma had previously been diagnosed with lung involvement of the non-specific interstitial pneumonitis (NSIP) type. CONCLUSION We confirm that SSc patients are at significantly increased risk for lung cancer. However, ECP does not influence this risk. NSIP may be a risk factor for lung cancer in SSc patients.
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Affiliation(s)
- Sabriye Topuzoglu
- Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Robert Knobler
- Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Oliver Movadat
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Ventzislav Petkov
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Dagmar Foedinger
- Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Ulrike Just
- Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Hubert Pehamberger
- Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Christian Jantschitsch
- Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria
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Lambova S. Cardiac manifestations in systemic sclerosis. World J Cardiol 2014; 6:993-1005. [PMID: 25276300 PMCID: PMC4176808 DOI: 10.4330/wjc.v6.i9.993] [Citation(s) in RCA: 114] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 05/11/2014] [Accepted: 07/15/2014] [Indexed: 02/06/2023] Open
Abstract
Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis (SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography (especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.
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Gerede DM, Turhan S, Hural R, Acıbuca A, Kucuksahin O, Ozcan OU, Goksuluk H, Vurgun VK, Erol C. Evaluation of global function of the heart in scleroderma patients. Echocardiography 2014; 32:912-9. [PMID: 25250771 DOI: 10.1111/echo.12774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVE Scleroderma is a connective tissue disease characterized by diffuse vascular lesions and fibrosis of the skin and major organs including lungs, kidneys, and heart. When cardiac involvement is clinically evident, it is recognized as a poor prognostic factor. The early detection of cardiac involvement in scleroderma would be desirable both for implementation of preventive measures in the early stages of the disease and for optimal treatment. METHODS Left (LV) and right (RV) ventricular function were examined in 31 scleroderma patients and 21 healthy controls. Conventional and tissue Doppler echocardiography was used to evaluate systolic and diastolic function. Systolic indices including systolic (S) velocity, isovolumetric acceleration (IVA), ejection time (ET), and isovolumetric contraction time (IVCT) were measured. Early diastolic (E) velocity, late diastolic (A) velocity, E/A and E'/A' ratios, isovolumetric relaxation time (IVRT), and deceleration time (DT) were the diastolic measurements obtained. Myocardial performance index (Tei index) calculated by 2 different methods was used to assess global ventricular function. RESULTS In our study; mitral S velocity, biventricular ET, E', E/A, E'/A', RV IVA, LV IVA, and tricuspid S velocity were significantly lower in scleroderma patients. Mitral DT, IVCT, and biventricular IVRT, were significantly higher in scleroderma patients (P < 0.0001). In addition, RV and LV Tei indices were significantly increased in scleroderma patients compared with the control group (P < 0.0001 and P < 0.001, respectively). CONCLUSIONS In scleroderma patients, global function was depressed prior to the onset of clinical symptoms. Biventricular diastolic and systolic function abnormalities were also observed.
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Affiliation(s)
| | - Sibel Turhan
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
| | - Refika Hural
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
| | - Aynur Acıbuca
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
| | - Orhan Kucuksahin
- Department of Rheumatology, Ankara University School of Medicine, Ankara, Turkey
| | - Ozgur Ulas Ozcan
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
| | - Huseyin Goksuluk
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
| | - Veysel Kutay Vurgun
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
| | - Cetin Erol
- Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
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Rodriguez-Reyna TS, Morelos-Guzman M, Hernandez-Reyes P, Montero-Duarte K, Martinez-Reyes C, Reyes-Utrera C, Vazquez-La Madrid J, Morales-Blanhir J, Nunez-Alvarez C, Cabiedes-Contreras J. Assessment of myocardial fibrosis and microvascular damage in systemic sclerosis by magnetic resonance imaging and coronary angiotomography. Rheumatology (Oxford) 2014; 54:647-54. [DOI: 10.1093/rheumatology/keu350] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Tigen K, Sunbul M, Ozen G, Durmus E, Kivrak T, Cincin A, Ozben B, Atas H, Direskeneli H, Basaran Y. Regional myocardial dysfunction assessed by two-dimensional speckle tracking echocardiography in systemic sclerosis patients with fragmented QRS complexes. J Electrocardiol 2014; 47:677-83. [DOI: 10.1016/j.jelectrocard.2014.07.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Indexed: 01/16/2023]
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Papagoras C, Achenbach K, Tsifetaki N, Tsiouris S, Fotopoulos A, Drosos AA. Heart involvement in systemic sclerosis: a combined echocardiographic and scintigraphic study. Clin Rheumatol 2014; 33:1105-11. [PMID: 24847773 DOI: 10.1007/s10067-014-2666-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 03/17/2014] [Accepted: 05/02/2014] [Indexed: 12/19/2022]
Abstract
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 30 mmHg 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 51.8 years; four patients were younger than 40 years old and eight patients younger than 50 years. 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.
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Affiliation(s)
- Charalampos Papagoras
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece
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Ntusi NAB, Piechnik SK, Francis JM, Ferreira VM, Rai ABS, Matthews PM, Robson MD, Moon J, Wordsworth PB, Neubauer S, Karamitsos TD. Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis--a clinical study using myocardial T1-mapping and extracellular volume quantification. J Cardiovasc Magn Reson 2014; 16:21. [PMID: 24593856 PMCID: PMC3996013 DOI: 10.1186/1532-429x-16-21] [Citation(s) in RCA: 206] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 02/17/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc. METHODS 19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification. RESULTS Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices. CONCLUSIONS Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc.
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Affiliation(s)
- Ntobeko AB Ntusi
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - Stefan K Piechnik
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - Jane M Francis
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - Vanessa M Ferreira
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - Aitzaz BS Rai
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - Paul M Matthews
- GlaxoSmithKline Clinical Imaging Centre, London, UK
- Division of Brain Sciences, Department of Medicine, Imperial College, London, UK
| | - Matthew D Robson
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - James Moon
- Institute of Cardiovascular Science, University College London & Heart Hospital, London, UK
| | - Paul B Wordsworth
- Nuffield Department of Orthopaedics & NIHR Oxford Musculoskeletal Biomedical Research Unit, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre and John Radcliffe Hospital, Oxford, UK
| | - Stefan Neubauer
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
| | - Theodoros D Karamitsos
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, Level 0, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford OX3 9DU, United Kingdom
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Suzuki T, Ogasawara S, Ohsako-Higami S, Fukasawa C, Hara M, Kamatani N. Dipyridamole stress thallium perfusion scan for evaluating myocardial involvement in systemic sclerosis. Mod Rheumatol 2014; 11:210-6. [DOI: 10.3109/s101650170006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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