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1
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Yamamoto A, Nagao M, Shirai Y, Nakao R, Sakai A, Kaneko K, Arashi H, Minami Y, Sakai S, Yamaguchi J. Cardiac magnetic resonance imaging T1 mapping and late gadolinium enhancement entropy: Prognostic value in patients with systemic sclerosis. J Cardiol 2023; 82:343-348. [PMID: 37031795 DOI: 10.1016/j.jjcc.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND Systemic sclerosis (SSc) affects the myocardium, thereby resulting in a poor prognosis. Late gadolinium enhancement (LGE) entropy, derived from routine cardiac magnetic resonance (CMR) LGE images, is an index that reflects the complexity of the left ventricular myocardium. The aim of this study was to investigate whether LGE entropy can serve as a prognostic factor in patients with SSc. METHODS Twenty-four patients with SSc, who underwent CMR-T1 mapping and LGE to identify myocardial damage, were enrolled, and LGE entropy was measured. Extracellular volume (ECV) values were calculated using the same CMR-LGE images. The endpoint was major adverse cardiac events (MACEs), comprising all-cause death, hospitalization due to heart failure, and the onset of sustained ventricular tachycardia and ventricular fibrillation. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of LGE entropy was analyzed using Kaplan-Meier analysis. RESULTS The ROC curve analysis demonstrated a cut-off value of 7.39 for MACE with LGE entropy and had a sensitivity and specificity of 80 % and 79 %, respectively. Patients with LGE entropy ≥7.39 had a significantly higher MACE rate than those with LGE entropy <7.39 (p = 0.010). Moreover, LGE entropy ≥7.39 was a poor prognostic factor in patients without elevated ECV values. CONCLUSIONS LGE entropy can be used to predict MACE and allows for further risk stratification in addition to ECV determination.
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Affiliation(s)
- Atsushi Yamamoto
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan; Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, Tokyo, Japan.
| | - Michinobu Nagao
- Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Yurie Shirai
- Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Risako Nakao
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Akiko Sakai
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Koichiro Kaneko
- Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroyuki Arashi
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yuichiro Minami
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Shuji Sakai
- Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Junichi Yamaguchi
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
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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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Mousseaux E, Agoston-Coldea L, Marjanovic Z, Baudet M, Reverdito G, Bollache E, Kachenoura N, Messas E, Soulat G, Farge D. Diastolic Function Assessment of Left and Right Ventricles by MRI in Systemic Sclerosis Patients. J Magn Reson Imaging 2022; 56:1416-1426. [PMID: 35258133 DOI: 10.1002/jmri.28143] [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: 01/10/2022] [Revised: 02/21/2022] [Accepted: 02/25/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Heart involvement is frequent although often clinically silent in systemic sclerosis (SSc) patients. Early identification of cardiac involvement can be improved by noninvasive methods such as MRI, in addition to transthoracic echocardiography (TTE). PURPOSE To assess the ability of phase-contrast (PC)-MRI to detect subclinical left (LV) and right (RV) ventricular diastolic dysfunction in SSc patients. STUDY TYPE Prospective. POPULATION Thirty-five consecutive SSc patients (49 ± 14 years) and 35 sex- and age-matched healthy controls (48.6 ± 13.5 years) who underwent TTE and MRI in the same week. FIELD STRENGTH/SEQUENCE 5 T/PC-MRI using a breath-hold velocity-encoded gradient echo sequence. ASSESSMENT LV TTE (E/E') and LV and RV PC-MRI indices of diastolic function (LV early and late transmitral [EM , EfM , AM , AfM ] and RV transtricuspid [ET , EfT , AT , AfT ] peak filling flow velocities and flow rates, as well as LV [ E M ' ] and RV [ E T ' ] peak longitudinal myocardial velocities during diastole) were measured. STATISTICAL TESTS Two-tailed t-test, Wilcoxon test, or Fischer test for comparison of variables between SSc and healthy control groups; sensitivity, specificity, receiver-operating-characteristic (ROC) area under the curve (AUC) to assess discriminative ability of variables. A P-value <0.05 was considered statistically significant. RESULTS TTE LV E/E' and MRI EM / E M ' and ET / E T ' were significantly higher in SSc patients than in controls (8.27 ± 1.25 vs. 6.70 ± 1.66; 9.43 ± 2.7 vs. 6.51 ± 1.50; 6.51 [4.70-10.40] vs. 4.13 [3.22-5.75], respectively) and separated SSc patients and healthy controls with good sensitivity (68%, 71%, and 80%), specificity (85%, 94%, and 62%), and AUC (0.787, 0.807, and 0.765). LV EfM was significantly higher in SSc patients than in controls (347.1 ± 113.7 vs. 284.7 ± 94.6) as RVAfT (277 [231-355] vs. 220 [154-253] mL/sec) with impaired relaxation pattern (EfT /AfT , 0.95 [0.87-1.21] vs. 1.12 [0.93-1.47]). DATA CONCLUSION MRI was able to detect LV and RV diastolic dysfunction in SSc patients with good accuracy in the absence of LV systolic dysfunction at echocardiography. Use of MRI can allow to better assess the early impact of myocardial fibrosis related to SSc. LEVEL OF EVIDENCE 1 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Elie Mousseaux
- Paris-Cardiovascular Research Center INSERM 970, Université de Paris, Paris, France.,Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France
| | - Lucia Agoston-Coldea
- Paris-Cardiovascular Research Center INSERM 970, Université de Paris, Paris, France.,Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France
| | - Zora Marjanovic
- Service d'Hématologie, Hôpital Saint Antoine (APHP), Paris, France
| | - Mathilde Baudet
- Cardiology Department, APHP, Lariboisiere Hospital, Paris, France
| | - Guillaume Reverdito
- Paris-Cardiovascular Research Center INSERM 970, Université de Paris, Paris, France.,Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France
| | - Emilie Bollache
- Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Paris, France
| | - Nadjia Kachenoura
- Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Paris, France
| | - Emmanuel Messas
- Paris-Cardiovascular Research Center INSERM 970, Université de Paris, Paris, France.,Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France
| | - Gilles Soulat
- Paris-Cardiovascular Research Center INSERM 970, Université de Paris, Paris, France.,Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France
| | - Dominique Farge
- Unité de Médecine Interne (UF 04): CRMR MATHEC, Maladies Auto-Immunes et Thérapie Cellulaire, Centre de Référence des Maladies Auto-Immunes Systémiques Rares d'Ile-de-France, FAI2R, Hôpital Saint-Louis, Assistance Publique des Hôpitaux de Paris, Paris, France.,Recherche Clinique Appliquée à l'hématologie, Institut de Recherche Saint Louis, Université de Paris, Paris, France.,Department of Medicine, McGill University, Montreal, Quebec, Canada
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Palumbo P, Ruscitti P, Cannizzaro E, Berardicurti O, Conforti A, Di Cesare A, Di Cola I, Giacomelli R, Splendiani A, Barile A, Masciocchi C, Cipriani P, Di Cesare E. Unenhanced Cardiac Magnetic Resonance may improve detection and prognostication of an occult heart involvement in asymptomatic patients with systemic sclerosis. Sci Rep 2022; 12:5125. [PMID: 35332224 PMCID: PMC8948177 DOI: 10.1038/s41598-022-09064-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 03/11/2022] [Indexed: 11/09/2022] Open
Abstract
Systemic sclerosis (SSc) is an uncommon autoimmune disease. Aim of the study was to detect the occult cardiac involvement in asymptomatic SSc patients of recent onset (indicative of a more aggressive disease) with unenhanced Cardiac Magnetic Resonance (CMR). Our historical prospective study included naïve SSc patients of recent onset. Modified Rodnan Skin Score (mRSS) and Scleroderma Clinical Trial Consortium Damage Index (SCTC-DI) were calculated. Cardiac volumes and global myocardial strain were assessed and also compared with healthy group values. Pericardial involvement was further recorded. Thirty-one patients met inclusion criteria (54 ± 12 years; 1 M). Mean duration of disease was 6.8 years. All patients showed preserved systolic function. Higher incidence of pericardial involvement was founded in patients with disease accrual damage (OR: 9.6, p-value 0.01). Radial and longitudinal strain values resulted significantly different between healthy and SSc patients. GRS and GLS showed an independent predictive validity on damage accrual (HR: 1.22 and 1.47, respectively). Best C-index for disease progression was reached when strain values and pericardial evaluation were added to conventional risk factors (0.97, p-value: 0.0001). Strain analysis by CMR-TT may show a high capability both in identifying early cardiac involvement and stratifying its clinical aggressiveness, regardless of the standard damage indices and CMR contrast-dependent biomarker.
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Affiliation(s)
- Pierpaolo Palumbo
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, Via Saragat -località Campo di Pile, 67100, L'Aquila, Italy. .,SIRM Foundation, Italian Society of Medical and Interventional Radiology (SIRM), 20122, Milan, Italy.
| | - Piero Ruscitti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Ester Cannizzaro
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, Via Saragat -località Campo di Pile, 67100, L'Aquila, Italy
| | - Onorina Berardicurti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Alessandro Conforti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Annamaria Di Cesare
- Ospedale "Infermi" di Rimini, Viale Luigi Settembrini, 2, 47923, Rimini, Italy
| | - Ilenia Di Cola
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Roberto Giacomelli
- Rome Biomedical Campus University, via Álvaro del Portillo 200, 00128, Roma, Italy
| | - Alessandra Splendiani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Antonio Barile
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Carlo Masciocchi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Paola Cipriani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, Italy
| | - Ernesto Di Cesare
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazzale Salvatore Tommasi 1, 67100, L'Aquila, Italy
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De Luca G, Bombace S, Monti L. Heart Involvement in Systemic Sclerosis: the Role of Magnetic Resonance Imaging. Clin Rev Allergy Immunol 2022; 64:343-357. [PMID: 35072931 DOI: 10.1007/s12016-022-08923-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/06/2022] [Indexed: 12/12/2022]
Abstract
Systemic sclerosis (SSc) is a severe connective tissue disease characterized by diffuse vascular damage and aberrant activation of immune system, resulting in inflammation and fibrosis of skin and internal organs, including the heart. Cardiac involvement is frequent in SSc, even though often unrecognized due to the occult nature at early stages and to the lack of a defined diagnostic algorithm. Once clinically evident, heart involvement is associated with a poor prognosis, representing the leading cause of death in about one third of SSc patients. Thus, its early recognition and monitoring are of crucial importance to allow a prompt therapeutic intervention and to improve patients' outcomes. Cardiac Magnetic Resonance (CMR) is a non-invasive, non-radiating imaging technique of great importance for the assessment of cardiovascular system, and represents the modality of choice for the morpho-functional and structural characterization of the heart. In SSc, CMR allows a precise definition of biventricular and biatrial size and function, and a detailed tissue characterization. CMR has been therefore extensively proposed in SSc as a non-invasive diagnostic tool to characterize heart involvement, particularly myocardial involvement. In this review, we summarize the most recent evidences to support the use of CMR in SSc as an important tool to recognize and characterize scleroderma heart disease. Furthermore, the unmet needs and the future perspectives of a CMR-based approach for the early detection of SSc heart involvement are discussed.
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Dumitru RB, Bissell LA, Erhayiem B, Kidambi A, Dumitru AMH, Fent G, Abignano G, Donica H, Burska A, Greenwood JP, Biglands J, Schlosshan D, Del Galdo F, Plein S, Buch MH. Cardiovascular outcomes in systemic sclerosis with abnormal cardiovascular MRI and serum cardiac biomarkers. RMD Open 2021; 7:rmdopen-2021-001689. [PMID: 34663635 PMCID: PMC8524374 DOI: 10.1136/rmdopen-2021-001689] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 09/06/2021] [Indexed: 12/17/2022] Open
Abstract
Objectives To explore the prognostic value of subclinical cardiovascular (CV) imaging measures and serum cardiac biomarkers in systemic sclerosis (SSc) for the development of CV outcomes of primary heart involvement (pHI). Methods Patients with SSc with no clinical SSc-pHI and no history of heart disease underwent cardiovascular magnetic resonance (CMR) imaging, and measurement of serum high-sensitivity-troponin I (hs-TnI) and N-terminal-pro-brain natriuretic peptide (NT-proBNP). Follow-up clinical and CV outcome data were recorded. CV outcomes were defined as myocarditis, arrhythmia and/or echocardiographic functional impairment including systolic dysfunction and/or diastolic dysfunction. Results Seventy-four patients with a median (IQR) age of 57 (49, 63) years, 32% diffuse cutaneous SSc, 39% interstitial lung disease, 30% Scl70+ were followed up for median (IQR) 22 (15, 54) months. Ten patients developed CV outcomes, comprising one patient with myocarditis and systolic dysfunction and nine arrhythmias: three non-sustained ventricular tachycardia and six supraventricular arrhythmias. The probability of CV outcomes was considerably higher in those with NT-proBNP >125 pg/mL versus normal NT-proBNP (X2=4.47, p=0.035). Trend for poorer time-to-event was noted in those with higher extracellular volume (ECV; indicating diffuse fibrosis) and hs-TnI levels versus those with normal values (X2=2.659, p=0.103; X2=2.530, p=0.112, respectively). In a predictive model, NT-proBNP >125 pg/mL associated with CV outcomes (OR=5.335, p=0.040), with a trend observed for ECV >29% (OR=4.347, p=0.073). Conclusion These data indicate standard serum cardiac biomarkers (notably NT-proBNP) and CMR indices of myocardial fibrosis associate with adverse CV outcomes in SSc. This forms the basis to develop a prognostic model in larger, longitudinal studies.
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Affiliation(s)
- Raluca B Dumitru
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds, West Yorkshire, UK
| | - Lesley-Anne Bissell
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds, West Yorkshire, UK
| | - Bara Erhayiem
- Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK
| | - Ananth Kidambi
- Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK.,Leeds Teaching Hospitals NHS Trust Department of Cardiology, Leeds, West Yorkshire, UK
| | - Ana-Maria H Dumitru
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK.,Faculty of Business Economics and Law, University of Surrey, Guildford, Surrey, UK
| | - Graham Fent
- Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK
| | - Giuseppina Abignano
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds, West Yorkshire, UK
| | - Helena Donica
- Department of Biochemical Diagnostics, Medical University of Lublin, Lublin, Lubelskie, Poland
| | - Agata Burska
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds, West Yorkshire, UK
| | - John P Greenwood
- Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK.,Leeds Teaching Hospitals NHS Trust Department of Cardiology, Leeds, West Yorkshire, UK
| | - John Biglands
- National Institute for Health Research, Leeds Biomedical Research Centre, Leeds, West Yorkshire, UK
| | - Dominik Schlosshan
- Leeds Teaching Hospitals NHS Trust Department of Cardiology, Leeds, West Yorkshire, UK
| | - Francesco Del Galdo
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds, West Yorkshire, UK
| | - Sven Plein
- Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK.,Leeds Teaching Hospitals NHS Trust Department of Cardiology, Leeds, West Yorkshire, UK
| | - Maya H Buch
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, UK .,Centre for Musculoskeletal Research, School of Biological Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.,NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
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Modulation of microRNome by Human Cytomegalovirus and Human Herpesvirus 6 Infection in Human Dermal Fibroblasts: Possible Significance in the Induction of Fibrosis in Systemic Sclerosis. Cells 2021; 10:cells10051060. [PMID: 33946985 PMCID: PMC8146000 DOI: 10.3390/cells10051060] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/23/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023] Open
Abstract
Human cytomegalovirus (HCMV) and Human herpesvirus 6 (HHV-6) have been reportedly suggested as triggers of the onset and/or progression of systemic sclerosis (SSc), a severe autoimmune disorder characterized by multi-organ fibrosis. The etiology and pathogenesis of SSc are still largely unknown but virological and immunological observations support a role for these beta-herpesviruses, and we recently observed a direct impact of HCMV and HHV-6 infection on the expression of cell factors associated with fibrosis at the cell level. Since miRNA expression has been found profoundly deregulated at the tissue level, here we aimed to investigate the impact on cell microRNome (miRNome) of HCMV and HHV-6 infection in in vitro infected primary human dermal fibroblasts, which represent one of the main SSc target cells. The analysis, performed by Taqman arrays detecting and quantifying 754 microRNAs (miRNAs), showed that both herpesviruses significantly modulated miRNA expression in infected cells, with evident early and late effects and deep modulation (>10 fold) of >40 miRNAs at each time post infection, including those previously recognized for their key function in fibrosis. The correlation between these in vitro results with in vivo observations is strongly suggestive of a role of HCMV and/or HHV-6 in the multistep pathogenesis of fibrosis in SSc and in the induction of fibrosis-signaling pathways finally leading to tissue fibrosis. The identification of specific miRNAs may open the way to their use as biomarkers for SSc diagnosis, assessment of disease progression and possible antifibrotic therapies.
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8
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Cioffi G, Viapiana O, Orsolini G, Ognibeni Sonographer F, Dalbeni A, Gatti D, Adami G, Fassio A, Rossini M, Giollo A. Left ventricular hypertrophy predicts poorer cardiovascular outcome in normotensive normoglycemic patients with rheumatoid arthritis. Int J Rheum Dis 2021; 24:510-518. [PMID: 33719195 DOI: 10.1111/1756-185x.14082] [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: 10/11/2020] [Revised: 01/24/2021] [Accepted: 01/25/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Patients with rheumatoid arthritis (RA) develop early changes in left ventricular (LV) geometry and experience cardiovascular events in excess than in the general population. This study was designed to assess prevalence, predictors and prognostic role of LV hypertrophy (LVH) in a selected group of RA patients with normal blood pressure and glycemia who should be at low risk for LVH. METHODS We prospectively analyzed 241 normotensive normoglycemic RA patients (mean age 53 ± 12 years, 61% women) involved in a primary prevention program for cardiovascular diseases who were followed-up for 40 (24-56) months. LVH was detected by echocardiography and defined as LV mass ≥49.2 g/m2.7 for men and ≥46.7 g/m2.7 for women. Primary outcome was a composite of cardiovascular death/hospitalization. RESULTS LVH was detected in 39 patients (16%). Older age (>53 years), greater body mass index (BMI > 25 kg/m2 ), longer duration of RA disease, anti-cyclic citrullinated peptide antibody (ACPA) positivity and concentric LV geometry were the variables associated with LVH. During the follow-up, a cardiovascular event occurred in 12 of 39 (31%) patients with LVH and in 22 of 202 (11%; P < .001) patients without LVH. LVH independently predicted cardiovascular events (hazards ratio 3.28 [95% CI 1.03-9.20], P = .03) at Cox regression analysis together with C-reactive protein and ACPA positivity. CONCLUSIONS Nearly one-sixth of normotensive normoglycemic RA patients analyzed in a primary prevention program for cardiovascular diseases has LVH which is associated with obesity and older age, and strongly predicts cardiovascular event in these subjects.
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Affiliation(s)
- Giovanni Cioffi
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy.,Division of Cardiac Rehabilitation, S. Pancrazio Hospital, Trento, Italy
| | - Ombretta Viapiana
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
| | - Giovanni Orsolini
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
| | | | - Andrea Dalbeni
- Department of Medicine, General Medicine and Hypertension and Liver Unit, University of Verona & Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Davide Gatti
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
| | - Giovanni Adami
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
| | - Angelo Fassio
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
| | - Maurizio Rossini
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
| | - Alessandro Giollo
- Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy
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9
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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: 17] [Impact Index Per Article: 3.4] [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
- * E-mail:
| | - 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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10
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Bucciarelli-Ducci C, Ostenfeld E, Baldassarre LA, Ferreira VM, Frank L, Kallianos K, Raman SV, Srichai MB, McAlindon E, Mavrogeni S, Ntusi NAB, Schulz-Menger J, Valente AM, Ordovas KG. Cardiovascular disease in women: insights from magnetic resonance imaging. J Cardiovasc Magn Reson 2020; 22:71. [PMID: 32981527 PMCID: PMC7520984 DOI: 10.1186/s12968-020-00666-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
The presentation and identification of cardiovascular disease in women pose unique diagnostic challenges compared to men, and underrecognized conditions in this patient population may lead to clinical mismanagement.This article reviews the sex differences in cardiovascular disease, explores the diagnostic and prognostic role of cardiovascular magnetic resonance (CMR) in the spectrum of cardiovascular disorders in women, and proposes the added value of CMR compared to other imaging modalities. In addition, this article specifically reviews the role of CMR in cardiovascular diseases occurring more frequently or exclusively in female patients, including Takotsubo cardiomyopathy, connective tissue disorders, primary pulmonary arterial hypertension and peripartum cardiomyopathy. Gaps in knowledge and opportunities for further investigation of sex-specific cardiovascular differences by CMR are also highlighted.
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Affiliation(s)
- Chiara Bucciarelli-Ducci
- Bristol Heart Institute, Bristol National Institute of Health Research (NIHR) Biomedical Research Centre, University Hospitals Bristol and University of Bristol, Bristol, UK
| | - Ellen Ostenfeld
- Department of Clinical Sciences Lund, Clinical Physiology, Skåne University Hospital Lund, Lund University, Getingevägen 5, SE-22185 Lund, Sweden
| | | | - Vanessa M. Ferreira
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Luba Frank
- University of Texas Medical Branch, Galveston, TX USA
| | | | | | | | - Elisa McAlindon
- Heart and Lung Centre, New Cross Hospital, Wolverhampton, UK
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11
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Palumbo P, Cannizzaro E, Di Cesare A, Bruno F, Schicchi N, Giovagnoni A, Splendiani A, Barile A, Masciocchi C, Di Cesare E. Cardiac magnetic resonance in arrhythmogenic cardiomyopathies. Radiol Med 2020; 125:1087-1101. [PMID: 32978708 DOI: 10.1007/s11547-020-01289-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022]
Abstract
Over the past few years, the approach to the 'arrhythmic patient' has profoundly changed. An early clinical presentation of arrhythmia is often accompanied by non-specific symptoms and followed by inconclusive electrocardiographic findings. In this scenario, cardiac magnetic resonance (CMR) has been established as a clinical tool of fundamental importance for a correct prognostic stratification of the arrhythmic patient. This technique provides a high-spatial-resolution tomographic evaluation of the heart, which allows studying accurately the ventricular volumes, identifying even segmental kinetic anomalies and properly detecting diffuse or focal tissue alterations through an excellent tissue characterization, while depicting different patterns of fibrosis distribution, myocardial edema or fatty substitution. Through these capabilities, CMR has a pivotal role for the adequate management of the arrhythmic patient, allowing the identification of those phenotypic manifestations characteristic of structural heart diseases. Therefore, CMR provides valuable information to reclassify the patient within the wide spectrum of potentially arrhythmogenic heart diseases, the definition of which remains the major determinants for both an adequate treatment and a poor prognosis. The purpose of this review study was to focus on the role of CMR in the evaluation of the main cardiac clinical entities associated with arrhythmogenic phenomena and to present a brief debate on the main pathophysiological mechanisms involved in the arrhythmogenesis process.
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Affiliation(s)
- Pierpaolo Palumbo
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, AQ, Italy.
| | | | - Annamaria Di Cesare
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Federico Bruno
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, AQ, Italy
| | - Nicolò Schicchi
- Department of Radiology, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Di Ancona, Ancona, Italy
| | - Andrea Giovagnoni
- Department of Radiology, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Di Ancona, Ancona, Italy
| | - Alessandra Splendiani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, AQ, Italy
| | - Antonio Barile
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, AQ, Italy
| | - Carlo Masciocchi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio 1, 67100, L'Aquila, AQ, Italy
| | - Ernesto Di Cesare
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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12
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Haematopoietic stem cell transplantation in systemic sclerosis: Challenges and perspectives. Autoimmun Rev 2020; 19:102662. [PMID: 32942028 DOI: 10.1016/j.autrev.2020.102662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 04/07/2020] [Indexed: 12/12/2022]
Abstract
Systemic Sclerosis is chronic progressive autoimmune disease, characterised by microangiopathy and fibrosis. Due to disease heterogeneity, in terms of extent, severity, and rate of progression, optimal therapeutic interventions are still lacking. Haematopoietic stem cells may be a new therapeutic option in this disease and, although the results of the first trials are encouraging, several issues remain to be addressed. On these bases, the stem cells transplantation is an area of active investigation, and an overview of the current available literature may help to define the role of this therapeutic strategy. Although the promising results, some unmet needs remain, including the transplantation protocols and their effects on immune system, the selection of the ideal patient and the pre-transplant cardiopulmonary evaluations. An improvement in these fields will allow us to optimize the haematopoietic stem cell therapies in SSc.
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13
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Wolf M, Montesi SB. Novel Imaging Strategies in Systemic Sclerosis. Curr Rheumatol Rep 2020; 22:57. [PMID: 32785794 DOI: 10.1007/s11926-020-00926-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE OF REVIEW Imaging modalities such as computed tomography, ultrasound, magnetic resonance imaging, and molecular imaging are being used to evaluate for disease in systemic sclerosis (SSc) patients. Here, we review novel imaging strategies to detect organ and vascular complications of SSc and novel imaging techniques for assessing interstitial lung disease and pulmonary hypertension in other conditions that may have further applicability to SSc. RECENT FINDINGS Imaging techniques can be used to identify disease in the lungs, pulmonary vascular system, heart, skin, vascular tissue, and gastrointestinal tract of SSc patients. These show promise in detecting early disease, many without the use of ionizing radiation. Novel imaging techniques in patients with SSc can be used to detect disease in multiple susceptible organs. These imaging strategies have potential for early disease detection, as well as potential for incorporation into clinical trials to accelerate the development of SSc therapies.
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Affiliation(s)
- Molly Wolf
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, 55 Fruit Street, BUL-148, Boston, MA, 02116, USA.,Harvard Medical School, Boston, MA, USA
| | - Sydney B Montesi
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, 55 Fruit Street, BUL-148, Boston, MA, 02116, USA. .,Harvard Medical School, Boston, MA, USA.
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14
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Myocarditis in Scleroderma. J Clin Rheumatol 2020; 26:e146. [DOI: 10.1097/rhu.0000000000001039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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15
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Pradella S, Grazzini G, Letteriello M, De Amicis C, Grassi R, Maggialetti N, Carbone M, Palumbo P, Carotti M, Di Cesare E, Giovagnoni A, Cozzi D, Miele V. Masses in right side of the heart: spectrum of imaging findings. ACTA BIO-MEDICA : ATENEI PARMENSIS 2020; 91:60-70. [PMID: 32945280 PMCID: PMC7944673 DOI: 10.23750/abm.v91i8-s.9940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 06/08/2020] [Indexed: 11/25/2022]
Abstract
Primary heart tumors are rare, benign tumors represent the majority of these. If a cardiac mass is found, the probability that it is a metastasis or a so-called “pseudo-mass” is extremely higher than a primary tumor. The detection of a heart mass during a transthoracic echocardiography (TE) is often unexpected. The TE assessment can be difficult, particularly if the mass is located at the level of the right chambers. Cardiac Computed Tomography (CCT) can be useful in anatomical evaluation and Cardiac Magnetic Resonance (CMR) for masses characterization as well. We provide an overview of right cardiac masses and their imaging futures. (www.actabiomedica.it)
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Affiliation(s)
- Silvia Pradella
- Department of Radiology, Careggi University Hospital, Florence, Italy.
| | - Giulia Grazzini
- Department of Radiology, Careggi University Hospital, Florence, Italy.
| | - Mayla Letteriello
- Department of Radiology, Careggi University Hospital, Florence, Italy.
| | | | - Roberta Grassi
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Nicola Maggialetti
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy.
| | - Mattia Carbone
- Department of Radiology, S. Giovanni and Ruggi D'Aragona Hospital, Salerno, Italy.
| | - Pierpaolo Palumbo
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Marina Carotti
- Università politecnica delle Marche, School of Medicine and University Hospital "Umberto I-Lancisi-Salesi", Department of Radiology, Ancona, Italy.
| | - Ernesto Di Cesare
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Andrea Giovagnoni
- Università politecnica delle Marche, School of Medicine and University Hospital "Umberto I-Lancisi-Salesi", Department of Radiology, Ancona, Italy.
| | - Diletta Cozzi
- Department of Radiology, Careggi University Hospital, Florence, Italy.
| | - Vittorio Miele
- Department of Radiology, Careggi University Hospital, Florence, Italy.
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16
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Acanfora C, Bruno F, Palumbo P, Arrigoni F, Natella R, Mazzei MA, Carotti M, Ruscitti P, Di Cesare E, Splendiani A, Giacomelli R, Masciocchi C, Barile A. Diagnostic and interventional radiology fundamentals of synovial pathology. ACTA BIO-MEDICA : ATENEI PARMENSIS 2020; 91:107-115. [PMID: 32945285 PMCID: PMC7944671 DOI: 10.23750/abm.v91i8-s.9993] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 06/11/2020] [Indexed: 01/15/2023]
Abstract
The synovial membrane is a specialized mesenchymal tissue that lines the diarthrodial joints surfaces, bursae, and tendon sheaths of the body. This article aims to provide an overview of the fundamentals of synovial tissue, with particular regard to the imaging findings of the main pathologic processes that can affect the synovia and the role of image-guided interventions. (www.actabiomedica.it)
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Affiliation(s)
- Chiara Acanfora
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Federico Bruno
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Pierpaolo Palumbo
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Francesco Arrigoni
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Raffaele Natella
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy.
| | - Maria Antonietta Mazzei
- Unit of Diagnostic Imaging, Department of Radiological Sciences, Azienda Ospedaliero-Universitaria Senese, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
| | - Marina Carotti
- Department of Radiology - Division of Special and Pediatric Radiology, University Hospital "Umberto I - Lancisi - Salesi", Ancona, Italy.
| | - Piero Ruscitti
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Ernesto Di Cesare
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Alessandra Splendiani
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Roberto Giacomelli
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Carlo Masciocchi
- Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Antonio Barile
- Department of Applied Clinical Science and Biotechnology, University of L'Aquila, L'Aquila, Italy.
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17
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Di Benedetto P, Guggino G, Manzi G, Ruscitti P, Berardicurti O, Panzera N, Grazia N, Badagliacca R, Riccieri V, Vizza CD, Radchenko G, Liakouli V, Ciccia F, Cipriani P, Giacomelli R. Interleukin-32 in systemic sclerosis, a potential new biomarker for pulmonary arterial hypertension. Arthritis Res Ther 2020; 22:127. [PMID: 32487240 PMCID: PMC7268373 DOI: 10.1186/s13075-020-02218-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 05/13/2020] [Indexed: 02/07/2023] Open
Abstract
Background Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great value to improve current diagnostic methods and develop new strategies for evaluating patients with suspected PAH. Interleukin-32 (IL-32) is a proinflammatory cytokine expressed in damaged vascular cells, and the present study aimed to assess if this cytokine could be a new biomarker of PAH during SSc. Methods The IL-32 expression was evaluated in the sera and skin samples of 18 SSc-PAH patients, 21 SSc patients without PAH, 15 patients with idiopathic PAH (iPAH) and 14 healthy controls (HCs), by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). Receiver-operating characteristic (ROC) curves were performed to evaluate the cut-off of IL-32 in identifying patients with PAH. Furthermore, in SSc patients, correlation analyses were performed between IL-32 sera levels and mean pulmonary artery pressure (mPAP) evaluated by right heart catheterization (RHC) and systolic pulmonary artery pressure (sPAP), obtained by echocardiography. Additionally, the number of skin IL-32+ cells was correlated with modified Rodnan skin score (mRSS). Results In SSc-PAH patients, IL-32 sera levels were significantly higher when compared with SSc patients without PAH and patients affected by iPAH. The analysis of ROC curve showed that IL-32 sera levels above 11.12 pg/ml were able to predict patients with PAH (sensitivity = 90%, specificity = 100%). Furthermore, the IL-32 sera levels of patients with SSc correlated with both mPAP and sPAP. In the skin derived from SSc-PAH patients, the number of IL-32+ cells was significantly increased when compared with the skin derived from SSc patients without PAH, correlating with the mRSS. Conclusion Our study suggested that sera determination of IL-32 may be a promising approach to evaluate the presence of PAH in SSc patients and together with longitudinal future studies could help to increase the understanding how these biomarkers mirror the vascular changes and the inflammatory process during SSc.
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Affiliation(s)
- Paola Di Benedetto
- Clinical Pathology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giuliana Guggino
- Rheumatology Section, Department of Internal Medicine, University of Palermo, Palermo, Italy
| | - Giovanna Manzi
- Department of Cardiovascular and Respiratory Sciences, Sapienza University of Rome, Rome, Italy
| | - Piero Ruscitti
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Onorina Berardicurti
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Noemi Panzera
- Clinical Pathology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Nicolò Grazia
- Clinical Pathology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Roberto Badagliacca
- Department of Cardiovascular and Respiratory Sciences, Sapienza University of Rome, Rome, Italy
| | - Valeria Riccieri
- Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, Rome, Italy
| | - Carmine Dario Vizza
- Department of Cardiovascular and Respiratory Sciences, Sapienza University of Rome, Rome, Italy
| | - Ganna Radchenko
- Secondary Hypertension Department with Pulmonary Hypertension Center, State Institute National Scientific Center "MD Strazhesko Institute of Cardiology" of Ukrainian National Academy of Medical Science, Kyiv, Ukraine
| | - Vasiliki Liakouli
- Rheumatology Section, Department of Clinical and Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Francesco Ciccia
- Rheumatology Section, Department of Clinical and Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Paola Cipriani
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Roberto Giacomelli
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
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18
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The Role of Cardiovascular Magnetic Resonance in Inflammatory Arthropathies and Systemic Rheumatic Diseases. CURRENT RADIOLOGY REPORTS 2020. [DOI: 10.1007/s40134-020-0346-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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19
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Arbeláez-Cortés Á, Quintero-González DC, Cuesta-Astroz Y, Villadiego JS, González-Buriticá H, Rueda JM. Restrictive cardiomyopathy in a patient with systemic sclerosis and Fabry disease: a case-based review. Rheumatol Int 2019; 40:489-497. [PMID: 31599343 DOI: 10.1007/s00296-019-04453-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 09/26/2019] [Indexed: 12/29/2022]
Abstract
Systemic sclerosis (SSc) is a rare immune-mediated vasculopathy characterized by fibrosis of the skin and internal organs. Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene producing α-galactosidase-A enzyme (α-Gal A) deficiency. Being a systemic disease, cardiac involvement in FD has a high mortality rate due to heart failure and arrhythmia. The coexistence of these two entities has not been reported previously. We describe the case of a female patient with limited SSc (lcSSc), a diagnosis based on the presence of sclerodactyly, Raynaud phenomenon, microvascular involvement, and positive anti-centromere antibodies. On follow-up, she developed chest pain, a second-degree A-V block, and restrictive cardiomyopathy (without cardiovascular risk factors). Although heart involvement is common in these two entities, the abnormal thickening of lateral and inferior wall, the infiltration pattern and the conduction system disorders presented herein are more characteristic in a heterozygous female with a cardiac variant of FD. The diagnosis of FD was confirmed with high globotriaosylsphingosine (Lyso-Gb3) levels and identification of GLA gene mutation. The patient was treated with enzymatic replacement (agalsidase alpha) following mild improvement in ventricular mass at 6th month, without clinical deterioration. The related literature on SSc associated with FD is also reviewed.
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Affiliation(s)
- Álvaro Arbeláez-Cortés
- Internal Medicine, Universidad Libre, Cali, Colombia. .,Arthritis and Rheumatology Clinic, Centro Médico Imbanaco, Cali, Colombia.
| | | | - Yesid Cuesta-Astroz
- School of Microbiology, Universidad de Antioquia, Medellín, Colombia.,Instituto Colombiano de Medicina Tropical, Universidad CES, Sabaneta, Colombia
| | | | - Herman González-Buriticá
- Internal Medicine, Universidad Libre, Cali, Colombia.,Arthritis and Rheumatology Clinic, Centro Médico Imbanaco, Cali, Colombia
| | - Jorge M Rueda
- Internal Medicine, Universidad Libre, Cali, Colombia.,Arthritis and Rheumatology Clinic, Centro Médico Imbanaco, Cali, Colombia
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20
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Mrsic Z, Mousavi N, Hulten E, Bittencourt MS. The Prognostic Value of Late Gadolinium Enhancement in Nonischemic Heart Disease. Magn Reson Imaging Clin N Am 2019; 27:545-561. [DOI: 10.1016/j.mric.2019.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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21
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Margaritopoulos GA, Kokosi MA, Wells AU. Diagnosing complications and co-morbidities of fibrotic interstitial lung disease. Expert Rev Respir Med 2019; 13:645-658. [PMID: 31215263 DOI: 10.1080/17476348.2019.1632196] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction: Interstitial lung diseases (ILDs) represent a heterogeneous group of rare disorders that include more than 200 entities, mostly associated with high mortality. In recent years, the progress regarding the understanding of the pathogenesis of these diseases led to the approval of specific treatments. In ILDs, the presence of comorbidities has a significant impact on the quality of life and the survival of patients and, therefore, their diagnosis and treatment has a pivotal role in management and could improve overall outcome. Areas covered: We discuss key diagnostic issues with regard to the most frequent comorbidities in ILDs. Treatment options are also discussed as the decision to investigate more definitively in order to identify specific comorbidities (including lung cancer, pulmonary hypertension, GE reflux, and obstructive sleep apnoea) is critically dependent upon whether comorbidity-specific treatments are likely to be helpful in individual patients, judged on a case by case basis. Expert opinion: The extent to which clinicians proactively pursue the identification of comorbidities depends on realistic treatment goals in individual patients.
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Affiliation(s)
| | - Maria A Kokosi
- a Interstitial Lung Disease Unit , Royal Brompton Hospital , London , UK
| | - Athol U Wells
- a Interstitial Lung Disease Unit , Royal Brompton Hospital , London , UK
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22
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Poindron V, Chatelus E, Canuet M, Gottenberg JE, Arnaud L, Gangi A, Gavand PE, Guffroy A, Korganow AS, Germain P, Sibilia J, El Ghannudi S, Martin T. T1 mapping cardiac magnetic resonance imaging frequently detects subclinical diffuse myocardial fibrosis in systemic sclerosis patients. Semin Arthritis Rheum 2019; 50:128-134. [PMID: 31301817 DOI: 10.1016/j.semarthrit.2019.06.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 05/28/2019] [Accepted: 06/17/2019] [Indexed: 11/26/2022]
Abstract
OBJECTIVES cardiac involvement is the second most frequent systemic sclerosis (SSc) related cause of death. It remains mostly asymptomatic in the early stage and is underdiagnosed with routine screening. Cardiac magnetic resonance imaging (CMR) could improve cardiac assessment of patients and noteworthily, new sequences allow the detection of diffuse myocardial fibrosis (DMF) by native T1 mapping. The aim of this study was to determine the prevalence of cardiac involvement by CMR native T1 mapping and its correlation with echocardiography data and non-cardiac manifestations in SSc patients. METHODS patients fulfilling the ACR/EULAR classification criteria for SSc were prospectively included between 2014 and 2016. They underwent CMR at 1.5T, including native T1 and T2 mapping, and Late Gadolinium Enhancement (LGE) as a part of routine follow up. Routine biological tests (mainly BNP and CRP) were centralized in the hospital laboratory. RESULTS seventy-two unselected patients were included. Thirty six patients (50%) had elevated T1 (ET1) (mean T1 1097±14 ms). CMR cardiac functional parameters were similar in ET1 and normal T1 (NT1). Echocardiography was normal in 18 (50%) of ET1. ET1 and NT1 groups were similar for cardiovascular risk factors and ischemic heart disease. ET1 was not correlated with any clinical or echocardiographic parameter or antibody profile. Thirty-six percent of patients with ET1 had no cardiac symptoms, normal echocardiography and CMR LVEF, and no LGE. CONCLUSION native T1 mapping detects left ventricular ET1 (potential DMF) in 50% of patients with SSc and a third of them had a normal conventional screening including standard CMR. In the future, further studies are needed to confirm the benefit of use of native T1 mapping as a part of routine follow up to detect earlier pejorative cardiac involvement in SSc patients.
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Affiliation(s)
- Vincent Poindron
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Clinical Immunology and Internal Medicine, University Hospital of Strasbourg, France.
| | - Emmanuel Chatelus
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Rheumatology, University Hospital of Strasbourg, France
| | - Matthieu Canuet
- Department of Pneumology, University Hospital of Strasbourg, France
| | - Jacques-Eric Gottenberg
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Rheumatology, University Hospital of Strasbourg, France
| | - Laurent Arnaud
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Rheumatology, University Hospital of Strasbourg, France
| | - Afshin Gangi
- Department of Radiology, University Hospital of Strasbourg, France
| | - Pierre-Edouard Gavand
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Clinical Immunology and Internal Medicine, University Hospital of Strasbourg, France
| | - Aurélien Guffroy
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Clinical Immunology and Internal Medicine, University Hospital of Strasbourg, France
| | - Anne-Sophie Korganow
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Clinical Immunology and Internal Medicine, University Hospital of Strasbourg, France
| | - Philippe Germain
- Department of Radiology, University Hospital of Strasbourg, France
| | - Jean Sibilia
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Rheumatology, University Hospital of Strasbourg, France
| | - Soraya El Ghannudi
- Department of Radiology, University Hospital of Strasbourg, France; Department of Nuclear Medicine, University Hospital of Strasbourg, France; ICube, UMR 7357, University of Strasbourg, France
| | - Thierry Martin
- National Referral Center for Systemic Autoimmune Diseases RESO, University Hospital of Strasbourg, France; Clinical Immunology and Internal Medicine, University Hospital of Strasbourg, France
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23
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Mesenchymal stem cells of Systemic Sclerosis patients, derived from different sources, show a profibrotic microRNA profiling. Sci Rep 2019; 9:7144. [PMID: 31073190 PMCID: PMC6509164 DOI: 10.1038/s41598-019-43638-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 04/24/2019] [Indexed: 02/06/2023] Open
Abstract
Systemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the miRs expression profile, to identify the gene modulation in these two MSCs source. MicroRNAs (miRs) are RNAs sequences, regulating gene expression and MSCs, derived from different tissues, may differently respond to the SSc microenvironment. The miRs array was used for the miRs profiling and by DIANA-mirPath tool we identified the biological functions of the dysregulated miRs. In SSc-BM-MSCs, 6 miRs were significantly down-regulated and 4 miRs up-regulated. In SSc-A-MSCs, 11 miRs were significantly down-regulated and 3 miRs up-regulated. Interestingly, in both the sources, the involved pathways included the senescence mechanisms and the pro-fibrotic behaviour. Furthermore, both the MSCs sources showed potential compensatory ability. A deeper knowledge of this miRs signature might give more information about some pathogenic steps of the disease and in the same time clarify the possible therapeutic role of autologous MSCs in the regenerative therapy in SSc.
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24
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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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25
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Sugiyama K, Kobayashi H, Kobayashi Y, Yokoe I, Takei M, Kitamura N. Association of cardiac magnetic resonance-detected myocardial abnormalities with disease characteristics and brain natriuretic peptide levels in systemic sclerosis without cardiac symptoms. Int J Rheum Dis 2019; 22:1016-1022. [PMID: 30924296 DOI: 10.1111/1756-185x.13540] [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: 07/26/2018] [Revised: 01/29/2019] [Accepted: 02/13/2019] [Indexed: 11/26/2022]
Abstract
AIM This study aimed to evaluate the association between myocardial abnormalities and left ventricular (LV) geometry as assessed using cardiac magnetic resonance imaging (CMRI) in systemic sclerosis (SSc) patients without cardiac symptoms. METHODS SSc patients without cardiac symptoms or cardiovascular risk factors underwent contrast CMRI. CMRI were assessed for structural and functional LV parameters and myocardial fibrosis based on myocardial late gadolinium enhancement (LGE). The correlation between brain natriuretic peptide (BNP) levels and LGE status was evaluated. RESULTS Among 49 patients, 27 (55%) showed LGE positivity. The most common identified LGE pattern was a linear pattern. LGE was not consistent with coronary artery distribution. There was no difference in ejection fraction between those with and without LGE. LV morphological changes were observed in 29% of SSc patients. An abnormal LV structure was detected in 44% and 14% of patients in the LGE+ and LGE- groups, respectively. The BNP levels were higher by 57% in the LGE+ group than in the LGE-group. Receiver operating characteristic analysis showed that BNP levels reliably detected myocardial abnormalities (area under the curve, 0.72; 95% confidence interval 0.58-0.88). CONCLUSIONS Myocardial abnormalities were common in SSc patients without cardiac symptoms. We suggest that LV morphological changes may have resulted from myocardial abnormalities. BNP may be useful as a screening tool for the detection of myocardial abnormalities in SSc patients.
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Affiliation(s)
- Kaita Sugiyama
- Division of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Hitomi Kobayashi
- Division of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Yasuyuki Kobayashi
- Department of Advanced Biomedical Imaging Informatics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Isamu Yokoe
- Division of Internal Medicine, Kyoundo Hospital, Tokyo, Japan
| | - Masami Takei
- Division of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Noboru Kitamura
- Division of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
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26
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Khan NA, Khan RA, Tonelli AR, Highland KB, Chaisson NF, Jacob M, Renapurkar R, Dweik RA, Heresi GA. Pulmonary Edema Following Initiation of Parenteral Prostacyclin Therapy for Pulmonary Arterial Hypertension: A Retrospective Study. Chest 2019; 156:45-52. [PMID: 30776364 DOI: 10.1016/j.chest.2019.02.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 01/27/2019] [Accepted: 02/01/2019] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Pulmonary edema may complicate the use of pulmonary arterial hypertension (PAH)-targeted therapies. We aimed to determine the proportion of patients who develop pulmonary edema after initiation of parenteral prostacyclin therapy, to identify its risk factors, and to assess its implications for hospital length of stay and mortality. METHODS A retrospective cohort study of patients with PAH at the initiation of parenteral prostacyclin between 1997 and 2015 enrolled in the Cleveland Clinic PAH registry. Pulmonary edema was defined as at least one symptom or clinical sign and radiographic evidence of pulmonary edema. We determined patient characteristics predictive of pulmonary edema as well as the association between pulmonary edema and hospital length of stay (LOS) and 6-month mortality. RESULTS One hundred and fifty-five patients were included (median age, 51 years; female, 72%; white, 85%; idiopathic, 64%; and connective tissue disease [CTD], 23%). Pulmonary edema developed in 33 of 155 patients (21%). Independent predictors of pulmonary edema were high right atrial pressure (RAP), CTD etiology, and the presence of three or more risk factors for left heart disease (LHD). Pulmonary edema was associated with a 4.5-day increase in hospital LOS (95% CI, 1.4-7.5 days; P < .001) and a 4-fold increase in 6-month mortality (OR, 4.3; 95% CI, 1.28-14.36; P = .031). CONCLUSIONS Pulmonary edema occurred in 21% of patients with PAH initiated on parenteral prostacyclin. Three or more risk factors for LHD, CTD-PAH, and a high baseline RAP were independent predictors of pulmonary edema. Pulmonary edema was associated with a prolonged hospital LOS and increased 6-month mortality.
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Affiliation(s)
- Nauman A Khan
- Department of Hospital Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Rizwan A Khan
- Department of Internal Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Adriano R Tonelli
- Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH
| | - Kristin B Highland
- Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH
| | - Neal F Chaisson
- Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH
| | - Miriam Jacob
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH
| | - Rahul Renapurkar
- Department of Thoracic Imaging, Imaging Institute, Cleveland Clinic, Cleveland, OH
| | - Raed A Dweik
- Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH
| | - Gustavo A Heresi
- Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH.
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27
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Guerra F, Stronati G, Fischietti C, Ferrarini A, Zuliani L, Pomponio G, Capucci A, Danieli MG, Gabrielli A. Global longitudinal strain measured by speckle tracking identifies subclinical heart involvement in patients with systemic sclerosis. Eur J Prev Cardiol 2018; 25:1598-1606. [PMID: 29966435 DOI: 10.1177/2047487318786315] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Systemic sclerosis is characterised by progressive cutaneous and organ fibrosis. Among all organs, a subclinical heart involvement is difficult to detect through conventional imaging. Design We evaluated whether speckle tracking-derived global longitudinal strain could help detect early subclinical systolic dysfunction in systemic sclerosis patients without overt clinical involvement. Methods A case-control, single-centre study on 52 systemic sclerosis patients and 52 age and gender-matched controls. Patients with structural heart disease, heart failure, atrial fibrillation and pulmonary hypertension were excluded. For every patient, standard echocardiographic and speckle tracking-derived variables for the systolic and diastolic function of the left ventricle and right ventricle were acquired. Results Traditional parameters of left and right systolic function did not differ between systemic sclerosis patients and controls (all P = ns). Left and right ventricular global longitudinal strain was significantly impaired in patients with systemic sclerosis when compared to controls (-19.2% vs. -21.1%; P = 0.009 and -18.2% vs. -22.3%; P = 0.012, respectively). Systemic sclerosis patients had a 2.5-fold increased risk of subclinical left ventricular systolic impairment (odds ratio 2.5, 95% confidence interval 1.1-5.5; P = 0.027) and a 3.3-fold increased risk of subclinical right ventricular systolic impairment when compared to controls (odds ratio 3.3, 95% confidence interval 1.4-7.7; P = 0.004). Alterations in the myocardial deformation pattern of systemic sclerosis patients were homogeneous in the right ventricle and eccentric in the left ventricle. Conclusions While traditional echocardiographic parameters are ineffective in detecting subclinical systolic impairment, reduced global longitudinal strain is common in patients with systemic sclerosis and significant for both ventricles. Global longitudinal strain could become a low-cost, non-invasive and reliable tool in order to detect early cardiac involvement in systemic sclerosis patients.
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Affiliation(s)
- Federico Guerra
- 1 Cardiology and Arrhythmology Clinic, Marche Polytechnic University, Italy
| | - Giulia Stronati
- 1 Cardiology and Arrhythmology Clinic, Marche Polytechnic University, Italy
| | | | | | - Lucia Zuliani
- 2 Clinica Medica, Marche Polytechnic University, Italy
| | | | - Alessandro Capucci
- 1 Cardiology and Arrhythmology Clinic, Marche Polytechnic University, Italy
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28
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Lee DC, Hinchcliff ME, Sarnari R, Stark MM, Lee J, Koloms K, Hoffmann A, Carns M, Thakrar A, Aren K, Varga J, Aquino A, Carr JC, Benefield BC, Shah SJ. Diffuse cardiac fibrosis quantification in early systemic sclerosis by magnetic resonance imaging and correlation with skin fibrosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2018; 3:159-169. [PMID: 29808171 DOI: 10.1177/2397198318762888] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Purpose To evaluate the utility of cardiac magnetic resonance (CMR) T1 mapping in early systemic sclerosis (SSc) and its association with skin score. Methods Twenty-four consecutive patients with early SSc referred for cardiovascular evaluation and 12 controls without SSc were evaluated. All patients underwent cine, T1 mapping, and late gadolinium enhanced (LGE) CMR imaging. T1 mapping indices were compared between SSc patients and controls (extracellular volume fraction [ECV], gadolinium partition coefficient [λ], pre-contrast T1, and post-contrast T1). The association between T1 mapping parameters and the modified Rodnan skin score (mRSS) was determined. Results There were no significant differences in cardiac structure/function between SSc patients and controls on cine imaging, and 8/24 (33%) SSc patients had evidence of LGE (i.e., focal myocardial fibrosis). Of the T1 mapping parameters (indices indicative of diffuse myocardial fibrosis), ECV differentiated SSc patients from controls the best, followed by λ, even when the eight SSc patients with LGE were excluded. ECV had a sensitivity and specificity of 75% and 75% for diffuse myocardial fibrosis (optimal abnormal cut-off value of >27% [area under ROC curve=0.85]). In the 16 patients without evidence of LGE, each of the 4 CMR T1 mapping parameters (ECV, λ, Pre-T1 and Post-T1) correlated with mRSS (R=0.51-0.65, P=0.007-0.043), indicating a correlation between SSc cardiac and skin fibrosis. Conclusions The four T1 mapping indices are significantly correlated with mRSS in patients with early SSc. Quantification of diffuse myocardial fibrosis using ECV should be considered as a marker for cardiac involvement in SSc clinical studies.
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Affiliation(s)
- Daniel C Lee
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611.,Division of Cardiology, Bluhm Cardiovascular Institute, 251 E Huron Street, Chicago, IL 60611
| | - Monique E Hinchcliff
- Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611.,Northwestern University Institute for Public Health and Medicine, 633 N St Clair Street, 18floor, Chicago, IL 60611
| | - Roberto Sarnari
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611
| | - Madeline M Stark
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611
| | - Jungwha Lee
- Northwestern University Institute for Public Health and Medicine, 633 N St Clair Street, 18floor, Chicago, IL 60611.,Department of Radiology, 676 N. St. Clair Street Suite 800, Chicago, Illinois, 60611
| | - Kimberly Koloms
- Northwestern University Institute for Public Health and Medicine, 633 N St Clair Street, 18floor, Chicago, IL 60611.,Department of Radiology, 676 N. St. Clair Street Suite 800, Chicago, Illinois, 60611
| | - Aileen Hoffmann
- Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611
| | - Mary Carns
- Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611
| | - Anjali Thakrar
- Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611
| | - Kathleen Aren
- Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611
| | - John Varga
- Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611
| | - Alejandro Aquino
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611
| | - James C Carr
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611.,Division of Cardiology, Bluhm Cardiovascular Institute, 251 E Huron Street, Chicago, IL 60611.,Division of Rheumatology 240 E. Huron Street M300, Chicago, IL 60611.,Northwestern University Institute for Public Health and Medicine, 633 N St Clair Street, 18floor, Chicago, IL 60611.,Department of Radiology, 676 N. St. Clair Street Suite 800, Chicago, Illinois, 60611
| | - Brandon C Benefield
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611
| | - Sanjiv J Shah
- Feinberg Cardiovascular Research Institute, 303 E. Chicago Avenue, Tarry 14-725, Chicago, IL 60611.,Division of Cardiology, Bluhm Cardiovascular Institute, 251 E Huron Street, Chicago, IL 60611
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Towards the Clinical Management of Cardiac Involvement in Systemic Inflammatory Conditions—a Central Role for CMR. CURRENT CARDIOVASCULAR IMAGING REPORTS 2018. [DOI: 10.1007/s12410-018-9451-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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30
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Bournia VK, Tountas C, Protogerou AD, Panopoulos S, Mavrogeni S, Sfikakis PP. Update on assessment and management of primary cardiac involvement in systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2018; 3:53-65. [PMID: 35382127 PMCID: PMC8892878 DOI: 10.1177/2397198317747441] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2017] [Indexed: 09/26/2023]
Abstract
Primary cardiac involvement is a common and severe complication of systemic sclerosis, which may affect all of the hearts' structural components, including pericardium, myocardium, endocardium, cardiac valves, and conduction system. While cardiac disease can be clinically silent and only diagnosed in autopsy, new imaging modalities such as speckle-tracking echocardiography and cardiovascular magnetic resonance may reveal various abnormal findings in the majority of patients. Cardiovascular magnetic resonance evaluation should include assessment of left and right ventricular function, inflammation (STIR T2-weighted sequences (T2-W) for edema detection), and fibrosis (T1-weighted sequences 15 min after Gd-DTPA contrast medium injection (late-gadolinium enhancement). Notably, cardiac disease is responsible for about one-fourth of systemic sclerosis-related deaths. Systematic studies for the assessment and therapy of systemic sclerosis-related cardiac complications, as well as relevant guidelines from the European League Against Rheumatism and the American College of Rheumatology, are currently lacking. However, research advances reviewed herein allow for a better understanding of the mechanisms that alter cardiac function. Implementation of such knowledge should reduce cardiac morbidity and mortality in systemic sclerosis patients.
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Affiliation(s)
- Vasiliki-Kalliopi Bournia
- First Department of Propaedeutic
and Internal Medicine and Joined Rheumatology Program, Medical School,
National and Kapodistrian University of Athens, Laikon Hospital, Athens -
Greece
| | - Christos Tountas
- First Department of Propaedeutic
and Internal Medicine and Joined Rheumatology Program, Medical School,
National and Kapodistrian University of Athens, Laikon Hospital, Athens -
Greece
| | - Athanase D. Protogerou
- Cardiovascular Prevention and
Research Unit, Department of Pathophysiology, Medical School, National and
Kapodistrian University of Athens, Athens - Greece
| | - Stylianos Panopoulos
- First Department of Propaedeutic
and Internal Medicine and Joined Rheumatology Program, Medical School,
National and Kapodistrian University of Athens, Laikon Hospital, Athens -
Greece
| | | | - Petros P. Sfikakis
- First Department of Propaedeutic
and Internal Medicine and Joined Rheumatology Program, Medical School,
National and Kapodistrian University of Athens, Laikon Hospital, Athens -
Greece
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31
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Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis. J Clin Rheumatol 2018; 24:25-33. [DOI: 10.1097/rhu.0000000000000623] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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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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34
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Allanore Y, Distler O, Walker UA, Khanna D, Furst DE, Meune C. Points to consider when doing a trial primarily involving the heart. Rheumatology (Oxford) 2017; 56:v12-v16. [PMID: 28992169 DOI: 10.1093/rheumatology/kex198] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Indexed: 12/13/2022] Open
Abstract
Cardiac involvement contributes to the severity of SSc and should carefully be investigated and managed in SSc patients. Although it is commonly sub-clinical, once symptomatic it has a poor prognosis. Several complementary tools (circulating biomarkers, electrocardiography, echocardiography, scintigraphy or MRI) allow the assessment of all the various cardiac structures (endocardium, myocardium and pericardium) and heart function. Treatment remains empirical but cardiac trials in SSc can add data to the treatment of this complication.
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Affiliation(s)
- Yannick Allanore
- Department of Rheumatology A, Cochin Hospital and Cochin Institute, AP-HP, Paris-Descartes University, Paris, France
| | - Oliver Distler
- Department of Rheumatology, University Hospital Zurich, Zurich
| | - Ulrich A Walker
- Rheumatology Department, University of Basel, Basel, Switzerland
| | - Dinesh Khanna
- Department of Medicine, University of Michigan, University of Michigan Scleroderma Program, Ann Arbor, MI
| | - Daniel E Furst
- Department of Rheumatology, David Geffen School of Medicine, University of California in Los Angeles, Los Angeles, CA, USA
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35
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Zhou W, Lodhi F, Srichai MB. Role of Cardiac Imaging in Cardiovascular Diseases in Females. CURRENT RADIOLOGY REPORTS 2017. [DOI: 10.1007/s40134-017-0242-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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36
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Olivotti L, Cosmi D, Nicolino A, Martinelli L, Moshiri S, Danzi GB. Large Left Ventricular Aneurysm and Multifocal Myocardial Involvement in a Patient With Systemic Sclerosis. Can J Cardiol 2017; 33:950.e5-950.e6. [PMID: 28668148 DOI: 10.1016/j.cjca.2017.03.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 02/28/2017] [Accepted: 03/19/2017] [Indexed: 01/19/2023] Open
Abstract
A 43-year-old man with systemic sclerosis and chest pain had negative T waves in precordial electrocardiographic leads. The echocardiogram showed a large left ventricular apical accessory chamber. The coronary arteries were normal. Cardiac magnetic resonance imaging (MRI) showed a large fibrotic aneurysm and a small patch of midwall late enhancement in the septum. The aneurysm was surgically removed. At the 8-month follow-up, cardiac MRI showed the appearance of a new nodular lesion in the anterior wall, causing a localized wall motion abnormality. Myocardial involvement in patients with systemic sclerosis can be severe, and cardiac MRI evaluation is fundamental.
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Affiliation(s)
- Luca Olivotti
- Cardiovascular Department, Santa Corona Hospital, Pietra Ligure (SV), Italy.
| | - Deborah Cosmi
- Cardiovascular Department, Santa Corona Hospital, Pietra Ligure (SV), Italy
| | - Annamaria Nicolino
- Cardiovascular Department, Santa Corona Hospital, Pietra Ligure (SV), Italy
| | | | - Shahram Moshiri
- Cardiovascular Department, Santa Corona Hospital, Pietra Ligure (SV), Italy
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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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Farge D, Burt RK, Oliveira MC, Mousseaux E, Rovira M, Marjanovic Z, de Vries-Bouwstra J, Del Papa N, Saccardi R, Shah SJ, Lee DC, Denton C, Alexander T, Kiely DG, Snowden JA. Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners. Bone Marrow Transplant 2017; 52:1495-1503. [PMID: 28530671 PMCID: PMC5671927 DOI: 10.1038/bmt.2017.56] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 01/29/2017] [Indexed: 02/07/2023]
Abstract
Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3–10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016.
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Affiliation(s)
- D Farge
- Department of Internal Medicine, Unité Clinique de Médecine Interne, Maladies Auto-immunes et Pathologie Vasculaire, UF 04, Hôpital Saint-Louis, AP-HP Assistance Publique des Hôpitaux de Paris, INSERM UMRS 1160, Paris Denis Diderot University, Paris, France
| | - R K Burt
- Department of Medicine, Division of Immunotherapy, Northwestern University, Chicago, IL, USA
| | - M-C Oliveira
- Departamento de Clínica Médica, Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - E Mousseaux
- Hôpital Européen Georges Pompidou, AP-HP Assistance Publique des Hôpitaux de Paris, INSERM UMR 970, Université Paris Descartes, Paris, France
| | - M Rovira
- Department of Hematology, HSCT Unit, Hospital Clinic, Barcelona, Spain
| | - Z Marjanovic
- Department of Hematology, Saint-Antoine Hospital Paris, Assistance Publique des Hôpitaux de Paris, APHP, Paris, France
| | | | - N Del Papa
- Department of Rheumatology, Scleroderma Clinic, Osp. G. Pini, Milan, Italy
| | - R Saccardi
- Department of Hematology, Cord Blood Bank, Careggi University Hospital, Florence, Italy
| | - S J Shah
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - D C Lee
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - C Denton
- UCL Division of Medicine Royal Free Campus, London, UK
| | - T Alexander
- Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany
| | - D G Kiely
- Sheffield Pulmonary Vascular Disease Unit, M-floor, Royal Hallamshire Hospital, Sheffield, UK
| | - J A Snowden
- Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, University of Sheffield, Sheffield, UK
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Lagan J, Schmitt M, Miller CA. Clinical applications of multi-parametric CMR in myocarditis and systemic inflammatory diseases. Int J Cardiovasc Imaging 2017; 34:35-54. [PMID: 28130644 PMCID: PMC5797564 DOI: 10.1007/s10554-017-1063-9] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 01/03/2017] [Indexed: 12/22/2022]
Abstract
Cardiac magnetic resonance (CMR) has changed the management of suspected viral myocarditis by providing a ‘positive’ diagnostic test and has lead to new insights into myocardial involvement in systemic inflammatory conditions. In this review we analyse the use of CMR tissue characterisation techniques across the available studies including T2 weighted imaging, early gadolinium enhancement, late gadolinium enhancement, Lake Louise Criteria, T2 mapping, T1 mapping and extracellular volume assessment. We also discuss the use of multiparametric CMR in acute cardiac transplant rejection and a variety of inflammatory conditions such as sarcoidosis, systemic lupus erythrematous, rheumatoid arthritis and systemic sclerosis.
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Affiliation(s)
- Jakub Lagan
- North West Heart Centre, University Hospital of South Manchester, Manchester, UK
- Institute of Cardiovascular Sciences, Faculty of Medical & Human Sciences, University of Manchester, Manchester, M13 9NT, UK
| | - Matthias Schmitt
- North West Heart Centre, University Hospital of South Manchester, Manchester, UK
| | - Christopher A Miller
- North West Heart Centre, University Hospital of South Manchester, Manchester, UK.
- Institute of Cardiovascular Sciences, Faculty of Medical & Human Sciences, University of Manchester, Manchester, M13 9NT, UK.
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Suliman YA, Agrawal H, Furst DE. Clinical Trial Design in Systemic Sclerosis. SCLERODERMA 2017:623-635. [DOI: 10.1007/978-3-319-31407-5_46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Margaritopoulos GA, Antoniou KM, Wells AU. Comorbidities in interstitial lung diseases. Eur Respir Rev 2017; 26:160027. [PMID: 28049126 PMCID: PMC9488735 DOI: 10.1183/16000617.0027-2016] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 04/16/2016] [Indexed: 12/20/2022] Open
Abstract
Fibrosing lung disorders include a large number of diseases with diverse behaviour. Patients can die because of the progression of their illness, remain stable or even improve after appropriate treatment has been instituted. Comorbidities, such as acute and chronic infection, gastro-oesophageal reflux, pulmonary hypertension, lung cancer, cardiovascular diseases, and obstructive sleep apnoea, can pre-exist or develop at any time during the course of the disease and, if unidentified and untreated, may impair quality of life, impact upon the respiratory status of the patients, and ultimately lead to disease progression and death. Therefore, early identification and accurate treatment of comorbidities is essential.
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Affiliation(s)
| | - Katerina M Antoniou
- Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Greece
| | - Athol U Wells
- Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
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43
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Gerster M, Peker E, Nagel E, Puntmann VO. Deciphering cardiac involvement in systemic inflammatory diseases: noninvasive tissue characterisation using cardiac magnetic resonance is key to improved patients’ care. Expert Rev Cardiovasc Ther 2016; 14:1283-1295. [DOI: 10.1080/14779072.2016.1226130] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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44
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Di Cesare E, Splendiani A, Barile A, Squillaci E, Di Cesare A, Brunese L, Masciocchi C. CT and MR imaging of the thoracic aorta. Open Med (Wars) 2016; 11:143-151. [PMID: 28352783 PMCID: PMC5329815 DOI: 10.1515/med-2016-0028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Accepted: 03/07/2016] [Indexed: 12/25/2022] Open
Abstract
At present time, both CT and MRI are valuable techniques in the study of the thoracic aorta. Nowadays, CT represents the most widely employed technique for the study of the thoracic aorta. The new generation CTs show sensitivities up to 100% and specificities of 98-99%. Sixteen and wider row detectors provide isotropic pixels, mandatory for the ineludible longitudinal reconstruction. The main limits are related to the X-ray dose expoure and the use of iodinated contrast media. MRI has great potential in the study of the thoracic aorta. Nevertheless, if compared to CT, acquisition times remain longer and movement artifact susceptibility higher. The main MRI disadvantages are claustrophobia, presence of ferromagnetic implants, pacemakers, longer acquisition times with respect to CT, inability to use contrast media in cases of renal insufficiency, lower spatial resolution and less availability than CT. CT is preferred in the acute aortic disease. Nevertheless, since it requires iodinated contrast media and X-ray exposure, it may be adequately replaced by MRI in the follow up of aortic diseases. The main limitation of MRI, however, is related to the scarce visibility of stents and calcifications.
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Affiliation(s)
- Ernesto Di Cesare
- Dipartimento di Scienze Cliniche Applicate e biotecnologiche, Università degli studi di L'Aquila, Via Vetoio 1, 67100 L'Aquila, Italy , Tel 00390862368306, Fax 00390862368797
| | - Alessandra Splendiani
- Dipartimento di Scienze Cliniche Applicate e biotecno-logiche Università degli studi di L'Aquila, Italy
| | - Antonio Barile
- Dipartimento di Scienze Cliniche Applicate e biotecno-logiche Università degli studi di L'Aquila, Italy
| | - Ettore Squillaci
- Dipartimento di Diagnostica per Immagini Universi-tà Tor Vergata Roma, Italy
| | - Annamaria Di Cesare
- Dipartimento di Scienze Cliniche Applicate e biotecno-logiche Università degli studi di L'Aquila, Italy
| | - Luca Brunese
- Dipartimento di medicina e Scienza della salute, Universita del Molise, Campobasso, Italy
| | - Carlo Masciocchi
- Dipartimento di Scienze Cliniche Applicate e biotecno-logiche Università degli studi di L'Aquila, Italy
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Zulian F. Systemic Sclerodermas. TEXTBOOK OF PEDIATRIC RHEUMATOLOGY 2016:384-405.e9. [DOI: 10.1016/b978-0-323-24145-8.00027-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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46
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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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47
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Barison A, Gargani L, De Marchi D, Aquaro GD, Guiducci S, Picano E, Cerinic MM, Pingitore A. Early myocardial and skeletal muscle interstitial remodelling in systemic sclerosis: insights from extracellular volume quantification using cardiovascular magnetic resonance. Eur Heart J Cardiovasc Imaging 2015; 16:74-80. [DOI: 10.1093/ehjci/jeu167] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Abstract
Systemic sclerosis is an orphan connective tissue disease characterized by alterations of the microvasculature, disturbances of the immune system and massive deposition of collagen and other matrix substances in the skin and internal organs. A major achievement of the recent years has been the validation of new classification criteria, allowing earlier diagnosis and earlier treatment of systemic sclerosis, before irreversible fibrosis and organ damage appeared ("window of opportunity"). Raynaud's phenomenon is usually the first sign of the disease and is considered as the main sentinel sign for the identification of very early systemic sclerosis. Systemic sclerosis is clinically heterogeneous and disease course remains unpredictable. Its prognosis depends on cardiopulmonary involvement and recent studies aim to identify serum or genetic biomarkers predictive of severe organ involvement. Moreover, the prospective follow-up of large cohorts has provided and will offer critical material to identify strong prognostic factors. Whereas the outcomes of vascular manifestations of the disease has been recently improved due to targeted therapy, recent data have highlighted that mortality has not changed over the past 40 years. This reflects the absence of efficacy of current available drugs to counteract the fibrotic process. Nevertheless, several targeted immunity therapies, commonly with proven efficacy in other immune diseases, are about to be investigated in systemic sclerosis. Indeed, promising results in small and open studies have been reported. This article deals with recent insights into classification criteria, pathogenesis, organ involvements, outcome and current and possible future therapeutic options in systemic sclerosis.
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49
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Agoston G, Gargani L, Miglioranza MH, Caputo M, Badano LP, Moreo A, Muraru D, Mondillo S, Moggi Pignone A, Matucci Cerinic M, Sicari R, Picano E, Varga A. Left atrial dysfunction detected by speckle tracking in patients with systemic sclerosis. Cardiovasc Ultrasound 2014; 12:30. [PMID: 25090937 PMCID: PMC4134332 DOI: 10.1186/1476-7120-12-30] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Accepted: 07/28/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Cardiac involvement is a relevant clinical finding in systemic sclerosis (SSc) and is associated with poor prognosis. Left atrial (LA) remodeling and/or dysfunction can be an early sign of diastolic dysfunction. Two-dimensional speckle tracking echocardiography (STE) is a novel and promising tool for detecting very early changes in LA myocardial performance. AIM To assess whether STE strain parameters may detect early alterations in LA function in SSc patients. METHODS Forty-two SSc patients (Group 1, age 50 ± 14 years, 95% females) without clinical evidence for cardiac involvement and 42 age- and gender-matched control subjects (Group 2, age 49 ± 13 years, 95% females) were evaluated with comprehensive 2D and Doppler echocardiography, including tissue Doppler imaging analysis. Positive peak left atrial longitudinal strain (ϵ pos peak), second positive left atrial longitudinal strain (sec ϵ pos peak), and negative left atrial longitudinal strain (ϵ neg peak) were measured using a 12-segment model for the LA, by commercially available semi-automated 2D speckle-tracking software (EchoPac PC version 108.1.4, GE Healthcare, Horten, Norway). RESULTS All SSc patients had a normal left ventricular ejection fraction (63.1 ± 4%). SSc patients did not differ from controls in E/A (Group 1 = 1.1 ± 0.4 vs Group 2 = 1.3 ± 0.4, p = .14) or pulmonary arterial systolic pressure (Group 1 = 24.1 ± 8 mmHg vs Group 2 = 21 ± 7 mmHg, p = .17). SSc patients did not show significantly different indexed LA volumes (Group 1 = 24.9 ± 5.3 ml/m2 vs Group 2 = 24.7 ± 4.4 ml/m2, p = .8), whereas E/e' ratio was significantly higher in SSc (Group 1 = 7.6 ± 2.4 vs Group 2 = 6.5 ± 1.7, p<0.05), although still within normal values. LA strain values were significantly different between the two groups (ϵ pos peak Group 1 = 31.3 ± 4.2% vs Group 2 = 35.0 ± 7.6%, p < .01, sec ϵ pos peak Group 1 = 18.4 ± 4 vs Group 2 = 21.4 ± 7.6, p < 0.05). CONCLUSION 2D speckle-tracking echocardiography is a sensitive tool to assess impairment of LA mechanics, which is detectable in absence of changes in LA size and volume, and may represent an early sign of cardiac involvement in patients with SSc.
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Affiliation(s)
- Gergely Agoston
- 2nd Department of Medicine and Cardiology Center, University of Szeged, Korányi Fasor 6, 6720 Szeged, Hungary
| | - Luna Gargani
- Institute of Clinical Physiology, National Council of Research, Pisa, Italy
| | - Marcelo Haertel Miglioranza
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
- Cardiology Institute of Rio Grande do Sul, Porto Alegre, Brazil
| | - Maria Caputo
- Department of Cardiovascular Diseases, University of Siena, Siena, Italy
| | - Luigi Paolo Badano
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
| | - Antonella Moreo
- Cardiology Department, Niguarda Ca’ Granda Hospital, Milan, Italy
| | - Denisa Muraru
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
| | - Sergio Mondillo
- Department of Cardiovascular Diseases, University of Siena, Siena, Italy
| | | | - Marco Matucci Cerinic
- Department of Biomedicine, Division of Rheumatology, University of Florence, Florence, Italy
| | - Rosa Sicari
- Institute of Clinical Physiology, National Council of Research, Pisa, Italy
| | - Eugenio Picano
- Institute of Clinical Physiology, National Council of Research, Pisa, Italy
| | - Albert Varga
- 2nd Department of Medicine and Cardiology Center, University of Szeged, Korányi Fasor 6, 6720 Szeged, Hungary
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Satoh H, Sano M, Suwa K, Saitoh T, Nobuhara M, Saotome M, Urushida T, Katoh H, Hayashi H. Distribution of late gadolinium enhancement in various types of cardiomyopathies: Significance in differential diagnosis, clinical features and prognosis. World J Cardiol 2014; 6:585-601. [PMID: 25068019 PMCID: PMC4110607 DOI: 10.4330/wjc.v6.i7.585] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Revised: 03/21/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.
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