{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:03:04Z","timestamp":1782205384136,"version":"3.54.5"},"reference-count":77,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by progressive fibrosis, systemic inflammation and vascular dysfunction, with manifestations that can affect multiple organs, including the heart. Cardiac involvement in SSc is often underdiagnosed, although it can have serious consequences on the prognosis, especially the occurrence of arrhythmias. These rhythm disturbances can result from direct damage to the myocardium, the conduction system, or the coronary microcirculation. Equally, the medication used can have iatrogenic consequences manifested by severe arrhythmias. Methodology: The aim of this study was to provide a synthesis of incidence, pathogenic mechanisms, diagnostic methods, and therapeutic strategies of arrhythmias associated with SSc. The potential effects of immunomodulatory therapies, such as conventional immunosuppressants and biological therapies, on cardiac electrical function were also analyzed. This narrative review could present the state of the art on arrhythmias associated with SSc, which could serve as a practical guide. In clinical practice, it is necessary to establish a team that includes cardiologists and rheumatologists as well as other specialists to contribute to a correct diagnosis followed by an optimal therapy in patients with SSc. Results: Current data suggest that diffuse myocardial fibrosis, silent ischemia, and inflammatory infiltration may alter the propagation of the electrical impulse in the heart, favoring the occurrence of arrhythmias. Atrioventricular blocks, ventricular tachyarrhythmias, and atrial fibrillation are the most commonly reported rhythm abnormalities in SSc. Also, some therapies used in the treatment of the disease may influence the arrhythmic risk. Conclusions: Cardiac arrhythmias in SSc can have a significant impact on the prognosis of patients, which is why a multidisciplinary approach is essential. Collaboration between rheumatologists, cardiologists, and electrophysiologists is crucial for the early identification and appropriate management of arrhythmic risk in this patient group.<\/jats:p>","DOI":"10.3390\/life15101608","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:29:38Z","timestamp":1760599778000},"page":"1608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Arrhythmias in Systemic Sclerosis: A Call for Interdisciplinarity Teams"],"prefix":"10.3390","volume":"15","author":[{"given":"Diana Elena","family":"Costan","sequence":"first","affiliation":[{"name":"Department of Medical Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Rheumatology, Clinic Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8097-2573","authenticated-orcid":false,"given":"Veronica","family":"Ungurean","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Rheumatology, Clinic Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica Claudia","family":"Dobos","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Rheumatology, Clinic Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-8194","authenticated-orcid":false,"given":"Anca","family":"Ouatu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Cristina","family":"Morariu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5249-4562","authenticated-orcid":false,"given":"Alexandru Florinel","family":"Oancea","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Mihaela","family":"Godun","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana-Elena","family":"Floria","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos Traian","family":"Marcu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genoveva Livia","family":"Baroi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu Marcel","family":"Stanciu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Knieling","sequence":"additional","affiliation":[{"name":"Discipline of Forensic Medicine, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7144-2506","authenticated-orcid":false,"given":"Daniela Maria","family":"Tanase","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-8121","authenticated-orcid":false,"given":"Codrina","family":"Ancuta","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences II, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Rheumatology, Clinic Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-1503","authenticated-orcid":false,"given":"Mariana","family":"Floria","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Internal Medicine, Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1590\/abd1806-4841.20152890","article-title":"Localized Scleroderma: Clinical Spectrum and Therapeutic Update","volume":"90","author":"Careta","year":"2015","journal-title":"An. Bras. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1136\/ard.45.5.384","article-title":"Regressive systemic sclerosis","volume":"45","author":"Black","year":"1986","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"iv39","DOI":"10.1093\/rheumatology\/kel315","article-title":"Cardiac Arrhythmias and Conduction Disturbances in Autoimmune Rheumatic Diseases","volume":"45","author":"Maisch","year":"2006","journal-title":"Rheumatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1093\/rheumatology\/keab190","article-title":"Incidence and Prevalence of Systemic Sclerosis Globally: A Comprehensive Systematic Review and Meta-Analysis","volume":"60","author":"Bairkdar","year":"2021","journal-title":"Rheumatology"},{"key":"ref_5","first-page":"920","article-title":"Heart Rate Turbulence Impairment and Ventricular Arrhythmias in Patients with Systemic Sclerosis","volume":"33","author":"Bienias","year":"2010","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Vrancianu, C.A., Gheorghiu, A.M., Popa, D.E., Chan, J.S.K., Satti, D.I., Lee, Y.H.A., Hui, J.M.H., Tse, G., Ancuta, I., and Ciobanu, A. (2022). Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis\u2014A Systematic Literature Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112963"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1161\/CIRCULATIONAHA.116.025312","article-title":"Atrial Fibrillation and Ventricular Arrhythmias","volume":"135","author":"Gillis","year":"2017","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1093\/rheumatology\/ket377","article-title":"Cardiac Arrhythmias and Conduction Defects in Systemic Sclerosis","volume":"53","author":"Vacca","year":"2014","journal-title":"Rheumatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.5114\/ada.2021.106203","article-title":"Sinoatrial Conduction Abnormalities\u2014An Underestimated Cardiac Complication in Women with Systemic Sclerosis","volume":"38","author":"Kramarz","year":"2021","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1093\/rheumatology\/keac065","article-title":"Myocardial Fibrosis and Arrhythmic Burden in Systemic Sclerosis","volume":"61","author":"Ross","year":"2022","journal-title":"Rheumatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e013405","DOI":"10.1161\/JAHA.119.013405","article-title":"Cardiovascular Manifestations of Systemic Sclerosis: A Danish Nationwide Cohort Study","volume":"8","author":"Butt","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sharifkazemi, M., Nazarinia, M., Arjangzade, A., Goldust, M., and Hooshanginezhad, Z. (2022). Diagnosis of Simultaneous Atrial and Ventricular Mechanical Performance in Patients with Systemic Sclerosis. Biology, 11.","DOI":"10.3390\/biology11020305"},{"key":"ref_13","unstructured":"(2025, August 26). Right Ventricular and Atrial Functions in Systemic Sclerosis Patients without Pulmonary Hypertension|Herz. Available online: https:\/\/link.springer.com\/article\/10.1007\/s00059-014-4113-2."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"H156","DOI":"10.1152\/ajpheart.00485.2019","article-title":"Right Ventricular Function Correlates of Right Atrial Strain in Pulmonary Hypertension: A Combined Cardiac Magnetic Resonance and Conductance Catheter Study","volume":"318","author":"Tello","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ijcard.2008.11.093","article-title":"Pulmonary Hypertension in Systemic Sclerosis Determines Cardiac Autonomic Dysfunction Assessed by Heart Rate Turbulence","volume":"141","author":"Bienias","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1177\/23971983211020617","article-title":"Autonomic Nervous System Dysfunction Correlates with Microvascular Damage in Systemic Sclerosis Patients","volume":"6","author":"Masini","year":"2021","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"CMAMD.S4940","DOI":"10.4137\/CMAMD.S4940","article-title":"Autonomic Dysfunction Predicts Early Cardiac Affection in Patients with Systemic Sclerosis","volume":"3","author":"Othman","year":"2010","journal-title":"Clin. Med. Insights Arthritis Musculoskelet. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.biopha.2017.07.091","article-title":"Renin-Angiotensin-Aldosterone (RAAS): The Ubiquitous System for Homeostasis and Pathologies","volume":"94","author":"Patel","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Maranduca, M.A., Cosovanu, M.A., Clim, A., Pinzariu, A.C., Filip, N., Drochioi, I.C., Vlasceanu, V.I., Timofte, D.V., Nemteanu, R., and Plesa, A. (2023). The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases. Diagnostics, 13.","DOI":"10.3390\/diagnostics13223398"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111119","DOI":"10.1016\/j.mce.2020.111119","article-title":"The Angiotensin-(1\u201312)\/Chymase Axis as an Alternate Component of the Tissue Renin Angiotensin System","volume":"529","author":"Ferrario","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1042\/CS20220261","article-title":"CGP42112: The Full AT2 Receptor Agonist and Its Role in the Renin\u2013Angiotensin\u2013Aldosterone System: No Longer Misunderstood","volume":"136","author":"Restrepo","year":"2022","journal-title":"Clin. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1136\/ard.2010.135772","article-title":"Involvement of Functional Autoantibodies against Vascular Receptors in Systemic Sclerosis","volume":"70","author":"Riemekasten","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/ar4457","article-title":"Autoantibodies to Angiotensin and Endothelin Receptors in Systemic Sclerosis Induce Cellular and Systemic Events Associated with Disease Pathogenesis","volume":"16","author":"Kill","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1196\/annals.1351.002","article-title":"Angiotensin-Converting Enzyme in Systemic Sclerosis: From Endothelial Injury to a Genetic Polymorphism","volume":"1069","author":"Guiducci","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.autrev.2010.09.014","article-title":"Atherosclerosis and Macrovascular Involvement in Systemic Sclerosis: Myth or Reality","volume":"10","author":"Nussinovitch","year":"2011","journal-title":"Autoimmun. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1097\/BOR.0000000000000115","article-title":"Is Atherosclerosis Accelerated in Systemic Sclerosis? Novel Insights","volume":"26","author":"Soriano","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1167952","DOI":"10.3389\/fendo.2023.1167952","article-title":"The Role of Epicardial Adipose Tissue Dysfunction in Cardiovascular Diseases: An Overview of Pathophysiology, Evaluation, and Management","volume":"14","author":"Li","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Doukbi, E., Soghomonian, A., Sengen\u00e8s, C., Ahmed, S., Ancel, P., Dutour, A., and Gaborit, B. (2022). Browning Epicardial Adipose Tissue: Friend or Foe?. Cells, 11.","DOI":"10.3390\/cells11060991"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"qyad037","DOI":"10.1093\/ehjimp\/qyad037","article-title":"Epicardial Adipose Tissue in Patients with Systemic Sclerosis","volume":"1","author":"Wang","year":"2023","journal-title":"Eur. Heart J. Imaging Methods Pract."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Conte, M., Petraglia, L., Cabaro, S., Valerio, V., Poggio, P., Pilato, E., Attena, E., Russo, V., Ferro, A., and Formisano, P. (2022). Epicardial Adipose Tissue and Cardiac Arrhythmias: Focus on Atrial Fibrillation. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.932262"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1007\/s00296-024-05699-x","article-title":"Heart Involvement in Patients with Systemic Sclerosis\u2014What Have We Learned about It in the Last 5 Years","volume":"44","author":"Nadel","year":"2024","journal-title":"Rheumatol. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e23009","DOI":"10.1097\/MD.0000000000023009","article-title":"Systemic Sclerosis and Risk of Cardiovascular Disease","volume":"99","author":"Cen","year":"2020","journal-title":"Medicine"},{"key":"ref_33","first-page":"8","article-title":"Cardiovascular Disease in Systemic Sclerosis","volume":"3","author":"Cannarile","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_34","first-page":"233","article-title":"Electrolyte Disorders and Arrhythmogenesis","volume":"18","author":"Turitto","year":"2011","journal-title":"Cardiol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.resinv.2024.11.003","article-title":"Advancements in the Treatment of Interstitial Lung Disease in Systemic Sclerosis with the Approval of Mycophenolate Mofetil","volume":"62","author":"Takada","year":"2024","journal-title":"Respir. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Baqir, M., Makol, A., Osborn, T.G., Bartholmai, B.J., and Ryu, J.H. (2017). Mycophenolate Mofetil for Scleroderma-Related Interstitial Lung Disease: A Real World Experience. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177107"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8858671","DOI":"10.1155\/carm\/8858671","article-title":"Arrhythmia as a Possible Complication of Mycophenolate Mofetil in Systemic Sclerosis: A Case Report","volume":"2025","author":"Moradi","year":"2025","journal-title":"Case Rep. Med."},{"key":"ref_38","first-page":"166","article-title":"Treatment of Early Diffuse Systemic Sclerosis Skin Disease","volume":"31","author":"Frech","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/s13256-022-03644-9","article-title":"Methotrexate-Induced Acute Cardiotoxicity Requiring Veno-Arterial Extracorporeal Membrane Oxygenation Support: A Case Report","volume":"16","author":"Shah","year":"2022","journal-title":"J. Med. Case Rep."},{"key":"ref_40","first-page":"1","article-title":"Effect of Azathioprine on Skin and Lung Parameters in Patients with Systemic Sclerosis: A Systematic Literature Review","volume":"12","author":"Torun","year":"2025","journal-title":"Med. Res. Arch."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"rky034.046","DOI":"10.1093\/rap\/rky034.046","article-title":"83. Asymptomatic Cardiac Arrhythmia in Systemic Sclerosis","volume":"2","author":"Baron","year":"2018","journal-title":"Rheumatol. Adv. Pract."},{"key":"ref_42","first-page":"626","article-title":"Transient, High-Grade Atrioventricular Block from High-Dose Cyclophosphamide","volume":"40","author":"Agarwal","year":"2013","journal-title":"Tex. Heart Inst. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Papadimitriou, T.-I., van Caam, A., van der Kraan, P.M., and Thurlings, R.M. (2022). Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020316"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1177\/1715163515597451","article-title":"Corticosteroid-Induced Bradycardia","volume":"148","author":"Stroeder","year":"2015","journal-title":"Can. Pharm. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4274\/qrheumatol.galenos.2023.87587","article-title":"SCLERODERMA RENAL CRISIS","volume":"1","author":"Albayrak","year":"2023","journal-title":"Rheumatol. Q."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e004918","DOI":"10.1136\/rmdopen-2024-004918","article-title":"Vasodilator Drugs and Heart-Related Outcomes in Systemic Sclerosis: An Exploratory Analysis","volume":"10","author":"Carrat","year":"2024","journal-title":"RMD Open"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1136\/ard.2005.044727","article-title":"Effects of Acute Administration of Iloprost on the Cardiac Autonomic Nervous System and Ventricular Repolarisation in Patients with Systemic Sclerosis","volume":"65","author":"Guideri","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/2397198317747441","article-title":"Update on Assessment and Management of Primary Cardiac Involvement in Systemic Sclerosis","volume":"3","author":"Bournia","year":"2018","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_49","first-page":"305","article-title":"Unveiling the Dual Benefits of Bosentan in Systemic Sclerosis: Risk and Relief","volume":"52","author":"Lammi","year":"2025","journal-title":"J. Rheumatol."},{"key":"ref_50","first-page":"375","article-title":"Pulmonary Arterial Hypertension Incidence in Patients With Systemic Sclerosis Treated With Bosentan for Digital Ulcers: Evidence From the SPRING-SIR Registry","volume":"52","author":"Cacciapaglia","year":"2025","journal-title":"J. Rheumatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1136\/ard.2010.130658","article-title":"Bosentan Treatment of Digital Ulcers Related to Systemic Sclerosis: Results from the RAPIDS-2 Randomised, Double-Blind, Placebo-Controlled Trial","volume":"70","author":"Denton","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_52","first-page":"S127","article-title":"Predictive Value of Vascular Disease Biomarkers for Digital Ulcers in Systemic Sclerosis Patients","volume":"33","author":"Silva","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"993","DOI":"10.4330\/wjc.v6.i9.993","article-title":"Cardiac manifestations in systemic sclerosis","volume":"6","author":"Sevdalina","year":"2014","journal-title":"World J. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/jcpt.13621","article-title":"Angiotensin-Converting Enzyme Inhibitors Prior to Scleroderma Renal Crisis in Systemic Sclerosis: A Systematic Review and Meta-Analysis","volume":"47","author":"Xiong","year":"2022","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1136\/ard-2022-222564","article-title":"Continued Treatment with Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease: Data from SENSCIS-ON","volume":"81","author":"Allanore","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1513\/AnnalsATS.202301-081OC","article-title":"Nintedanib Therapy Alone and Combined with Mycophenolate in Patients with Systemic Sclerosis\u2013Associated Interstitial Lung Disease: Systematic Reviews and Meta-Analysis","volume":"21","author":"Herman","year":"2024","journal-title":"Annals ATS"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1136\/annrheumdis-2020-217331","article-title":"Safety and Tolerability of Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease: Data from the SENSCIS Trial","volume":"79","author":"Seibold","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1002\/acr2.11483","article-title":"Effect of Nintedanib on Progression of Systemic Sclerosis-Associated Interstitial Lung Disease Over 100 Weeks: Data From a Randomized Controlled Trial","volume":"4","author":"Assassi","year":"2022","journal-title":"ACR Open Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1093\/rheumatology\/keac674","article-title":"Beneficial Effects of Nintedanib on Cardiomyopathy in Patients with Systemic Sclerosis: A Pilot Study","volume":"62","author":"Ninagawa","year":"2023","journal-title":"Rheumatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/ejhf.3467","article-title":"Add-on Rituximab for Primary Heart Involvement Associated with Systemic Sclerosis: A Step Forward in the Tailored Treatment of Myocarditis?","volume":"27","author":"Tonutti","year":"2025","journal-title":"Eur. J. Heart Fail."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e005493","DOI":"10.1136\/rmdopen-2025-005493","article-title":"Combination Therapy of Rituximab and Mycophenolate in Patients with Systemic Sclerosis and Primary Cardiac Involvement Refractory to Cyclophosphamide: A Retrospective Exploratory Analysis of 10 Cases","volume":"11","author":"Adjailia","year":"2025","journal-title":"RMD Open"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e002477","DOI":"10.1136\/rmdopen-2022-002477","article-title":"Effectiveness and Safety of Tocilizumab in Patients with Systemic Sclerosis: A Propensity Score Matched Controlled Observational Study of the EUSTAR Cohort","volume":"8","author":"Kuster","year":"2022","journal-title":"RMD Open"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Fu, Z.-C., Ji, J., Cheng, X.-G., Shi, R.-G., Mo, X.-F., and Yang, Z.-Z. (2025). Tocilizumab Combined with Cyclophosphamide for the Treatment of Rapidly Progressive Refractory Systemic Sclerosis with Predominant Cardiac Involvement: A Case Report. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1614714"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/eurheartj\/ehac262","article-title":"2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) Endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"43","author":"Zeppenfeld","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1093\/rheumatology\/kew488","article-title":"Consensus Best Practice Pathway of the UK Systemic Sclerosis Study Group: Management of Cardiac Disease in Systemic Sclerosis","volume":"56","author":"Bissell","year":"2017","journal-title":"Rheumatology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.3899\/jrheum.100316","article-title":"Anti-Th\/To Are Common Antinucleolar Autoantibodies in Italian Patients with Scleroderma","volume":"37","author":"Ceribelli","year":"2010","journal-title":"J. Rheumatol."},{"key":"ref_67","unstructured":"Paik, J.J., Choi, D.Y., Mukherjee, M., Hsu, S., Wigley, F., Shah, A.A., and Hummers, L.K. (2025, September 01). Troponin Elevation Independently Associates with Mortality in Systemic Sclerosis. Available online: https:\/\/www.clinexprheumatol.org\/abstract.asp?a=17767."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.hlc.2018.08.026","article-title":"Epidemiology of Sudden Cardiac Death: Global and Regional Perspectives","volume":"28","author":"Wong","year":"2019","journal-title":"Heart Lung Circ."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Basyal, B., Ullah, W., and Derk, C.T. (2023). Pericardial Effusions and Cardiac Tamponade in Hospitalized Systemic Sclerosis Patients: Analysis of the National Inpatient Sample. BMC Rheumatol., 7.","DOI":"10.1186\/s41927-023-00360-9"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1093\/rheumatology\/kead368","article-title":"Prognostic Significance of Pericardial Effusion in Systemic Sclerosis-Associated Pulmonary Hypertension: Analysis from the PHAROS Registry","volume":"63","author":"Luo","year":"2024","journal-title":"Rheumatology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Palumbo, P., Ruscitti, P., Cannizzaro, E., Berardicurti, O., Conforti, A., Di Cesare, A., Di Cola, I., Giacomelli, R., Splendiani, A., and Barile, A. (2022). Unenhanced Cardiac Magnetic Resonance May Improve Detection and Prognostication of an Occult Heart Involvement in Asymptomatic Patients with Systemic Sclerosis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-09064-5"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.3899\/jrheum.210040","article-title":"Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography\/Computed Tomography in Patients With Systemic Sclerosis","volume":"48","author":"Feher","year":"2021","journal-title":"J. Rheumatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s00259-022-06081-4","article-title":"Assessment of Myocardial Fibrosis in Patients with Systemic Sclerosis Using [68Ga]Ga-FAPI-04-PET-CT","volume":"50","author":"Treutlein","year":"2023","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s13023-021-01844-y","article-title":"French Recommendations for the Management of Systemic Sclerosis","volume":"16","author":"Hachulla","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure: Developed by the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) With the Special Contribution of the Heart Failure Association (HFA) of the ESC","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Naranjo, M., and Hassoun, P.M. (2021). Systemic Sclerosis-Associated Pulmonary Hypertension: Spectrum and Impact. Diagnostics, 11.","DOI":"10.3390\/diagnostics11050911"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2147\/OARRR.S228234","article-title":"Pulmonary Arterial Hypertension in Systemic Sclerosis: Challenges in Diagnosis, Screening and Treatment","volume":"11","author":"Saygin","year":"2019","journal-title":"Open Access Rheumatol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/10\/1608\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:49:09Z","timestamp":1760600949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/10\/1608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":77,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["life15101608"],"URL":"https:\/\/doi.org\/10.3390\/life15101608","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}