AB0556 PRIMARY SYSTEMIC SCLEROSIS HEART INVOLVEMENT (PSSCHI): A SYSTEMATIC LITERATURE REVIEW (SLR), CONSENSUS-BASED DEFINITION AND PRELIMINARY VALIDATION.
Authors: C. Bruni, M. H. Buch, P. Seferovic, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2020)

Background: pSScHI may cause tissue, functional and conduction abnormalities with varied clinical manifestations. The absence of a clear definition of pSScHI impairs the significance and ability of focussed research, frequently not allowing the distinction between primary and secondary involvement. Objectives: We aimed to establish an expert consensus definition for pSScHI, to be used in clinical trials and everyday clinical practice, and to start its validation process. Methods: A SLR for cardiac manifestations and alterations in SSc was conducted using PubMed, Web of Science and Embase. Articles published from inception to December 31 st , 2018 were identified. Inclusion criteria included papers in English on adult SSc patients, with heart involvement as outcome. We excluded non-human studies, secondary heart involvement (eg PAH, drugs, infections), reviews and case reports. PRISMA recommendations were followed where applicable. Extracted data were categorized into relevant domains (signs, symptoms, anatomical site involved, physiological abnormalities, pathological changes, prognostic outcomes), which informed the consensus definition. Sixteen senior experts (7 rheumatologists, 8 cardiologists, 1 pathologist) discussed the data and, using a nominal group technique, added expert opinion, provided statements to consider and ranked them. Consensus was attained for agreement &gt;70%. Sixteen clinical cases were evaluated in two rounds to test for face validity, feasibility, inter- and intra-rater reliability and criterion validity (gold standard set by agreed evaluation between expert rheumatologist, cardiologist and methodologist). Results: 2593 publications were identified and screened, 251 full texts were evaluated,172 met eligibility criteria. Data from the 7 domains were extracted and used to develop the World Scleroderma Foundation – Heart Failure Association (WSF-HFA) consensus-derived definition of pSSc-HI, as follows: “pSScHI comprises cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications*. pSScHI may be sub-clinical and must be confirmed through diagnostic investigation. The pathogenesis of pSScHI comprises one or more of inflammation, fibrosis and vasculopathy. *Non SSc-specific cardiac conditions (e.g. Ischaemic heart disease, arterial hypertension, drug toxicity, other cardiomyopathy, primary valvular disease) and/or SSc non cardiac conditions (e.g. PAH, Renal involvement, ILD).” Face validity was determined by a 100% agreement on credibility; application was feasible, with a median 60 (5-600) seconds taken per case; inter rater agreement was moderate [mKappa (95%CI) 0.56 (0.46-1.00) and 0.55 (0.44-1.00) for the two rounds] and intra rater agreement was good [mKappa (95%CI) 0.77 (0.47-1,00)]. Content validity was reached based on the wide variety of patients in the SLR, criterion validity was reached with 78 (73-84) % correctness. Conclusion: Using a SLR and modified nominal technique, we have developed a preliminary pSScHI consensus-based definition and started a validation process for it to be used in clinical research and clinical practice. Acknowledgments: Aleksandra Djokovic, Giacomo De Luca, Raluca B. Dumitru, Alessandro Giollo, Marija Polovina, Yossra Atef Suliman, Kostantinos Bratis, Alexia Steelandt, Ivan Milinkovic, Anna Baritussio, Ghadeer Hasan, Anastasia Xintarakou, Yohei Isomura, George Markousis-Mavrogenis, Silvia Bellando-Randone, Lorenzo Tofani, Sophie Mavrogeni, Luna Gargani, Alida L.P. Caforio, Carsten Tschoepe, Arsen Ristic, Karin Klingel, Sven Plein, Elijah Behr, Yannick Allanore, Masataka Kuwana, Christopher Denton, Daniel E. Furst, Dinesh Khanna, Thomas Krieg, Renzo Marcolongo. Disclosure of Interests: Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Petar Seferovic: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim