POS0843 IMMUNOSUPPRESSIVE THERAPY TO TREAT NEWLY DIAGNOSED PRIMARY HEART INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS: AN ITALIAN CARDIAC MAGNETIC RESONANCE BASED STUDY
Authors: G. De Luca, V. Batani, C. Campochiaro, A. Tonutti, A. Palmisano, G. Peretto, S. Sala, S. Rodolfi, F. Motta, C. Selmi, M. Francone, L. Monti, A. Esposito, L. Dagna, M. Matucci-Cerinic, M. De Santis
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), and is associated with a poor prognosis. SSc-pHI has been historically related to myocardial fibrosis and vascular damage; however, myocardial inflammation is increasingly reported and can be non-invasively detected by novel cardiac magnetic resonance (CMR) techniques. Therapeutic strategies to treat SSc-pHI remain elusive. <h3>Objectives:</h3> to evaluate the efficacy of immunosuppressive therapy on CMR features and clinical outcomes in patients with CMR-proven SSc-pHI. <h3>Methods:</h3> we retrospectively analyzed data from SSc patients with pHI [1] confirmed by CMR, who start or modify immunosuppressive therapy as indication for the newly diagnosed pHI and who had a follow-up CMR after 6 to 18 months. Patients were recruited from two national referral centers for SSc. All patients underwent a comprehensive baseline evaluation of disease characteristics and organ involvement, particularly cardiac involvement, including: recording of signs and symptoms of heart disease, serum levels of high-sensitive troponin T and brain natriuretic peptide (BNP) or NT-proBNP, inflammatory markers, standard 12-leads ECG, 24h ECG Holter, echocardiography and CMR at baseline and during follow-up. A p value &lt;0.05 was considered as statistically significant. <h3>Results:</h3> 35 patients with SSc-pHI (females 77.1%; median age 59 [46-64] years; anti-topoisomerase-I positivity 48.6%; diffuse cutaneous subset 34.3%) were enrolled (Table 1). The majority of patients (74.3%) had signs of active myocardial inflammation at baseline CMR, i.e. edema at short-tau inversion recovery (STIR) images and/or increase of T2 mapping; late gadolinium enhancement (LGE) areas were detected in 6 (17.4%) patients, while extra-cellular volume (ECV) and T1 mapping increase in 23 (65.7%) patients each (Table 2). Mycophenolate mofetil was started (up to 2000 mg per day) in 15 patients (42.9%) or increased (up to 3000 mg per day) in 7 (20.0%) cases; 7 patients (20.0%) received rituximab, 3 patients (8.6%) azathioprine (combined with prednisone in 1 case), while intravenous cyclophosphamide (combined with pulse steroids), subcutaneous tocilizumab and hydroxychloroquine were started in one patient each. No other patients received steroids. The median duration of immunosuppressive therapy was 12.0 [6.0 – 15.5] months. At the follow-up CMR (performed after a median time 12.0 [6.5 – 16.0] months), signs of active myocardial inflammation were detectable in 14 patients (40%) (p=0.003), and STIR images suggestive for edema were still present in only 5 cases (14.3%) (p=0.002). A consistently significant reduction of T2 mapping (from 53.0 [49.0–55.0] to 51.0 [50.0–54.0], p &lt;0.001), native T1 mapping (from 1050.0 [1007.0–1084.0] to 1039.0 [1020.5–1080.5], p=0.022) and ECV% (from 34.0 [31.0–36.75] to 33.0 [29.0–34.25], p=0.041) were observed. As expected, LGE areas did not improve over time (p=ns). No significant changes emerged with respect to left and right ventricular function or pericardial disease. The amelioration of CMR features was paralleled by significant reduction of BNP (p=0.008), high-sensitive troponin T (p=0.003) and C-reactive protein (p=0.010) serum levels (Table 2), as well as by improving of dyspnea NYHA class (from 0.0 [0.0 – 1.75 to 0.0 – 0.5, p=0.042). Overall, the arrhythmic burden at 24h ECG-Holter did not significantly change (p=ns), even though a trend for a reduction of number of ventricular ectopic beats was observed (p=0.092). No treatment-related adverse events were recorded. <h3>Conclusion:</h3> our study shows that immunosuppression is a therapeutic strategy which can effectively treat newly diagnosed SSc-pHI. Immunosuppression may thus curb signs of myocardial inflammation at CMR, significantly reducing cardiac enzymes, inflammatory markers and overall clinical burden. Larger prospective randomized studies are needed to confirm these data. <h3>REFERENCES:</h3> [1] Bruni C, et al. J Scleroderma Relat Disord. 2022 Feb;7(1):24-32. doi: 10.1177/23971983211053246. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>