Immunosuppressive therapy to treat newly diagnosed primary heart involvement in patients with systemic sclerosis: An Italian cardiac magnetic resonance based study

Background: Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), and is associated with a poor prognosis. Therapeutic strategies to treat SSc-pHI are not yet defined. Objectives: To evaluate the efficacy of immunosuppressive therapy on cardiac magnetic resonance (CMR) features in patients with CMR-proven SSc-pHI. Methods: The data from SSc patients with CMR-proven pHI who start or modify immunosuppressive therapy as indication for the newly diagnosed pHI and who had a follow-up CMR with parametric mapping after 6 to 18 months were analyzed. All patients underwent a comprehensive baseline evaluation of disease characteristics and organ involvement. In all patients, cardiac involvement was investigated at baseline and at follow up with CMR, evaluating: myocardial edema at STIR images, native-T1 and T2-mapping, extracellular volume fraction (ECV), and late gadoliunum enhancement (LGE). A p value <0.05 was considered as statistically significant. Results: Out of a cohort of 684 SSc patients, 35 (5.1 %) with SSc-pHI (females 77.1 %; median age 59 [46-64] years; anti-topoisomerase-I positivity 48.6 %; diffuse disease 34.3 %) were selected. In the majority of patients (74.3 %) at baseline CMR, signs of active myocardial inflammation (edema at STIR and/or increased T2- mapping) were found. Mycophenolate mofetil (MMF) was started in 15 (42.9 %) or increased in 7 (20.0 %) cases; 7 patients (20.0 %) received rituximab, 3 (8.6 %) azathioprine, while 3 patients were treated each one with cyclophosphamide (with pulse steroids), tocilizumab and hydroxychloroquine (with steroids). The median duration of immunosuppression was 12.0 [6.0-15.5] months. At follow-up CMR (performed after a median time 12.0 [6.5-16.0] months), increased T2-mapping suggestive for active myocardial inflammation was present in only 14 patients (40 %) (p = 0.003), and edema at STIR was present in 5 cases only (14.3 %) (p = 0.002). A significant reduction of T2-mapping (from 53.0 [49.0-55.0] to 51.0 [50.0-54.0] ms, p < 0.001), native-T1- mapping (from 1050.0 [1007.0-1084.0] to 1039.0 [1020.5-1080.5] ms, p = 0.022) and ECV (from 34.0 [31.0-36.75] to 33.0 [29.0-34.25] %, p = 0.041) was observed, especially in those with baseline increased mapping (T2-mapping from 53.0 [53.0-56.0] to 52.0 [50.0-57.0] ms; T1-mapping from 1066.0 [1050.0-1089.0] to 1057.0 [1027.5-1090.0] ms, p < 0.0001 for both]. The amelioration of the CMR features was paralleled by significant reduction of NT-proBNP (p = 0.008), high-sensitive troponin T (p = 0.003) and C-reactive protein (p = 0.010). No treatment-related adverse events were recorded. Conclusions: Our data show that immunosuppression is a therapeutic strategy which has the potentiality to treat newly diagnosed SSc-pHI, by curbing signs of myocardial inflammation at CMR, and by significantly reducing cardiac enzymes, inflammatory markers and overall clinical burden. Larger prospective randomized studies are needed to confirm these data.