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Introduction Primary heart involvement (pHI) is a major organ complication of systemic sclerosis (SSc), accounting for a significant share of SSc-related deaths. Since pHI is often asymptomatic and its presentation is variable, a multiparametric assessment is mandatory. Echocardiography is central in pHI screening. Coronary flow velocity reserve (CFR) assessed by echocardiography has been demonstrated to identify SSc patients with coronary microvascular dysfunction (CMD), which appears to be involved in the pathogenesis of SSc-pHI. 1 Anti-endothelin type A and anti-angiotensin type 1 receptors antibodies (anti-ETAR and anti-AT1R) have been associated with the microvascular manifestations of SSc. Our study aims to evaluate a possible association between anti-GPCRs antibodies and CMD in SSc.Material and Methods Adult patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were enrolled; patients with coronary artery disease, pulmonary arterial hypertension and other cardiomyopathies were excluded. Demographic and clinical data were recorded, as well as the presence of pHI according to the current definition. 2 Serum levels of anti-ETAR and anti-AT1R antibodies were assessed by ELISA: the seropositive threshold was provided by the manufacturer (>10 U/ml). Echocardiography with CFR assessment was performed on all patients by an experienced cardiologist: according to the literature, CFR <2.5 was considered marker of CMD and CFR values < 2 indicated severe CMD.Results Thirty-one patients were enrolled. The median disease duration was 1 year (IQR 1-4), the median age was 58 (48-63) years, the majority of patients had diffuse cutaneous SSc (61%) and positive anti- topoisomerase I antibodies (55%). pHI was diagnosed in 26% patients, while CMD in 70%. CMD was not associated with organ involvement, including pHI, but CFR values < 2 were associated with a diagnosis of pHI. Serum anti-ETAR and anti-AT1R levels strongly correlated with each other (p<0.001). Positive anti-ETAR and anti-AT1R were associated with significantly lower CFR values (p=0.002 and p=0.05), and both anti-ETAR and anti-AT1R titers inversely correlated with CFR values on echo (rho =-0.41, p=0.03 and rho=-0.37, p=0.05, respectively), with a moderate diagnostic value on ROC analysis (AUC 0.74 and 0.72 ) and a good positive predictive value (93% and 92%) for CMD. A longer time from Raynaud’s phenomenon was associated with higher anti-GPCRs titers (p=0.04 and p=0.02).Conclusions Anti-ETAR and anti-AT1R antibodies appear to be associated with the development of CMD is SSc and their determination may be useful in the early assessment of SSc-pHI.References Vacca A, et al. Ann Rheum Dis. 2006.Bruni C, et al. JSRD. 2022.Abstract P.050 Figure 1