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Background/objectives Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. Methods Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. Results The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p<0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p<0.0001), pulmonary hypertension (3.71 [1.84-7.25], p<0.0002), valvulopathy (6.33 [3.41-11.62], p<0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p<0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p=0.0015). Female sex (0.46 [0.25-0.88], p=0.0147) and antimalarials (0.28 [0.17-0.45], p<0.000) proved to be protective factors. Conclusions Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.