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Depression is common and independently associated with increased morbidity and mortality in patients with heart failure (HF), but no studies have demonstrated that treating depression improves outcomes in this high-risk population. Selective serotonin reuptake inhibitors used to treat depression have ancillary (e.g., anti-inflammatory) effects that might be of particular benefit to patients with HF. In this study, 469 adults aged ≥45 (mean age, 62) with symptomatic systolic heart failure (mean left ventricular ejection fraction, 30%) and major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition criteria) depressive symptoms were randomized to receive placebo or sertraline (50 mg initially, titrated towa…