OBJECTIVE:Depression exacerbates the burden of heart failure and independently predicts mortality. The aim of this study was to investigate which specific symptoms of depression predict all-cause mortality in systolic heart failure patients. METHODS:Consecutive outpatients with heart failure and impaired left ventricular ejection fraction (LVEF), attending an Australian metropolitan heart function clinic between 2001 and 2011, were enrolled. The Cardiac Depression Scale (CDS) was completed as a component of usual care. Baseline clinical characteristics were drawn from hospital databases. The primary end-point was all-cause mortality, obtained from the Australian National Death Index. RESULTS:A total of 324 patients (68.5% male) were included (mean age at enrolment = 66.8 ± 14.36 years), with a median follow-up time of 6.7 years (95% CI 5.97-7.39) and a mortality rate of 50% by the census date. Mean LVEF = 31.0 ± 11.31%, with 25% having NYHA functional class of III or IV. Factor analysis of the CDS extracted six symptom dimensions: Hopelessness, Cognitive Impairment, Anhedonia/Mood, Irritability, Worry, and Sleep Disturbance. Cox regression analyses identified Hopelessness (HR 1.024, 95% CI 1.004-1.045, p = .018) and Cognitive Impairment (HR 1.048, 95% CI 1.005-1.093, p = .028) as independent risk markers of all-cause mortality, following adjustment of known prognostic clinical factors. CONCLUSION:Hopelessness and cognitive impairment are stronger risk markers for all-cause mortality than other symptoms of depression in systolic heart failure. These data will allow more specific risk assessment and potentially new targets for more effective treatment and management of depression in this population.