Depression is a common comorbidity in heart failure (HF); however, the mechanisms related to a poorer outcome of depressed patients with HF remain unclear. Objective: To evaluate the role of severe depression in the outcome of patients with decompensated HF. Methods: A total of 43 patients with advanced HF, EF < 40.0%, and hospitalized for cardiac compensation were consecutively studied. After history taking and physical examination, the patients underwent laboratory tests including BNP

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... ation. After the diagnosis of depression was made, the Hamilton-D scale was applied. Severe depression was defined by a score equal to or greater than 18. The clinical and laboratory variables according to the presence or absence of severe depression were analyzed using logistic regression. The ROC curve defined the cut-off point for BNP. Results: Severe or very severe depression was identified in 24 (55.8%) patients. Severely depressed patients did not differ from non-depressed patients as regards age, gender and renal function, but showed less cardiac impairment (EF 23.4 ± 7.2% vs 19.5 ± 5.2%; p = 0.046) and higher BNP levels (2,582.8 ± 1,596.6 pg/ml vs 1,206.6 ± 587.0 pg/ml; p < 0.001). However, patients with BNP levels higher than 1,100 pg/ml had a 12.0-fold higher chance (odds ratio [95% CI] = 2.61 -55.26) of developing severe depression. Conclusion: Patients with severe depression showed a higher degree of neurohormonal stimulation despite their lower degree of ventricular dysfunction. The pathophysiological changes related to depression, leading to increased neurohormonal stimulation and cytokines, probably contributed to this more intense clinical manifestation even in the presence of less cardiac damage.