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Background: Major depression is common in patients with heart failure (HF), and has been associated with higher tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), affecting the prognosis in these patients. We compared the effect of anti-depressive medication with tricyclic antidepressants (TA), serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) on endothelial function and inflammatory process in patients with congestive HF. Methods: A population of 250 patients with HF(154 of which suffering from major depression) were recruited. Patients with major depression were under selective serotonine reuptake inhibitors (SSRIs, n=120) or tricyclic antidepressants (TCA) and/or serotonin/norepinephrine reuptake inhibitors (SNRIs) (n=34). Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Results: Levels of TNF-α and CRP were not significantly different between HF patients with depression under treatment (4.70±0.17pg/ml and 15.13±1.75mg/dl) and those without depression (5.02±1.99pg/ml and 19.5±3.1mg/dl, p=NS for all). There was no difference in EDD and EID between patients under SNRIs (44.7±1.6% and 63.2±1.1%), SSRIs (45.1±3.1% and 58.2±1.2%) and non depressive patients (43.0±2.1% and 63.2±2.2%), p=NS for all. However, TNF-α and CRP were significantly lower in patients receiving TCA/SNRI (4.3±0.4pg/ml and 7.3±1.1mg/dL) compared to patients under SSRIs (4.8±0.2pg/ml and 17.4±2.2mg/dl p<0.05 for both) or those without depression (5.01±3.2pg/ml and 19.5±3.2mg/dl, p<0.05 for both). Similarly, TCA/SNRI had lower heart rate (70.7±0.53bpm) compared to SSRIs (74.5±1.3bpm, p<0.05) or those without depression (74.2±6.3bpm, p<0.05). Treatment with SNRI/TCA was an independent predictor for TNF-α (β=0.036 (SE: 0.016) and CRP (β=0.099 (SE: 0.048), p=0.041). Conclusions: Patients with HF and depression receiving NSSRIs have lower TNF-α and CRP compared to those receiving SSRIs or those receiving no anti-depressives. These findings suggest that the type of antidepressive medication may affect inflammatory process in patients with heart failure. 667The homeostatic chemokines CCL19 and CCL21 are elevated in heart failure and may regulate myocardial hypertrophy