Abstract: We recently observed a case of patient affected to severe CHF due to ischemic cardiomyopathy ( NYHA class IIIb) submitted to Bosentan treatment. During therapy we recruited an increase in cardiac output and ejection fraction, and lowering in LV systolic volume and pulmonary pressure, however we observed clinical systemic impairment characterized to cacexya, dyarrhea inappetite asthenia and fluid retention. Laboratory analysis showed an impairment of renal and liver function, reduced levels of albumina and haemoglobin (microcitemic anemia), increased levels of C-reactive protein and total bilirubin. Specific laboratory examination demonstrated an increase of plasma renin activity (PRA) but no significant variation in Brain Natriuretic Peptide (BNP) soon after treatment. This clinical adverse effects returned after drugs suspension besides, we observed a normalization of albuminemia, regression of anemic state, renal impairment, and lowering of inflammatory markers, PRA , and bilirubin levels. These findings suggest two potential mechanisms for the exacerbation of CHF conditions observed in clinical trials with ET receptor antagonism.