Rapid exacerbation of heart failure, better known as acute decompensated heart failure, is associated, despite current medical treatments, with a high morbi-mortality. The incoherent patient and/or treatment stratification, due to the absence of reliable prognostic bio-markers reflecting not only the patient’s pathological status but also outcome, as well as the insufficient comprehension of the mechanisms triggering and/or maintaining decompensation, is involved in this incoherent patient/treatment stratification. The present project, using a recently developed a murine model mimicking acute decompensation of heart failure patients after dietary change with excessive salt ingestion, should reveal O-GlcNAcase inhibition as a new treatment for acute de compensation, the mechanisms involved and relevant biomarkers of acute decompensation, which will improve patient and treatment stratification, but might also reveal new targets for the treatment of decompensated heart failure.