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15?and?16 Indeed, in the CUORE trial, patients randomized to ultrafiltration had a significantly lower frequency of rehospitalization for congestive HF than did control subjects. This beneficial effect was maintained for up to 1 year. The reduction in rehospitalizations was associated with maintenance of a more stable body weight, renal function and lower diuretic dose in the first 6 months after discharge compared with control subjects. The reduction of rehospitalizations for HF, observed in our trial as well as in the UNLOAD trial, confirms that congestion represents one of the major prognostic determinants, but it also indicates that decongestion alone is not sufficient, because we achieved similar decongestion in both groups but the ultrafiltration-treated patients had a greater freedom from rehospitalization. Basically, our study patients were not refractory to diuretics; indeed, during the index CT99021 hospitalization, both groups had a similar body weight reduction, and both clinical stability and congestion resolution were achieved in a fairly similar time. This was possibly due to our prudential recommendation of incomplete (PLX4032 even if hypervolemia was not completely resolved at the end of ultrafiltration, long-term clinical benefit was greater than that obtained with standard therapy. This emphasizes the fact that the ��quality�� of the fluid withdrawn, more than its amount, was the major causative factor for the different outcome observed in the 2 groups. The mechanisms underlying the long-term positive effect of ultrafiltration remain unclear, and they can not be fully elucidated by our data. However, based on earlier studies, it is likely that differences in neurohumoral response to fluid withdrawal might play a role, despite a similar capacity of ultrafiltration and PDGFRB diuretic therapy to improve symptoms and promote short-term clinical stabilization in patients without refractory HF.15 Indeed, the decongestion obtained with ultrafiltration, compared with diuretic therapy, does not elicit, or even turns off, neurohumoral compensatory mechanisms, resulting in long-term maintenance of the clinical benefit and, consequently, in a reduction of further hospitalizations.15?and?18 When ultrafiltration is repeated, as in our study, to treat rehospitalized patients, these differences in neurohumoral response are expected to increase in parallel with the length of the considered follow-up and the number of rehospitalizations.