The main findings of our study are that (i) plasma levels of endocan—a novel marker of endothelial dysfunction—are markedly elevated in patients with chronic HF as compared to previously reported values in healthy subjects or patients with CAD; (ii) endocan levels are increased irrespective of comorbidities, such as CAD, PAD, AH, DM, KI, or HLP; and (iii) plasma endocan levels are an independent predictor of HF-related morbidity and mortality. Here, ESM1 is linked to hydrops fetalis.