The reasons probably lay in the fact that some other DPP-4 regulated substrates are also cardioactive, such as stromal cell-derived factor-1 and brain natriuretic peptide [45], which is why controversies exist about the role of DPP-4 inhibitors in deterioration of HF and increased number of hospitalizations in these patients [44]. This evidence concerns the gene DPP4 and hydrops fetalis.