Apart from endothelium, ET-1 is also produced by smooth muscle cells, cardiomyocytes, and cardiac fibroblasts.[7] Circulating ET-1 is increased in pulmonary arterial hypertension, systematic hypertension, aging, diabetes, and myocardial infarction.[7,52] This meta-analysis showed that high plasma level of ET-1 was significantly correlated with mortality or adverse outcomes in patients with HF. This evidence concerns the gene EDN1 and diabetes mellitus.