We examined the role of serum ET-1 concentration as a prognostic biomarker in a contemporary population with HF and reduced ejection fraction (HFrEF), including its value when added to other established biomarkers, evaluated the relationship between serum ET-1 and decline in kidney function in HFrEF, and investigated whether ET-1 modifies the response to SGLT-2 inhibition in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure).15 This evidence concerns the gene SLC5A2 and hydrops fetalis.