Arfsten H, Bartko PE, Pavo N, et al. - A total of 249 heart failure with reduced ejection fraction (HFrEF) patients were recruited in a study by the researchers in order to evaluate a broad spectrum of neurohumoral biomarkers in patients with HFrEF to investigate their capability to prognosticate progression of secondary mitral regurgitation (sMR). About 18% exhibited progressive sMR within 3 years following study enrollment out of 191 individuals with non-severe sMR at baseline. Progression of sMR was related to higher levels of MR-proADM, MR-proANP, copeptin, and CT-pro-ET1 and not with NT-proBNP. Hence, elevated plasma levels of neurohumoral cardiac biomarkers were predictors of sMR progression in patients with HFrEF and added readily available incremental prognostic information for risk stratification. To prognosticate progressive sMR, NT-proBNP was not useful in the present analysis. In comparison, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures, MR-proADM, a marker of the forward failure and peripheral released vasoactive CT-proET1, increased on the basis of a progressive loading burden by sMR and may, therefore, serve as better predictors of sMR progression.