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Some of these peptides have vasodilating effects (including NPs, adrenomedullin and bradykinin), and others have vasoconstrictor effects (angiotensin I and II and endothelin [ET]-1, among others).22 Neprilysin serum levels (sNEP) exhibited significant prognostic value in both chronic and acutely decompensated HF.2326 However, in patients with HFpEF results were controversial, perhaps due to different sNEP quantification methods.27,28 It is not only the prognostic role of sNEP that has been controversial: even blood sNEP concentrations can be very dissimilar with large differences among studies some showing lower levels in HFpEF than in controls and others showing higher levels in HFpEF than in HFrEF patients.23,27,29 The correct quantification of sNEP remains a challenge that needs to be overcome to suppress potential biases regarding the interpretation of the different studies.30 Interestingly, some sNEP quantification methods showed that circulating sNEP was catalytically active.31 With the hypothesis that higher sNEP levels would correlate with lower NP levels, worse diastolic function, and subsequent clinical incident HFpEF, Reddy et al