Plasma neprilysin concentration during recovery from acute illness

This commentary refers to ‘The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin’, by M. Arrigo et al., on pages 1794–1798. Our group recently described that the removal of failing ventricles and the implantation of a total artificial heart in heart failure (HF) patients led to a marked decrease in soluble neprilysin (sNEP) concentration and activity, both partially recovering afterward.1 These data, in conjunction with a positive trans-cardiac gradient and a neutral trans-pulmonary gradient observed in patients with impaired cardiac systolic function, indicate the heart as a critical source of sNEP in HF. In their letter, Takahama et al. 2 addressed the question whether plasma sNEP concentrations are altered during recovery from acute HF. Using a different assay compared to the one we use, they observed lower sNEP concentrations compared to what we previously measured in patients admitted for acute HF3 and found no significant differences between admission and discharge. Based on those results, they proposed that sNEP could be an indicator of major haemodynamic alterations rather than HF severity.