Proenkephalin in Heart Failure

Heart Fail Clin. 2018 Jan;14(1):1-11. doi: 10.1016/j.hfc.2017.08.001. Epub 2017 Sep 28.


The opioid system is activated in heart failure, which may be cardioprotective but may also be counter-regulatory. Recently, systemic proenkephalin activation has been investigated in various conditions predicting mortality and kidney injury. In acute heart failure, proenkephalin independently predicts mortality and heart failure rehospitalization in addition to traditional risk markers. It also predicts worsening renal function, increasingly recognized as an important risk predictor for poor outcome in heart failure. This article explores the role of enkephalins and delta-opioid receptors in the heart, then reviews studies measuring proenkephalin levels in the circulation and their associations with prognosis.

Keywords: Delta-opioid receptor; Enkephalin; Heart failure; PENK; Proenkephalin; Renal function.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Pressure / physiology*
  • Enkephalins / metabolism*
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Heart Rate / physiology*
  • Humans
  • Myocardial Contraction / physiology*
  • Protein Precursors / metabolism*
  • Receptors, Opioid, delta / metabolism*


  • Enkephalins
  • Protein Precursors
  • Receptors, Opioid, delta
  • proenkephalin