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Heart failure and cardiomyopathies
Original research article
Bioactive adrenomedullin, proenkephalin A and clinical outcomes in an acute heart failure setting
  1. John Molvin1,2,
  2. Amra Jujic1,2,
  3. Silvia Navarin3,4,
  4. Olle Melander2,5,
  5. Giada Zoccoli3,4,
  6. Oliver Hartmann6,
  7. Andreas Bergmann6,
  8. Joachim Struck6,
  9. Erasmus Bachus2,
  10. Salvatore Di Somma3,4 and
  11. Martin Magnusson1,2
  1. 1Department of Cardiology, Skånes universitetssjukhus Malmö, Malmoe, Sweden
  2. 2Department of Clinical Science, Lunds University Faculty of Medicine, Malmoe, Sweden
  3. 3Departments of Medical-Surgery Sciences and Translational Medicine, School of Medicine and Psychology, Sapienza - University, Sant' Andrea Hospital, Roma, Italy
  4. 4GREAT Network; Emergency Medicine, Department of Medical-Surgery Sciences and Translational Medicine, University Sapienza Rome, Sant'Andrea Hospital, Rome, Italy
  5. 5Department of Internal Medicine, Skånes universitetssjukhus Malmö, Malmoe, Sweden
  6. 6Sphingotec GmbH, Hennigsdorf, Berlin, Germany
  1. Correspondence to Dr Martin Magnusson; martin.magnusson{at}med.lu.se

Abstract

Objectives In an acute heart failure (AHF) setting, proenkephalin A 119–159 (penKid) has emerged as a promising prognostic marker for predicting worsening renal function (WRF), while bioactive adrenomedullin (bio-ADM) has been proposed as a potential marker for congestion. We examined the diagnostic value of bio-ADM in congestion and penKid in WRF and investigated the prognostic value of bio-ADM and penKid regarding mortality, rehospitalisation and length of hospital stay in two separate European AHF cohorts.

Methods Bio-ADM and penKid were measured in 530 subjects hospitalised for AHF in two cohorts: Swedish HeArt and bRain failure inVESTigation trial (HARVEST-Malmö) (n=322, 30.1% female; mean age 75.1+11.1 years; 12 months follow-up) and Italian GREAT Network Rome study (n=208, 54.8% female; mean age 78.5+9.9 years; no follow-up available).

Results PenKid was associated with WRF (area under the curve (AUC) 0.65, p<0.001). In multivariable logistic regression analysis of the pooled cohort, penKid showed an independent association with WRF (adjusted OR (aOR) 1.74, p=0.004). Bio-ADM was associated with peripheral oedema (AUC 0.71, p<0.001), which proved to be independent after adjustment (aOR 2.30, p<0.001). PenKid was predictive of in-hospital mortality (OR 2.24, p<0.001). In HARVEST-Malmö, both penKid and bio-ADM were predictive of 1-year mortality (aOR 1.34, p=0.038 and aOR 1.39, p=0.030). Furthermore, bio-ADM was associated with rehospitalisation (aOR 1.25, p=0.007) and length of hospital stay (β=0.702, p=0.005).

Conclusion In two different European AHF cohorts, bio-ADM and penKid perform as suitable biomarkers for early detection of congestion severity and WRF occurrence, respectively, and are associated with pertinent clinical outcomes.

  • bioactive adrenomedullin
  • proenkephalin
  • acute heart failure
  • congestion
  • worsening renal function

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/openhrt-2019-001048

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    Footnotes

    • SDS and MM contributed equally.

    • Contributors All authors substantially contributed to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting the work or revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding MM was supported by grants from the Medical Faculty of Lund University Skane University Hospital, the Crafoord Foundation, the Ernhold Lundstroms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the Southwest Skanes Diabetes Foundation, the Kockska foundation, the Research Funds of Region Skåne and the Swedish Heart and Lung foundation, the Wallenberg Center for Molecular Medicine, Lund University, and the Knut and Alice Wallenberg foundation. Role of the Sponsors: The funding organizations had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation or approval of the manuscript.

    • Competing interests OH, AB and JS are employed by Sphingotec GmbH, the company that provides the penKid and bio-ADM assays used in this study. EB is an employee of Astra Zeneca.

    • Patient consent for publication Not required.

    • Ethics approval The study was approved by the Ethical Review Board at Lund University, Sweden (HARVEST-Malmö) and by the Ethical Committee of Sapienza University (GREAT Network Rome).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.