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Circulating Secretoneurin Concentrations After Cardiac Surgery: Data From the FINNish Acute Kidney Injury Heart Study

Brynildsen, Jon MD1,2; Petäjä, Liisa MD3,4; Myhre, Peder L. MD, PhD1,2; Lyngbakken, Magnus N. MD, PhD1,2; Nygård, Ståle PhD5,6; Stridsberg, Mats MD, PhD7; Christensen, Geir MD, PhD, MHA2,8; Ottesen, Anett H. MSc, PhD1,2,8; Pettilä, Ville MD, PhD3,4; Omland, Torbjørn MD, PhD, MPH1,2; Røsjø, Helge MD, PhD1,2

doi: 10.1097/CCM.0000000000003670
Online Clinical Investigations
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Objectives: Secretoneurin is associated with cardiomyocyte Ca2+ handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known.

Design: Prospective, observational, single-center sub-study of a multicenter study.

Setting: Prospective observational study of survival in patients undergoing cardiac surgery.

Patients: A total of 619 patients undergoing cardiac surgery.

Interventions: Patients underwent either isolated coronary artery bypass graft surgery, single noncoronary artery bypass graft surgery, two procedures, or three or more procedures. Procedures other than coronary artery bypass graft were valve surgery, surgery on thoracic aorta, and other cardiac surgery.

Measurements and Main Results: We measured preoperative and postoperative secretoneurin concentrations and adjusted for European System for Cardiac Operative Risk Evaluation II, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T concentrations in multivariate analyses. During 961 days of follow-up, 59 patients died (9.5%). Secretoneurin concentrations were higher among nonsurvivors compared with survivors, both before (168 pmol/L [quartile 1–3, 147–206 pmol/L] vs 160 pmol/L [131–193 pmol/L]; p = 0.039) and after cardiac surgery (173 pmol/L [129–217 pmol/L] vs 143 pmol/L [111–173 pmol/L]; p < 0.001). Secretoneurin concentrations decreased from preoperative to postoperative measurements in survivors, whereas we observed no significant decrease in secretoneurin concentrations among nonsurvivors. Secretoneurin concentrations were weakly correlated with established risk indices. Patients with the highest postoperative secretoneurin concentrations had worse outcome compared with patients with lower secretoneurin concentrations (p < 0.001 by the log-rank test) and postoperative secretoneurin concentrations were associated with time to death in multivariate Cox regression analysis: hazard ratio lnsecretoneurin 2.96 (95% CI, 1.46–5.99; p = 0.003). Adding postoperative secretoneurin concentrations to European System for Cardiac Operative Risk Evaluation II improved patient risk stratification, as assessed by the integrated discrimination index: 0.023 (95% CI, 0.0043–0.041; p = 0.016).

Conclusions: Circulating postoperative secretoneurin concentrations provide incremental prognostic information to established risk indices in patients undergoing cardiac surgery.

1Division of Medicine, Akershus University Hospital, Lørenskog, Norway.

2Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

3Division of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki, Helsinki, Finland.

4Helsinki University Hospital, Helsinki, Finland.

5Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, Norway.

6University of Oslo, Oslo, Norway.

7Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

8Institute for Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway.

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Akershus University Hospital and the Research Council of Norway supported this study. The FINNish Acute Kidney Injury Study got the special state subsidy (EVO) grants from Helsinki University (TYH 2013343, TYH 2013106, and T102010070), from Academy of Finland.

Dr. Petäjä’s institutions received funding from EVO grants from Helsinki University (TYH 2013343, TYH 2013106, and T102010070), and they disclosed that the Academy of Finland supported FINNish Acute Kidney Injury Study. Drs. Christensen, Omland, and Røsjø disclosed that they are partners in a patent (PCT/GB0818650.4) filed by the University of Oslo regarding the use of secretoneurin as a biomarker in patients with cardiovascular disease and patients with critical illness, and they have financial interests in CardiNor AS, which holds the license to commercialize secretoneurin. They have also received personal fees from CardiNor AS. Drs. Myhre, Omland, and Røsjø have also received personal fees from Novartis. Dr. Omland received funding as a member of the editorial board of the journal Circulation, and from Abbott, Bayer, Roche, and Novartis. He has also received research funding from Abbott, Roche, Singulex, and AstraZeneca. Dr. Omland has served on advisory boards and received speaker´s honoraria and travel funding from Roche Diagnostics and Roche Diagnostics provided high-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide kits at a reduced price via Akershus University Hospital. Drs. Omland and Rosjo disclosed that Akershus University Hospital and the Research Council of Norway supported this study. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Helge Røsjø, MD, PhD, Division of Medicine, Akershus University Hospital, Sykehusveien 25, 1478 Lørenskog, Norway. E-mail: helge.rosjo@medisin.uio.no

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