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Delrue L, Vanderheyden M, Beles M, et al. Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure. ESC Heart Fail. 2021;8(6):4780-4790doi: 10.1002/ehf2.13659.
Delrue, L., Vanderheyden, M., Beles, M., Paolisso, P., Di Gioia, G., Dierckx, R., Verstreken, S., Goethals, M., Heggermont, W., & Bartunek, J. (2021). Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure. ESC heart failure, 8(6), 4780-4790. https://doi.org/10.1002/ehf2.13659
Delrue, Leen, et al. "Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure." ESC heart failure vol. 8,6 (2021): 4780-4790. doi: https://doi.org/10.1002/ehf2.13659
Delrue L, Vanderheyden M, Beles M, Paolisso P, Di Gioia G, Dierckx R, Verstreken S, Goethals M, Heggermont W, Bartunek J. Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure. ESC Heart Fail. 2021 Dec;8(6):4780-4790. doi: 10.1002/ehf2.13659. Epub 2021 Nov 01. PMID: 34725968.
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ESC Heart Fail. 2021 Dec;8(6):4780-4790. doi: 10.1002/ehf2.13659. Epub 2021 Nov 01.

Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure.

ESC heart failure

Leen Delrue, Marc Vanderheyden, Monika Beles, Pasquale Paolisso, Giuseppe Di Gioia, Riet Dierckx, Sofie Verstreken, Marc Goethals, Ward Heggermont, Jozef Bartunek

Affiliations

  1. Cardiovascular Center, OLV Hospital, Moorselbaan 164, Aalst, 9300, Belgium.
  2. Department of Advanced Biomedical Sciences, University of Naples Frederico II, Naples, Italy.

PMID: 34725968 DOI: 10.1002/ehf2.13659

Abstract

AIMS: We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF).

METHODS AND RESULTS: In the first stage, 83 HF-related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age-matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up-regulated in non-survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P < 0.01 and 334.7 ± 138.7 vs. 228.2 ± 83.1 μg/mL, P < 0.01, respectively). While no significant transmyocardial gradient was detected, cytokine stimulation of human endothelial cells induced SERPINA3 secretion. In an independent validation cohort with a de novo or worsened HF (n = 387), circulating SERPINA3 levels > 316 μg/mL were associated with increased all-cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5-3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2-3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N-terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all-cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure.

CONCLUSION: In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Keywords: Biomarkers; Cardiomyopathy; Heart failure; Inflammation; Prognosis

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