Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Prognostic Value of Combined Biomarkers in Patients With Heart Failure: The Heartmarker Score

  • Jonna A. van der Stam (Clinical Laboratory, Catharina Hospital Eindhoven) ;
  • Sjoerd Bouwmeester (Department of Cardiology, Catharina Hospital) ;
  • Saskia L. M. van Loon (Clinical Laboratory, Catharina Hospital Eindhoven) ;
  • Natal A. W. van Riel (Department of Biomedical Engineering, Eindhoven University of Technology) ;
  • Lukas R. Dekker (Department of Cardiology, Catharina Hospital) ;
  • Arjen-Kars Boer (Clinical Laboratory, Catharina Hospital Eindhoven) ;
  • Patrick Houthuizen (Department of Cardiology, Catharina Hospital) ;
  • Volkher Scharnhorst (Clinical Laboratory, Catharina Hospital Eindhoven)
  • Received : 2022.07.21
  • Accepted : 2022.11.07
  • Published : 2023.05.01
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Abstract

Background: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF. Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity. Results: HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity. Conclusions: The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.

Keywords

Acknowledgement

The trial was partly financed by a grant from the Netherlands Enterprise Agency (Grant No: RVO ITEA 161006) and a grant from the Catharina Research Fund.

References

  1. New York Heart Association. Criteria Committee. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston: Little Brown, 1994.
  2. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726. https://doi.org/10.1093/eurheartj/ehab368
  3. Goldman L, Cook EF, Mitchell N, Flatley M, Sherman H, Cohn PF. Pitfalls in the serial assessment of cardiac functional status. How a reduction in 'ordinary' activity may reduce the apparent degree of cardiac compromise and give a misleading impression of improvement. J Chronic Dis 1982;35:763-71. https://doi.org/10.1016/0021-9681(82)90087-X
  4. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation 1981;64:1227-34. https://doi.org/10.1161/01.CIR.64.6.1227
  5. Caraballo C, Desai NR, Mulder H, Alhanti B, Wilson FP, Fiuzat M, et al. Clinical implications of the New York Heart Association classification. J Am Heart Assoc 2019;8:e014240. https://doi.org/10.1161/JAHA.119.014240
  6. Raphael C, Briscoe C, Davies J, Ian Whinnett Z, Manisty C, Sutton R, et al. Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure. Heart 2007;93:476-82. https://doi.org/10.1136/hrt.2006.089656
  7. Spinar J, Spinarova L, Malek F, Ludka O, Krejci J, Ostadal P, et al. Prognostic value of NT-proBNP added to clinical parameters to predict twoyear prognosis of chronic heart failure patients with mid-range and reduced ejection fraction–A report from FAR NHL prospective registry. PLoS One 2019;14:e0214363. https://doi.org/10.1371/journal.pone.0214363
  8. Gardner RS, Özalp F, Murday AJ, Robb SD, McDonagh TA. N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J 2003;24:1735-43. https://doi.org/10.1016/j.ehj.2003.07.005
  9. Kang SH, Park JJ, Choi DJ, Yoon CH, Oh IY, Kang SM, et al. Prognostic value of NT-proBNP in heart failure with preserved versus reduced EF. Heart 2015;101:1881-8. https://doi.org/10.1136/heartjnl-2015-307782
  10. Poelzl G, Trenkler C, Kliebhan J, Wuertinger P, Seger C, Kaser S, et al. FGF23 is associated with disease severity and prognosis in chronic heart failure. Eur J Clin Invest 2014;44:1150-8. https://doi.org/10.1111/eci.12349
  11. Koller L, Kleber ME, Brandenburg VM, Goliasch G, Richter B, Sulzgruber P, et al. Fibroblast growth factor 23 is an independent and specific predictor of mortality in patients with heart failure and reduced ejection fraction. Circ Heart Fail 2015;8:1059-67. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002341
  12. Roy C, Lejeune S, Slimani A, de Meester C, Ahn As SA, Rousseau MF, et al. Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction. ESC Heart Fail 2020;7:2494-507. https://doi.org/10.1002/ehf2.12816
  13. Mendez Fernandez AB, Ferrero-Gregori A, Garcia-Osuna A, MirabetPerez S, Pirla-Buxo MJ, Cinca-Cuscullola J, et al. Growth differentiation factor 15 as mortality predictor in heart failure patients with non-reduced ejection fraction. ESC Heart Fail 2020;7:2223-9. https://doi.org/10.1002/ehf2.12621
  14. Gaggin HK, Szymonifka J, Bhardwaj A, Belcher A, de Berardinis B, Motiwala S, et al. Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure. JACC Heart Fail 2014;2:65-72. https://doi.org/10.1016/j.jchf.2013.10.005
  15. Kempf T, von Haehling S, Peter T, Allhoff T, Cicoira M, Doehner W, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol 2007;50:1054-60. https://doi.org/10.1016/j.jacc.2007.04.091
  16. Emdin M, Aimo A, Vergaro G, Bayes-Genis A, Lupón J, Latini R, et al. sST2 predicts outcome in chronic heart failure beyond NT-proBNP and high-sensitivity troponin T. J Am Coll Cardiol 2018;72:2309-20. https://doi.org/10.1016/j.jacc.2018.08.2165
  17. Bouwens E, Brankovic M, Mouthaan H, Baart S, Rizopoulos D, van Boven N, et al. Temporal patterns of 14 blood biomarker candidates of cardiac remodeling in relation to prognosis of patients with chronic heart failureThe Bio- SH i FT study. J Am Heart Assoc 2019;8:e009555. https://doi.org/10.1161/JAHA.118.009555
  18. Masson S, Agabiti N, Vago T, Miceli M, Mayer F, Letizia T, et al. The fibroblast growth factor-23 and vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk. J Intern Med 2015;277:318-30. https://doi.org/10.1111/joim.12232
  19. Gaggin HK and Januzzi JL. Biomarkers and diagnostics in heart failure. Biochim Biophys Acta 2013;1832:2442-50. https://doi.org/10.1016/j.bbadis.2012.12.014
  20. Sun RR, Lu L, Liu M, Cao Y, Li XC, Liu H, et al. Biomarkers and heart disease. Eur Rev Med Pharmacol Sci 2014;18:2927-35.
  21. Yap J, Lim FY, Gao F, Teo LL, Lam CSP, Yeo KK. Correlation of the New York Heart Association classification and the 6‐minute walk distance: A systematic review. Clin Cardiol 2015;38:621-8. https://doi.org/10.1002/clc.22468
  22. Felker GM, Whellan D, Kraus WE, Clare R, Zannad F, Donahue M, et al. N-terminal pro-brain natriuretic peptide and exercise capacity in chronic heart failure: data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study. Am Heart J 2009;158:S37-44. https://doi.org/10.1016/j.ahj.2009.07.011
  23. Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, et al. Universal definition and classification of heart failure: A report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail 2021;27:387-413. https://doi.org/10.1002/ejhf.2115
  24. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2016;29:277-314. https://doi.org/10.1016/j.echo.2016.01.011
  25. Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor DW, et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 1985;132:919-23.
  26. Demers C, McKelvie RS, Negassa A, Yusuf S; RESOLVD Pilot Study Investigators. Reliability, validity, and responsiveness of the six-minute walk test in patients with heart failure. Am Heart J 2001;142:698-703. https://doi.org/10.1067/mhj.2001.118468
  27. Masson S, Latini R, Anand IS, Vago T, Angelici L, Barlera S, et al. Direct comparison of B-type natriuretic peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data. Clin Chem 2006;52:1528-38. https://doi.org/10.1373/clinchem.2006.069575
  28. Ky B, French B, McCloskey K, Rame JE, McIntosh E, Shahi P, et al. Highsensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail 2011;4:180-7. https://doi.org/10.1161/CIRCHEARTFAILURE.110.958223
  29. Kuster N, Huet F, Dupuy AM, Akodad M, Battistella P, Agullo A, et al. Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure. ESC Heart Fail 2020;7:2230-9. https://doi.org/10.1002/ehf2.12680
  30. Grande D, Leone M, Rizzo C, Terlizzese P, Parisi G, Gioia MI, et al. A multiparametric approach based on NT-proBNP, ST2, and galectin3 for stratifying one year prognosis of chronic heart failure outpatients. J Cardiovasc Dev Dis 2017;4:9. https://doi.org/10.3390/jcdd4030009
  31. Pocock SJ, Ariti CA, McMurray JJV, Maggioni A, Køber L, Squire IB, et al. Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J 2013;34:1404-13. https://doi.org/10.1093/eurheartj/ehs337
  32. Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, et al. The Seattle heart failure model: prediction of survival in heart failure. Circulation 2006;113:1424-33 https://doi.org/10.1161/CIRCULATIONAHA.105.584102