Prognostic significance of the preoperative level of biomarker NT-proBNP in myocardial revascularization with cardiopulmonary bypass (pilot study)

The objective: to study the relationship between the preoperative blood levels of the N-terminal segment of B-type natriuretic peptide precursor (NT-proBNP) and echocardiographic and pulmonary artery catheter (PAC) data before and after on-pump coronary artery bypass grafting (CABG), and to evaluate the biomarker as a predictor of postoperative myocardial dysfunction.

Material and methods. The study involved 63 patients aged 51[39–64] years with ischemic heart disease who underwent CABG. NT-proBNP blood level was determined before surgery. PAC and transesophageal echocardiography (TEE) data were analyzed at the stages: I – after anesthesia induction, II – at the end of surgery. Correlation analysis, logistic regression with calculation of odds ratio (OR) and 95% confidence interval (95% CI) and ROC analysis with calculation of area under ROC curve (AUC) were used.

Results. The median preoperative NT-proBNP blood level was 418.3[225.5–950.45] pg/mL. At stage I, NT-proBNP moderately correlated with mean and wedge pulmonary artery pressures, as well as with TEE parameters of the left ventricle (LV) sizes and function. At stage II, the biomarker moderately correlated only with TEE parameters. NT-proBNP >579 pg/mL was a predictor of LV area contraction fraction (LVACF) 605 pg/mL was a predictor of LV end-systolic area index (LVESAI) >9 cm2 / m2 (OR1.0015, 95% CI 1.0004–1.0026, p=0.008, AUC0.834) at the end of surgery. NT-proBNP10 (OR1.0016, 95% CI 1.0005–1.0026, p=0.003, AUC0.808), intra-aortic balloon pumping (IABP) (OR1.0019, 95% CI 1.0007–1.0030, p=0.001, AUC0.914) and intensive care unit length of stay >24 hours (OR1.0020, 95% CI 1.0007–1.0032, p=0.002, AUC0.771). NTproBNP >953 pg/mL was a predictor of the refractory heart failure (RHF) (OR1.0017, 95% CI 1.0006–1.0027, p=0.003, AUC0.866).

Conclusion. In 50.8% of patients before on-pump CABG, NT-proBNP blood level exceeded the upper limit of normal and varied within the range of 355–3232 pg/ml. NT-proBNP values moderately correlated with perioperative TEE parameters. There were no persistent correlations with PAC data. Preoperative NT-proBNP values of about 600 pg/mL were predictors of LVESAI >9 cm2 /m2 (AUC0,834) and LVACF 950 pg/mL was a predictor of RHF after on-pump CABG (AUC0.866).

1. Hunt P.J., Richards A.M., Nicholls M.G., Yandle T.G., Doughty R.N., Espiner E.A. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (Oxf). 1997;47(3):287–296. DOI: 10.1046/j.1365–2265.1997.2361058.x

2. Collins S.P., Ronan-Bentle S., Storrow A.B. Diagnostic and prognostic usefulness of natriuretic peptides in emergency department patients with dyspnea. Ann Emerg Med. 2003;41(4):532–45. DOI: 10.1067/mem.2003.113. PMID: 12658254.

3. Lubarsky L., Mandell K. B-type natriuretic peptide: practical diagnostic use for evaluating ventricular dysfunction. Congest Heart Fail. 2004;10(3):140–143. DOI: 10.1111/j.1527–5299.2004.03278.x.

4. Mareev V. Yu., Fomin I.V., Ageev F. T., Begrambekova Yu.L., Vasyuk Yu.A., Garganeeva A.A., Gendlin G.E., Glezer M.G., Gautier S.V., Dovzhenko T.V., Kobalava Zh.D., Koziolova N.A., Koroteev A.V., Mareev Yu.V., Ovchinnikov A.G., Perepech N.B., Tarlovskaya E.I., Chesnikova A.I., Shevchenko A.O., Arutyunov G.P., Belenkov Yu.N., Galyavich A. S., Gilyarevsky S.R., Drapkina O.M., Duplyakov D.V., Lopatin Yu.M., Sitnikova M. Yu., Skibitsky V.V., Shlyakhto E.V. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(6S):8–158. (In Russ.) DOI: 10.18087/cardio.2475

5. McDonagh T.A., Metra M., Adamo M., Gardner R.S., Baumbach A., Böhm M., Burri H., Butler J., Čelutkienė J., Chioncel O., Cleland J.G.F., Coats A.J.S., Crespo-Leiro M.G., Farmakis D., Gilard M., Heymans S., Hoes A.W., Jaarsma T., Jankowska E.A., Lainscak M., Lam C. S.P., Lyon A.R., McMurray J.J.V., Mebazaa A., Mindham R., Muneretto C., Francesco Piepoli M., Price S., Rosano G.M.C., Ruschitzka F., Kathrine Skibelund A.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022;24(1):4–131. DOI: 10.1002/ejhf.2333.

6. Mueller C., McDonald K., de Boer R.A., Maisel A., Cleland J.G.F., Kozhuharov N., Coats A.J.S., Metra M., Mebazaa A., Ruschitzka F., Lainscak M., Filippatos G., Seferovic P.M., Meijers W.C., Bayes-Genis A., Mueller T., Richards M., Januzzi J. L. Jr.; Heart Failure Association of the European Society of Cardiology. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur J Heart Fail. 2019;21(6):715–731. DOI: 10.1002/ejhf.1494.

7. Yancy C.W., Jessup M., Bozkurt B., Butler J., Casey D.E. Jr., Colvin M.M., Drazner M.H., Filippatos G.S., Fonarow G.C., Givertz M.M., Hollenberg S.M, Lindenfeld J., Masoudi F.A., McBride P.E., Peterson P.N., Stevenson L.W., Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628–651. DOI: 10.1016/j.cardfail.2017.04.014.

8. Yeh H.M., Lau H.P., Lin J.M., Sun W.Z., Wang M.J., Lai L.P. Preoperative plasma N-terminal pro-brain natriuretic peptide as a marker of cardiac risk in patients undergoing elective non-cardiac surgery. Br J Surg. 2005;92(8):1041–1045. DOI: 10.1002/bjs.4947.

9. Duceppe E., Parlow J., MacDonald P., Lyons K., McMullen M., Srinathan S., Graham M., Tandon V., Styles K., Bessissow A., Sessler D.I., Bryson G., Devereaux P.J. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. Can J Cardiol. 2017;33(1):17–32. DOI: 10.1016/j.cjca.2016.09.008.

10. Halvorsen S., Mehilli J., Cassese S., Hall T.S., Abdelhamid M., Barbato E., De Hert S., de Laval I., Geisler T., Hinterbuchner L., Ibanez B., Lenarczyk R., Mansmann U.R., McGreavy P., Mueller C., Muneretto C., Niessner A., Potpara T.S., Ristić A., Sade L.E., Schirmer H., Schüpke S., Sillesen H., Skulstad H., Torracca L., Tutarel O., Van Der Meer P., Wojakowski W., Zacharowski K.; ESC Scientific Document Group. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J. 2022;43(39):3826–3924. DOI: 10.1093/eurheartj/ehac270.

11. Lurati Buse G., Bollen Pinto B., Abelha F., Abbott T.E.F., Ackland G., Afshari A., De Hert S., Fellahi J.L., Giossi L., Kavsak P., Longrois D., M’Pembele R., Nucaro A., Popova E., Puelacher C., Richards T., Roth S., Sheka M., Szczeklik W., van Waes J., Walder B., Chew M.S. ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation. Eur J Anaesthesiol. 2023;40(12):888–927. DOI: 10.1097/EJA.0000000000001865.

12. Cerrahoglu M., Iskesen I., Tekin C., Onur E., Yildirim F., Sirin B.H. N-terminal ProBNP levels can predict cardiac failure after cardiac surgery. Circ J. 2007;71(1):79–83. DOI: 10.1253/circj.71.79.

13. Comanici M., Nadarajah D., Katumalla E., Cyclewala S., Raja S.G. Use of Preoperative Natriuretic Peptide in Predicting Mortality After Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis. J Cardiothorac Vasc Anesth. 2023;37(9):1785–1792. DOI: 10.1053/j.jvca.2023.04.020.

14. Göçer S., Ilkeli E., Düzgün A.C. Diagnostic accuracy of copeptin and NT-proBNP level in predicting mortality and postoperative prognosis in coronary surgery with respect to EuroSCORE risk. Kardiochir Torakochirurgia Pol. 2022;19(4):205–210. DOI: 10.5114/kitp.2022.122090.

15. Thanh B.D., Son N.H., Pho D.C., Bac N.D., Nga V.T., Dung Q.A., Anh D.D., Linh D.D., Viet H.T.B., Anh B.D.T., Tan H.T., Hung P.N. The Role of Serial NT-ProBNP Level in Prognosis and Follow-Up Treatment of Acute Heart Failure after Coronary Artery Bypass Graft Surgery. Open Access Maced J Med Sci. 2019 20;7(24):4411–4415. DOI: 10.3889/oamjms.2019.872.

16. Wang J., Liu H., Zeng J., Su X., Zhao Y., Zheng Z. Utility of Preoperative N-Terminal Pro-B-Type Natriuretic Peptide in the Prognosis of Coronary Artery Bypass Grafting. Am J Cardiol. 2023; 201: 131–138. DOI: 10.1016/j.amjcard.2023.05.047.

17. Zhang C., Jiang L., Xu L., Tian J., Liu J., Zhao X., Feng X., Wang D., Zhang Y., Sun K., Xu B., Zhao W., Hui R., Gao R., Yuan J., Song L. Implications of N-terminal pro-B-type natriuretic peptide in patients with three-vessel disease. Eur Heart J. 2019;40(41):3397–3405. DOI: 10.1093/eurheartj/ehz394.

18. Rao R.A., Varghese S.S., Ansari F., Rao A., Meng E., El-Diasty M. The Role of Natriuretic Peptides in Predicting Adverse Outcomes After Cardiac Surgery: An Updated Systematic Review. Am J Cardiol. 2024; 210: 16–36. DOI: 10.1016/j.amjcard.2023.09.101.

19. Burzhunova M.G., Guseva O.G., Rybakov V. Yu., Krichevsky L.A., Kozlov I.A. The Informative Value of N-Terminal Pro-type B Natriuretic Peptide in Cardiac Surgical Patients with Hypercreatininemia. General Reanimatology. 2011;7(6):40–45. (In Russ.) DOI: 10.15360/1813-9779-2011-6-40

20. Kozlov I.A., Kharlamova I. Ye. Increased B-type Natriuretic Peptide (NT-proBNP) Level as a Risk Factor in Cardiosurgical Patients. General Reanimatology. 2010;6(1):49–55. (In Russ.) DOI: 10.15360/1813-9779-2010-1-49

21. Laletin D.A., Bautin A.E., Rubinchik V.E., Naumenko V.S., Alekseyev A.A., Mikhailov A.P. Parallels between the hemodynamic profile and biomarkers activity in different forms of acute heart failure in the early period after aortocoronary bypass. Messenger of Anesthesiology and Resuscitation. 2015;12(2):27–33. (In Russ.) DOI: 10.21292/2078-5658-2015-12-2-27-33

22. Lednev P. V., Belov Yu.V., Komarov R.N., Stonogin A. V. The role of N-terminal pro-brain natriuretic peptide in prediction of postoperative atrial fibrillation. Pirogov Russian Journal of Surgery. 2016;(1):414. (In Russ.) DOI: 10.17116/hirurgia201614–14

23. Petrova O., Motreva A., Martianova Yu., Kadykova A., Shashin S., Tarasov D. Aminoterminal brain natriuretic propeptide in the diagnosis of myocardial damage after coronary bypass surgery on a working heart. Patologiya krovoobrashcheniya i kardiokhirurgiya = Circulation Pathology and Cardiac Surgery. 2013;17(3):18–21. (In Russ.) DOI: 10.21688/1681-3472-2013-3-18-21

24. Flerov E.V., Iumatov A. E., Iavorovskiĭ A.G., Shitikov I.I., Sablin I.N., Paramonov V.A., Pavlov I.V. Volumetric monitoring of the right ventricle during heart surgery. Anesteziol Reanimatol. 1997;(5):23–28. (In Russ) PMID: 9432887

25. Kuzkov V.V., Kirov M. Yu. Invazivnyj monitoring gemodinamiki v intensivnoj terapii i anesteziologii. 2 izd. Arhangel’sk: Severnyj gosudarstvennyj medicinskij universitet, 2015. 392. (In Russ.). ISBN978-5-91702-180-5

26. Lang R.M., Badano L.P., Mor-Avi V., Afilalo J., Armstrong A., Ernande L., Flachskampf F.A., Foster E., Goldstein S.A., Kuznetsova T., Lancellotti P., Muraru D., Picard M.H., Rietzschel E.R., Rudski L., Spencer K.T., Tsang W., Voigt J.U. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16(3):233–270. DOI: 10.1093/ehjci/jev014.

27. Vieillard Baron A., Schmitt J.M., Beauchet A. et al. Early preload adaptation in septic shock? A transesophageal echocardiographic study. Anesthesiology. 2001;94(3):400–406. DOI: 10. 1097/00000542 200103000-00007

28. Duchnowski P. The Role of the N-Terminal of the Prohormone Brain Natriuretic Peptide in Predicting Postoperative Multiple Organ Dysfunction Syndrome. J Clin Med. 2022;11(23):7217. DOI: 10.3390/jcm11237217.

29. Thet M.S., Hlwar K.E., Thet K.S., Han K.P.P., Oo A.Y. Preoperative B-Type Natriuretic Peptides to Predict Postoperative Atrial Fibrillation in Cardiac Surgery: A Systematic Review and Meta-Analysis. Heart Lung Circ. 2024;33(1):23–32. DOI: 10.1016/j.hlc.2023.10.015.

30. Fox A.A. Perioperative B-type Natriuretic Peptide/N-terminal pro-B-type Natriuretic Peptide: Next Steps to Clinical Practice. Anesthesiology. 2015;123(2):246–8. DOI: 10.1097/ALN.0000000000000729.

31. Crescenzi G., Landoni G., Bignami E., Belloni I., Biselli C., Rosica C., Guarracino F., Marino G., Zangrillo A. N-terminal B-natriuretic Peptide after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2009;23(2):147–50. DOI: 10.1053/j.jvca.2008.10.002.

32. Holm J., Vidlund M., Vanky F., Friberg O., Håkanson E., Svedjeholm R. Preoperative NT-proBNP independently predicts outcome in patients with acute coronary syndrome undergoing CABG. Scand Cardiovasc J Suppl. 2013;47(1):28–35. DOI: 10.3109/14017431.2012.731518.

33. Bibbins-Domingo K., Gupta R., Na B., Wu A.H., Schiller N.B., Whooley M.A. N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease. JAMA. 2007;297(2):169–176. DOI: 10.1001/jama.297.2.169.

34. Cuthbertson B.H., Croal B. L., Rae D., Gibson P.H., McNeilly J.D., Jeffrey R.R., Smith W. C., Prescott G.J., Buchan K.G., El-Shafei H., Gibson G.A., Hillis G.S. N-terminal pro-B-type natriuretic peptide levels and early outcome after cardiac surgery: a prospective cohort study. Br J Anaesth. 2009;103(5):647–653. DOI: 10.1093/bja/aep234

35. Kragelund C., Grønning B., Køber L., Hildebrandt P., Steffensen R. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med. 2005;352(7):666–675. DOI: 10.1056/NEJMoa042330.

36. Liu H., Wang C., Liu L., Zhuang Y., Yang X., Zhang Y. Perioperative application of N-terminal pro-brain natriuretic peptide in patients undergoing cardiac surgery. J Cardiothorac Surg. 2013;8:1. DOI: 10.1186/1749-8090-8-1.

37. Kozlov I.A., Sokolov D.A. Assessment of the Myocardial Stress Biomarker NT-proBNP in Real Clinical Practice. General Reanimatology. 2023;19(1):4–12. DOI: 10.15360/1813 9779 2023 1 2272

38. Shetty N. S., Patel N., Gaonkar M., Li P., Arora G., Arora P. Natriuretic Peptide Normative Levels and Deficiency: The National Health and Nutrition Examination Survey. JACC Heart Fail. 2024;12(1):50–63. DOI: 10.1016/j.jchf.2023.07.018.

39. Tsutsui H., Albert N.M., Coats A.J.S., Anker S.D., Bayes-Genis A., Butler J., Chioncel O., Defilippi C.R., Drazner M.H., Felker G.M., Filippatos G., Fiuzat M., Ide T., Januzzi J.L. Jr, Kinugawa K., Kuwahara K., Matsue Y., Mentz R.J., Metra M., Pandey A., Rosano G., Saito Y., Sakata Y., Sato N., Seferovic P.M., Teerlink J., Yamamoto K., Yoshimura M. Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Eur J Heart Fail. 2023;25(5):616–631. DOI: 10.1002/ejhf.2848.

40. Goetze J. P., Christoffersen C., Perko M., Arendrup H., Rehfeld J. F., Kastrup J., Nielsen L.B. Increased cardiac BNP expression associated with myocardial ischemia. FASEB J. 2003;17(9):1105–1107. DOI: 10.1096/fj.02–0796fje.

41. Neuen B.L., Vaduganathan M., Claggett B.L., Beldhuis I., Myhre P., Desai A.S., Skali H., Mc Causland F.R., McGrath M., Anand I., Zile M.R., Pfeffer M.A., McMurray J.J.V., Solomon S.D. Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2025;13(1):28–39. DOI: 10.1016/j.jchf.2024.08.009.

42. Fox A.A., Collard C.D., Shernan S.K., Seidman C.E., Seidman J.G., Liu K.Y., Muehlschlegel J.D., Perry T.E., Aranki S.F., Lange C., Herman D.S., Meitinger T., Lichtner P., Body S.C. Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting. Anesthesiology. 2009;110(4):738–747. DOI: 10.1097/aln.0b013e31819c7496.

43. Gibson P.H., Croal B. L., Cuthbertson B.H., Rae D., McNeilly J.D., Gibson G., Jeffrey R.R., Buchan K.G., El-Shafei H., Hillis G.S. Use of preoperative natriuretic peptides and echocardiographic parameters in predicting new-onset atrial fibrillation after coronary artery bypass grafting: a prospective comparative study. Am Heart J. 2009;158(2):244–251. DOI: 10.1016/j.ahj.2009.04.026.

44. Dzybinskaya Y. V., Krichevsky L. A., Kharlamova I. E., Kozlov I. A. Transesophageal Echocardiography in the Assessment of Indications for and Contraindications to Early Activation after Myocardial Revascularization. General Reanimatology. 2011;7(1):42–47. DOI: 10.15360/1813-9779-2011-1-42

45. Paromov K. V., Volkov D. A., Nizovtsev N. V., Kirov M. Yu. Myocardial function after offpump coronary artery bypass grafting with combined epidural and inhalation anesthesia. Messenger of Anesthesiology and Resuscitation. 2020;17(5):6–14. (In Russ.) DOI: 10.21292/2078-5658-2020-17-5-6 14

46. Cuthbertson B.H., Croal B. L., Rae D., Harrild K., Gibson P.H., Prescott G. J., Kengne A.P., Hillis G.S. N-terminal pro-B-type natriuretic peptide concentrations and long-term outcome after cardiac surgery: a prospective cohort study. Br J Anaesth. 2013;110(2):214–221. DOI: 10.1093/bja/aes379.

47.