Возможности использования биомаркеров крови для прогнозирования вероятности возникновения желудочковых тахиаритмий у больных хронической сердечной недостаточностью со сниженной фракцией выброса левого желудочка: обзор литературы

Действующая однофакторная шкала прогноза риска желудочковых тахиаритмий у больных хронической сердечной недостаточностью со сниженной фракцией выброса левого желудочка, по мнению большинства экспертов, не отвечает требованиям современной медицины и должна быть модифицирована. Такая позиция направляет усилия исследователей на поиск дополнительных прогностических факторов, к которым можно отнести биомаркеры крови, отражающие состояние кардиомиоцитов и внеклеточного матрикса сердца, а также позволяющие оценить эндогенные и экзогенные влияния, оказываемые на эти структуры. Такие сведения могут оказаться важными для определения вероятности наличия в миокарде проаритмогенного субстрата и электрофизиологических условий, необходимых для реализации его потенциала. Представленные в данном обзоре данные позволяют сделать вывод о том, что концентрации биомаркеров крови могут предоставить дополнительную информацию для оценки персонализированного аритмического риска, что должно помочь избежать клинической недооценки риска внезапной сердечной смерти и стать определяющим в принятии решения об имплантации кардиовертера-дефибриллятора.

1. Kaptoge S, Pennells L, De Bacquer D, et al. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. Lancet Glob Heal. 2019;7: e1332-45. https://doi.org/10.1016/S2214-109X(19)30318-3.

2. Packer M. What causes sudden death in patients with chronic heart failure and a reduced ejection fraction? Eur Heart J. 2020;41: 1757-63. https://doi.org/10.1093/eurheartj/ehz553.

3. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al. Reduced Ejection Fraction, Sudden Cardiac Death, and Heart Failure Death in the Mode Selection Trial (MOST): Implications for Device Selection in Elderly Patients with Sinus Node Disease. Journal of Cardiovascular Electrophysiology. 2008;19(11): 1160-1166. https://doi.org/10.1111/j.1540-8167.2008.01209.x.

4. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction. N Engl J Med. 2002;346: 877-83. https://doi.org/10.1056/NEJMoa013474.

5. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure. N Engl J Med. 2005;352: 225-37. https://doi.org/10.1056/NEJMoa043399.

6. Хроническая сердечная недостаточность. Клинические рекомендации 2020. Российский кардиологический журнал. 2020;25(11): 4083. https://doi.org/10.15829/1560-4071-2020-4083.

7. McDonagh TA, Metra M, Adamo M, et al. 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. European Heart Journal. 2021;42: 3599-3726. https://doi.org/10.1093/eurheartj/ehab368.

8. Илов НН, Пальникова ОВ, Стомпель ДР, и др. Стратификация риска внезапной сердечной смерти у пациентов с сердечной недостаточностью: достаточно ли одной фракции выброса левого желудочка? Российский кардиологический журнал. 2021;26(1): 3959. https://doi.org/10.15829/1560-4071-2021-3959.

9. Merchant FM, Jones P, Wehrenberg S, Lloyd MS, Saxon LA. Incidence of Defibrillator Shocks After Elective Generator Exchange Following Uneventful First Battery Life. J Am Heart Assoc. 2014;3. https://doi.org/10.1161/JAHA.114.001289.

10. Amara N, Boveda S, Defaye P, et al. Implantable cardioverter-defibrillator therapy among patients with non-ischaemic vs. ischaemic cardiomyopathy for primary prevention of sudden cardiac death. EP Eur. 2017;20: 65- 72. https://doi.org/10.1093/europace/euw379.

11. Paar V, Jirak P, Larbig R, et al. Pathophysiology of Calcium Mediated Ventricular Arrhythmias and Novel Therapeutic Options with Focus on Gene Therapy. Int J Mol Sci. 2019;20: 5304. https://doi.org/10.3390/ijms20215304.

12. Priori SG, Blomstrom-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the Europea. Eur Heart J. 2015;36: 2793-2867l. https://doi.org/10.1093/eurheartj/ehv316.

13. Frangogiannis NG. The extracellular matrix in ischemic and nonischemic heart failure. Circ Res. 2019;125: 117-46. https://doi.org/10.1161/CIRCRESAHA.119.311148.

14. Shomanova Z, Ohnewein B, Schernthaner C, et al. Classic and Novel Biomarkers as Potential Predictors of Ventricular Arrhythmias and Sudden Cardiac Death. J Clin Med. 2020;9: 578. https://doi.org/10.3390/jcm9020578.

15. Tsu-Juey W, J.C OJ, Chun H, et al. Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry. J Am Coll Cardiol. 1998;32:1 87- 96. https://doi.org/10.1016/S0735-1097(98)00184-3.

16. Атабеков ТА, Баталов РЕ, Сазонова СИ, и др. Роль стимулирующего фактора роста, экспрессируемого геном 2, и галектина-3 в прогнозировании развития желудочковых тахиаритмий у пациентов с ишемической кардиомиопатией. Кардиоваскулярная терапия и профилактика. 2021;20(3): 2676. https://doi.org/10.15829/1728-8800-2021-2676.

17. FDA-NIH Biomarker Working Group et al. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. - 2016. PMID 27010052

18. Morrow DA, de Lemos JA. Benchmarks for the Assessment of Novel Cardiovascular Biomarkers. Circulation. 2007;115: 949-52. https://doi.org/10.1161/CIRCULATIONAHA.106.683110.

19. Califf RM. Biomarker definitions and their applications. Exp Biol Med. 2018;243: 213-21. https://doi.org/10.1177/1535370217750088.

20. Braunwald E. Biomarkers in Heart Failure. N Engl J Med. 2008;358: 2148-59. https://doi.org/10.1056/NEJMra0800239.

21. Gopal DM, Sam F. New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction—Insight into Dilated Cardiomyopathy. J Cardiovasc Transl Res. 2013;6: 516-27. https://doi.org/10.1007/s12265-013-9462-3.

22. Maisel AS, Duran JM, Wettersten N. Natriuretic Peptides in Heart Failure. Heart Fail Clin. 2018;14: 13-25. https://doi.org/10.1016/j.hfc.2017.08.002.

23. Burger AJ. A Review of the Renal and Neurohormonal Effects of B-Type Natriuretic Peptide. Congest Hear Fail. 2005;11: 30-8. https://doi.org/10.1111/j.1527-5299.2005.03794.x.

24. Tada H, Ito S, Shinbo G, et al. Significance and Utility of Plasma Brain Natriuretic Peptide Concentrations in Patients with Idiopathic Ventricular Arrhythmias. Pacing Clin Electrophysiol. 2006;29: 1395-403. https://doi.org/10.1111/j.1540-8159.2006.00553.x.

25. Tapanainen JM, Lindgren KS, Mäkikallio TH, et al. J Am Coll Cardiol. 2004;43(5): 757-763. https://doi.org/10.1016/j.jacc.2003.09.048.

26. Vrtovec B, Knezevic I, Poglajen G, et al. Relation of B-Type Natriuretic Peptide Level in Heart Failure to Sudden Cardiac Death in Patients With and Without QT Interval Prolongation. Am J Cardiol. 2013;111: 886-90. https://doi.org/10.1016/j.amjcard.2012.11.041.

27. Christ M, Sharkova J, Bayrakcioglu S, et al. B-type natriuretic peptide levels predict event-free survival in patients with implantable cardioverter defibrillators. Eur J Heart Fail. 2007;9: 272-9. https://doi.org/10.1016/j.ejheart.2006.07.004.

28. Scott PA, Townsend PA, Ng LL, et al. Defining potential to benefit from implantable cardioverter defibrillator therapy: The role of biomarkers. Europace. 2011;13: 1419- 27. https://doi.org/10.1093/europace/eur147.

29. Shah NN, Ayyadurai P, Saad M, et al. Galectin-3 and soluble ST2 as complementary tools to cardiac MRI for sudden cardiac death risk stratification in heart failure: A review. JRSM Cardiovasc Dis. 2020;9: 204800402095784. https://doi.org/10.1177/2048004020957840.

30. Skali H, Gerwien R, Meyer TE, et al. Soluble ST2 and Risk of Arrhythmias, Heart Failure, or Death in Patients with Mildly Symptomatic Heart Failure: Results from MADIT-CRT. J Cardiovasc Transl Res. 2016;9: 421-8. https://doi.org/10.1007/s12265-016-9713-1.

31. Ahmad T, Fiuzat M, Neely B, et al. Biomarkers of Myocardial Stress and Fibrosis as Predictors of Mode of Death in Patients With Chronic Heart Failure. JACC Hear Fail. 2014;2: 260-8. https://doi.org/10.1016/j.jchf.2013.12.004.

32. Pascual-Figal DA, Ordoñez-Llanos J, Tornel PL, et al. Soluble ST2 for Predicting Sudden Cardiac Death in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction. J Am Coll Cardiol. 2009;54: 2174-9. https://doi.org/10.1016/j.jacc.2009.07.041.

33. Daidoji H, Arimoto T, Nitobe J, et al. Circulating Heart-Type Fatty Acid Binding Protein Levels Predict the Occurrence of Appropriate Shocks and Cardiac Death in Patients With Implantable Cardioverter-Defibrillators. J Card Fail. 2012;18: 556-63. https://doi.org/10.1016/j.cardfail.2012.04.006.

34. May BMM, Kochi ANN, Magalhães APAPA, et al. Growth/differentiation factor-15 (GDF-15) as a predictor of serious arrhythmic events in patients with nonischemic dilated cardiomyopathy. J Electrocardiol. 2022;70: 19-23. https://doi.org/10.1016/j.jelectrocard.2021.10.002.

35. Kwon JS, Kim YS, Cho AS, et al. Regulation of MMP/TIMP by HUVEC transplantation attenuates ventricular remodeling in response to myocardial infarction. Life Sci. 2014;101: 15-26. https://doi.org/10.1016/j.lfs.2014.02.009.

36. Stanciu AE. Cytokines in heart failure. Adv Clin Chem. 2019;93: 63-113. https://doi.org/10.1016/bs.acc.2019.07.002.

37. Kanoupakis EM, Manios EG, Kallergis EM, et al. Serum Markers of Collagen Turnover Predict Future Shocks in Implantable Cardioverter-Defibrillator Recipients With Dilated Cardiomyopathy on Optimal Treatment. J Am Coll Cardiol. 2010;55: 2753-9. https://doi.org/10.1016/j.jacc.2010.02.040.

38. Шаленкова МА, Требунский КС, Колосова КС. Новый биомаркер галектин-3: возможности применения для диагностики и прогноза течения сердечно-сосудистых заболеваний и болезней почек. Лечение и профилактика. 2019;9 (3): 47-52.

39. de Boer RA, Yu L, van Veldhuisen DJ. Galectin-3 in Cardiac Remodeling and Heart Failure. Curr Heart Fail Repю 2010;7: 1-8. https://doi.org/10.1007/s11897-010-0004-x.

40. Vergaro G, Del Franco A, Giannoni A, et al. Galectin-3 and myocardial fibrosis in nonischemic dilated cardiomyopathy. Int J Cardiol. 2015;184: 96-100. https://doi.org/10.1016/j.ijcard.2015.02.008.

41. Barman HA, Durmaz E, Atici A, et al. The relationship between galectin‐3 levels and fragmented QRS (fQRS) in patients with heart failure with reduced left ventricular ejection fraction. Ann Noninvasive Electrocardiol. 2019;24. https://doi.org/10.1111/anec.12671.

42. Oz F, Onur I, Elitok A, et al. Galectin-3 correlates with arrhythmogenic right ventricular cardiomyopathy and predicts the risk of ventricular arrhythmias in patients with implantable defibrillators. Acta Cardiol. 2017;72: 453-9. https://doi.org/10.1080/00015385.2017.1335371.

43. Erdogan O, Karaayvaz E, Erdogan T, et al. A new biomarker that predicts ventricular arrhythmia in patients with ischemic dilated cardiomyopathy: Galectin-3. Rev Port Cardiol. 2021. https://doi.org/10.1016/J.REPC.2020.12.013.

44. Akbulut T, Saylik F, Sipal A. The association of galectin-3 level with ventricular arrhythmias and left ventricular strain in heart failure patients with implantable cardioverter defibrillator. Acta Cardiol. 2021: 1-7. https://doi.org/10.1080/00015385.2021.1968155.

45. Kochi AN, Pimentel M, Andrades M, et al. Predictors of total mortality and serious arrhythmic events in non-ischemic heart failure patients: The role of galectin-3. Arq Bras Cardiol. 2021;117: 531-41. https://doi.org/10.36660/abc.20200353.

46. Zhang Y, Zhang R, An T, et al. The Utility of Galectin-3 for Predicting Cause-Specific Death in Hospitalized Patients With Heart Failure. J Card Fail. 2015;21: 51-9. https://doi.org/10.1016/j.cardfail.2014.10.006.

47. Гаспарян АЖ, Шлевков НБ, Скворцов АА. Возможности современных биомаркеров для оценки риска развития желудочковых тахиаритмий и внезапной сердечной смерти у больных хронической сердечной недостаточностью. Кардиология. 2020;60(4): 101-108. https://doi.org/10.18087/cardio.2020.4.n478.

48. Biasucci LM, Bellocci F, Landolina M, et al. Risk stratification of ischaemic patients with implantable cardioverter defibrillators by C-reactive protein and a multi-markers strategy: results of the CAMI-GUIDE study. Eur Heart J. 2012;33: 1344-50. https://doi.org/10.1093/eurheartj/ehr487.

49. Cheng A, Zhang Y, Blasco-Colmenares E, et al. Protein Biomarkers Identify Patients Unlikely to Benefit From Primary Prevention Implantable Cardioverter Defibrillators. Circ Arrhythmia Electrophysiol. 2014;7: 1084-91. https://doi.org/10.1161/CIRCEP.113.001705.

50. Beresewicz A. Alterations in electrical and contractile behavior of isolated cardiomyocytes by hydrogen peroxide: Possible ionic mechanisms. J Mol Cell Cardiol. 1991;23: 899-918. https://doi.org/10.1016/0022-2828(91)90133-7.

51. Sovari AA. Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress. Cardiol Res Pract. 2016;2016: 1-7. https://doi.org/10.1155/2016/9656078.

52. Zhou Y, Zhao S, Chen K, et al. Predictive value of gamma-glutamyltransferase for ventricular arrhythmias and cardiovascular mortality in implantable cardioverter-defibrillator patients. BMC Cardiovasc Disord. 2019;19: 1-7. https://doi.org/10.1186/s12872-019-1114-3.

53. Pabon MA, Manocha K, Cheung JW, et al. Linking Arrhythmias and Adipocytes: Insights, Mechanisms, and Future Directions. Front Physiol. 2018;9: 1-12. https://doi.org/10.3389/fphys.2018.01752.

54. Wu CC, Chang CS, Hsu CC, et al. Elevated plasma adiponectin levels are associated with abnormal corrected QT interval in patients with stable angina. Int Heart J. 2020;61: 29-38. https://doi.org/10.1536/ihj.19-270.

55. Yuhong W, Lilei Y, Huang HB. GW28-e1210 Leptin promotes acute ischemia-induced ventricular arrhythmia by increasing nerve activity of left stellate ganglion. J Am Coll Cardiol. 2017;70: C49-C49. https://doi.org/10.1016/j.jacc.2017.07.167.

56. Kiuchi MG, Nolde JM, Villacorta H, et al. New Approaches in the Management of Sudden Cardiac Death in Patients with Heart Failure-Targeting the Sympathetic Nervous System. Int J Mol Sci. 2019;20. https://doi.org/10.3390/ijms20102430.

57. Shen L, Jhund PS, Petrie MC, et al. Declining risk of sudden death in heart failure. N Engl J Med. 2017;377: 41- 51. https://doi.org/10.1056/NEJMoa1609758.

58. Caron KMI, James LR, Kim H-S, et al. Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene. Proc Natl Acad Sci. 2004;101: 3106-11.

59. Сокольская МА. Антагонисты альдостерона в профилактике внезапной сердечной смерти. Анналы Аритмологии. 2006;4: 49-56.

60. Weidner K, Behnes M, Weiß C, et al. Impact of chronic kidney disease on recurrent ventricular tachyarrhythmias in ICD recipients. Heart Vessels. 2019;34: 1811-22. https://doi.org/10.1007/s00380-019-01415-z.

61. Deo R, Sotoodehnia N, Katz R, et al. Cystatin C and Sudden Cardiac Death Risk in the Elderly. Circ Cardiovasc Qual Outcomes. 2010;3: 159-64. https://doi.org/10.1161/CIRCOUTCOMES.109.875369.

62. Parham WA, Mehdirad AA, Biermann KM, et al. Hyperkalemia revisited. Texas Hear Inst J. 2006;33(1): 40-47.

63. Mozaffarian D, Anker SD, Anand I, et al. Prediction of Mode of Death in Heart Failure. Circulation. 2007;116: 392- 8. https://doi.org/10.1161/CIRCULATIONAHA.106.687103.

64. Shen L, Claggett BL, Jhund PS, et al. Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE. Clin Res Cardiol. 2021;110: 1334-49. https://doi.org/10.1007/s00392-021-01888-x.

65. Vazquez R, Bayes-Genis A, Cygankiewicz I, et al. The MUSIC Risk score: a simple method for predicting mortality in ambulatory patients with chronic heart failure. Eur Heart J. 2009;30: 1088-96. https://doi.org/10.1093/eurheartj/ehp032.

66. Poole-Wilson PA, Uretsky BF, Thygesen K, et al. Mode of death in heart failure: findings from the ATLAS trial. Heart. 2003;89(1): 42-48. https://doi.org/10.1136/heart.89.1.42

67. Disertori M, Rigoni M, Pace N, et al. Myocardial Fibrosis Assessment by LGE Is a Powerful Predictor of Ventricular Tachyarrhythmias in Ischemic and Nonischemic LV Dysfunction: A Meta-Analysis. JACC Cardiovasc Imaging. 2016;9: 1046-55. https://doi.org/10.1016/j.jcmg.2016.01.033.

68. Lepojärvi ES, Piira O-P, Pääkkö E, et al. Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties. Front Physiol. 2015;6. https://doi.org/10.3389/fphys.2015.00200.

69. Verma A, Kilicaslan F, Martin DO, et al. Preimplantation B-type natriuretic peptide concentration is an independent predictor of future appropriate implantable defibrillator therapies. Heart. 2006;92: 190-5. https://doi.org/10.1136/hrt.2004.058198.

70. Manios EG, Kallergis EM, Kanoupakis EM, et al. Amino-terminal pro-brain natriuretic peptide predicts ventricular arrhythmogenesis in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators. Chest. 2005;128: 2604-10. https://doi.org/10.1378/chest.128.4.2604.

71. Klingenberg R, Zugck C, Becker R, et al. Raised B-type natriuretic peptide predicts implantable cardioverter- defibrillator therapy in patients with ischaemic cardiomyopathy. Heart. 2006;92: 1323-4. https://doi.org/10.1136/hrt.2005.076117.

72. Levine YC, Rosenberg MA, Mittleman M, et al. B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias. Heart Rhythm. 2014;11: 1109-16. https://doi.org/10.1016/j.hrthm.2014.04.024.

73. Sardu C, Marfella R, Santamaria M, et al. Stretch, injury and inflammation markers evaluation to predict clinical outcomes after implantable cardioverter defibrillator therapy in heart failure patients with metabolic syndrome. Front Physiol. 2018;9. https://doi.org/10.3389/fphys.2018.00758.