CHOICE OF MANAGEMENT METHOD OF MYOCARDIAL REVASCULARIZATION IN PATIENTS WITH LOW LEFT VENTRICULAR EJECTION FRACTION (<35 %): A RANDOMIZED PROSPECTIVE STUDY

Purpose. Make a comparative assessment of supportive methods of myocardial revascularization in ischemic heart disease patients with low left ventricular ejection fraction (<35 %) conducted under CPB with cardioplegic cardiac arrest and on a beating heart combined with intraoperative use of IABP or levosimendan.

Materials and methods. The study included 90 patients with coronary artery disease and left ventricular ejection fraction <35 %, which was performed CABG under normothermic CPB. Patients were randomized into 4 groups: IABP+CP (CPB with cardioplegia and IABP) (n=30), IABP+CPB (beating heart on a parallel CBP and IABP) (n=14), LS+CP (CBP with cardioplegia and levosimendan) (n=30), LS+CBP (beating heart on a parallel CBP and IABP) (n=16). The primary endpoint wastroponinI.Hemodynamic parameters, the markers of myocardial damage and heart failure, postoperative complications, length of ICU stay, length of hospital stay was evaluated.

Results. In LS+CP and LS+CBP groups was revealed reduction in blood pressure (p=0.002 and p=0.013 respectively) and increase in heart rate (p=0.0008 and p=0.0002 respectively) before CBP in comparison with IABP. The average area under the curve (AUC) of troponin I concentration in LS+CP group was less than in IABP+CP group: 11.75 (6.28–13.29) ng/ml vs 24.43 (12.52–27.88) ng/ml, p=0.013. In LS+CP group was revealed decrease in length of ICU stay (2 (2–3) days) compared with IABP+CP group (4 (3–4) days, p=0.0002) and IABP+CBP group (4 (3–6) days, p=0.0008). Preoperative BNP concentration ≥203 pg/mL was a predictor of necessity for inotropic support with sensitivity 60 % (95 % CI 47.1–72.0) and specificity 93.75 % (95 % CI 69.8–99.8) (AUC 0.728; p=0.0001). Preoperative NTproBNP concentration ≥8.24 fmol/L was a predictor of necessity for inotropic support in the postoperative period with sensitivity 77.78 % (95 % CI 64.4–88.0) and specificity 66.67 % (95 % CI 38.4–88.2) (AUC 0.745; p=0.0012). In singlefactor regression analysis the independent effect on necessity for inotropic support in the early postoperative period exert the concentration of preoperative BNP (OR=1.01; 95 % CI 1.001–1.014; p=0.033). Belonging to LS+CP group reduces the risk of ICU stay for more than 3 days on 72 % (OR=0.28; 95 % CI 0.09–0.82; p=0.021). In multivariate regression analysis, a risk factor for 30-day mortality was the concentration of troponin I on the second postoperative day (OR=1.15; 95 % CI 1.03–1.27; p=0.010) and the preoperative concentration NTproBNP was a risk factor for the 1 year mortality (OR=1.02; 95 % CI 1.001–1.032; p=0.006). 6 hours CPK level after CBP was a predictor of atrial fibrillation development in the early postoperative period (OR=1.003; 95 % CI 1.001–1.005; p=0.003) and prolonged hospital stay for more than 14 days (OR=0.996; 95 % CI: 0.994–0.999; p=0.007)

Conclusion. CABG on a beating heart under CPB in ischemic heart disease patients with low left ventricular ejection fraction (regardless of the hemodynamic support method) does not lead to significant decrease in serum concentration of Troponin I in the postoperative period. Intraoperative levosimendan infusion together with cardioplegic cardiac arrest improves early postoperative period, which is expressed in significant reduction in ICU stay. Thus, the most preferred method to support myocardial revascularization in ischemic heart disease patients with low left ventricular ejection fraction is combination of a standard methodology for CABG with cardioplegic myocardial protection accompanied by intraoperative infusion of levosimendan.

Key words: cardiopulmonary bypass; coronary artery bypass surgery; beating heart; IABP; levosimendan.

1. Hunt S. A., Baker D. W., Chin M. H., Cinquegrani M. P., Feldman A. M., Francis G. S. et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guideli). Circulation. 2001; 104 (24): 2996–3007.

2. Adams K. F., Fonarow G. C., Emerman C. L., LeJemtel T. H., Costanzo M. R., Abraham W. T. et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: Rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am. Heart J. 2005; 149 (2): 209–216.

3. Mickleborough L. L., Carson S., Tamariz M., Ivanov J. Results of revascularization in patients with severe left ventricular dysfunction. J. Thorac. Cardiovasc. Surg. 2000; 119 (3): 550–557.

4. Ammirati E., Rimoldi O. E., Camici P. G. Is there evidence supporting coronary revascularization in patients with left ventricular systolic dysfunction? Circ. J. 2011; 75 (1): 3–10.

5. Caparrelli D. J., Ghazoul M., Diethrich E. B. Indications for coronary artery bypass grafting in 2009: What is left to surgery. J. Cardiovasc. Surg. (Torino). 2009; 50 (1): 19–28.

6. Miyahara K., Matsuura A., Takemura H., Saito S., Sawaki S., Yoshioka T. et al. On-pump beating-heart coronary artery bypass grafting after acute myocardial infarction has lower mortality and morbidity. J. Thorac. Cardiovasc. Surg. 2008; 135 (3): 521–526. DOI:10.1016/j.jtcvs.2007.10.006.

7. Narayan P., Rogers C. A., Bayliss K. M., Rahaman N. C., Panayiotou N., Angelini G. D. et al. On-pump coronary surgery with and without cardioplegic arrest: comparison of inflammation, myocardial, cerebral and renal injury and early and late health outcome in a single-centre randomised controlled trial. Eur. J. Cardiothorac. Surg. 2011; 39 (5): 675–683. DOI: 10.1016/j.ejcts.2010.08.032.

8. Pegg T. J., Selvanayagam J. B., Francis J. M., Karamitsos T. D., Maunsell Z., Yu L.-M. et al. A randomized trial of on-pump beating heart and conventional cardioplegic arrest in coronary artery bypass surgery patients with impaired left ventricular function using cardiac magnetic resonance imaging and biochemical markers. Circulation. 2008; 118 (21): 2130– 2138. DOI: 10.1161/CIRCULATIONAHA.108.785105.

9. Christenson J. T., Schmuziger M., Simonet F. Effective surgical management of high-risk coronary patients using preoperative intra-aortic balloon counterpulsation therapy. Cardiovasc. Surg. 2001; 9 (4): 383–390.

10. Kantrowitz A., Tjonneland S., Freed P. S., Phillips S. J., Butner A. N., Sherman J. L. Intraaortic balloon pumping. JAMA. 1968; 203 (11): 988.

11. Moulopoulos S. D., Topaz S., Kolff W. J. Diastolic balloon pumping (with carbon dioxide) in the aorta-a mechanical assistance to the failing circulation. Am. Heart J. 1962; 63: 669–675.

12. Janssen P. M., Datz N., Zeitz O., Hasenfuss G. Levosimendan improves diastolic and systolic function in failing human myocardium. Eur. J. Pharmacol. 2000; 404 (1–2): 191– 199.

13. Labriola C., Siro-Brigiani M., Carrata F., Santangelo E., Amantea B. Hemodynamic effects of levosimendan in patients with low-output heart failure after cardiac surgery. Int. J. Clin. Pharmacol. Ther. 2004; 42 (4): 204–211.

14. Nieminen M. S., Akkila J., Hasenfuss G., Kleber F. X., Lehtonen L. A., Mitrovic V. et al. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J. Am. Coll. Cardiol. 2000; 36 (6): 1903–1912.

15. Ломиворотов В. В., Бобошко В. А., Чернявский А. М., Корнилов И. А., Князькова Л. Г. Сравнительная оценка профилактического использования внутриаортальной баллонной контрпульсации и левосимендана у пациентов ИБС с низкой фракцией выброса левого желудочка. Общая реаниматология. 2012; VIII (2): 41–47. Lomivorotov V. V., Boboshko V. A., Chernyavskiy A. M., Kornilov I. A., Knyaz′kova L. G. Sravnitel′naya otsenka profilakticheskogo ispol′zovaniya vnutriaortal′noy ballonnoy kontrpul′satsii i levosimendana u patsientov IBS s nizkoy fraktsiey vybrosa levogo zheludochka. Obshchaya reanimatologiya. 2012; VIII (2): 41–47.

16. Jatene A. D. Left ventricular aneurysmectomy. Resection or reconstruction. J. Thorac. Cardiovasc. Surg. 1985; 89 (3): 321–331.

17. Patel N. D., Barreiro C. J., Williams J. A., Bonde P. N., Waldron M., Natori S. et al. Surgical ventricular remodeling for patients with clinically advanced congestive heart failure and severe left ventricular dysfunction. J. Heart. Lung. Transplant. 2005; 24 (12): 2202–2210.

18. Youn Y.-N., Chang B.-C., Hong Y.-S., Kwak Y.-L., Yoo K.-J. Early and mid-term impacts of cardiopulmonary bypass on coronary artery bypass grafting in patients with poor left ventricular dysfunction: a propensity score analysis. Circ. J. 2007; 71 (9): 1387–1394.

19. Darwazah A. K., Bader V., Isleem I., Helwa K. Myocardial revascularization using on-pump beating heart among patients with left ventricular dysfunction. J. Cardiothorac. Surg. 2010; 5: 109.

20. Izumi Y., Magishi K., Ishikawa N., Kimura F. On-pump beating-heart coronary artery bypass grafting for acute myocardial infarction. Ann. Thorac. Surg. 2006; 81 (2): 573–576.

21. Erkut B., Dag O., Kaygin M. A., Senocak M., Limandal H. K., Arslan U. et al. On-pump beating-heart versus conventional coronary artery bypass grafting for revascularization in patients with severe left ventricular dysfunction: early outcomes. Can. J. Surg. 2013; 56 (6): 398–404.

22. Ferrari E., Stalder N., Von Segesser L. K. On-pump beating heart coronary surgery for high risk patients requiring emergency multiple coronary artery bypass grafting. J. Cardiothorac. Surg. 2008; 3 (3). DOI: 10.1186/1749-8090-3-38.

23. Lomivorotov V. V., Boboshko V. A., Efremov S. M., Kornilov I. A., Chernyavskiy A. M., Lomivorotov V. N. et al. Levosimendan versus an intra-aortic balloon pump in highrisk cardiac patients. J. Cardiothorac. Vasc. Anesth. 2012; 26 (4): 596–603.

24. Чернявский А. М., Несмачный А. С., Бобошко А. В., Николаев Д. А., Бобошко В. А., Эфендиев В. У. и др. Хирургическое лечение ишемической болезни сердца у пациентов с низкой фракцией выброса левого желудочка на работающем сердце в условиях искусственного кровообращения: непосредственные результаты. Патология кровообращения и кардиохирургия. 2015; 19 (1): 35–42. Chernyavskiy A. M., Nesmachnyy A. S., Boboshko A. V., Nikolaev D. A., Boboshko V. A., Efendiev V. U. i dr. Khirurgicheskoe lechenie ishemicheskoy bolezni serdtsa u patsientov s nizkoy fraktsiey vybrosa levogo zheludochka na rabotayushchem serdtse v usloviyakh iskusstvennogo krovoobrashcheniya: neposredstvennye rezul′taty. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2015; 19 (1): 35–42.

25. Carmona P., Paredes F., Mateo E., Mena-Durán A. V., Hornero F., Martínez-León J. Is off-pump technique a safer procedure for coronary revascularization? A propensity score analysis of 20 years of experience. Interact. Cardiovasc. Thorac. Surg. 2016; 16.

26. Puskas J. D., Williams W. H., Duke P. G., Staples J. R., Glas K. E., Marshall J. J. et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus co. J. Thorac. Cardiovasc. Surg. 2003; 125 (4): 797–808.

27. Brown J. M., Poston R. S., Gammie J. S., Cardarelli M. G., Schwartz K., Sikora J. A. H. et al. Off-pump versus on-pump coronary artery bypass grafting in consecutive patients: decision-making algorithm and outcomes. Ann. Thorac. Surg. 2006; 81 (2): 555–561.

28. Magee M. J., Hebert E., Herbert M. A., Prince S. L., Dewey T. M., Culica D. V. et al. Fewer grafts performed in off-pump bypass surgery: patient selection or incomplete revascularization? Ann. Thorac. Surg. 2009; 87 (4): 1113–1118.

29. Di Mauro M., Iacò A. L., Contini M., Teodori G., Vitolla G., Pano M. et al. Reoperative coronary artery bypass grafting: analysis of early and late outcomes. Ann. Thorac. Surg. 2005; 79 (1): 81–87.

30. Adams J. E., Bodor G. S., Dávila-Román V. G., Delmez J. A., Apple F. S., Ladenson J. H. et al. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 1993; 88 (1): 101–106.

31. Cuthbertson B. H., McKeown A., Croal B. L., Mutch W. J., Hillis G. S. Utility of B-type natriuretic peptide in predicting the level of periand postoperative cardiovascular support required after coronary artery bypass grafting. Crit. Care. Med. 2005; 33 (2): 437–442.

32. Hutfless R., Kazanegra R., Madani M., Bhalla M. A., Tulua-Tata A., Chen A. et al. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery. J. Am. Col. Cardiol. 2004; 43 (10): 1873–1879.

33. Еременко А. А., Колпаков П. Е., Бабаев М. А., Ревуненков Г. В., Фоминых М. В. Применение левосимендана у кардиохирургических больных с хронической сердечной недостаточностью. Анестезиология и реаниматология. 2010; 2: 24–26. Eremenko A. A., Kolpakov P. E., Babaev M. A., Revunenkov G. V., Fominykh M. V. Primenenie levosimendana u kardiokhirurgicheskikh bol′nykh s khronicheskoy serdechnoy nedostatochnost′yu. Anesteziologiya i reanimatologiya. 2010; 2: 24–26.

34. Ломиворотов В. В., Бобошко В. А., Бобошко А. В., Чернявский А. М., Николаев Д. А., Корнилов И. А. и др. Использование интраоперационной внутриаортальной баллонной контрпульсации и левосимендана в кардиохирургии. Кардиология и сердечно-сосудистая хирургия. 2013; 6 (2): 75–81. Lomivorotov V. V., Boboshko V. A., Boboshko A. V., Chernyavskiy A. M., Nikolaev D. A., Kornilov I. A. i dr. Ispol′zovanie intraoperatsionnoy vnutriaortal′noy ballonnoy kontrpul′satsii i levosimendana v kardiokhirurgii. Kardiologiya i serdechno-sosudistaya khirurgiya. 2013; 6 (2): 75–81.

35. Ломиворотов В. В., Бобошко А. В., Бобошко В. А., Чернявский А. М., Николаев Д. А., Корнилов И. А. и др. Интраоперационное применение левосимендана и внутриаортальной баллонной контрпульсации в кардиохирургии у пациентов высокого риска. Сибирский научный медицинский журнал. 2015; 35 (3): 65–73. Lomivorotov V. V., Boboshko A. V., Boboshko V. A., Chernyavskiy A. M., Nikolaev D. A., Kornilov I. A. i dr. Intraoperatsionnoe primenenie levosimendana i vnutriaortal′noy ballonnoy kontrpul′satsii v kardiokhirurgii u patsientov vysokogo riska. Sibirskiy nauchnyy meditsinskiy zhurnal. 2015; 35 (3): 65–73.