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中华胸部外科电子杂志 ›› 2022, Vol. 09 ›› Issue (01) : 1 -11. doi: 10.3877/cma.j.issn.2095-8773.2022.01.01

国际胸外科专栏

Exploring the role of prophylactic levosimendan in coronary surgery
Giuseppe Gatti1,†(), Marina Bollini1, Aldostefano Porcari1, Federico Biondi1, Alessandro Ceschia1, Davide Stolfo1, Francesco Bianco2, Lorella Dreas1   
  1. 1. Cardio-Thoracic and Vascular Department, Trieste University Hospital, Trieste, Italy
    2. Department of Nephrology, Trieste University Hospital, Trieste, Italy
  • 收稿日期:2021-11-30 接受日期:2022-02-09 出版日期:2022-02-28
  • 通信作者: Giuseppe Gatti

Exploring the role of prophylactic levosimendan in coronary surgery

Giuseppe Gatti1(), Marina Bollini1, Aldostefano Porcari1, Federico Biondi1, Alessandro Ceschia1, Davide Stolfo1, Francesco Bianco2, Lorella Dreas1   

  1. 1. Cardio-Thoracic and Vascular Department, Trieste University Hospital, Trieste, Italy
    2. Department of Nephrology, Trieste University Hospital, Trieste, Italy
  • Received:2021-11-30 Accepted:2022-02-09 Published:2022-02-28
  • Corresponding author: Giuseppe Gatti
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Giuseppe Gatti, Marina Bollini, Aldostefano Porcari, Federico Biondi, Alessandro Ceschia, Davide Stolfo, Francesco Bianco, Lorella Dreas. Exploring the role of prophylactic levosimendan in coronary surgery[J]. 中华胸部外科电子杂志, 2022, 09(01): 1-11.

Giuseppe Gatti, Marina Bollini, Aldostefano Porcari, Federico Biondi, Alessandro Ceschia, Davide Stolfo, Francesco Bianco, Lorella Dreas. Exploring the role of prophylactic levosimendan in coronary surgery[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2022, 09(01): 1-11.

Background:

The role of prophylactic levosimendan in coronary surgery has not been established conclusively.

Methods:

Postoperative outcomes of 139 patients (mean age, 68.2±9.6 years) having preoperative left ventricular ejection fraction (LVEF) ≤40% and undergoing isolated coronary surgery (2013-2017) were reviewed retrospectively. In 42 (30.2%) patients (L-group), an intravenous infusion of levosimendan was started 24 hours before operation. The remaining 97 (69.8%) patients were the control group (C-group). A comparison between the two groups regarding outcome of surgery was performed also after propensity matching.

Results:

Although the risk profile in L-patients was higher than in C-patients (median European System for Cardiac Operative Risk Evaluation II, 10.5% vs. 6.5%, P=0.013) due to higher prevalence of New York Heart Association class III-IV, LVEF ≤30%, and preoperative intra-aortic balloon pump, in-hospital mortality was equivalent (4.8% vs. 3.1%, P=0.48). However, low cardiac output, multiple blood transfusion, and any major complication early after surgery were more frequent in L-patients. After one-to-one propensity matching, which resulted in 15 pairs with similar baseline characteristics the use of levosimendan was associated with a trend towards an increased blood use (P=0.077), a higher frequency of any major complication (P=0.053), and lower peak serum levels of cardiac troponin I (P=0.088). No intergroup differences concerning mid-term survival or outcomes were found even for matched patients.

Conclusions:

When compared with traditional inotropes alone, prophylactic use of levosimendan showed clear benefits/drawbacks neither concerning immediate nor mid-term outcomes after coronary surgery. There could be any advantage in terms of myocardial preservation.

关键词: Coronary artery bypass grafting (CABG), left ventricular dysfunction, levosimendan, morbidity/mortality, prophylaxis
Background:

The role of prophylactic levosimendan in coronary surgery has not been established conclusively.

Methods:

Postoperative outcomes of 139 patients (mean age, 68.2±9.6 years) having preoperative left ventricular ejection fraction (LVEF) ≤40% and undergoing isolated coronary surgery (2013-2017) were reviewed retrospectively. In 42 (30.2%) patients (L-group), an intravenous infusion of levosimendan was started 24 hours before operation. The remaining 97 (69.8%) patients were the control group (C-group). A comparison between the two groups regarding outcome of surgery was performed also after propensity matching.

Results:

Although the risk profile in L-patients was higher than in C-patients (median European System for Cardiac Operative Risk Evaluation II, 10.5% vs. 6.5%, P=0.013) due to higher prevalence of New York Heart Association class III-IV, LVEF ≤30%, and preoperative intra-aortic balloon pump, in-hospital mortality was equivalent (4.8% vs. 3.1%, P=0.48). However, low cardiac output, multiple blood transfusion, and any major complication early after surgery were more frequent in L-patients. After one-to-one propensity matching, which resulted in 15 pairs with similar baseline characteristics the use of levosimendan was associated with a trend towards an increased blood use (P=0.077), a higher frequency of any major complication (P=0.053), and lower peak serum levels of cardiac troponin I (P=0.088). No intergroup differences concerning mid-term survival or outcomes were found even for matched patients.

Conclusions:

When compared with traditional inotropes alone, prophylactic use of levosimendan showed clear benefits/drawbacks neither concerning immediate nor mid-term outcomes after coronary surgery. There could be any advantage in terms of myocardial preservation.

Key words: Coronary artery bypass grafting (CABG), left ventricular dysfunction, levosimendan, morbidity/mortality, prophylaxis
Table 1 Baseline characteristics of patients and risk profiles
Characteristic Overall series Matched pairs
L-group (n=42) C-group (n=97) P L-group (n=15) C-group (n=15) P
Age     0.95     0.89
  <60 years 10 (23.8) 22 (22.7)   4 (26.7) 3 (20.0)  
  60-70 years 12 (28.6) 26 (26.8)   6 (40.0) 6 (40.0)  
  ≥70 years 20 (47.6) 49 (50.5)   5 (33.3) 6 (40.0)  
Female 1 (2.4) 10 (10.3) 0.21 1 (6.7) 1 (6.7) 1
Hypertension treated with drugs 33 (78.6) 83 (85.6) 0.44 12 (80.0) 13 (86.7) 1
Body mass index >30 kg/m2 8 (19.0) 21 (21.6) 0.91 2 (13.3) 2 (13.3) 1
Diabetes     0.26     0.8
  No history 16 (38.1) 51 (52.6)   6 (40.0) 5 (33.3)  
  Insulin-dependent diabetes 4 (9.5) 9 (9.3)   1 (6.7) 2 (13.3)  
  Non-insulin-dependent diabetes 22 (52.4) 37 (38.1)   8 (53.3) 8 (53.3)  
Poor mobility 0 2 (2.1) 0.89 0 0 -
Chronic lung disease 7 (16.7) 10 (10.3) 0.44 3 (20.0) 2 (13.3) 1
eGFR*     0.39     0.86
  >85 mL/min 13 (31.0) 40 (41.2)   5 (33.3) 4 (26.7)  
  50-85 mL/min 17 (40.5) 38 (39.2)   8 (53.3) 8 (53.3)  
  ≤50 mL/min 12 (28.6) 19 (19.6)   2 (13.3) 3 (20.0)  
Extracardiac arteriopathy 16 (38.1) 37 (38.1) 0.85 7 (46.7) 7 (46.7) 1
NYHA class     0.0018     0.79
  I 10 (23.8) 54 (55.7)   4 (26.7) 6 (40.0)  
  II 3 (7.1) 9 (9.3)   1 (6.7) 1 (6.7)  
  III 12 (28.6) 18 (18.6)   4 (26.7) 2 (13.3)  
  IV 17 (40.5) 16 (16.5)   6 (40.0) 6 (40.0)  
CCS class 4 25 (59.5) 61 (62.9) 0.85 8 (53.3) 8 (53.3) 1
Recent myocardial infarction     0.93     0.87
  No history 26 (61.9) 58 (59.8)   10 (66.7) 8 (53.3)  
  Within 7-90 days 10 (23.8) 21 (21.6)   3 (20.0) 5 (33.3)  
  Within 1-7 days 4 (9.5) 13 (13.4)   1 (6.7) 1 (6.7)  
  Within 24 h 2 (4.8) 5 (5.2)   1 (6.7) 1 (6.7)  
Coronary artery disease     0.65     1
  Two-vessel 9 (21.4) 16 (16.5)   2 (13.3) 2 (13.3)  
  Three-vessel 33 (78.6) 81 (83.5)   13 (86.7) 13 (86.7)  
Left main coronary artery disease 21 (50.0) 40 (41.2) 0.44 6 (40.0) 5 (33.3) 1
LVEF     <0.0001     1
  31-40% 14 (33.3) 86 (88.7)   9 (60.0) 10 (66.7)  
  21-30% 25 (59.5) 10 (10.3)   6 (40.0) 5 (33.3)  
  <21% 3 (7.1) 1 (1.0)   0 0  
Cardiac reoperation 0 1 (1.0) 0.67 0 0 -
Critical preoperative state 23 (54.8) 36 (37.1) 0.081 6 (40.0) 5 (33.3) 1
  VT, VF or aborted sudden death 4 (9.5) 5 (5.2) 0.56 1 (6.7) 1 (6.7) 1
  Use of adrenergic agents 1 (2.4) 14 (14.4) 0.071 1 (6.7) 2 (13.3) 1
  Use of IABP 22 (52.4) 22 (22.7) 0.0011 3 (20.0) 4 (26.7) 1
  Acute renal failure (diuresis <10 mL/h) 1 (2.4) 2 (2.1) 0.61 0 0 -
Surgical priority     0.35     1
  Elective 9 (21.4) 12 (12.4)   2 (13.3) 2 (13.3)  
  Urgent 31 (73.8) 73 (75.3)   12 (80.0) 12 (80.0)  
  Emergency 1 (2.4) 7 (7.2)   0 0  
  Salvage 1 (2.4) 5 (5.2)   1 (6.7) 1 (6.7)  
Expected operative risk (by EuroSCORE II)[12], % 10.5 (6.4-25.8) 6.5 (2.6-13) 0.013 8.6 (4.8-12) 6.2 (4.9-9) 0.8
Table 2 Operative data
Data Overall series Matched pairs
L-group (n=42) C-group (n=97) P L-group (n=15) C-group (n=15) P
No. of coronary anastomoses 3.9±1 3.7±1.1 0.27 3.9±0.8 4.1±1 0.61
Grafts     0.31     1
  Bilateral ITA 40 (95.2) 84 (86.6)   15 (100.0) 14 (93.3)  
  Single ITA 2 (4.8) 12 (12.4)   0 1 (6.7)  
  SVGs alone 0 1 (1)   0 0  
  SVG use 39 (92.9) 84 (86.6) 0.39 15 (100.0) 14 (93.3) 1
Surgical technique     0.35     0.34
  Off-pump 2 (4.8) 10 (10.3)   0 1 (6.7)  
  On-pump 40 (95.2) 85 (87.6)   15 (100.0) 13 (86.7)  
  On-pump beating heart 0 2 (2.1)   0 1 (6.7)  
Cross-clamp time, min 86.7±22.5 86.4±38.9 0.96 85.7±16.5 90.1±23.6 0.73
Cardiopulmonary bypass            
  Time, min 111.5±28.8 110.1±42.4 0.85 111.4±27 113.6±32.4 0.98
  Rapid starting 4 (9.5) 8 (8.2) 1 3 (20.0) 0 0.22
  Prolonged (>30 min) weaning 3 (7.1) 14 (14.4) 0.23 2 (13.3) 3 (20.0) 1
Length of the operation, min 292.2±45.2 273.9±54.9 0.058 295.2±46.2 279.5±51.2 0.37
Table 3 In-hospital outcomes
Complication Overall series Matched series
L-group C-group P L-group C-group P
n=42 n=97 n=15 n=15
In-hospital death 2 (4.8) 3 (3.1) 0.48 1 (6.7) 0 1
  30-day death 2 (4.8) 1 (1.0) 0.22 1 (6.7) 0 1
Neurological dysfunction 6 (14.3) 6 (6.2) 0.18 2 (13.3) 2 (13.3) 1
  Transitory 4 (9.5) 8 (8.2) 0.93 1 (6.7) 1 (6.7) 1
  Permanent 3 (7.1) 2 (2.1) 0.33 1 (6.7) 1 (6.7) 1
Prolonged (>48 h) invasive ventilation 11 (26.2) 18 (18.6) 0.31 3 (20.0) 1 (6.7) 0.6
Atrial fibrillation, new-onset 15/40‡ (37.5) 35/92‡ (38.0) 0.89 6/15‡ (40.0) 8/15‡ (53.3) 0.46
VT, VF or aborted sudden death 3 (7.1) 1 (1.0) 0.082 1 (6.7) 0 1
Myocardial infarction 2 (4.8) 3 (3.1) 0.48 0 1 (6.7) 1
Low cardiac output 19 (45.2) 15 (15.5) <0.0002 5 (33.3) 1 (6.7) 0.17
Prolonged (>12 h) use of adrenergic agent 36 (85.7) 86 (88.7) 0.62 15 (100.0) 14 (93.3) 1
Use of norepinephrine 39 (92.9) 79 (81.4) 0.084 15 (100.0) 11 (73.3) 0.11
Intraoperative use of IABP 4 (9.5) 3 (3.1) 0.24 2 (13.3) 0 0.48
Use of VA-ECMO 1 (2.4) 2 (2.1) 1 1 (6.7) 0 1
Acute kidney injury 6 (14.3) 6 (6.2) 0.18 2 (13.3) 1 (6.7) 1
Renal replacement therapy 5 (11.9) 4 (4.1) 0.13 1 (6.7) 0 1
Mesenteric ischemia 1 (2.4) 0 0.3 1 (6.7) 0 1
Multiorgan failure 2 (4.8) 4 (4.1) 1 2 (13.3) 0 0.48
48-h chest tube output/BSA, mL/m2 537 (287-863) 451 (256-827) 0.4 383 (286-620) 561 (304-1002) 0.25
No. of transfused patients 21 (50.0) 31 (32.0) 0.068 8 (53.3) 4 (26.7) 0.26
No. of transfused RBC units per patient 0.5 (0-3) 0 (0-1) 0.064 1 (0-2.5) 0 (0-0.5) 0.077
Multiple transfusion (>2 RBC units) 11 (26.2) 12 (12.4) 0.044 4 (26.7) 0 0.11
Mediastinal re-exploration 6 (14.3) 6 (6.2) 0.18 2 (13.3) 0 0.48
Deep sternal wound infection¡ì 4 (9.5) 6 (6.2) 0.72 1 (6.7) 1 (6.7) 1
Any major complication# 27 (64.3) 35 (36.1) 0.0039 8 (53.3) 2 (13.3) 0.053
In-hospital stay, days 14 (11-25) 13 (9-18) 0.051 15 (11-27.5) 13 (9-15.5) 0.19
Intensive care unit stay, days 4 (3-7) 3 (2-5) 0.042 4 (3-6.5) 3 (2-4) 0.34
Figure 1 Non-parametric curves of (A,B) freedom from all-cause death, (C,D) cardiac or CV deaths, and (E,F) MACCEs during the follow-up period according to the levosimendan use. The overall (A, C and E) and matched series (B, D and F). Comparison between curves was made by the log-rank test and the P values were 0.54 (A), 0.3 (B), 0.5 (C), 0.32 (D), 0.73 (E), and 0.99 (F). CV, cerebrovascular; MACCEs, major adverse cardiac and cerebrovascular events.
Table 4 Crude rates and adjusted risk estimates of all-cause death, cardiac or CV deaths, and MACCEs during the follow-up period according to the levosimendan use (n=135)*
Event L-group (n=41) C-group (n=94) HR 95% CI P
All-cause death          
  Crude 5 (12.2%) 12 (12.8%) 0.95 0.31-2.89 0.92
  Multiple covariates-adjusted†     0.76 0.16-3.57 0.73
  EuroSCORE II-adjusted[12]     1.31 0.453.8 0.62
Cardiac or CV deaths          
  Crude 3 (7.3%) 5 (5.3%) 1.41 0.32-6.18 0.7
  Multiple covariates-adjusted†     0.84 0.07-10.3 0.89
  EuroSCORE II-adjusted[12]     1.42 0.336.14 0.64
MACCEs          
  Crude 10 (25%) 23 (24.5%) 1 0.42-2.34 1
  Multiple covariates-adjusted†     0.85 0.3-2.41 0.77
  EuroSCORE II-adjusted[12] 1.12 0.53-2.37 0.76
1
Pichette M, Liszkowski M, Ducharme A. Preoperative Optimization of the Heart Failure Patient Undergoing Cardiac Surgery[J]. Can J Cardiol, 2017, 33(1): 72-79.
2
Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for Hemodynamic Support after Cardiac Surgery[J]. N Engl J Med, 2017, 376(21): 2021-2031.
3
Zangrillo A, Alvaro G, Pisano A, et al. A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design[J]. Am Heart J, 2016, 177: 66-73.
4
Cholley B, Caruba T, Grosjean S, et al. Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial[J]. JAMA, 2017, 318(6): 548-556.
5
Mehta RH, Leimberger JD, van Diepen S, et al. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery[J]. N Engl J Med, 2017, 376(21): 2032-2042.
6
Grieshaber P, Lipp S, Arnold A, et al. Impact of prophylactic administration of Levosimendan on short-term and long-term outcome in high-risk patients with severely reduced left-ventricular ejection fraction undergoing cardiac surgery - a retrospective analysis[J]. J Cardiothorac Surg, 2016, 11(1): 162.
7
Anastasiadis K, Antonitsis P, Vranis K, et al. Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting: a randomized pilot study[J]. Interact Cardiovasc Thorac Surg, 2016, 23(5): 740-747.
8
Lomivorotov VV, Boboshko VA, Efremov SM, et al. Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients[J]. J Cardiothorac Vasc Anesth, 2012, 26(4): 596-603.
9
Kandasamy A, Simon HA, Murthy P, et al. Comparison of Levosimendan versus Dobutamine in Patients with Moderate to Severe Left Ventricular Dysfunction Undergoing Off-pump Coronary Artery Bypass Grafting: A Randomized Prospective Study[J]. Ann Card Anaesth, 2017, 20(2): 200-206.
10
Pollesello P, Parissis J, Kivikko M, et al. Levosimendan meta-analyses: Is there a pattern in the effect on mortality?[J]. Int J Cardiol, 2016, 209: 77-83.
11
Gatti G, Morra L, Castaldi G, et al. Preoperative Intra-Aortic Counterpulsation in Cardiac Surgery: Insights From a Retrospective Series of 588 Consecutive High-Risk Patients[J]. J Cardiothorac Vasc Anesth, 2018, 32(5): 2077-2086.
12
Nashef SA, Roques F, Sharples LD, et al. EuroSCORE II[J]. Eur J Cardiothorac Surg, 2012, 41(4): 734-744.
13
Biancari F, Ruggieri VG, Perrotti A, et al. European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG registry): Study Protocol for a Prospective Clinical Registry and Proposal of Classification of Postoperative Complications[J]. J Cardiothorac Surg, 2015, 10: 90.
14
Gatti G, Soso P, Dell'Angela L, et al. Routine use of bilateral internal thoracic artery grafts for left-sided myocardial revascularization in insulin-dependent diabetic patients: early and long-term outcomes[J]. Eur J Cardiothorac Surg, 2015, 48(1): 115-120.
15
Plaschke K, Bent F, Rosenhagen C, et al. The inhibitory in-vitro effect of high-dose levosimendan on platelet function may be mediated through its action as a phosphodiesterase inhibitor[J]. Coron Artery Dis, 2012, 23(3): 215-220.
16
Brunner SN, Bogert NV, Schnitzbauer AA, et al. Levosimendan protects human hepatocytes from ischemia-reperfusion injury[J]. PLoS One, 2017, 12(11): e0187839.
17
Boldt J, Brosch C, Suttner S, et al. Prophylactic use of the phospodiesterase III inhibitor enoximone in elderly cardiac surgery patients: effect on hemodynamics, inflammation, and markers of organ function[J]. Intensive Care Med, 2002, 28(10): 1462-1469.
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