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Ann Thorac Surg 2004;77:2051-2055
© 2004 The Society of Thoracic Surgeons


Original article: cardiovascular

Beating versus arrested heart coronary revascularization: evaluation by cardiac troponin I release

Kifah Alwan, MD, PhDa, Pierre-Emmanuel Falcoz, MD*b, Jihad Alwan, MDa, Walid Mouawad, MDa, Georges Oujaimi, MDa, Sidney Chocron, MD, PhDb, Joseph-Philippe Etievent, MDb

a Department of Thoracic and Cardiovascular Surgery, Centre Hospitalier du Nord, Jdeidet, Zgharta, Lebanon
b Department of Thoracic and Cardiovascular Surgery, Hôpital Jean-Minjoz, Besançon, France

Accepted for publication November 7, 2003.

* Address reprint requests to Dr Falcoz, Department of Thoracic and Cardiovascular Surgery, Hôpital Jean-Minjoz, Boulevard Fleming, 25000 Besançon, France
e-mail: pierre-emmanuel.falcoz{at}wanadoo.fr


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: This prospective randomized study aimed to compare beating and arrested heart revascularization in patients undergoing first elective coronary artery bypass graft, with cardiac troponin I release used to evaluate myocardial injury.

METHODS: Seventy patients were randomly assigned to a beating or arrested heart revascularization group. Cardiac troponin I concentrations were measured in serial venous blood samples drawn preoperatively in both groups: after aortic unclamping at 6, 9, 12, and 24 hours in the arrested heart group and after the last anastomosis at 6, 9, 12, and 24 hours in the beating heart group. Analysis of covariance with repeated measures was performed to test the effect of group and time on cardiac troponin I concentration.

RESULTS: The total amount of cardiac troponin I released was higher in the arrested heart revascularization group than in the beating heart revascularization group (8.25 ± 6.16 vs 3.18 ± 4.75 µg, p < 0.0001). Cardiac troponin I concentrations were significantly higher in the arrested heart group at hours 6, 9, 12, and 24 than in the beating heart group (p < 0.0001).

CONCLUSIONS: The lower release of cardiac troponin I in the beating heart revascularization group indicates that conventional coronary artery bypass graft with cardioplegic arrest causes more damage to the heart than off-pump myocardial revascularization.


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Coronary artery bypass grafting (CABG) using cardiopulmonary bypass is a widely used, safe, and effective procedure with a low mortality rate [1, 2]. However, in spite of improvement in perfusion techniques, the morbidity associated with cardiopulmonary bypass is still significant [35]. The potential benefits gained by avoiding cardiopulmonary bypass and cardioplegic arrest have led to renewed interest in off-pump coronary artery bypass surgery [68].

Cardiac troponin I (CTnI) has been shown to be a sensitive and specific marker of myocardial injury during open-heart surgery [9, 10]. We have already used it to compare different methods of myocardial protection [1113].

The aim of this prospective randomized study was to compare beating heart revascularization (BHR) and arrested heart revascularization (AHR) in patients with a satisfactory preoperative ejection fraction undergoing first elective CABG, using CTnI to evaluate myocardial injury.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Patient selection
After approval by our Institutional Review Board, informed consent was obtained from all eligible patients. Seventy patients (49 men and 21 women, mean age 64 ± 10 years) scheduled for first elective CABG were enrolled in a prospective randomized trial comparing beating and arrested heart coronary revascularization. All patients were eligible for both off-pump and on-pump revascularization. Not included in this study were patients with aortic incompetence, ejection fraction below 0.30, concomitant heart valve disease or unstable angina, or those undergoing reoperation.

Coronary artery stenoses causing a loss of 70% or more of the cross-sectional area were considered to be significant lesions. For the left main coronary artery, a loss of 50% was considered significant.

The decision as to which vessels were to be grafted was made before randomization. The study took place over a 7-month period. An independent data manager supervised patient registration. The surgical team was told to which group a patient had been randomized shortly before incision.

Operative technique
Standard open-heart techniques were employed for all patients. All operations were performed through total median sternotomy. Full heparinization was used (3 mg/kg), which enabled intraoperative collection and readministration of blood. Patients were randomly assigned to one of two surgical procedures by a computer-generated randomization table.

Arrested heart revascularization group
Cannulation for cardiopulmonary bypass was carried out in the usual fashion with a single-stage venous cannulation technique and active normothermia (37°C). The left ventricle was vented by a catheter introduced through the right superior pulmonary vein. The route of delivery was exclusively antegrade. High-potassium ([K+]=20 meq/L) warm blood cardioplegia (37°C) was injected into the aortic root immediately after aortic cross-clamping and until cardiac arrest was achieved with a minimal amount of 800 mL. A dose of 400 mL ([K+] = 10 meq/L) was reinjected into the aortic root after each but the last distal anastomosis. Proximal graft anastomoses to the aorta were performed during aortic cross clamping, immediately after the corresponding distal anastomosis. The cardioplegia technique used, described previously [13], is based on the one described by Calafiore and colleagues [14]. A two-minute warm reperfusion, composed exclusively of 37°C oxygenated blood with a constant flow rate of 200 mL/min, was performed immediately after the last distal anastomosis, once the mammary artery(ies) was (were) unclamped.

Beating heart revascularization group
Operations were performed with the Octopus device stabilizer (Octopus Tissue Stabilizer, Medtronic Inc, Eden Prairie, MN), with great care taken to maintain hemodynamic stability (mean arterial blood pressures greater than or equal to 65 mm Hg) throughout the operation. Better exposure of the circumflex marginal branch system was achieved by gradual rotation of the heart and prior grafting of the anterior descending coronary artery to the internal mammary artery. No intracoronary shunts were used. Procedure time defines the time included between the beginning of exposure of the heart and the end of the last anastomosis, when the heart was placed back in the pericardium.

Measurements of cardiac marker proteins
Serial venous blood samples were drawn preoperatively in both groups as well as after aortic unclamping at 6, 9, 12, and 24 hours in the arrested heart group and after anastomosis of the left internal mammary artery to the left anterior descending artery at 6, 9, 12, and 24 hours in the beating heart group. The CTnI concentration was determined by immunoassay with the Stratus II analyzer (Dade Behring, Maurepas, France). This analyzer uses two CTnI-specific monoclonal antibodies, which recognize different epitopes and avoid cross-reactivity with human skeletal muscle isoforms. The upper reference limit in a control population was 0.4 µg/L. Creatine kinase isoenzime MB (CK-MB) was measured at hour 6.

Electrocardiogram
A 12-lead electrocardiogram (ECG) was recorded before surgery, at 2 hours, and then daily after surgery. Electrocardiogram diagnosis criteria for perioperative myocardial infarction (PMI) were new Q-waves of more than 0.04 ms and a reduction in R-waves of more than 25% in at least two leads. The CTnI diagnosis criteria for PMI were CTnI peak concentrations of more than 3.7 µg/L and CTnI concentration of more than 3.1 µg/L at 12 hours, or more than 2.5 µg/L at 24 hours, as determined by Mair and colleagues [15]. Acquired conduction defects were considered.

Statistical analysis
Sample sizes were calculated for a two-sided significance level of {alpha} = 0.05 and a power of 1– ß = 0.8 to detect a difference of 0.5 µg/L in CTnI concentration between groups. The standard deviation (SD) of CTnI measurements, determined in a previous study [9], was SD = 0.75. The number of subjects required was 35 per group.

Statistical analysis was performed with SAS software, version 8.02 (SAS Institute Inc, Cary, NC). One-way analysis of covariance with repeated measures was performed to test the effect of the type of bypass revascularization and time on CTnI concentration.

Categorical data were compared with the {chi}2 test or Fischer's exact test and quantitative variables, with the two-group t test. Values are expressed as mean ± SD. A value of p less than or equal to 0.05 was considered statistically significant.


    Results
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Preoperative data
No patient suffered from aortic incompetence or renal dysfunction. Preoperative and angiographic data are shown in Table 1. The mean age was significantly lower in the BHR group than in the AHR group (p = 0.03). The number of patients suffering from diabetes mellitus, preoperative atrial fibrillation, left bundle branch block, or right bundle branch block did not differ markedly between groups (p = not significant [NS]). The repartition of coronary angiographic data did not differ between groups.


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Table 1. Preoperative Patient Profile by Group

 
Operative data
Operative and postoperative data are shown in Table 2. At least one mammary artery was used in all patients. The number of distal anastomoses was equivalent in both groups. Sequential grafts were performed in 14 patients in the AHR group and 12 in the BHR group (p = NS). Saphenous vein grafts were used in 9 patients in the AHR group and 7 in the BHR group (p = NS). In the AHR group, cardiopulmonary bypass time was 49.9 ± 18.7 minutes, whereas cross-clamp time was 37.3 ± 16.6 minutes. In the BHR group, procedure time was 47.5 ± 23.6 minutes.


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Table 2. Operative and Postoperative Data by Group

 
Postoperative data
No patient died during the postoperative course. There were no cases of acquired right bundle branch block in either group (p = NS). Four patients in the BHR group and one in the AHR group had an acquired left bundle branch block (p = NS). Acquired atrial fibrillation occurred in 5 BHR and 6 AHR patients (p = NS) during the first 10 postoperative days. For each group, the difference between preoperative and postoperative ejection fraction was of no statistical significance (6% ± 0.1% in the BHR group vs 8% ± 0.1% in the AHR group, p = NS).

Five patients in each group had ECG evidence of PMI (p = NS). Four patients in the AHR group and 2 in the BHR group showed CTnI evidence of PMI (p = NS). All patients with CTnI evidence of PMI had electrocardiographic evidence of PMI, save 1 in the AHR group.

Twenty-nine BHR patients and 23 AHR patients required no inotropic support (p = 0.09). Six patients in the BHR group, and 12 in the AHR group (p = NS), received either dopamine hydrochloride (3 to 5 µg · kg–1 · min–1) or dobutamine (3 to 5 µg · kg–1 · min–1). One patient from the BHR group, and none from the AHR group (p = NS), received epinephrine (0.2 to 0.5 µg · kg–1 · min–1). No patient in either group needed an intraaortic balloon pump (p = NS). The total amount of CTnI released was significantly higher (p = 0.0064) in patients requiring inotropic support (overall 10.6 ± 8.8 µg, respectively, 8.9 ± 9.7 µg in the BHR group and 11.4 ± 8.6 µg in the AHR group) than in those not requiring inotropic support (overall 3.9 ± 3.2 µg, respectively, 2.0 ± 1.5 µg in the BHR group and 6.3 ± 3.2 µg in the AHR group). The CK-MB at hour 6 was significantly higher in the AHR group (p < 0.0001).

Cardiac troponin I features
Figure 1 shows the time course of cardiac troponin I concentration according to the surgical procedure. On the whole, the two curves differ significantly (p < 0.001). The total amount of CTnI released was higher in the AHR group than in the BHR group (8.2 ± 6.2 vs 3.2 ± 4.8 µg, p < 0.0001). For each sample drawn, CTnI concentrations were significantly higher in the AHR group than in the BHR group at hours 6, 9, 12, and 24: 2.4 ± 1.7 µg/L vs 0.6 ± 0.7 µg/L at hour 6; 2.1 ± 1.7 µg/L vs 0.7 ± 0.8 µg/L at hour 9; 2.1 ± 1.9 µg/L vs 1.0 ± 1.7 µg/L at hour 12; and 1.6 ± 1.6 µg/L vs 0.9 ± 1.6 µg/L at hour 24 (p < 0.0001 for the pattern).



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Fig 1. Time course of CTnI concentration according to the surgical procedure. The two curves differ significantly (p < 0.0001). The CTnI concentration was significantly higher in the arrested heart group than in the beating heart group at hours 6, 9, 12, and 24 (p < 0.0001). Values are expressed as mean ± standard error of the mean. {square} = arrested heart revascularization; {diamondsuit} = beating heart revascularization. (CTnI = cardiac troponin I.)

 

    Comment
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Off-pump myocardial revascularization has gained increasing popularity due to its potential to avoid the damage induced by cardiopulmonary bypass, aortic cannulation, and cross-clamping. However, in the framework of BHR, a less optimal operative field may result in incomplete procedure [16]. Conventional CABG with cardioplegic arrest induces global ischemia-reperfusion and myocardial injury. The procedure of off-pump myocardial revascularization requires a period of coronary artery occlusion, which results in local ischemia. Intracoronary shunts were not used in the present study in order to avoid any possible damage to the coronary artery endothelium [17].

The aim of this prospective randomized study was to determine CTnI release in off-pump and on-pump revascularization. With regard to preoperative and operative data, randomization created two equivalent groups for all of the variables studied except age. Cardiac troponin I release was consistently and significantly higher in every sample drawn on-pump. This indicates more widespread myocardial injury in the AHR group, whereas the lower release in the BHR group suggests limited myocardial injury. This confirms the results of Wan and colleagues [18] and Ascione and colleagues [19], who found a significantly higher release of CTnI in patients who had conventional CABG compared with beating heart operations. As the decision concerning the vessels to be grafted was taken before randomization, and in no case was the planned program aborted, the number of bypasses per patient was equivalent in both groups, as was the number of arterial sequential grafts. Conversely to results found by others [20, 21], our study did not show a reduced need for inotropic support in the BHR group.

A higher release of CTnI in the AHR group was to be expected since AHR results in a global ischemia, whereas BHR leads to a local ischemia. In a previous experimental study, we showed that CTnI release depends on the volume of myocardium subject to ischemia [22], which is obviously smaller in BHR than in AHR. Due to the large difference in the volume of myocardium subject to ischemia in BHR and AHR, the same level of CTnI released in the general circulation can indicate a myocardial infarction in the local ischemia model and only a slight myocardial ischemia in the global ischemia model. It is our opinion that this difference suggests that the criteria of myocardial infarction defined by Mair and colleagues [15] (CTnI peak concentrations of > 3.7 µg/L and CTnI concentration of > 3.1 µg/L at 12 hours or > 2.5 µg/L at 24 hours) no longer apply to off-pump surgery. We assume that the values likely to show a perioperative myocardial infarction in BHR are closer to medical than on-pump cutpoints.

In conclusion, our study shows that conventional CABG with cardioplegic arrest causes more damage to the heart than does off-pump myocardial revascularization, as indicated by the lower release of CTnI in the beating heart revascularization.


    Acknowledgments
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
The authors thank Nancy Richardson-Peuteuil for her editorial assistance.


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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