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Eur J Cardiothorac Surg 2005;27:1043-1050
© 2005 Elsevier Science NL
a Cardiac Surgery Unit, Magna Graecia University, Policlinico Mater Domini Via T.C., Catanzaro 88100, Italy
b Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy
Received 27 December 2004; received in revised form 31 January 2005; accepted 21 February 2005.
* Corresponding author. Address: Viale dei Pini, 28, 80131 Naples, Italy. Tel.: +39 081 7441531; fax: +39 081 5536350. (E-mail: frankono{at}libero.it).
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Key Words: Coronary artery bypass surgery • Cardiopulmonary bypass • Coronary sinus • Retrograde perfusion • Off-pump
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Moreover, despite substantial advances in perioperative care, hospital mortality remains significant, ranging from 4.6 to 9.2%, especially in patients with triple-vessel disease or left main stem disease and severe angina [3]. Emergency coronary artery bypass grafting (CABG) in the presence of acute myocardial ischemia is associated with increased risk for postoperative cardiac dysfunction and low cardiac output syndrome [4]. The proportion of patients undergoing urgent coronary artery bypass grafting is increasing significantly, being as much as 48% of all the coronary artery bypass grafting procedures [5].
Two recent trials have clearly demonstrated that patients with unstable angina and non-ST elevation myocardial infarction (UA/NSTEMI) at high or intermediate risk, defined by triple vessel disease, left main stem disease, left ventricle dysfunction and/or diabetes mellitus, will benefit from early surgical therapy [6,7]. Many perioperative features of unstable angina need to be better understood, and the major issue of the myocardial protection is still debated. In patients with acute myocardial ischemia, continuous warm blood cardioplegia has been advocated as a superior myocardial protection in comparison to cold crystalloid cardioplegia [8]. However, warm blood cardioplegia has been found by other authors to be associated with interstitial myocardial edema and temporary cardiac dysfunction [9]. Therefore, well-established myocardial protection techniques, which yield excellent results in other patients, may fail in this situation. On the other hand, some authors have demonstrated better results with off-pump techniques in high-risk patients, such as those with unstable angina [10].
However, most of these data result from multivariate analyses of single-center experiences, and few reports exist comparing different surgical strategies in patients with unstable angina and unstable haemodynamics, despite maximal medical therapy, requiring emergent surgical revascularization. Therefore it was the aim of our study to evaluate in-hospital results of patients undergoing CABG for UA/NSTEMI, comparing beating-heart surgery with two different techniques of on-pump revascularization, in a double-center experience.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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The study population was divided in three groups, according to the surgical strategy. Group A (126 patients) consisted of patients undergoing on-pump CABG with only antegrade delivery of warm blood cardioplegia. Sixty-seven patients undergoing on-pump CABG with antegrade and intermittent retrograde warm blood cardioplegia defined Group B. Sixty-nine patients underwent off-pump CABG (Group C).
The postoperative protocol following CABG consisted of 12-lead ECG, color-Doppler echocardiography, biochemical markers of myocardial damage (MB-CK mass, Myoglobin, Troponin I). The study protocol was approved by the Institutional Review Board and informed consent was obtained from each patient.
Exclusion criteria were associated with cardiac disease (valvular, aortic disease, congenital pathology) or previous cardiac surgery.
2.2. Anesthetic technique
Anesthesia was performed by the same group of anesthetists (n=3) and consisted of propofol infusion at 3mg/kg per hour and fentanyl administration at 0.10mg every 20min. Neuromuscular blockade was achieved with pancuronium bromide. Alpha-adrenergic drugs were used as required to maintain mean systemic arterial pressure between 50 and 60mmHg.
2.3. Surgical technique
Operations were undertaken immediately within 12h of coronary angiography. Surgery was performed by four surgeons. The assignment criteria to each surgeon were completely random and the choice of surgical strategy was left to the surgeon.
In all patients, CABG was performed through a median sternotomy. Left internal mammary artery was harvested as a pedicle and anastomosed to the left anterior descending artery in all cases. The radial artery was harvested by the aid of harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, OH), always used in a pedicled fashion and always anastomosed to the ascending aorta. Right internal mammary artery was harvested as a pedicle and never used as a free graft. Internal saphenous vein was harvested from the best side, as detected by preoperative Doppler scanning.
Heparin was given at a dose of 300IU/kg to achieve a target activated clotting time (ACT) 
480. Proximal anastomoses were performed with aortic partial clamping, before the distal anastomoses in cases of off-pump surgery, and after aortic declamping in on-pump patients.
In patients undergoing on-pump CABG, our standard CPB circuit was used: a Dideco (Mirandola-Modena) tubing set, which included a 40µm filter, a Stockert roller pump (Stockert Instrumente, Munich, Germany) and a hollow fibre membrane oxygenator (Monolyth, Sorin Biomedica, Saluggia, Italy). The extracorporeal circuit was primed with 1000ml of Ringer lactate and 40mg of heparin. Non-pulsatile flow with an output of 2.4l/m2 per minute was used. Systemic temperature was kept at 34°C. Blood recovery with an autotransfusion device (Autotrans Dideco, Mirandola, Modena) was performed intra-operatively in all cases. A threshold level of hemoglobin (8g/dl) was used for blood transfusion.
Myocardial protection was achieved with intermittent hyperkalemic blood cardioplegia. In 126 patients, cardioplegia was administered through the aortic root every 20minute (500ml of blood containing 20mEq/L of K+ over 3minute delivered into the aortic root at a pressure of 70mmHg and a temperature of 34°C) (Group A); in 67 patients (Group B) after cardiac arrest was achieved with an antegrade infusion according to the above-mentioned protocol, the aortic root was vented and retrograde delivery of cardioplegia was started via an auto-inflating coronary sinus cannula at a flow rate of 200ml/minute for 2min. Coronary sinus pressure was monitored continuously and maintained less than 30mmHg throughout the procedure. Repeated doses of 3minute were administered every 20minute always by retrograde route alone.
In patients belonging to off-pump surgery (Group C), the stabilisation of the targeted vessel was achieved with the Octopus tissue stabilizer (Medtronic Inc., Minneapolis, MN). The coronary was exposed and snared only proximally, above the chosen point for anastomosis, by using a Silastic tape or a 4-0 Prolene suture with a soft plastic snugger. Visualisation was enhanced by using a surgical blower-humidifier device connected to a regulated gas source. Intra-coronary shunts were used in all cases. In two patients, lateral wall revascularization was done without a shunt, because of the severe arterial wall calcification. The first grafted vessel was always the left anterior descending artery, then proximal anastomoses with saphenous vein segments or radial artery were performed, and finally distal anstomoses were completed.
2.4. ECG
Twelve-lead electrocardiographic recordings were performed preoperatively, on admission in intensive therapy unit postoperatively, and then daily thereafter until hospital discharge or whenever judged necessary. All patients had continuous electrocardiogram monitoring for the first 48h postoperatively. The incidence of dysrhythmias, both atrial and ventricular, was recorded together with transient ischemic events (ST segment elevation >1mm).
2.5. Echocardiography
All studies were performed using a trans-thoracic Acuson Sequoia C256 echocardiography system (Acuson Corporation, Mountain View, CA) with probe 3V2C always by the same two physicians in a blind manner, preoperatively, at the time of hospital admission, and before hospital discharge. LVEF, wall motion score index (W.M.S.I.) and indexed left ventricular mass (I.L.V.M.) were recorded. A value of ILVM >125g/m2 was considered to be a marker of left ventricular hypertrophy.
2.6. Biochemistry
Blood samples were collected from the central venous line, the tip of the cannula was located in the lower part of the right atrium as confirmed by chest X-ray postoperative control. Determination of blood TnI, CK, MB-CK mass, and myoglobin were conducted preoperatively before anesthetic induction, and postoperatively at 12, 24, 48, and 72h postoperatively.
The assays were carried out using diagnostic kits provided by Beckman Coulter TM for TnI (Access Immunoassay System—AccuTnITM) and MB-CK mass (Access Immunoassay System—MB-CK), by Beckman Instruments for Myoglobin (Access Immunoassay System—MYOGLOBIN).
2.7. Definition of AMI
Perioperative AMI was defined when new Q waves greater than 0.04ms, or a reduction in R waves greater than 25% in at least two leads were detected, and new akinetic/dyskinetic segment was identified at echocardiography, and TnI peaked above 3.7µg/l [12].
2.8. Statistical analysis
The data were statistically analyzed using SPSS 10.0 (SPSS, Chicago, IL).
The preoperative variables were: patient's age and gender, body surface area, hyperlipidemia, hypertension, diabetes mellitus, smoking habits, left ventricular hypertrophy, prior cerebrovascular accident, peripheral vascular disease, chronic obstructive pulmonary disease, recent myocardial infarction (<4 week), prior AMI (>4 weeks), NYHA class, left ventricular ejection fraction (LVEF; categorized as >50, <50 and >30, <30%), number of diseased vessels, left main disease, chronic renal failure, dialysis, and preoperative life-threatening arrhythmias.
The following criteria were used for definition of co-morbidities: hypertension, SBP >140mmHg and/or DBP >90mmHg or ongoing treatment with any anti-hypertensive medication; insulin-dependent and non-insulin dependent diabetes mellitus, fasting blood glucose >140mg/dl on at least two occasions or use of anti-diabetic medication (either oral drugs or insulin); chronic renal failure, preoperative serum creatinine level greater than 200µmol/L or a previous history of renal dysfunction; dialysis, patients on dialysis therapy or haemofiltration before surgical treatment.
The intra-operative variables consisted of surgeons, anesthetists, aortic cross-clamp time (also dichotomised in more or less than 90min), cardiopulmonary bypass time (also dichotomised in more or less than 180min), number and type of grafts, route of cardioplegia administration, intra-operative defibrillation, need for intra-ortic balloon counterpulsation, and post-cross-clamp removal inotropic support.
Inotropic support was defined as low dose when enoximone or dobutamine were administered at dosage lower than 5µg/kg per minute. A medium dose of inotropes was considered when dobutamine or enoximone were at dosage between 5 and 10µg/kg per minute for more than 6h postoperatively. A high dose was defined when epinephrine was added to dobutamine or dopamine infusion >10µg/kg per minute.
The postoperative variables and complications of the operation were: operative mortality, which is death during the same hospitalization or in the first 30 days after the operation; hospital stay; postoperative arrhythmias, which were considered to be a complication only if they were life-threatening or needed medical treatment; low cardiac output state; adverse outcome, which is total postoperative morbidity.
The continuous variables were expressed as mean values±SD, and categorical data as proportions. Comparisons of continuous variables were made with two-tailed t test (paired or unpaired when appropriate). Categorical variables were compared with the 
2 test or Fisher exact test. One-way analysis of variance (ANOVA) was used to evaluate the significance of the differences among the three groups. If the F value was significant and variance was homogeneous, Tukey's multiple comparison test was used to assess the differences between the individual groups; otherwise, Tamhane's T2 test was used. The Kruskal–Wallis test was used to compare the three groups in terms of dicotomous variables. A P value of less than 0.05 was considered significant.
2.9. Limitation of the study
Although assignment of a patient to the surgeon and to the anesthetist was random, the surgical strategy was left to the surgeon, therefore no real randomisation was done.
Certainly the location of the coronary lesions, the dominance or hypoplasy of the vessels, the tightness of the stenosis, the presence of generalized or localized left ventricular function were considered in planning the surgical strategy. Intra-myocardial coronaries, severe and diffuse calcified lesions, preferentially indicated on-pump surgery, whereas moderate to severe comorbidities preferentially mandate off-pump surgery. On the other side, left ventricular function was not accounted in the surgical planning. However, all surgeons were skilled in all the three different strategies, and the prevalence of a surgeon to the others was not evidenced between the three groups (Table 2).
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However, we think that these cannot be considered significant bias: first, the haemodynamic status of patients with unstable ongoing angina is the most important determinant of the surgical results, and this specific variable, as demonstrated by preoperative enzymes, is similar between the three groups. Second, if off-pump surgery group have less diseased vessels compared to the other two groups, this is because it has more often diseased left main stem, which is a high-risk condition for mortality and morbidity: therefore we think the three groups can be considered at similar risk-profile [3]. According to this, left main stem disease in this clinical setting may be suggested as an indication to off-pump, rather than a bias.
Finally, despite a different prevalence of hypertension, no differences were found in left ventricular hypertrophy, the groups therefore being similar in terms of suffering viable myocardium.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Due to the postoperative low output syndrome, more patients of Group A (14/126—11.1%) required postoperative intra-aortic balloon pump, compared to either Group B (2/67—3%; P=.05) or Group C (3/69—4.3%; P=.009). Again, such difference was not significant when Groups B and C were considered.
Similarly, patients undergoing isolated antegrade cardioplegia developed postoperative paroxysmal atrial fibrillation (AF) more often (45/126 patients—48.1%), compared to Group B (12/67—17.9%; P=.0008) and Group C (3/69—4.3%; P=.0001). Similarly, patients undergoing combined route of cardioplegia delivery demonstrated a higher incidence of atrial fibrillation compared to off-pump surgery (P=.002).
As far as inotropic support was considered, more patients of Group A required high doses of postoperative inotropes (21/126—16.7%) compared to both Group B (0/67—0%; P=.0001) and C (4/69—5.8%; P=.03); on the other side more patients belonging to both Group A (33/126—26.2%) and B (11/67—16.4%) required postoperative medium doses of inotropes compared to off-pump group (0/69—0%; P=.0001 and P=.0021, respectively). Finally, more patients belonging to Group B (24/67—35.8%) did not require any inotropic support at all when compared to Group A (18/126—14.3%; P=.002); similarly, a higher percentage of off-pump patients did not require inotropes (45/69—45.2%; P=.001) during the postoperative course, compared to Group A.
Moreover, total postoperative morbidity, defined as ‘adverse outcome’, proved to be significantly higher in Group A (39/126—30.9% vs. Group B 6/67—8.9%; P=.007; and vs. Group C 6/69—8.7%; P=.005).
When biochemical markers of myocardial damage were considered, troponin I demonstrated significant higher values in patients undergoing isolated antegrade cardioplegia, compared to Groups B and C, as shown in Fig. 1.
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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The aim of this study was to evaluate the results of three different surgical strategies of myocardial protection in patients with ongoing UA/NSTEMI undergoing urgent/emergent CABG.
Some authors demonstrated higher hospital mortality in patients with unstable angina undergoing urgent or emergent CABG [17,18]. Blood cardioplegia reduced the morbidity and mortality in patients undergoing urgent coronary artery bypass grafting for unstable angina, as was demonstrated by Teoh and their associates [17]. Bjessmo et al. reported a mortality rate of 3.4%, and found almost 85% of the early deaths due to cardiac causes [18]. In the same series were identified 13% perioperative non-fatal myocardial infarctions, raising the question of the adequacy of perioperative myocardial protection techniques. These data are consistent with the findings of Naunheim and associates, who demonstrated that total ischemic time remains the most important intra-operative variable in predicting a major adverse outcome, clearly addressing the importance of myocardial protection techniques [19]. However, only 25 and 50% of patients reported in the series of Bjessmo et al. underwent retrograde cold blood cardioplegia or combined antegrade and retrograde cold blood cardioplegia, respectively [18]. In a group of patients undergoing emergency surgical procedures for acute coronary occlusion, Beyersdorf and colleagues showed that improved techniques of myocardial protection, including warm blood cardioplegic induction, multidose cold blood cardioplegia for maintenance, and controlled reperfusion, resulted in a decrease in the overall mortality despite an increased number of risk factors [4]. Our study reported an overall 5.7% of hospital mortality. Despite total hospital mortality, which was slightly higher than that of series reporting conventional elective CABG, in-hospital mortality varied widely between the three groups, being significant in patients undergoing isolated antegrade cardioplegia on cardiopulmonary bypass. Our data strongly suggested combined antegrade and retrograde myocardial protection if on-pump strategy is done, because of the difficulty of cardioplegia delivering through the only antegrade flow, whereas a better cardioplegia delivering to the suffering myocardial territories may be obtained through the associated retrograde flow.
Similarly, off-pump revascularization could be a valid option. In the last 15 years, CABG without CPB has developed into a viable alternative to on-pump CABG. While the results of elective off-pump surgery have been comparable to those of on-pump, with similar mortality rates, non-elective CABG (urgent, emergent and salvage) carries an increased risk in most risk-stratification models, as was seen in a comparison analysis of six scoring systems by Geissler and colleagues [20]. Chamberlain et al. have recently published an observational study, evaluating the effectiveness of off-pump in high-risk patients, where they found a significantly lower incidence of need for IABP, transfusion requirements, pulmonary complications and shorter intensive care unit and in-hospital stays when cardiopulmonary bypass is avoided [10]. They were unable to demonstrate any difference in the incidence of perioperative MI, renal complications, infective complications or new atrial fibrillation. They did not demonstrate any significant in-hospital survival benefit. However, patients undergoing on-pump surgery underwent only isolated antegrade cardioplegia administrattion [10]. Mohr and associates used the off-pump technique in patients with acute myocardial infarction and impaired left ventricular function [21]. The mean number of grafts was 1.8 and only 23% of the patients received a graft to marginal branch of the left circumflex artery. The mortality rate was 3.8%, perioperative myocardial infarction rate was 2.7%, and improved compared with an equivalent population operated on with CPB [21]. Our study similarly reported a lower intra-aortic balloon pumping, lower perioperative MI, and lower postoperative total morbidity in patients undergoing off-pump surgery, compared to isolated antegrade cardioplegia. However, when compared to combined antegrade and retrograde cardioplegia, no differences exist in hospital outcome. Hernandez and co-workers in the Northern New England Cardiovascular Disease Study Group were also unable to show any significant difference in outcomes in a multicentre off-pump vs. on-pump surgery comparison, except for a lower incidence of postoperative AF, as in our study, and an almost significant difference in the use of intra- and postoperative IABP. In this study, however, on-pump surgery was extremely variable, according to each surgeon's choice. Moreover the patients in the off-pump group had a lower median in-hospital stay [22]. Another recent study by van Dijk et al. on behalf of the Octopus Study Group, showed a shorter hospital stay in the OPCABG group. In this study, myocardial protection was obtained with cold crystalloid cardioplegia [23]. The present study similarly demonstrated a shorter hospital stay, in both off-pump patients and antegrade and retrograde cardioplegia group.
Recently TnI has been shown to be a specific marker of cardiac damage with a higher specificity and a wider diagnostic window as compared to CK-MB measurements [12]. Therefore, it is widely accepted that TnI should be able to detect even minor differences of myocardial ischemia. Although some authors demonstrated lower troponin release in patients undergoing elective off-pump surgery, others reported similar enzymatic release [24,25]. Moreover, perioperative enzymatic leakage, between off-pump and on-pump CABG, should be questioned when UA/NSTEMI with ongoing myocardial damage is considered. Our study reported significantly higher values of postoperative troponin I in patients undergoing on-pump CABG with antegrade cardioplegia, demonstrating a poor quality of myocardial protection. This was the substrate for the observed higher mortality, perioperative myocardial infarction and total morbidity. However, there were no differences between on-pump and off-pump surgery when more homogeneous cardioplegic delivery is obtained, as in patients undergoing combined warm blood antegrade and retrograde cardioplegia.
In conclusion, patients with UA/NSTEMI having OPCABG seem to do better on most counts when compared to simple myocardial protection technique on cardiopulmonary bypass, as isolated warm blood antegrade cardioplegia. We therefore suggest that on-pump CABG with isolated antegrade cardioplegia in patients with UA/NSTEMI should be avoided. However, more homogeneous techniques of cardioplegia delivery, as combined antegrade and retrograde warm blood cardioplegia, obtained similar results to off-pump surgery.
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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  P. Voisine, P. Mathieu, D. Doyle, J. Perron, R. Baillot, G. Raymond, J. Metras, and F. Dagenais Influence of time elapsed between myocardial infarction and coronary artery bypass grafting surgery on operative mortality Eur. J. Cardiothorac. Surg., March 1, 2006; 29(3): 319 - 323. [Abstract] [Full Text] [PDF]
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