Gen Thorac Cardiovasc Surg DOI 10.1007/s11748-013-0358-6
ORIGINAL ARTICLE
Optimal coronary artery bypass grafting strategy for acute coronary syndrome Hiroyuki Nishi • Taichi Sakaguchi • Shigeru Miyagawa • Yasushi Yoshikawa • Satsuki Fukushima • Daisuke Yoshioka Tetsuya Saito • Koichi Toda • Yoshiki Sawa
•
Received: 24 September 2013 / Accepted: 2 December 2013 Ó The Japanese Association for Thoracic Surgery 2013
Abstract Objective Conventional coronary artery bypass grafting (CABG) using cardiopulmonary bypass and cardiac arrest is associated with higher mortality and morbidity rates in acute coronary syndrome (ACS) patients undergoing surgery. Although off-pump CABG (OPCAB) is beneficial for high-risk patients, its efficacy for ACS is unknown, with on-pump beating CABG an adjunctive method. We investigated the effects of OPCAB and on-pump beating CABG for ACS. Methods We evaluated 121 consecutive patients with ACS (91 males, 30 females; mean age 69.5 ± 10.3 years) who underwent CABG since 2000. Seventy-five had unstable angina (UA) and 46 acute myocardial infarction (AMI) [nonST elevation (NSTEMI): 22, ST elevation (STEMI): 24]. We assessed CABG for acute coronary syndrome under our primary OPCAB strategy, and compared perioperative status between UA and AMI patients. Results (1) Sixty-five (87 %) with UA underwent OPCAB, 8 on-pump beating CABG, and 2 conventional CABG. Conversion from OPCAB was seen in 4 patients. In-hospital mortality was 1.3 %. (2) All UA patients who had intra-aortic balloon pumping (IABP) underwent OPCAB. No patients with preoperative IABP experienced conversion from OPCAB. (3) In AMI patients, hospital mortality was higher (8.9 %) and the ratios for OPCAB, Presented at the 64th Annual Scientific Meeting of the Japanese Association for Thoracic Surgery. H. Nishi T. Sakaguchi S. Miyagawa Y. Yoshikawa S. Fukushima D. Yoshioka T. Saito K. Toda Y. Sawa (&) Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan e-mail: [email protected]; [email protected]
on-pump beating CABG, and conventional CABG were 39, 57, and 4 %, respectively. Mortality was exclusively seen in patients with STEMI who underwent conventional CABG. Conclusions OPCAB might have beneficial effects for ACS patients with UA, while IABP was found essential for completing OPCAB. In AMI patients, on-pump beating CABG might be reasonable for avoiding conversion from OPCAB and ischemic perfusion injury. Keywords Acute coronary syndrome Coronary artery bypass grafting Myocardial infarction Beating heart surgery
Introduction Despite recent advances in coronary artery bypass grafting (CABG) technology, the results for acute coronary syndrome (ACS) are still unfavorable as compared to elective CABG [1–7]. Patients with ACS often require percutaneous catheter intervention (PCI) or CABG to relieve myocardial ischemia on an emergency basis [8], and are more likely to have greater risk of postoperative morbidities as compared to those undergoing an elective operation. Furthermore, ACS represents a continuum from unstable angina (UA) to acute myocardial infarction (AMI) with or without ST-segment elevation, and previous studies of ACS have presented a variety of ratios of patients with UA or AMI. Thus, previously reported results are not consistent and difficult to generalize [1–7, 9–11]. Although patients with UA showed relatively lower mortality in those previous studies, high mortality rates have been noted in patients undergoing surgery after confirmation of ST-segment elevation myocardial infarction (STEMI) [9–11].
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With recent developments in surgical instruments such as stabilization devices and intracoronary shunts, CABG without cardiopulmonary bypass (CPB) has become widely accepted as a primary strategy [12, 13]. This type of offpump CABG (OPCAB) has several benefits by avoiding the adverse effects of CPB and cardiac arrest such as postperfusion syndrome, and is considered to provide favorable results especially for high-risk older patients [14], and those with renal or neurological dysfunction [15]. However, this technique is not always beneficial, because patients requiring intra-operative conversion from offpump to on-pump surgery have been reported to have a worse outcome than those with successfully completed OPCAB surgery [16]. Furthermore, intermediate strategies such as beating heart surgery with CPB (on-pump beating CABG) have also been utilized for CABG [17]. Although these OPCAB and on-pump beating CABG methods may have benefits to reduce postoperative morbidity for managing high-risk patients in an emergency situation, the exact roles of OPCAB and on-pump beating CABG for patients with ACS who are in critical condition requiring emergency CABG have not been established. In addition, the extent of myocardial ischemia may have an impact on these strategies. In this study, we evaluated our results of CABG for ACS under our primary OPCAB strategy to clarify the optimal strategy for choosing between OPCAB and on-pump beating CABG.
Patients and methods OPCAB was introduced as a primary surgical strategy for CABG at our institution in 2000, after which a total of 595 patients have undergone isolated CABG. Of those, 121 patients were diagnosed with ACS and enrolled in this study (91 males, 30 females; mean age 69.5 ± 10.3 years). The definitions of ACS and AMI followed American College of Cardiology/American Heart Association Guidelines published in 2007 [18]. Briefly, diagnosis of AMI was made based on conventional electrocardiography (ECG) findings, in addition to enzyme or cardiac troponin criteria, and confirmed using acute coronary angiography. Patients with ongoing angina without AMI characteristics in ECG findings and no leakage of cardiac biomarkers were defined as UA. There were seventy-five patients diagnosed with UA, and AMI was present in 46. Of these, 24 had STEMI and 22 were non-STEMI (NSTEMI). Intra-aortic balloon pumping (IABP) was utilized preoperatively in 46 patients. Eighteen patients had a history of cardiogenic shock and 4 were in cardiogenic shock at the time of treatment. The baseline characteristics of each group are shown in Table 1.
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Table 1 Patients’ characteristics in UA and AMI groups
Age (years)
UA (n = 75)
AMI (n = 46)
p value
69.2 ± 10.2
70.3 ± 10.6
NS
Gender (male/female)
54/21
35/11
NS
Hypertension
44 (59 %)
29 (63 %)
NS
Diabetes
31 (41 %)
23 (50 %)
NS
Hyperlipidemia
33 (44 %)
6 (13 %)
NS
Chronic obstructive lung disease
3 (4 %)
7 (15 %)
NS
Cerebrovascular disease
12 (16 %)
8 (17 %)
NS
Renal dysfunction
40 (53 %)
23 (50 %)
NS
Left ventricular ejection fraction
58.6 ± 15.4
46.6 ± 13.1
\0.01
Preoperative IABP
16 (21 %)
30 (65 %)
\0.01
Preoperative PCPS
0
4 (9 %)
\0.01
Cardiogenic shock
2 (3 %)
16 (35 %)
\0.01
STEMI
–
24 (52 %)
–
UA unstable angina, AMI acute myocardial infarction, IABP intraaortic balloon pumping, PCPS percutaneous cardio-pulmonary support
Although we adopted a primary OPCAB strategy for isolated CABG in 2000, the selection of the operative method to perform CABG for ACS in the present patients was based on the preference of the attending surgeon, who assessed preoperative hemodynamics, concomitant diseases, and extent of ACS, and finally made a decision to use OPCAB, on-pump beating CABG, or conventional CABG with cardiac arrest. We evaluated preoperative status and perioperative outcomes in each group, as well as the ratio of selected adjunctive methods for CABG in each. We also investigated the ratio of conversion from OPCAB to on-pump CABG and factors related to completion of OPCAB to clarify the optimal strategy for ACS patients. Informed consent for this study was obtained from each patient or their family member, following institutional review board approval of the study. Surgical technique A median sternotomy was routinely performed and the internal thoracic artery (ITA) harvested. Intravenous heparin (200 IU/kg for OPCAB, 300 IU/kg for on-pump CABG) was administered just before completion of ITA and saphenous vein graft (SVG) harvest. OPCAB was performed using a single pericardium traction suture, an epicardial stabilizer (Octopus; Medtronic, Minneapolis, MN, USA), and a heart positioner (Starfish; Medtronic). All anastomoses were performed using 7-0 or 8-0 polypropylene sutures. Preconditioning was not routinely performed, while an intra-coronary shunt was routinely
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used, especially for left anterior descending artery (LAD) anastomosis. Our revascularization strategy includes performing an LAD graft, followed by the culprit lesion and then other vessels. For LAD revascularization, ITA was routinely applied. To achieve hemodynamic stability, a combination of the following actions was performed; Trendelenburg position and fluid transfusion were used to compensate for preload decrease, and inotropes were utilized to increase coronary blood flow and stroke volume. When on-pump CABG was selected, cardiopulmonary bypass was established by standard ascending aortic and right atrial cannulation, and the same devices were used when on-pump beating CABG was chosen. The graft strategy was the same as used for OPCAB. When cardiac arrest was selected, blood cardioplegia with antegrade or retrograde application was used for myocardial protection. The order of anastomosis was the culprit lesion first, followed by other vessels, with the bypass to LAD performed at the end. Statistical analysis Data were analyzed using Statview 5.0 (SAS Institute Inc, Cary, NC). Results are expressed as the mean ± standard deviation. A Mann–Whitney U test was used for comparison of continuous variables and Fisher’s exact test for comparisons of frequencies between the groups. Long-term survival and freedom from major adverse cardiac events were calculated using the Kaplan–Meier method. A p value of less than 0.05 was used to select variables for entry into the multivariate model. Statistical significance was accepted at p B 0.05.
Results Preoperative status The preoperative characteristics in each group are shown in Table 1. There were no statistically significant differences between the groups with regard to age, gender, and other comorbidities such as hypertension, diabetes, hypercholesteremia, chronic obstructive lung disease, and history of stroke. The number of diseased vessels and incidence of left main disease were equally distributed (Table 2). On the other hand, preoperative left ventricular ejection fraction (LVEF) was significantly lower in the AMI group as compared to the UA group, while the ratio of IABP and preoperative mechanical support was significantly higher in the patients with AMI. The rate of percutaneous catheter intervention (PCI) was higher in the AMI group as compared to the UA group (Table 2).
Table 2 Perioperative coronary artery disease related results in UA and AMI groups UA (n = 75)
AMI (n = 46)
p value
1 vessel disease
1 (1 %)
2 (5 %)
NS
2 vessel disease 3 vessel disease
19 (25 %) 55 (73 %)
7 (15 %) 37 (80 %)
NS NS
Number of diseased vessels
33 (44 %)
23 (50 %)
NS
Previous PCI
Left main trunk disease
16 (21 %)
17 (37 %)
NS
Failure of PCI
5 (7 %)
11 (24 %)
\0.05
Total bypass number
3.3 ± 1.0
3.2 ± 1.0
NS
Off-pump CABG
65 (87 %)
18 (39 %)
\0.05
On-pump beating CABG
8 (12 %)
26 (57 %)
\0.05
On-pump arrest CABG
2 (1 %)
2 (4 %)
NS
98.4 %
97.7 %
NS
Left internal thoracic artery
100 %
100 %
NS
Right internal thoracic artery
97.2 %
100 %
NS
Radial artery
100 %
83 %
NS
Gastroepiploic artery
83 %
100 %
NS
Saphenous vein
98.4 %
97.4 %
NS
Early graft patency
UA unstable angina, AMI acute myocardial infarction, PCI percutaneous catheter intervention, CABG coronary artery bypass grafting
Ratio of OPCAB and role of IABP in UA group OPCAB was completed in 65 of the UA patients (87 %). In patients with on-pump CABG, on-pump beating CABG was chosen in 8 and conventional cardiac arrest was adopted in 2. The reasons for using cardiopulmonary bypass were conversion from OPCAB in 4, unstable condition in 4, low ejection fraction in 1, and preoperative hemodynamic instability in 1. The mean number of distal anastomoses was 3.3 ± 1.0 in patients with OPCAB, 3.6 ± 1.1 in those with on-pump beating CABG, and 2.0 ± 0.0 in those with on-pump arrest. All patients who converted from OPCAB to on-pump CABG had on-pump beating CABG because of hemodynamic instability. Thirteen patients in the UA group had preoperative IABP, of whom 11 patients (85 %) were planned to undergo OPCAB. All of these were able to complete OPCAB and none required conversion from OPCAB to on-pump CABG. Furthermore, no patients who experienced intraoperative conversion from OPCAB to on-pump CABG had preoperative IABP. Patients who needed conversion from OPCAB to on-pump CABG did not have preoperative IABP. Ratio of OPCAB in AMI group Eighteen of 46 (39 %) AMI patients underwent OPCAB. When patients with preoperative cardiopulmonary bypass were excluded, the ratio was 44 %. On the other hand, the
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majority (57 %) of AMI patients underwent on-pump beating CABG. Of those, IABP was used in 20. Three patients converted from OPCAB to on-pump CABG and the main reason was preoperative hemodynamic instability. As for patients with STEMI, 25 % had OPCAB, while 55 % of patients with NSTEMI completed OPCAB. The mean number of distal anastomoses was 2.5 ± 0.8 in patients with OPCAB, 3.6 ± 1.0 in those with on-pump beating CABG, and 2.0 ± 0.0 in those with on-pump arrest.
Long-term outcomes
Postoperative outcomes (Table 3)
Discussion
Thirty-day mortality and in-hospital mortality rates in patients with UA were significantly lower than in those with AMI (0 vs. 4.4 %, p \ 0.05; 1.3 vs. 8.9 %, p \ 0.05, respectively). The cause of death in the 1 patient with UA was infection. This patient had preoperative IABP and underwent OPCAB, while LVEF was 41 % and chronic renal failure was present. Among the 4 patients with AMI who did not survive, 3 had preoperative percutaneous cardiopulmonary support and the other had LVEF of 30 % and was on IABP preoperatively. All had STEMI and all deaths were due to low cardiac output syndrome. There was no significant relationship between preoperative creatine phosphokinase (CK) or CK-MB and mortality (nonsurvivor vs. survivor: 519 ± 302 vs. 784 ± 1015 IU/L, NS; 56 ± 30 vs. 83 ± 139 IU/L, NS, respectively). Postoperative major complications were more frequent in the AMI group (22 %) as compared to the UA group (8 %). Significant differences were observed regarding occurrence of postoperative stroke, respiratory complications, and deep sterna infection. In four patients with stroke, 3 had on-pump beating CABG including 2 preoperative PCPS patients. There was no relationship between conversion from OPCAB to on-pump and postoperative complications. Early graft patency results are shown in Table 2. Total patency in patients with UA was 98.4 and 97.7 % in those with AMI. There were no significant differences for patency rates with regard to the type of graft in both groups.
The main finding in this study was that the ratio of OPCAB was higher in patients with UA than in those with AMI who were treated under our primary OPCAB strategy for ACS. Also, even though operative mortality in the UA patients was acceptable (1.3 %), the mortality rate in that group was still high (8.9 %). Recent reports of CABG for ACS have revealed various postoperative outcome findings, because the ratios of UA and AMI patients were quite different. Zembala et al. [3] reported that the 30-day mortality of their study cohort (UA 55 %, AMI 45 %) was 5.7 %, whereas Ben-Gal et al. [2] noted a 30-day mortality of 2.5 % in a study cohort that only included patients with non-ST elevated MI. Furthermore, Hagl et al. [9] reported a high mortality (20 %), but only included ST-elevated MI patients. Therefore, to elucidate the optimal strategy of CABG for ACS, it is better to distinguish UA from AMI patients and separately evaluate the results. In our patients with UA, the OPCAB completion rate was 87 % and the 30-day mortality rate was similar to previous reports of elective CABG cases [19, 20]. This favorable result may have been due to the various favorable effects of OPCAB. The advantage of OPCAB has been widely discussed and some evidence established. For example, OPCAB reduces the amount of bleeding or perioperative transfusion required [21, 22], and is associated with favorable outcome in patients with chronic kidney disease [15]. Avoidance of cardiopulmonary bypass also reduces possible side effects related to inflammatory response [23]. Also, an aorta-non-touch technique without using CPB has great advantage for avoiding postoperative stroke [24]. Although many reports have described no significant differences regarding postoperative outcome between OPCAB surgery and conventional on-pump CABG, recent consensus is that OPCAB is beneficial at least for CABG in high-risk patients. Patients with ACS are usually treated in an emergency situation and generally in critical condition, while they often have a history of treatment anti-platelet agents, as well as unknown or uncontrolled comorbidities. Therefore, these patients are high risk and OPCAB may provide favorable effects.
Table 3 Mortality and morbidity UA (n = 75)
AMI (n = 46)
p value
30-day mortality
0
2 (4.4 %)
\0.01
In-hospital mortality
1 (1.3 %)
4 (8.9 %)
\0.01
Reoperation for bleeding
3 (4.0 %)
3 (6.7 %)
NS
Stroke
0
4 (8.9 %)
\0.01
Pneumonia
2 (2.6 %)
7 (15.6 %)
\0.01
Deep sternal infection
1 (1.3 %)
1 (2.2 %)
\0.05
UA unstable angina, AMI acute myocardial infarction
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Overall survival was similar between the UA and AMI groups. The 10-year survival rate in the UA group was 72.3 %, while that in AMI was 49.6 %. In patients with AMI, there was no significant difference regarding longterm outcome between those with STEMI and with NSTEMI.
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The most serious disadvantage of OPCAB is conversion from OPCAB to on-pump CABG during the procedure, which can occur during displacement of the heart for exposure of the target vessels. The mortality rate for cases with conversion has been reported to be much higher than for those with other CABG procedures [16]. It is important to establish an optimal OPCAB strategy for patients with ACS to avoid intraoperative conversion. Preoperative placement of IABP facilitates safe heart luxation or manipulation during the procedure, and may be a viable option to overcome hemodynamic instability. Even when the heart was lifted for anastomosis of the lateral or inferior surface, the present patients with IABP had stable hemodynamics and it was not difficult to maintain blood pressure, because augmentation of diastolic pressure provided adequate coronary perfusion. Furthermore, following anastomosis of the LAD, it becomes easier to maintain a stable hemodynamic condition. One report found that delayed use of IABP was associated with increased mortality, whereas the rates of perioperative myocardial infarction and in-hospital mortality were significantly lower among patients for whom IABP was initiated preoperatively [25]. In the present study, no patients with UA who experienced intraoperative conversion from OPCAB to on-pump CABG had preoperative IABP, whereas UA patients who needed conversion from OPCAB to on-pump CABG did not have preoperative IABP. Therefore, we consider that IABP may have an important role for completion of OPCAB in patients with UA. Because of fibrinolytic therapy, PCI is the preferred first-line therapy for AMI [26]. However, since AMI patients who require CABG tend to have increased complications and multi-vessel disease, mortality associated with emergency CABG remains high [9]. Our results also showed higher rate of major adverse cardiac event, which was probably due to higher ratio of critical patients. Patients with AMI should be divided into two groups, those with NSTEMI and those with STEMI. Patients in the former group demonstrate ongoing ischemia and leakage of cardiac enzymes, though they are usually in a relatively stable condition like UA patients. Although some patients in the former group might undergo successful OPCAB with or without IABP, there is a lack of results. Various reports that included both STEMI and NSTEMI patients have rarely reported the success rate of OPCAB for patients with NSTEMI [1–7]. The strongest influence on perioperative risk has been found when the procedure was performed during evolving infarction, while the most frequent reason for mortality was reported to be low cardiac output and perioperative infarction, which are both strongly related to preoperative evolving infarction. Also, this situation is related to the occurrence of conversion from OPCAB to on-pump CABG. Therefore, it is important to establish an
optimal strategy according to individual patient status. On the other hand, patients with STEMI are usually in an extremely unstable condition, as some are in a shock condition and require preoperative PCPS. They also have a high mortality rate ranging from 21.3 to 46.7 % [27–29]. The only solution for this problem may be to maintain hemodynamic condition as stable as possible. Once surgery becomes a possible option, it is important to restore coronary blood flow and avoid global myocardial ischemia as soon as possible, which might achieve a faster postoperative cardiac recovery. A surgical approach allows complete revascularization and offers a variety of techniques depending on the condition and stability of the patient, while the questions of whether to use cardioplegia, perform assisted beating heart surgery, or even utilize an off-pump coronary bypass graft are the subjects of controversial discussions. Theoretically, OPCAB seems to be an ideal procedure for high-risk patients. However, as noted above, patients with AMI are in an unstable condition, with insufficient blood flow not only for the coronary arteries but also for other organs. An appropriate circulatory support system should be applied to improve hemodynamic status and compensate visceral organ perfusion in such cases. In addition, ischemic reperfusion injury is another issue to be considered. Aortic cross clamping and cardioplegic arrest might induce myocardial and systemic organ damage during a critical condition such as ongoing myocardium necrosis [30]. From these points of view, on-pump beating heart CABG is an attractive technique that maintains a heartbeat with the aid of cardiopulmonary bypass, but without aortic cross clamping or cardioplegic arrest. Avoidance of cardioplegic arrest can eliminate intraoperative global myocardial ischemia, which might contribute to myocardial protection. Furthermore, the beating heart can preserve native coronary blood flow, which might reduce myocardial injury. Also, conversion from OPCAB to on-pump, which causes death and serious complications, never occurs in patients who underwent on-pump surgery. In the present study, the main reason for operative mortality was postoperative low cardiac output due to global myocardium damage. To avoid further damage and improve the outcome of surgery, it might be useful to adopt on-pump beating CABG for AMI patients in critical condition. We consider that different approaches should be applied for surgical revascularization in patients with ACS according to the individual condition (Fig. 1). For patients with UA without leakage of cardiac enzymes, OPCAB is the preferred first choice operative procedure. If the patient had preoperative IABP, OPCAB can be completed with stable hemodynamics and conversion will rarely be needed. If they do not have preoperative IABP, that might be useful prior to surgery. On the other hand, for patients with
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4.
5.
6.
7. Fig. 1 Our strategy for coronary artery bypass grafting for acute coronary syndrome
NSTEMI who already have myocardial ischemia, even though OPCAB may be an ideal procedure if tolerated, onpump beating CABG should be applied whenever patients show signs of hemodynamic instability to avoid intraoperative conversion. Patients with STEMI are usually in an unstable condition, thus on-pump CABG should be used from the beginning. In such cases, on-pump beating CABG might be better to avoid the adverse effects of cardioplegic arrest and improve outcome in these critical situations. There are several limitations to our study. First, this was a clinical review of patients with ACS who underwent CABG and no random selection of surgical procedure choice was possible due to the critical conditions of the patients. Second, the number of patients in each study group was small, making it difficult to draw specific conclusions from the findings. Further study is needed to clarify the optimal method of CABG for ACS patients. In conclusion, in patients with ACS, OPCAB might have beneficial effects for those with UA, while IABP was found to be essential for completing OPCAB. In patients with AMI, on-pump beating CABG may be a reasonable option for avoiding conversion from OPCAB and ischemic perfusion injury. Conflict of interest
None.
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stroke in off-pump coronary artery bypass grafting versus onpump coronary artery bypass grafting versus percutaneous coronary intervention. Am J Cardiol. 2012;110:1773–8. Golding LA, Loop FD, Peter M, Cosgrove DM, Taylor PC, Phillips DF. Late survival following use of intraaortic balloon pump in revascularization operations. Ann Thorac Surg. 1980;30:48–51. Bradley EH, Herrin J, Wang Y, Barton BA, Webster TR, Mattera JA, et al. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med. 2006;355:2308–20. Tomasco B, Cappiello A, Fiorilli R, Leccese A, Lupino R, Romiti A, et al. Surgical revascularization for acute coronary insufficiency: analysis of risk factors for hospital mortality. Ann Thorac Surg. 1997;64:678–83. Sergeant P, Blackstone E, Meyns B. Early and late outcome after CABG in patients with evolving myocardial infarction. Eur J Cardiothorac Surg. 1997;11:848–56. Thompson CR, Buller CE, Sleeper LA, Antonelli TA, Webb JG, Jaber WA, et al. Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we use emergently revascularize Occluded Coronaries in cardiogenic shocK? J Am Coll Cardiol. 2000;36(3 Suppl A):1104–9. Perrault LP, Menasche´ P, Peynet J, Faris B, Bel A, de Chaumaray T, et al. On-pump, beating-heart coronary artery operations in high-risk patients: an acceptable trade-off? Ann Thorac Surg. 1997;64:1368–73.
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ORIGINAL ARTICLE
Optimal coronary artery bypass grafting strategy for acute coronary syndrome Hiroyuki Nishi • Taichi Sakaguchi • Shigeru Miyagawa • Yasushi Yoshikawa • Satsuki Fukushima • Daisuke Yoshioka Tetsuya Saito • Koichi Toda • Yoshiki Sawa
•
Received: 24 September 2013 / Accepted: 2 December 2013 Ó The Japanese Association for Thoracic Surgery 2013
Abstract Objective Conventional coronary artery bypass grafting (CABG) using cardiopulmonary bypass and cardiac arrest is associated with higher mortality and morbidity rates in acute coronary syndrome (ACS) patients undergoing surgery. Although off-pump CABG (OPCAB) is beneficial for high-risk patients, its efficacy for ACS is unknown, with on-pump beating CABG an adjunctive method. We investigated the effects of OPCAB and on-pump beating CABG for ACS. Methods We evaluated 121 consecutive patients with ACS (91 males, 30 females; mean age 69.5 ± 10.3 years) who underwent CABG since 2000. Seventy-five had unstable angina (UA) and 46 acute myocardial infarction (AMI) [nonST elevation (NSTEMI): 22, ST elevation (STEMI): 24]. We assessed CABG for acute coronary syndrome under our primary OPCAB strategy, and compared perioperative status between UA and AMI patients. Results (1) Sixty-five (87 %) with UA underwent OPCAB, 8 on-pump beating CABG, and 2 conventional CABG. Conversion from OPCAB was seen in 4 patients. In-hospital mortality was 1.3 %. (2) All UA patients who had intra-aortic balloon pumping (IABP) underwent OPCAB. No patients with preoperative IABP experienced conversion from OPCAB. (3) In AMI patients, hospital mortality was higher (8.9 %) and the ratios for OPCAB, Presented at the 64th Annual Scientific Meeting of the Japanese Association for Thoracic Surgery. H. Nishi T. Sakaguchi S. Miyagawa Y. Yoshikawa S. Fukushima D. Yoshioka T. Saito K. Toda Y. Sawa (&) Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan e-mail: [email protected]; [email protected]
on-pump beating CABG, and conventional CABG were 39, 57, and 4 %, respectively. Mortality was exclusively seen in patients with STEMI who underwent conventional CABG. Conclusions OPCAB might have beneficial effects for ACS patients with UA, while IABP was found essential for completing OPCAB. In AMI patients, on-pump beating CABG might be reasonable for avoiding conversion from OPCAB and ischemic perfusion injury. Keywords Acute coronary syndrome Coronary artery bypass grafting Myocardial infarction Beating heart surgery
Introduction Despite recent advances in coronary artery bypass grafting (CABG) technology, the results for acute coronary syndrome (ACS) are still unfavorable as compared to elective CABG [1–7]. Patients with ACS often require percutaneous catheter intervention (PCI) or CABG to relieve myocardial ischemia on an emergency basis [8], and are more likely to have greater risk of postoperative morbidities as compared to those undergoing an elective operation. Furthermore, ACS represents a continuum from unstable angina (UA) to acute myocardial infarction (AMI) with or without ST-segment elevation, and previous studies of ACS have presented a variety of ratios of patients with UA or AMI. Thus, previously reported results are not consistent and difficult to generalize [1–7, 9–11]. Although patients with UA showed relatively lower mortality in those previous studies, high mortality rates have been noted in patients undergoing surgery after confirmation of ST-segment elevation myocardial infarction (STEMI) [9–11].
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With recent developments in surgical instruments such as stabilization devices and intracoronary shunts, CABG without cardiopulmonary bypass (CPB) has become widely accepted as a primary strategy [12, 13]. This type of offpump CABG (OPCAB) has several benefits by avoiding the adverse effects of CPB and cardiac arrest such as postperfusion syndrome, and is considered to provide favorable results especially for high-risk older patients [14], and those with renal or neurological dysfunction [15]. However, this technique is not always beneficial, because patients requiring intra-operative conversion from offpump to on-pump surgery have been reported to have a worse outcome than those with successfully completed OPCAB surgery [16]. Furthermore, intermediate strategies such as beating heart surgery with CPB (on-pump beating CABG) have also been utilized for CABG [17]. Although these OPCAB and on-pump beating CABG methods may have benefits to reduce postoperative morbidity for managing high-risk patients in an emergency situation, the exact roles of OPCAB and on-pump beating CABG for patients with ACS who are in critical condition requiring emergency CABG have not been established. In addition, the extent of myocardial ischemia may have an impact on these strategies. In this study, we evaluated our results of CABG for ACS under our primary OPCAB strategy to clarify the optimal strategy for choosing between OPCAB and on-pump beating CABG.
Patients and methods OPCAB was introduced as a primary surgical strategy for CABG at our institution in 2000, after which a total of 595 patients have undergone isolated CABG. Of those, 121 patients were diagnosed with ACS and enrolled in this study (91 males, 30 females; mean age 69.5 ± 10.3 years). The definitions of ACS and AMI followed American College of Cardiology/American Heart Association Guidelines published in 2007 [18]. Briefly, diagnosis of AMI was made based on conventional electrocardiography (ECG) findings, in addition to enzyme or cardiac troponin criteria, and confirmed using acute coronary angiography. Patients with ongoing angina without AMI characteristics in ECG findings and no leakage of cardiac biomarkers were defined as UA. There were seventy-five patients diagnosed with UA, and AMI was present in 46. Of these, 24 had STEMI and 22 were non-STEMI (NSTEMI). Intra-aortic balloon pumping (IABP) was utilized preoperatively in 46 patients. Eighteen patients had a history of cardiogenic shock and 4 were in cardiogenic shock at the time of treatment. The baseline characteristics of each group are shown in Table 1.
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Table 1 Patients’ characteristics in UA and AMI groups
Age (years)
UA (n = 75)
AMI (n = 46)
p value
69.2 ± 10.2
70.3 ± 10.6
NS
Gender (male/female)
54/21
35/11
NS
Hypertension
44 (59 %)
29 (63 %)
NS
Diabetes
31 (41 %)
23 (50 %)
NS
Hyperlipidemia
33 (44 %)
6 (13 %)
NS
Chronic obstructive lung disease
3 (4 %)
7 (15 %)
NS
Cerebrovascular disease
12 (16 %)
8 (17 %)
NS
Renal dysfunction
40 (53 %)
23 (50 %)
NS
Left ventricular ejection fraction
58.6 ± 15.4
46.6 ± 13.1
\0.01
Preoperative IABP
16 (21 %)
30 (65 %)
\0.01
Preoperative PCPS
0
4 (9 %)
\0.01
Cardiogenic shock
2 (3 %)
16 (35 %)
\0.01
STEMI
–
24 (52 %)
–
UA unstable angina, AMI acute myocardial infarction, IABP intraaortic balloon pumping, PCPS percutaneous cardio-pulmonary support
Although we adopted a primary OPCAB strategy for isolated CABG in 2000, the selection of the operative method to perform CABG for ACS in the present patients was based on the preference of the attending surgeon, who assessed preoperative hemodynamics, concomitant diseases, and extent of ACS, and finally made a decision to use OPCAB, on-pump beating CABG, or conventional CABG with cardiac arrest. We evaluated preoperative status and perioperative outcomes in each group, as well as the ratio of selected adjunctive methods for CABG in each. We also investigated the ratio of conversion from OPCAB to on-pump CABG and factors related to completion of OPCAB to clarify the optimal strategy for ACS patients. Informed consent for this study was obtained from each patient or their family member, following institutional review board approval of the study. Surgical technique A median sternotomy was routinely performed and the internal thoracic artery (ITA) harvested. Intravenous heparin (200 IU/kg for OPCAB, 300 IU/kg for on-pump CABG) was administered just before completion of ITA and saphenous vein graft (SVG) harvest. OPCAB was performed using a single pericardium traction suture, an epicardial stabilizer (Octopus; Medtronic, Minneapolis, MN, USA), and a heart positioner (Starfish; Medtronic). All anastomoses were performed using 7-0 or 8-0 polypropylene sutures. Preconditioning was not routinely performed, while an intra-coronary shunt was routinely
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used, especially for left anterior descending artery (LAD) anastomosis. Our revascularization strategy includes performing an LAD graft, followed by the culprit lesion and then other vessels. For LAD revascularization, ITA was routinely applied. To achieve hemodynamic stability, a combination of the following actions was performed; Trendelenburg position and fluid transfusion were used to compensate for preload decrease, and inotropes were utilized to increase coronary blood flow and stroke volume. When on-pump CABG was selected, cardiopulmonary bypass was established by standard ascending aortic and right atrial cannulation, and the same devices were used when on-pump beating CABG was chosen. The graft strategy was the same as used for OPCAB. When cardiac arrest was selected, blood cardioplegia with antegrade or retrograde application was used for myocardial protection. The order of anastomosis was the culprit lesion first, followed by other vessels, with the bypass to LAD performed at the end. Statistical analysis Data were analyzed using Statview 5.0 (SAS Institute Inc, Cary, NC). Results are expressed as the mean ± standard deviation. A Mann–Whitney U test was used for comparison of continuous variables and Fisher’s exact test for comparisons of frequencies between the groups. Long-term survival and freedom from major adverse cardiac events were calculated using the Kaplan–Meier method. A p value of less than 0.05 was used to select variables for entry into the multivariate model. Statistical significance was accepted at p B 0.05.
Results Preoperative status The preoperative characteristics in each group are shown in Table 1. There were no statistically significant differences between the groups with regard to age, gender, and other comorbidities such as hypertension, diabetes, hypercholesteremia, chronic obstructive lung disease, and history of stroke. The number of diseased vessels and incidence of left main disease were equally distributed (Table 2). On the other hand, preoperative left ventricular ejection fraction (LVEF) was significantly lower in the AMI group as compared to the UA group, while the ratio of IABP and preoperative mechanical support was significantly higher in the patients with AMI. The rate of percutaneous catheter intervention (PCI) was higher in the AMI group as compared to the UA group (Table 2).
Table 2 Perioperative coronary artery disease related results in UA and AMI groups UA (n = 75)
AMI (n = 46)
p value
1 vessel disease
1 (1 %)
2 (5 %)
NS
2 vessel disease 3 vessel disease
19 (25 %) 55 (73 %)
7 (15 %) 37 (80 %)
NS NS
Number of diseased vessels
33 (44 %)
23 (50 %)
NS
Previous PCI
Left main trunk disease
16 (21 %)
17 (37 %)
NS
Failure of PCI
5 (7 %)
11 (24 %)
\0.05
Total bypass number
3.3 ± 1.0
3.2 ± 1.0
NS
Off-pump CABG
65 (87 %)
18 (39 %)
\0.05
On-pump beating CABG
8 (12 %)
26 (57 %)
\0.05
On-pump arrest CABG
2 (1 %)
2 (4 %)
NS
98.4 %
97.7 %
NS
Left internal thoracic artery
100 %
100 %
NS
Right internal thoracic artery
97.2 %
100 %
NS
Radial artery
100 %
83 %
NS
Gastroepiploic artery
83 %
100 %
NS
Saphenous vein
98.4 %
97.4 %
NS
Early graft patency
UA unstable angina, AMI acute myocardial infarction, PCI percutaneous catheter intervention, CABG coronary artery bypass grafting
Ratio of OPCAB and role of IABP in UA group OPCAB was completed in 65 of the UA patients (87 %). In patients with on-pump CABG, on-pump beating CABG was chosen in 8 and conventional cardiac arrest was adopted in 2. The reasons for using cardiopulmonary bypass were conversion from OPCAB in 4, unstable condition in 4, low ejection fraction in 1, and preoperative hemodynamic instability in 1. The mean number of distal anastomoses was 3.3 ± 1.0 in patients with OPCAB, 3.6 ± 1.1 in those with on-pump beating CABG, and 2.0 ± 0.0 in those with on-pump arrest. All patients who converted from OPCAB to on-pump CABG had on-pump beating CABG because of hemodynamic instability. Thirteen patients in the UA group had preoperative IABP, of whom 11 patients (85 %) were planned to undergo OPCAB. All of these were able to complete OPCAB and none required conversion from OPCAB to on-pump CABG. Furthermore, no patients who experienced intraoperative conversion from OPCAB to on-pump CABG had preoperative IABP. Patients who needed conversion from OPCAB to on-pump CABG did not have preoperative IABP. Ratio of OPCAB in AMI group Eighteen of 46 (39 %) AMI patients underwent OPCAB. When patients with preoperative cardiopulmonary bypass were excluded, the ratio was 44 %. On the other hand, the
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majority (57 %) of AMI patients underwent on-pump beating CABG. Of those, IABP was used in 20. Three patients converted from OPCAB to on-pump CABG and the main reason was preoperative hemodynamic instability. As for patients with STEMI, 25 % had OPCAB, while 55 % of patients with NSTEMI completed OPCAB. The mean number of distal anastomoses was 2.5 ± 0.8 in patients with OPCAB, 3.6 ± 1.0 in those with on-pump beating CABG, and 2.0 ± 0.0 in those with on-pump arrest.
Long-term outcomes
Postoperative outcomes (Table 3)
Discussion
Thirty-day mortality and in-hospital mortality rates in patients with UA were significantly lower than in those with AMI (0 vs. 4.4 %, p \ 0.05; 1.3 vs. 8.9 %, p \ 0.05, respectively). The cause of death in the 1 patient with UA was infection. This patient had preoperative IABP and underwent OPCAB, while LVEF was 41 % and chronic renal failure was present. Among the 4 patients with AMI who did not survive, 3 had preoperative percutaneous cardiopulmonary support and the other had LVEF of 30 % and was on IABP preoperatively. All had STEMI and all deaths were due to low cardiac output syndrome. There was no significant relationship between preoperative creatine phosphokinase (CK) or CK-MB and mortality (nonsurvivor vs. survivor: 519 ± 302 vs. 784 ± 1015 IU/L, NS; 56 ± 30 vs. 83 ± 139 IU/L, NS, respectively). Postoperative major complications were more frequent in the AMI group (22 %) as compared to the UA group (8 %). Significant differences were observed regarding occurrence of postoperative stroke, respiratory complications, and deep sterna infection. In four patients with stroke, 3 had on-pump beating CABG including 2 preoperative PCPS patients. There was no relationship between conversion from OPCAB to on-pump and postoperative complications. Early graft patency results are shown in Table 2. Total patency in patients with UA was 98.4 and 97.7 % in those with AMI. There were no significant differences for patency rates with regard to the type of graft in both groups.
The main finding in this study was that the ratio of OPCAB was higher in patients with UA than in those with AMI who were treated under our primary OPCAB strategy for ACS. Also, even though operative mortality in the UA patients was acceptable (1.3 %), the mortality rate in that group was still high (8.9 %). Recent reports of CABG for ACS have revealed various postoperative outcome findings, because the ratios of UA and AMI patients were quite different. Zembala et al. [3] reported that the 30-day mortality of their study cohort (UA 55 %, AMI 45 %) was 5.7 %, whereas Ben-Gal et al. [2] noted a 30-day mortality of 2.5 % in a study cohort that only included patients with non-ST elevated MI. Furthermore, Hagl et al. [9] reported a high mortality (20 %), but only included ST-elevated MI patients. Therefore, to elucidate the optimal strategy of CABG for ACS, it is better to distinguish UA from AMI patients and separately evaluate the results. In our patients with UA, the OPCAB completion rate was 87 % and the 30-day mortality rate was similar to previous reports of elective CABG cases [19, 20]. This favorable result may have been due to the various favorable effects of OPCAB. The advantage of OPCAB has been widely discussed and some evidence established. For example, OPCAB reduces the amount of bleeding or perioperative transfusion required [21, 22], and is associated with favorable outcome in patients with chronic kidney disease [15]. Avoidance of cardiopulmonary bypass also reduces possible side effects related to inflammatory response [23]. Also, an aorta-non-touch technique without using CPB has great advantage for avoiding postoperative stroke [24]. Although many reports have described no significant differences regarding postoperative outcome between OPCAB surgery and conventional on-pump CABG, recent consensus is that OPCAB is beneficial at least for CABG in high-risk patients. Patients with ACS are usually treated in an emergency situation and generally in critical condition, while they often have a history of treatment anti-platelet agents, as well as unknown or uncontrolled comorbidities. Therefore, these patients are high risk and OPCAB may provide favorable effects.
Table 3 Mortality and morbidity UA (n = 75)
AMI (n = 46)
p value
30-day mortality
0
2 (4.4 %)
\0.01
In-hospital mortality
1 (1.3 %)
4 (8.9 %)
\0.01
Reoperation for bleeding
3 (4.0 %)
3 (6.7 %)
NS
Stroke
0
4 (8.9 %)
\0.01
Pneumonia
2 (2.6 %)
7 (15.6 %)
\0.01
Deep sternal infection
1 (1.3 %)
1 (2.2 %)
\0.05
UA unstable angina, AMI acute myocardial infarction
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Overall survival was similar between the UA and AMI groups. The 10-year survival rate in the UA group was 72.3 %, while that in AMI was 49.6 %. In patients with AMI, there was no significant difference regarding longterm outcome between those with STEMI and with NSTEMI.
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The most serious disadvantage of OPCAB is conversion from OPCAB to on-pump CABG during the procedure, which can occur during displacement of the heart for exposure of the target vessels. The mortality rate for cases with conversion has been reported to be much higher than for those with other CABG procedures [16]. It is important to establish an optimal OPCAB strategy for patients with ACS to avoid intraoperative conversion. Preoperative placement of IABP facilitates safe heart luxation or manipulation during the procedure, and may be a viable option to overcome hemodynamic instability. Even when the heart was lifted for anastomosis of the lateral or inferior surface, the present patients with IABP had stable hemodynamics and it was not difficult to maintain blood pressure, because augmentation of diastolic pressure provided adequate coronary perfusion. Furthermore, following anastomosis of the LAD, it becomes easier to maintain a stable hemodynamic condition. One report found that delayed use of IABP was associated with increased mortality, whereas the rates of perioperative myocardial infarction and in-hospital mortality were significantly lower among patients for whom IABP was initiated preoperatively [25]. In the present study, no patients with UA who experienced intraoperative conversion from OPCAB to on-pump CABG had preoperative IABP, whereas UA patients who needed conversion from OPCAB to on-pump CABG did not have preoperative IABP. Therefore, we consider that IABP may have an important role for completion of OPCAB in patients with UA. Because of fibrinolytic therapy, PCI is the preferred first-line therapy for AMI [26]. However, since AMI patients who require CABG tend to have increased complications and multi-vessel disease, mortality associated with emergency CABG remains high [9]. Our results also showed higher rate of major adverse cardiac event, which was probably due to higher ratio of critical patients. Patients with AMI should be divided into two groups, those with NSTEMI and those with STEMI. Patients in the former group demonstrate ongoing ischemia and leakage of cardiac enzymes, though they are usually in a relatively stable condition like UA patients. Although some patients in the former group might undergo successful OPCAB with or without IABP, there is a lack of results. Various reports that included both STEMI and NSTEMI patients have rarely reported the success rate of OPCAB for patients with NSTEMI [1–7]. The strongest influence on perioperative risk has been found when the procedure was performed during evolving infarction, while the most frequent reason for mortality was reported to be low cardiac output and perioperative infarction, which are both strongly related to preoperative evolving infarction. Also, this situation is related to the occurrence of conversion from OPCAB to on-pump CABG. Therefore, it is important to establish an
optimal strategy according to individual patient status. On the other hand, patients with STEMI are usually in an extremely unstable condition, as some are in a shock condition and require preoperative PCPS. They also have a high mortality rate ranging from 21.3 to 46.7 % [27–29]. The only solution for this problem may be to maintain hemodynamic condition as stable as possible. Once surgery becomes a possible option, it is important to restore coronary blood flow and avoid global myocardial ischemia as soon as possible, which might achieve a faster postoperative cardiac recovery. A surgical approach allows complete revascularization and offers a variety of techniques depending on the condition and stability of the patient, while the questions of whether to use cardioplegia, perform assisted beating heart surgery, or even utilize an off-pump coronary bypass graft are the subjects of controversial discussions. Theoretically, OPCAB seems to be an ideal procedure for high-risk patients. However, as noted above, patients with AMI are in an unstable condition, with insufficient blood flow not only for the coronary arteries but also for other organs. An appropriate circulatory support system should be applied to improve hemodynamic status and compensate visceral organ perfusion in such cases. In addition, ischemic reperfusion injury is another issue to be considered. Aortic cross clamping and cardioplegic arrest might induce myocardial and systemic organ damage during a critical condition such as ongoing myocardium necrosis [30]. From these points of view, on-pump beating heart CABG is an attractive technique that maintains a heartbeat with the aid of cardiopulmonary bypass, but without aortic cross clamping or cardioplegic arrest. Avoidance of cardioplegic arrest can eliminate intraoperative global myocardial ischemia, which might contribute to myocardial protection. Furthermore, the beating heart can preserve native coronary blood flow, which might reduce myocardial injury. Also, conversion from OPCAB to on-pump, which causes death and serious complications, never occurs in patients who underwent on-pump surgery. In the present study, the main reason for operative mortality was postoperative low cardiac output due to global myocardium damage. To avoid further damage and improve the outcome of surgery, it might be useful to adopt on-pump beating CABG for AMI patients in critical condition. We consider that different approaches should be applied for surgical revascularization in patients with ACS according to the individual condition (Fig. 1). For patients with UA without leakage of cardiac enzymes, OPCAB is the preferred first choice operative procedure. If the patient had preoperative IABP, OPCAB can be completed with stable hemodynamics and conversion will rarely be needed. If they do not have preoperative IABP, that might be useful prior to surgery. On the other hand, for patients with
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4.
5.
6.
7. Fig. 1 Our strategy for coronary artery bypass grafting for acute coronary syndrome
NSTEMI who already have myocardial ischemia, even though OPCAB may be an ideal procedure if tolerated, onpump beating CABG should be applied whenever patients show signs of hemodynamic instability to avoid intraoperative conversion. Patients with STEMI are usually in an unstable condition, thus on-pump CABG should be used from the beginning. In such cases, on-pump beating CABG might be better to avoid the adverse effects of cardioplegic arrest and improve outcome in these critical situations. There are several limitations to our study. First, this was a clinical review of patients with ACS who underwent CABG and no random selection of surgical procedure choice was possible due to the critical conditions of the patients. Second, the number of patients in each study group was small, making it difficult to draw specific conclusions from the findings. Further study is needed to clarify the optimal method of CABG for ACS patients. In conclusion, in patients with ACS, OPCAB might have beneficial effects for those with UA, while IABP was found to be essential for completing OPCAB. In patients with AMI, on-pump beating CABG may be a reasonable option for avoiding conversion from OPCAB and ischemic perfusion injury. Conflict of interest
None.
8.
9.
10.
11.
12.
13.
14.
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