Abstract

Background: In this study, we present our results with complete revascularization in patients with acute coronary syndrome undergoing coronary artery bypass grafting on beating heart.

Methods: Between January 2014 and December 2014, a total of 48 patients (37 males; 11 females; mean age 62±10 years; range, 41 to 82 years) who underwent complete revascularization on beating heart with a diagnosis of acute coronary syndrome were retrospectively analyzed. Initial procedure consisted of the left internal thoracic artery-left anterior descending artery grafting in all patients. Following the revascularization of the left anterior descending artery, remaining anastomoses were performed. Postoperative intensive care unit parameters, 30-day mortality rate, and altered left ventricle systolic function were recorded.

Results: The mean number of bypass graft anastomoses were 2.7±1.2 (range, 1 to 5) during a mean time of 49.2±2 (range, 10 to 122) min. The mean time from the onset of angina symptoms to surgery was 32.3±40 (range, 1 to 216) hours. One-third of the patients did not require any inotropic support postoperatively, while three patients required intraaortic balloon pump support. Two patients requiring intensive inotropic support and IABP during the immediate postoperative period died on postoperative Days 1 and 3, respectively. Another patient died due to complications associated with prolonged intensive care unit stay on postoperative Day 27. The mean time to discharge was 8.4±3.8 (range, 3 to 27) days in the remaining patients.

Conclusion: Our study results suggest that complete revascularization on a beating heart can be safely applied in the first-line setting in experienced centers for the surgical management of acute coronary syndrome, as it reduces systemic inflammatory response which may, otherwise, result from cardiopulmonary bypass, prevents global ischemia, and enables rapid reperfusion.

Patients with acute coronary syndrome (ACS) may exhibit varying degrees of clinical severity at presentation from a hemodynamic stability to cardiogenic shock.[1] In hemodynamically unstable patients, apart from percutaneous coronary intervention (PCI), off-pump coronary artery bypass grafting (OPCABG) can be performed as the revascularization method.[1] While revascularization is frequently achieved by the use of stenting in the target lesion, only 5% of the cases with ACS are operated.[1]

Due to high risk of morbidity and mortality, coronary artery bypass grafting (CABG) in ACS patients is preferred for those who are hemodynamically unstable or not amenable to PCI, or in those who have severe threevessel disease or left main coronary artery (LMCA) lesions.[2] Surgical revascularization r educes t he r isk of major cardiovascular complications in multivessel ACS by enabling complete revascularization.[3] In patients with cardiogenic shock, as well as in stable cases requiring emergency/early surgery, OPCAB has been reported to have similar morbidity and mortality, compared to on-pump coronary artery bypass grafting (ONCABG) under cardiopulmonary bypass (CPB).[2,4-6]

Currently, no consensus on the ideal timing of CABG after ACS is available, partly due to the need to address the balance between the adverse effects of the systemic inflammatory response on injured myocardium caused by CPB against the benefits of the procedure in each patient individually.[1] Complete revascularization with OPCABG can be performed irrespective of the time from the onset of ACS symptoms to reduce the risk of ischemia-reperfusion injury and to prevent the systemic complications of CPB.[7] In this article, we present our results with complete revascularization in patients with ACS undergoing OPCABG.

Methods

Between January 2014 and December 2014, patients with ACS manifestations who underwent surgery in our unit were retrospectively analyzed. In our center, early revascularization is favored for patients with a diagnosis of ACS, and those with an indication for CABG are operated as early as possible. In addition, ONCABG is given precedence over other procedures. During this time period, OPCABG was successfully performed in 48 ACS patients, and none of the patients required CPB. Therefore, demographic characteristics and pre- and postoperative data of a total of 48 patients were analyzed.

The diagnosis of ACS was based to a spectrum of clinical presentations ranging from ST-segment elevation myocardial infarction (STEMI) to non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina.[8] Patients who had left main disease with a SYNTAX score of >32 and three-vessel disease with a SYNTAX score of ≥23 and two-vessel disease without suitability for PCI were considered eligible for surgery. Exclusion criteria were as follows: aforementioned anatomic criteria and ongoing angina and/or hemodynamic instability, and eligibility for PCI. The study protocol was approved by the local Ethics Committee. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Surgery was carried out under general anesthesia. All patients received high-dose nitroglycerine during surgery, as well as norepinephrine infusion to maintain perfusion pressure. After median sternotomy, a left internal thoracic artery (LITA) graft was prepared. Using standard sternum retractors and vacuumactivated stabilizer, distal anastomoses were performed. Initially, left anterior descending (LAD) artery/LITA anastomoses were done to ensure the perfusion of the LAD zone for the later stages of surgery. Subsequently, the coronary artery anastomoses were performed in the diagonal and circumflex artery zones, using several maneuvers including deep pericardial suspension, right-sided rotation of the operation table and rightsided manipulation of the heart, and release of the pericardium and soft tissues. Following completion of the left-sided distal anastomoses in the heart, proximal anastomoses were done using side-clamps. If bypass was also planned for the right coronary artery or its branches, their proximal anastomoses were, then, carried out simultaneously with the left-sided proximal anastomoses. After removal of the sideclamp, the planned right-sided coronary anastomoses were completed. After hemostasis, the surgery was terminated and the patients were transferred to the intensive care unit.

Statistical analysis
Statistical analysis was performed using the Microsoft Office, Excel software (Microsoft Office 2010). All numerical data were expressed in mean ± standard error, while categorical variables were expressed in percentage.

Results

The mean age of the overall patient group was 62±10 (range, 41 to 82) years, and 77% of the patients were males. Table 1 shows the demographic and preoperative data of the patients. The mean time from the onset of angina symptoms to surgery was 32.3±40 (range, 1 to 216) hours. Twelve patients had a preoperative ejection fraction of less than 50%, while the remaining subjects had normal systolic functions. The mean number of bypass graft anastomoses were 2.7±1.2 (range, 1 to 5) during a mean time of 49.2±2 (range, 10 to 122) min. Only 22 patients required blood transfusion. Three patients required revision due to postoperative bleeding (Table 2). Postoperatively, three patients required intra-aortic balloon pump (IABP) support, while 16 patients received no mechanical or pharmacological support. The mean time to discharge was 8.4±3.8 (range, 3 to 27) days. Three patients died in the postoperative period. Of these, two died on postoperative days 1 and 3, after the intensive postoperative inotropic and IABP support. Another patient died on postoperative day 27 due to complications associated with prolonged intensive care unit stay (Table 2). During the postoperative follow-up, no patients had arrhythmia, while none of them needed pacing. The remaining patients were discharged uneventfully with a time to discharge of 8.2±3.9 (range, 3 to 13) days. No patients had perioperative neurological complications and none of them had cardiac problems during follow-up.

Table 1: Preoperative demographical data of the patients

Table 2: Operative findings

Discussion

In patients with cardiogenic shock, surgical revascularization within the first six hours or after day 3 has been reported to reduce perioperative mortality and morbidity.[5,9] Surgery postponed until a period of less severe inflammation with the hope of reduced tissue fragility may prolong the duration of myocardial ischemia and lead to increased myocardial injury. Also, the use of a CPB device may be associated with increased systemic inflammatory response. Earliest possible complete surgical revascularization on a beating heart in patients with ACS may be undertaken in any stage of myocardial stunning with a low perioperative risk. In the present study, we included 48 patients who were surgically treated immediately following the diagnosis of ACS, regardless of the time from the onset of symptoms, and OPCABG was successfully performed with a postoperative mortality of 6% and no need for switch to CPB. Similarly, Fattouch et al.[10] showed that OPCABG reduced early mortality and morbidity in patients with STEMI compared to the conventional procedure. Only twothirds of the patients required low-dose postoperative inotropic support for a mean time of 43 hours. Three patients who died postoperatively had an increased mean intubation time, hospitalization, and need of inotropic support. When these patients were excluded, our results are consistent with the literature data..

In general, current guidelines on ACS management recommend revascularization with stenting of the target vessel in the angiography laboratory, while deferring intervention to other stenotic segments to a later stage.[11,12] In centers where CABG is mostly performed under CPB, complete revascularization is usually postponed, particularly in hemodynamically stable patients with the concerns of prolonged duration of surgery and systemic inflammatory response. However, since this approach leads to a delay in complete revascularization, myocardial remodeling is also delayed. In STEMI with multivessel disease, intervention on all vessels rather than the target lesion alone is associated with a reduced risk of major cardiovascular complications.[3,13] As a result, OPCABG may be safely performed with the advantage of early complete revascularization and low perioperative risk in centers with expertise in such procedures.[14] It also provides improved myocardial protection for ACS, compared to prolonged aortic cross-clamping.[13] The main advantages of OPCABG in high-risk patients include the reduced risk of neurological, renal, and respiratory complications, reduced re-operation due to bleeding, perioperative myocardial infarction, and mortality.[15,16] In addition, OPCABG has been shown to be associated with a reduced need for blood products, shortened duration of hospital and ICU stay with the benefits resulting from the presence of cardiac circulation during the stunning phase.[17-19] Similarly, our patients were extubated in the early postoperative period and less than half required blood replacement therapy. Therefore, not only the systemic inflammation due to myocardial infarction, but also the effects of CPB and blood products have been minimized.

In patients with ACS, severe narrowing or reduced blood flow in a vessel not caused by an infarction may reduce systolic functions, thereby, increasing the risk for cardiovascular events.[20] A stepwise approach or complete revascularization at the time of presentation have been reported to reduce the risk of major cardiovascular events in STEMI.[3,20] Early complete revascularization results in a rapid improvement in cardiac systolic functions and provides maximum long-term protection of ejection fraction. Although early surgical revascularization is basically similar to primary percutaneous transluminal coronary angioplasty (PTCA), it offers an additional benefit of enabling the surgeon to intervene on long segments or calcified lesions.[5] Although patients referred to CABG frequently have more complex coronary lesions, the 30-day and one-year mortality in both procedures have been reported to be comparable.[5] In our series, despite the confirmed diagnosis of ACS prior to surgery, the requirement for inotropic support was minimal and the patients were discharged on postoperative day 8 with systolic functions comparable to their baseline values.

Furthermore, revascularization with percutaneous interventions or CABG may be performed in cardiogenic shock developing after acute myocardial infarction (AMI). White et al.[5] reported similar outcomes with PTCA in patients with cardiogenic shock undergoing surgery within the first six hours. However, Weiss et al.[9] reported an increased risk of mortality in patients undergoing CABG within the first two days, compared to those who were operated three or more days later. On the other hand, Parikh et al.[21] reported similar risk levels in NSTEMI patients who were operated not more than 48 hours after admission. Delayed reperfusion in a hibernating-stunning heart may increase myocardial stress levels. When surgery is delayed in hemodynamically stable ACS patients, lowmolecular- weight heparin and clopidogrel used during this period may also increase the risk of bleeding.[21] A low level of 30-day mortality has been reported with OPCABG in hemodynamically stable patients who underwent emergency CABG.[4] Similarly, our patients underwent surgery immediately after the diagnosis was confirmed. Hemodynamic instability did not seem a factor affecting the operative success. According to our results, we can conclude that the patients who have hemodynamic instability have more benefits from OPCABG, compared to stable patients.

Moreover, intracoronary shunts are not routinely recommended in OPCABG, since they may be associated with an endothelial injury. These shunts should be preferred for bypass procedures involving less severe stenosis of coronary arteries supplying large zones.[22] In addition, cardiac manipulation poses a significant risk in OPCABG, particularly in hemodynamically unstable patients with cardiogenic shock. On the other hand, giving priority to the grafting of the lesion supplied by the collateral vessel may reduce this risk. Accordingly, shunts were not routinely utilized in our patients. Anastomosis was completed within 10 min, allowing early perfusion, and shunts were reserved for those with hemodynamic instability during anastomosis. Hemodynamic stability may be achieved by first carrying out LAD anastomosis, followed by the completion of the bypass on the left side, and finally by the anastomosis of the proximal segments. If right-sided bypass is required, priority should be given to the proximal anastomosis during other proximal anastomoses.

In conclusion, early revascularization in patients with acute myocardial infarction allows tissue perfusion at hibernation-stunning stage, before the development of myocardial necrosis, leading to an early improvement of cardiac functions. Subsequently, it increases the long-term life expectancy and functional capacity. In the presence of a coronary lesion causing infarction, complete revascularization improves the ventricular perfusion, thereby, offering the benefit of an increased collateral circulation. Our study results suggest that complete revascularization on a beating heart can be safely applied in the first-line setting in experienced centers for the surgical management of acute coronary syndrome, as it reduces systemic inflammatory response which may, otherwise, result from cardiopulmonary bypass, prevents global ischemia, and enables rapid reperfusion.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

References

1) Caceres M, Weiman DS. Optimal timing of coronary artery bypass grafting in acute myocardial infarction. Ann Thorac Surg 2013;95:365-72.

2) Harling L, Moscarelli M, Kidher E, Fattouch K, Ashrafian H, Athanasiou T. The effect of off-pump coronary artery bypass on mortality after acute coronary syndrome: a metaanalysis. Int J Cardiol 2013;169:339-48.

3) Bajaj NS, Kalra R, Aggarwal H, Ather S, Gaba S, Arora G, et al. Comparison of Approaches to Revascularization in Patients With Multivessel Coronary Artery Disease Presenting With ST-Segment Elevation Myocardial Infarction: Meta-analyses of Randomized Control Trials. J Am Heart Assoc 2015;4(12).

4) Moscarelli M, Harling L, Ashrafian H, Athanasiou T. Should we consider off-pump coronary artery bypass grafting in patients with acute coronary syndrome? Interact Cardiovasc Thorac Surg 2013;16:350-5.

5) White HD, Assmann SF, Sanborn TA, Jacobs AK, Webb JG, Sleeper LA, et al. Comparison of percutaneous coronary intervention and coronary artery bypass grafting after acute myocardial infarction complicated by cardiogenic shock: results from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial. Circulation 2005;112:1992-2001.

6) Ozkaynak B, Yildirim Ö, Aksüt M, Onk OA, Kayalar N, Ömeroglu SN, et al. Very long-term angiographic results of off-pump coronary artery bypass graft surgery. Turk Gogus Kalp Dama 2014;22:260-5.

7) Aksun M, Girgin S, Aksun S, Kestelli M, Bozok Ş, Yurekli I, et al. Comparison of intermittent antegrade cardioplegia and antegrade/retrograde continuous cardioplegia in terms of myocardial protection in cardiac surgery. Turk Gogus Kalp Dama 2015;23:26-31.

8) Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016;37:267-315.

9) Weiss ES, Chang DD, Joyce DL, Nwakanma LU, Yuh DD. Optimal timing of coronary artery bypass after acute myocardial infarction: a review of California discharge data. J Thorac Cardiovasc Surg 2008;135:503-11.

10) Fattouch K, Guccione F, Dioguardi P, Sampognaro R, Corrado E, Caruso M, et al. Off-pump versus on-pump myocardial revascularization in patients with ST-segment elevation myocardial infarction: a randomized trial. J Thorac Cardiovasc Surg 2009;137:650-6.

11) Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. Eur Heart J. 2012 Oct;33(20):2569- 619. doi: 10.1093/eurheartj/ehs215. Epub 2012 Aug 24. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569-619.

12) O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv 2013;82:1-27.

13) El-Hayek GE, Gershlick AH, Hong MK, Casso Dominguez A, Banning A, Afshar AE, et al. Meta-Analysis of Randomized Controlled Trials Comparing Multivessel Versus Culprit- Only Revascularization for Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention. Am J Cardiol 2015;115:1481-6.

14) Biancari F, Onorati F, Rubino AS, Mosorin MA, Juvonen T, Ahmed N, et al. Outcome of emergency coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2015;29:275-82.

15) Lemma M, Coscioni E, Tritto FP, Centofanti P, Fondacone C, Salica A, et al. On-pump versus off-pump coronary artery bypass surgery in high-risk patients: operative results of a prospective randomized trial (on-off study). J Thorac Cardiovasc Surg 2012;143:625-31.

16) Mack MJ, Pfister A, Bachand D, Emery R, Magee MJ, Connolly M, et al. Comparison of coronary bypass surgery with and without cardiopulmonary bypass in patients with multivessel disease. J Thorac Cardiovasc Surg 2004;127:167-73.

17) Chaudhry UA, Harling L, Rao C, Ashrafian H, Ibrahim M, Kokotsakis J, et al. Off-pump versus on-pump coronary revascularization: meta-analysis of mid- and long-term outcomes. Ann Thorac Surg 2014;98:563-72.

18) Deppe AC, Arbash W, Kuhn EW, Slottosch I, Scherner M, Liakopoulos OJ, et al. Current evidence of coronary artery bypass grafting off-pump versus on-pump: a systematic review with meta-analysis of over 16,900 patients investigated in randomized controlled trials†. Eur J Cardiothorac Surg 2016;49:1031-41.

19) Rahman A, Burma O, Uysal A, Bayar MK, Bestas A, Ustundag B. The effect of coronary artery bypass grafting with cardiopulmonary bypass and beating heart technique on cardiac performance. Turk Gogus Kalp Dama 2001;9:68-73.

20) Bangalore S, Kumar S, Poddar KL, Ramasamy S, Rha SW, Faxon DP. Meta-analysis of multivessel coronary artery revascularization versus culprit-only revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease. Am J Cardiol 2011;107:1300-10.

21) Parikh SV, de Lemos JA, Jessen ME, Brilakis ES, Ohman EM, Chen AY, et al. Timing of in-hospital coronary artery bypass graft surgery for non-ST-segment elevation myocardial infarction patients results from the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines). JACC Cardiovasc Interv 2010;3:419-27.

22) Saba D, Goren S, Tekin BH, Aytac IIK, Senkaya I, Ercan A, et al. The effects of position, ischemia and reperfusion to hemodynamics on the beating heart coronary bypass. Turk Gogus Kalp Dama 2003;11:26-31.