Despite technical advances in coronary artery bypass grafting (CABG),

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1 Early Detection and Control of Perioperative Ischemia After Coronary Artery Bypass Grafting Mohamed M. Abdel Aal MD* Ahmad A. AlShaer MD ** * Division of Cardiac Surgery, **Division of Anesthesia, Heart Sciences Department, King Fahad Cardiac Center, College of Medicine at King Saud University Riyadh, Kingdom of Saudi Arabia. malaal2@hotmail.com Codex : o4/24/1111 Background: Despite technical advances in coronary artery bypass grafting (CABG), early postoperative myocardial ischemia still remains a challenging problem. The aim of this study was to determine the clinical features, and management of early graft failure in the present CABG era. Methods: 670 patients underwent CABG at our institution between January 2007 and January Twelve patients out of them had ECG changes and biochemical criteria for myocardial ischemia. Post-operative myocardial ischemia was suspected if the following criteria were present: New changes in the ST- segment in the ECG, rise of biochemical enzymes, recurrent or sustained ventricular tachyarrhythmia, ventricular fibrillation (VF), hemodynamic deterioration and left ventricular failure. Patients with severe hemodynamic instability were rushed to the operating room. Results: 670 Patients underwent CABG; twelve patients out of them (1.79%) were identified as suspected of having post-operative ischemia or infarction. The median age was 63 years (range: years). The median time between the primary and re-operation was 9 hours. Nine patients (75%) out of twelve had circulatory collapse in the intensive care unit and were rushed to the operating room (OR), four of them with repeated ventricular fibrillation (VF) and five with new severe ST-changes with elevated creatine kinase (CK/CK-MB) value above 10%. Three patients (25%) out of twelve developed circulatory collapse after sternal closure. The angiography was done in two patients. Acute vein thrombosis were found in eight patients (66.6%) as well as incorrect anastomosis in two patients (16.6%) and stretched graft in one patient each (8.3%). In one patient no evident cause for their severely impaired hemodynamic status was found. There was one patient in-hospital death. Conclusion: Early graft failure generally presents with ST segment change and elevation of CK/CK-MB ratio. Graft occlusion or thrombosis is the leading cause of ischemia. Patients with circulatory collapse could be saved by an immediate reoperation without preceding angiography with low risk. Keywords: Coronary graft failure, coronary angiography, post-cabg. Despite technical advances in coronary artery bypass grafting (CABG), early postoperative complications are still associated with a significant in-hospital morbidity and mortality. Perioperative myocardial infarction (PMI) is one of the major complications after CABG. 1 Early ischemia or infarction after CABG is based upon different graft-related and non-graft-related mechanisms. Early graft failure like graft occlusion, graft kinking, overstretching, subtotal anastomotic stenosis, or graft spasm is the most common graft-related reasons for early ischemia after CABG. Graft occlusion can be caused by thrombosis due to poor quality of the graft or recipient artery, by technical deficiencies related to the newly inserted graft, or by the size of the native coronary artery. 2 The early detection of post-operative ischemia is important for optimal patient management to prevent in-hospital mortality. Early re-intervention like coronary artery stenting or immediate reoperation even in case of early graft failure may salvage or limit myocardial damage, thus improving patient outcome. 3 Clinical presentation of early graft failure is dominated by postoperative myocardial ischemia could be a result of a spasm, left ventricular dysfunction, life-threatening ventricular arrhythmias and 152 Journal of The Egyptian Society of Cardio-Thoracic Surgery Jul - Dec 2011

2 hemodynamics instability. Localized ST changes indicate a high probability of graft failure and especially in combination with high levels of creatine kinase (CK-MB) isoenzyme.4 Although cardiac isoforms of troponins, are supposed to be more specific and sensitive as indicators of myocardial necrosis than conventional cardiac enzymes like creatine kinase (CK) particularly in the postoperative period after cardiac surgery, the identification of patients with PMI induced by early graft failure remains unclear. 5 Coronary angiography remains the gold standard for assessment of graft patency, but this invasive procedure is not routinely performed after CABG. Coronary angiography has proven to be safe and precise to confirm early graft failure. 6 Our intentions with this study were to determine the incidence, clinical features and to identify early post-operative ischemia, visualize the cause and start treatment before permanent myocardial damage occurred in patients who underwent CABG. Patients & Methods Between January 2007 and January 2010, 670 patients were identified from the our database underwent isolated CABG at the Department of Cardiac Surgery in King Fahad cardiac center, Riyadh, Saudi Arabia. Twelve patients (1.79%) out of them developed signs of early post-operative ischemia. Operative Procedures Anesthesia was standardized in all patients. Left internal mammary artery (LIMA) and saphenous vein grafts were used as graft conduits in all patients. Proximal graft anastomoses to the aorta were performed with partial occlusion of the ascending aorta. Heparin was administered in order to achieve an activated coagulation time above 400 seconds. Standard cardiopulmonary bypass (CPB) technique was used with ascending aortic and two-stage venous cannulation. Myocardial protection was achieved using antegrade warm blood cardioplegic arrest and single aortic cross clamping for all distal anastomosis. Intra-operative graft flow measurement (Cardiomed, MediStim, Oslo, Norway) was routinely applied after CPB just before sternal closure under stable hemodynamic conditions for each graft. Postoperative Management: Postoperative management was standardized; patients were monitored with arterial pressure, pulmonary pressure, and central venous pressure immediately after the arrival on the intensive care unit. A 12-lead electrocardiogram (ECG) was obtained and repeated at least four times within the first 24 hours (hrs) and once every 24 hrs till patient discharge. CK and CK-MB values were obtained and analyzed immediately after surgery and six hourly during the first 24 hrs post-operatively,then 12 hourly in the second post-operative day and once daily for next 3 days post-operatively. Aspirin therapy restarted within the first post-operative while heparin administered intravenously (IV) after 24 hrs of surgery provided there is no significant bleeding. Hospital death was defined as death occurring during the first 30 days after CABG. Myocardial ischemia suspected if: (a) increase in the isoenzyme ratio of CK/CK-MB above 10%, (b) ischemic electrocardiographic episodes (new onset of elevated ST-segment change which were verified with the use of the ECG monitor print out (ECG complexes) and a 12 leads electrocardiogram., (c) recurrent episodes of, or sustained ventricular tachyarrhythmia as well as ventricular fibrillation, (d) hemodynamic deterioration and left ventricular failure despite maximum inotropic support. A diagnostic repeat angiography was performed in two patients who were more stable postoperatively. All unsatisfactory grafts were substituted, when possible with new graft material. If the graft was thrombosed, the thrombotic material has to be removed and the vessel rinsed for possible reuse. LIMA can be re-used if a good flow can be established. If a small caliber of LIMA was suspected to be a possible cause of ischemia, a vein graft was added. The incision in the coronary artery was extended to facilitate and improve the new anastomosis. Inotropic drugs, intra-aortic balloon pump (IABP) or left ventricular assist device (VAD) were used when required to wean the patient from cardiopulmonary bypass. Statistical analysis Baseline characteristics and other categorical variables are presented as median, mean ± standard deviation, or as percentage of total patients. Results 670 patients underwent CABG; twelve of them (1.79%) were identified as suspected of having post-operative ischemia or infarction and managed as described above. There were 2 females and 10 males with a median age of 63 years (range: years). The median number of grafts per patient was three. LIMA was used in 11 patients (91.6%). The median aortic cross-clamp time 58±12 minutes. The indications for emergency re-operation in this study were: 1. New changes in the ST-segment, 2. CK/CK-MB value above 10%, 3. Sustained VT or repeated VF, 4. Hemodynamic deterioration due to left ventricular failure. The median time between the primary and re-operation was 9 hours. Nine patients (75%) had circulatory collapse in the intensive care unit and were rushed to the OR with ongoing resuscitation, four of them with repeated VF and five with new severe ST-changes and elevated CK/CK-MB value above 10%.Three patients (25%) out of twelve developed circulatory collapse after sternal closure but before leaving the OR. Journal of The Egyptian Society of Cardio-Thoracic Surgery Volume 19, Number (3-4) 153

3 The angiography was done in two patients, showed graft failure because LIMA dissection and acute vein graft thrombosis. Data are summarized in table 1. No. of Patients % New ST change CK/CKMB > 10% Sustained arrhythmia Hemodynamic deterioration 3 25 Table 1: Indications for re-revascularization. CK: creatine kinase During re-operation, graft occlusions due to acute vein thrombosis were found in eight patients (66.6%) as well as incorrect anastomosis in two patients (16.6%) and one patient (8.3%) with stretched graft. One patient had no evident cause for severely impaired hemodynamic status (table 2). No. of patients % Graft occlusion Incorrect anastomosis Stretched graft No finding Table 2: Intra-operative findings. Most of the patients were weaned without problems from CPB with assistance of IABP which was inserted during re-operation in ten patients; two of them additionally required a temporary extracorporal membrane oxygenation (ECMO) and ventricular assisted device (VAD) (table 3). There was one patient in-hospital death (8.3%) due to severe left ventricular failure. Characteristics No. of patients % LIMA % IABP VAD ECMO Table 3: Procedure-related variables. Data are presented as median (range) or (%). LIMA; left internal mammary artery, IABP: intra-aortic balloon pulsation, VAD: ventricular assisted device and ECMO: extra-corporal membrane oxygenation. Discussion The detection and interpretation of perioperative myocardial ischemia following coronary bypass grafting still remains a challenging problem for the clinician. Graft failure is a constant finding in patients with circulatory collapse early after a CABG and survival after immediate re-operation is possible. 7 The diagnostic criteria to identify patients suspected of early myocardial ischemia or infarction after CABG surgery is more difficult to interpret and less specific than in un-operated patients. ECG changes, especially ST-elevation appearing in many or all leads, have been a recurrent matter of discussion; is it ischemia or post-operative pericarditis? The CPB, manipulation with the heart during surgery and possible suboptimal cardioplegia may also lead to elevated CK-MB values immediately after surgery 8. Clinical presentation of early graft failure is dominated by post-operative myocardial ischemia, left ventricular dysfunction, life-threatening ventricular arrhythmias and hemodynamic instability. Procedure related factors affecting myocardial protection such as hypothermia, type and application of cardioplegia and manipulation of the heart during on pump beating or off pump CABG techniques, may all lead to reperfusion injury and significant rise of CK-MB values 9. In the present study, localized ST-changes followed by an elevation of the CK/CK-MB ratio above 10% and ventricular arrhythmias were the predominant clinical presentation. Fabricus and associates 9 have reported a high mortality rate, ranging from 14.5% to 21.7% with substantial rate of nonfatal complications while Steuer and coworkers 10 reported 1.9% with early deaths in their study. Our hospital mortality was 8.3%, the cause of death was severe left ventricular dysfunction. Previous studies have reported that the incidence of perioperative ischemia is 8 to 35 % in patients undergoing CABG. 11 The lower incidence of early post-operative ischemia in our study (1.79%) is perhaps related to small volume and the presence of a lower risk population in our study. Thielmann and associates 12 demonstrated in their study that the incidence of early graft failure within 24 hrs after CABG is about 1 3%, leading to early post-operative myocardial ischemia and irreversible myocardial cell damage, strongly associated with a higher mortality within 30 days and a higher incidence of major adverse events. However, they mentioned that, the possible benefit of an emergency re-revascularization procedure like percutaneous coronary intervention (PCI) or a reoperation in their clinical setting of myocardial ischemia and its time-dependency is currently unknown. To date, there are no guidelines clearly clarifying this issue. Although, the exact time point of graft failure and the onset of symptoms mostly remain uncertain in the early postoperative course, recent clinical trials have been hypothesized and demonstrated that even delayed reperfusion of infarcted 154 Journal of The Egyptian Society of Cardio-Thoracic Surgery Jul - Dec 2011

4 myocardium may be beneficial by reducing myocardial infarct size, improving myocardial healing and preventing electrical instability 13. Holmvang and coworkers 14 found that the majority of patients presenting with myocardial ischemia after CABG had either graft failure, or incomplete or even inadequate revascularization demonstrated by repeat angiography. Their prospective study confirms that early (within 7 days) graft occlusion is not uncommon, occurring in 8% of vein grafts and 2% of IMA conduits. These occlusion rates are in accordance with previous findings. Importantly, these early graft occlusions are potentially detectable because they are associated with a rise in serum concentration of biochemical markers of infarction. In our study, ST-segment deviation and T-wave changes with rise in serum concentration of biochemical markers of infarction were usually associated with the independent predictor of acute ischemia. ECG, clinical presentation and serial postoperative biochemical data can identify the patients with early graft occlusion after CABG. Interpretation of the ECG data is not conclusive because pericardial involvement and change in heart position might cause ECG changes without concomitant graft occlusion. Some of the limitations associated with the ECG data might be solved if reliable continuous ECG ischemia monitoring in multiple leads could be performed in the ICU. A review by Califf and associates 15 recommend preprocedural and post-procedural ECGs combined with serial measurements of CK-MB for identification of patients with procedure-related myocardial infarction. However, the published consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction 16 points out the difficulties in diagnosing PMI defined as myocardial damage due to coronary artery occlusion, because myocardial damage can be caused by different mechanisms, including direct trauma during the surgical procedure. Nevertheless, the consensus report states that the higher the value for the cardiac biomarker, the greater the amount of damage to the myocardium, irrespective of the mechanism. Our study has limitations The primary limitation of this study is that it is a single centre and analysis of a small group of patients. Thus, our results may not be generalized to other centers. The indication for re-cabg, or conservative treatment was not prospectively defined, but the decision for a secondary revascularization strategy was made case by case. Therefore, the present study may contain a study bias. Clinical implications The feasibility and safety of re-revascularization following CABG at an early stage should encourage cardiac surgeons and cardiologists to implement collaborative efforts when signs of graft failure occur. In conclusion We found that the combination of ST segment change and elevation of CK/CK-MB ratio is highly effective in detecting early graft failure. Patients with graft failure can be re-operated with a low risk, if the patient is hemodynamically stable. Patients with circulatory collapse could be saved by an immediate re- operation without preceding angiography. References 1. Virani SS, Alam M, Mendoza CE, Arora H, Ferreira AC, de Marchena E. Clinical significance, angiographic characteristics, and short-term outcomes in 30 patients with early coronary artery graft failure. Neth Heart J January; 17(1): Thielmann M, Massoudy P, Schmermund A, Neuhauser M, Marggraf G, Kamler K, Herold U, Aleksic I, Mann K, Haude M, Heusch G, Erbel R, Jakob H. Diagnostic discrimination between graft-related and non-graft-related perioperative myocardial infarction with cardiac troponin I after coronary artery bypass surgery. Eur Heart J 2005;26: Lip, GY, Metcalfe, MJ. Have we identified the factors affecting prognosis following coronary artery bypass surgery? Br J Clin Pract 1994;48, Douglas JS. Percutaneous intervention in patients with prior coronary bypass surgery. In Topol EH (ed): Textbook of Interventional Cardiology. Philadelphia. W.B. Saunders Company, 1999, Fellahi J-L, Gue X, Richomme X, Monnier E, Guillon L, Riou B. Short- and long-term prognostic value of postoperative cardiac troponin I concentration in patients undergoing coronary artery bypass grafting. Anesthesiology 2003;99: Onorati F, De Feo M, Mastroroberto P, Cristodoro L, Pezzo F, Renzulli A, Cotrufo M. Determinants and prognosis of myocardial damage after coronary artery bypass grafting. Ann Thorac Surg 2005;79: Thielmann M, Massoudy P, Marggraf G, Knipp S, Schmermund A, Piotrowski J, Erbel R, Jakob H. Role of troponin I, myoglobin, and creatine kinase for the detection of early graft failure following coronary artery bypass grafting. Eur J Cardiothorac Surg 2004;26: Rasmussen C, Thiis JJ, Clemmensen P, Efsen F, Arendrup HC, Saunamäki K, Madsen JK, Pettersson G. Significance and management of early graft failure after coronary artery bypass grafting: feasibility and results of acute angiography and re-revascularization. Eur J Cardiothorac Surg 1997;12: Farbicius AM, Gerbes W, Hanke M, Garbade J, Autschbach R, Mohr F. Early angiographic control of perioperative ischemia after coronary artery bypass grafting. EurJ Cardiothorac Surg 2001;19: Steuer J, Horte LG, Lindahl B, Stahle E. 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