Abstract
Objective: There is wide variations in practice about the exact timing of coronary artery bypass grafting (CABG) post-acute myocardial infarction (AMI) and admission to hospital. This study aims to review current literature evidence to provide an up-to-date evaluation of the optimal CABG timing and parameters indicative of patient outcomes.
Method: Electronic literature search was done to look into articles that discussed acute myocardial presentation and their referral for CABG either as urgent in-patient or as elective cases. The evidence was synthesised based on each reported article and their outcomes.
Results: The timing of CABG following AMI have been explored in multiple studies, however there is no clear consensus on when to proceed with CABG following AMI and this remains controversial. The mortality rates vary with timing of CABG, but confounding factors such as age, poor pulmonary functions, renal insufficiency, poor left ventricular function and many others can all contribute to the variable reported outcomes.
Conclusion: There is need for large, multi-centre study to identify optimal timings for CABG in cases of complex coronary artery diseases or failed PCI in patients with acute MI. Upcoming guidelines should emphasize patient cohorts by taking their risk factors into consideration.
Introduction
Cardiovascular disease (CVD) accounts for an estimated 31% of all annual worldwide deaths.[1] Overtime, the development of atherosclerotic plaques will stenose the coronary vessel wall leading to ischaemia and increasing its susceptibility to rupture. Consequently, through thrombotic vessel occlusion, acute coronary syndrome (ACS) will manifest. ACS is one of the end products of CVD and stands as one of the leading causes of death in developed countries. ACS encompasses angina pectoris and acute myocardial infarctions (AMI).[2] AMI can be divided into either ST-segment elevation MI (STEMI) or non-ST-segment elevation MI (nSTEMI). The former is often associated with complete obstruction of coronary vessel from intraluminal thrombosis due to either erosion or sudden rupture of an atheromatous plaque within the coronary walls.[3] While an nSTEMI is the partial occlusion of a coronary vessel from either an enlarged or ruptured atheromatous plaque, leading to ischaemia. Continued ischaemia can lead to cardiac cell death, loss of heart muscle contractility and life-threatening arrhythmias.[2] Revascularisation procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are the gold standard treatment for ACS. However, successful outcome of treatment depends on effective patient selection and appropriate timing of intervention. Landmark randomised control trials (RCTs) such as; SYNTAX, EXCEL and NOBLE studies have identified sub-group of patients that would benefit from one intervention to the other. Although, there is a time delay in the effect associated with CABG, it is able to replace an occluded vessel entirely and treat multiple diffused lesions, while demonstrating greater durability by decreasing revascularisation rates. Usually patients who benefit from CABG than PCI are those with multiple complex comorbidities such as diabetes and multivessel disease. However, practical and financial constraints continue to pose a barrier for CABG management.[4] Often patients have to wait in hospital after an MI for several weeks before they are scheduled for CABG because of backlogging and the long queues for operation theatres [5].
Due to an ageing population, there has been a significant increase in patients with multivessel diseases and associated comorbidities, thus indicating a need for CABG in clinical practice.[6] However, evidence regarding optimal timing as well as factors determining outcomes, need to be addressed to optimise CABG. There is a clear correlation with patient selection and patient outcome, thus evidence pinpointing the target population that would benefit from CABG is welcomed.[7]Additionally, the lack of standardisation in reporting trial outcomes of cardiac surgery has been raised and adds to the confusing nature of the debate.[8] Development of a standardised outcome reporting system would strengthen the process of evidence-based care in cardiac surgery. The purpose of this literature review is to explore the evidence surrounding the timing of CABG reperfusion in STEMI and nSTEMI patients and draw conclusions about the optimal timing to improve outcomes in these patients.
Method
The literature review was conducted using the electronic database PubMed to find records published between 2005-2020 describing CABG timing and outcomes of post AMI. Records were limited to English and screened for relevant titles/abstracts that reported findings about CABG timing and outcome. Additional findings regarding parameters indicative of CABG patient outcome were also reviewed. Search terms included; CABG, STEMI/nSTEMI, optimal timing and outcome. The evidence was reviewed and synthesised based on each reported article.
PCI and trend of non-elective CABG
For many years, PCI has been preferred in treating STEMI, due to the relative ease of carrying out this procedure, as well as a quicker treatment time when compared to CABG.[9] During STEMI, the urgent need for reperfusion to reduce the risk of cardiac ischaemia and infarction is critical for patient survival. As shown in table 1, revascularisation strategies such as PCI and CABG are often compared, however in different contexts, different strategies will be indicated. The SYNTAX [Synergy Between PCI With Taxus and CABG] score is normally used to stratify CVD patients for either PCI or CABG and ranges from scores 0 to >60. According to literature, patients with low SYNTAX score (<22) is of class IIa and a low-intermediate SYNTAX score (<33) is of class IIb, both are indicated for PCI treatment. While patients with a high SYNTAX score (≥33) exhibit more complex disease and may involve multiple vessels (class I) and these patients will benefit from CABG.[10]
A number of studies have raised the importance of timing in the outcome of PCI and CABG for AMI. Various outcomes reported are subjected to different timing of interventions. However, regardless of timing, CABG has shown to exhibit greater future benefits such as long-lasting preventive effects, as well as significantly improving health-related quality of life (QoL).[11] While, PCI-treated patients have a lower stroke risk, PCI incur a higher revascularisation rate when compared to CABG-treated patients. CABG surgery remains the gold standard treatment option for nSTEMI patients with significant left main disease (LMD) or triple vessel disease (TVD).[12] CABG significantly reduces the risk of death associated with MI or stroke when compared to PCI with drug-eluting stents.[13] However, CABG is associated with an increased likelihood of cerebrovascular events.[14] Presumably higher incidence of stroke among patients is explained to be from an increased systemic inflammatory state caused by AMI.[15] Thus, PCI is preferred in early revascularisation of ischaemia, rather than opting for non-elective CABG.
Although non-elective CABG is rare and not recommended, in situations where patients who fail to have PCI or PCI is not indicated, urgent CABG will be required as last-line treatment. An emergency CABG for STEMI patients must be performed before a 6 hours lapse after the acute event, otherwise it must be postponed from 1 day to 1 month.[16] Patients undergoing non-elective CABG is associated with longer in-hospital stays and increase in healthcare costs, this is mainly due to differences in rates of preoperative stays and additional procedures like angiography and PCI. Moreover, non-elective CABG is reported to increase patients’ risk of myocardial infarction when compared to elective CABG.[17]
CABG offers survival advantage compared to medical therapy for life-threatening situations such as unstable angina and left ventricular (LV) dysfunction. A recent study reported that CABG achieved lower major adverse cardiac evets (MACE) and decreased mortality in patients with severely reduced LV ejection fraction (LVEF) when compared PCI.[18] As oppose to PCI only treating proximal singular lesions, CABG bypasses the proximal 2/3 of vessel, where current lesion and future threatening lesions may occur. This incurs a protective prognostic effect, whereby exhibiting improved long-term survival in the first 8-years for patients with TVD.[19]
Concept of hot CABG
It is widely accepted that ongoing ischemia, unstable refractory angina, and the burden of CVD may influence the timing of CABG and associated with greater hospital mortality rate (HM).[20]Despite CABG exhibit marked advantages of long-term benefits, disadvantages of major surgical risk and recovery time sways patients to less invasive interventions (PCI or thrombolytic therapy).
In the presence of ischaemia, CABG is indicated for patients within 24 hours of presentation, while postponement of CABG can be up to 4-30 days providing there are anatomical indications.[21]However, CABG is often preferred in the later settings, due to evidence showing an increased in mortality for patients being operated within the first 24 hours to 3 days after diagnosis of STEMI. This preference is supported by evidence showing that operative mortality declines with the delaying of CABG.
Advances in perioperative care and myocardial protection have allowed for postponement of CABG treatment in AMI.[14]Nichols et al. reported that patients undergoing CABG within 1 day of MI had higher rates of STEMI and significantly higher HM. Furthermore, patients who had CABG within 1-2 days and 3-7 days after MI, achieved similar mortality rates, suggesting that delaying CABG is possible without sacrificing outcomes.[20] STEMI patients operated within 3 days, were treated less frequently with PCI and glycoprotein IIb/IIIa inhibitors but displayed greater operative risk as expressed in the European System for Cardiac Operative Risk Evaluation (EuroSCORE). Consequently, patients endured longer intensive care and overall hospital stay.[21] Therefore, it can be inferred that emergency CABG within 3 days for patients with acute STEMI is contraindicated.
Contrastingly, a retrospective study investigating the outcome of haemodynamically stable patients treated with early CABG revealed that, STEMI patients had reduced perioperative complications and better survival compared to nSTEMI patients. Interestingly when CABG was performed within 6 hours, mortality was lower in STEMI patients than nSTEMI patients (1.8% vs 7.1%, P=0.041 ). Likewise, a 30-day mortality was significantly lower in STEMI than nSTEMI patients (2.7% vs 6.6% P=0.018 ). Overall, CABG significantly improved survival of both STEMI and nSTEMI patients after 1 year (94% vs 88%, P<0.001 ), after 5 years (87% vs 73%, P<0.001 ) and after 10 years (74% vs 57%, P<0.001 ).[22] Hence highlighting the long-term benefits of CABG in treating both STEMI and nSTEMI.
Similarly, early revascularization in STEMI patients without cardiogenic shock was associated with superior short/long‐term outcomes than nSTEMI patients. These benefits were identified in significantly younger STEMI patients whom were fast tracked for CABG. This suggests that immediate CABG should be implemented during or soon after coronary angiography.[22]
Literature about optimal timing of CABG for treating nSTEMI patients have been conflicting as well. It has been reported that nSTEMI patients who had CABG <24 hours achieved significantly better 5-year survival than patients being treated 24-72 hours (P=0.02 ). Contrastingly, CABG achieved a better 5-year survival, when nSTEMI patients were treated >72 hours to 21 days than within 24-72 hours.[23] Likewise, Parikh et al. argued that early (<48 hours) CABG is non-inferior to late (>48 hours) CABG, hence delaying CABG would be ideal to increase resources without compromising patient outcome.[24]
From the literature it can be inferred that appropriate patient selection for CABG is critical for determining a positive long-term outcome for the overall patient population presenting with AMI. From table 2, confounding factors can negatively affect the outcome of CABG and predicative of HM include; poor LVEF, age >70 years, prior CABG/treatment modalities, systemic comorbidities and previous history of stroke.[21, 25] Assman et al. reported that early CABG after AMI (<10 days) is accompanied with significantly increased mortality, especially in elderly patients or in patients with a severely impaired LVEF.[26] This reinforces that age and LVEF can predict patient recovery from CABG.[18, 27]
Clinical trials have identified patient population such as diabetics whom would benefit from CABG for revascularisation therapy rather than PCI.[28-30] From the FREEDOM trial, it has been shown that diabetic patients with multivessels disease treated with CABG achieved better QoL and intermediate health status between 6-24 months, although beyond 24 months there were no consistent significant difference observed between CABG and PCI using drug-eluting stents.[31] Interestingly, the positive outcomes of CABG for type 2 diabetic patients are not seen in type 1 diabetics. However, CABG has proved to be superior over PCI in treating ACS patients with type 1 diabetes. Hence an emphasis on preoperative glycaemic control is integral for CABG outcomes in diabetic patients.
Current guidelines:
The armamentarium available for the treatment of ACS can be split into either pharmaceutical or surgical interventions. Pharmaceuticals include; beta-blockers, anti-hyperlipidaemia drugs, anti-platelet therapy, ACE-inhibitors and hormones. The goal of these treatments is to correct the imbalance of nutrient supply and demand of the heart by lowering its workload, whilst simultaneously increasing blood supply. Alternatively, surgical revascularisation (PCI or CABG) is offered. Patients suspected of AMI are treated immediately with oxygen, glyceryl trinitrate and aspirin as well as undertaking an electrocardiogram (ECG) to diagnose for STEMI or nSTEMI.[32]