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]