4.3 Issues with current guidelines:
The current guidelines are based on the most up-to-date meta-analysis and scientific reports and their use has correlated with a consistent drop in ACS mortality rates.[38] However, there are still numerous issues and points of contention surrounding the guidelines, that needs to be raised and addressed to improve patient outcomes. Firstly, despite numerous studies showing the benefit of timely PPCI, evidence shows that some areas of the country are still unable to receive PPCI in a timely manner, this could be due to a number of different circumstances including accessibility of Cath labs.[39] Secondly, despite the focus on PPCI as the primary treatment for AMI, the number of CABG surgeries being performed has been consistently rising.[40] It is thought that improvements in diagnosis and screening tools such as GRACE and SYNTAX, have led to the increased recognition of high-risk patients that are more suitably managed by CABG.
STEMI and timing of CABG:
During our literature search, it became clear that far less research into optimal CABG timing has been carried out on STEMI patients compared to nSTEMI patients. This, along with the challenges already discussed above make drawing meaningful conclusions challenging. For example, many studies that compared early to late intervention did not distinguish between PCI or CABG. Similarly, studies that compared early and late CABG intervention did not distinguish between STEMI and nSTEMI patients.
The current common practice among cardiac surgeons is to delay CABG after STEMI for optimal clinical outcome. This view has formed in light of various studies that show a beneficial effect when CABG is delayed. One study reported that HM decreased when CABG surgery was delayed. 14.2% (<6 hours), 13.8% (6 hours to 1 day), 7.9% (1-3 days), 3.8% (4-7 days), 2.9% (7-14 days) and 2.7% (>15 days). These results supported the recommendation to delay CABG for 3 days in patients when possible.[41] Similarly, other studies showed that early CABG was associated with a higher mortality than late CABG (5.6% vs 3.8%, P < 0.001 ). Furthermore, it was shown that early CABG independently predicted mortality after controlling for clinical acuity and propensity matching (odds ratio [OR] = 1.43, P = 0.003 ).[42] Conversely, other studies reported that there was no difference in the overall mortality of patients receiving early or late CABG for STEMI. However, the incidences of rethoracotomy in these patients significantly changed with CABG timing. Patients operated within 24 hours, 1-3 days, and 4-30 days had rethoracotomy rates of 31%, 38% and 5% respectively. Thus, concluding that the risks of rethoracotomy increased in STEMI patients being treated with CABG within 3 days of presentation.[21]
nSTEMI and timing of CABG:
Although CABG is not the favoured method for surgical revascularisation in the majority of AMIs [32], it remains an important intervention in high-risk patients including those with multivessel disease.[12] Several studies have explored the effect of timing of CABG in patients with nSTEMI. Many of these have shown no significant difference in the overall outcome between early and late CABG. For example, one study compared the primary outcome of death, MI or stroke at 6 months in patients who had early versus late intervention and showed no significant difference (P=0.15 ).[43] Likewise, another study showed no significant difference in HM (OR: 1.12, 95% CI: 0.71-1.78 ) or the composite outcome of death, MI, congestive heart failure or cardiogenic shock (OR: 0.94, 95% CI: 0.69-1.28 ) between early and late CABG.[24] Similarly, a study showed no significant difference in the incidence of HM between early (<48 hours) and late (>48 hours) CABG (P=0.695 ).[25] However, it is worth noting from the RIDDLE-NSTEMI study comparing early (<2 hours) and late (<72 hours) invasive strategy (CABG or PCI) and showed that nSTEMI patients who were treated early achieved lower mortality risks than those treated late, with a significant reduction in risk of subsequent MIs being reported (4.3% vs 13% respectively, HR = 0.32, 95% CI: 0.13-0.74, P=0.008 ).[44]Conversely, another study found that HM was higher in patients who had CABG within 1 day after MI, however no distinction was made between STEMI and nSTEMI.[20]
However, numerous studies have reported that significant differences exist in secondary outcomes such as bleeding events, ischaemic complications and refractory ischaemia. In the ACCOAST study, patients receiving CABG in less than 2.98 days, between 2.98 - 6.95 days and over 6.95 days were compared. Major bleeding events occurred in 26%, 10.4% and 4.8% respectively (P< 0.001 ), showing that early revascularisation carried a significantly increased risk of bleeding.[45] However, the data gathered from another study showed that there was a significant reduction in the secondary outcome of death, MI or refractory ischaemia in early CABG (9.5%) compared to late CABG (12.9%).[43] The disagreement between these results illuminate the complexity and challenges of establishing the optimal timing for CABG post nSTEMI.
Comparison of CABG timing in STEMI and nSTEMI patients:
With a lack of RCTs, it is difficult to be certain that the outcomes described above are indeed due to the timing of CABG or other confounding factors. The majority of the retrospective studies showed that patients with early or late CABG are often dissimilar in many factors that could influence the outcome. For example, patients who are recognised as being more high-risk (through GRACE or SYNTAX scoring) tend to be treated via CABG earlier than those who are lower risk. Lower risk patients are typically revascularized with PCI and only have adjuvant CABG, if PCI fails.[5] Therefore, acuity of illness could be influencing the results described above.[43] However as discussed above, some studies did not report any significant difference in outcome despite higher-risk patients being treated earlier.[24]Similarly, in studies that propensity matched patients to remove variable clinical features, no significant difference in primary outcome was observed.[25]
This evidence for a range of confounding factors influencing CABG outcome, press the case for a more individualised approach to CABG revascularisation. As many different factors have been found to contribute to the clinical outcome of CABG intervention, assessing all these factors in an individual patient and making an informed choice for that patient based on their own unique risk could optimise CABG intervention. Steps towards this have already been taken in recent years with the introduction of the SYNTAX score.[10]Perhaps a similar system could be implemented to aid clinicians in deciding whether a patient will benefit from early or delayed CABG to treat STEMI or nSTEMI.
Factors predictive of outcomes:
There are clear differences in the data between STEMI and nSTEMI for optimal timing of CABG. The majority of nSTEMI studies show no significant difference between early and late intervention in overall outcome, but a slight preference for early intervention in secondary outcomes such as bleeding complications or acute ischaemia has been observed. In contrast, STEMI studies have shown increased mortality in early CABG compared to late. Despite these apparent differences, research into both types of MIs have revealed a whole host of confounding factors that influence the outcome of the CABG surgery, independent of the time it was performed. Therefore, these findings suggest that a more complex view of the optimal timing for CABG is needed for both STEMI and nSTEMI patients.
Patient characteristics are heavy predicative factors of CABG as shown in table 2. Body mass index (BMI), LMD, and renal insufficiency have all been identified to be independent predictors of long-term mortality in CABG.[23] Pathological signs of disease complexity, STEMI vs nSTEMI, health comorbidities can also radically determine therapeutic pathways. For instance, diabetic patients with chronic kidney disease (CKD) tend to exhibit more MACE after CABG[46]
Table 2 also shows that preoperative assessment of pulmonary function can provide prognostic values of CABG, with many patients developing respiratory insufficiency after CABG due to pre-existing chronic obstructive pulmonary disease (COPD).[47]Preoperative administration of dual antiplatelet therapy has shown to achieve protective effect against in-hospital death and decrease in bleeding risks in non-elective CABG.[23] While certain drugs such as clopidogrel can delay CABG intervention for AMI patients.[24] Preoperative measures of elevated biomarkers (C-reactive protein and Troponin I) have also shown to predict subsequent death, MI and stroke after patient revascularisation.[48, 49] These finding suggests that appropriate preoperative measures can provide crucial information for improving CABG outcome regardless of CABG timing.
It is clear that despite similar studies are being conducted to identify the optimal timing of CABG, different outcomes are being reported. This could be due to a lack of standardised definitions of early/late intervention and methods in reporting outcomes. Therefore, better diagnostic modalities for aiding the standardisation of definition would yield more convincing data regarding optimisation of CABG. Rather than focussing on the timing of CABG, it can be hypothesised that multiple confounding factors seem to play a bigger role in determining patients’ outcome.
Significance of left ventricular contribution and future directions of CABG:
Reduced LV function and scarring are often the end product of an AMI [50]. It has been observed that complications post-surgery is associated with increased LV scarring/infarct burden. Accordingly, studies have suggested that presence of scar tissue after CABG is predictive of cardiac functional recovery.[51, 52]
Cardiac Magnetic resonance (CMR) imaging has become gold standard imaging technique for assessment of cardiac volumes, function and mass. Assessment of size and extent of scarring/fibrosis by Late Gadolinium Enhancement (LGE) has aided the detection and assessment of AMI.[53] In a retrospective study investigating the utility of 1.5T CMR in predicting immediate and six-week outcomes after CABG surgery patients with high EuroSCORE (>16) and impaired LVEF (< 40%). Sheriff et al. observed a significant relationship between lower circumferential relaxation index (a CMR parameter) and the occurrence of immediate postoperative complications.[52] Thus, CMR would be suitable for use prior to CABG and provide additional prognostic information. Additionally, CMR can be used for monitoring assessing patient recovery process. It is reported that 6 months after CABG, cardiac segments with scar and no scar showed statistical improvement in functionality, although only a small percentage (6.3%) showed improved contractility in the former sub-group.[51] The concept of adding CMR-derived parameters into diagnosis may improve the accuracy of risk-scoring systems for clinicians to make informed decisions regarding CABG utility and hence, future research in this area is warranted.
Conclusion:
From current literature, conflicting finding from studies can be inferred that specific pathology and complexity of disease will affect the outcome of CABG and determine the optimal timing for CABG. Therefore, it is clear that optimising timing of CABG needs to take into account patient characteristics and distinctive pathological status. Cardiac diagnostic modalities like CMR can provide essential information pre/post CABG. In a time of personalised medicine, a need for greater cardiac screening methods and standardised development of scoring systems can aid the optimisation of CABG and accordingly the optimal time for this intervention.