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.