The brain‐before‐heart strategy for coronary artery bypass grafting in the severely atherosclerotic aorta: A single‐institution experience

Abstract Background Severe atherosclerosis of the ascending aorta (SAA) in patients undergoing surgical revascularization by coronary artery bypass grafting (CABG) is becoming an increasing problem as more elderly patients are diagnosed with coronary artery disease. Strokes and other neurologic insults are common complications in this group, with devastating impacts on outcomes and prognoses. Hypothesis Early detection of the atherosclerotic aorta and the application of a stroke prevention protocol will reduce the risk of stroke in patients with SAA. Methods In 2012, we adopted a protocol devised to preemptively detect and manage patients suspected of having SAA. From the time of the application of the protocol, we compared the immediate and late outcomes of CABG in SAA in the 8 years preceding the protocol in a “control” group (30 patients) and in the 8 years following the protocol in a “brain” group (69 patients). Results More patients with SAA were detected after the initiation of the protocol. They had significantly more history of stroke, renal dysfunction, and left main coronary disease. The percutaneous coronary intervention was utilized more after the protocol (26% vs. 7%) and there was far less utilization of replacement of the ascending aorta (12% vs. 37%). Postoperative stroke rates were significantly less after the protocol (2% vs. 18%), with an almost twofold reduction in stroke associated with SAA even after risk adjustment. The composite endpoints of cardiac death, nonfatal myocardial infarction, and stroke were significantly reduced after initiating the protocol at a median of 2.3 years from the time of revascularization. Conclusion Early detection of SAA and individualized therapeutic strategies for revascularization is effective in reducing athero‐embolic brain injury and are associated with better prognosis.


| INTRODUCTION
Severe ascending aortic atherosclerosis (SAA) has been shown to be the most important predictor of stroke in coronary artery bypass grafting (CABG). 1 The increasing number of elderly patients undergoing surgical revascularization in recent years has brought greater attention to SAA in CABG, as atherosclerotic disease increases with age. 2 The underlying potential risk for athero-embolic events is closely correlated with the severity of atherosclerosis in the ascending aorta and adds a considerable risk of spontaneous embolic strokes with diminished survival during the long-term postoperative course. 3 Surgical manipulation of the ascending aorta during cardiac surgery procedures, and in particular the application and removal of the aortic cross-clamp, is associated with the highest number of detectable emboli in the middle cerebral artery by Doppler ultrasound. 4 Increasing awareness of SAA is the first crucial step in limiting and preventing its devastating complications. 5 Increasing awareness starts with a multitude of gradual steps that include taking a proper history, performing focused preoperative imaging, and careful intraoperative assessment of atheroma by scanning the ascending aorta. The revascularization strategy and planned surgical techniques will need to be custom-tailored to the individual. This includes opting for percutaneous coronary intervention (PCI) rather than CABG, hybrid revascularization (PCI + CABG), performing CABG without cardiopulmonary bypass (CPB) support

| METHODS
In an effort to reduce the incidence of stroke post-CABG in patients with SAA, our local heart team initiated a stroke prevention protocol starting in July 2012. This was conveniently labeled the "brainbefore-heart" revascularization strategy. The strategy is predicated on increasing awareness of ascending aortic atherosclerosis to prevent the devastating complication of perioperative stroke. This was conducted through a stepwise process involving an initial risk stratification, preoperative noninvasive imaging, individualized revascularization planning, intraoperative assessment of the ascending aorta, and the use of alternative surgical techniques guided by the site and burden of atheroma ( Figure 1).
A high index of suspicion is given to patients who present with any of the following: a history of stroke, peripheral vascular disease, carotid artery disease, left main stenosis, and/or heavy calcification on coronary angiography. For preoperative imaging, patients who are >60 years of age undergo a plain computed tomography (CT) scan of the chest to detect signs of calcification in the thoracic aorta. Carotid doppler ultrasound (US) is done routinely before CABG.
The extent and burden of atheroma in the ascending aorta are subjected to careful assessment and preoperative planning by the heart team to decide whether to pursue surgical revascularization, PCI, or a hybrid approach. All patients undergoing CABG are subjected intraoperatively to epiaortic US (EAU) scanning and careful digital palpation of the ascending aorta to choose a soft spot for cannulation. Depending on the site and burden of atheroma in the ascending aorta, the surgical team can tailor an individualized surgical strategy involving any of the following surgical techniques: routine CABG with cross-clamp, OPCAB, FACAB, or ARCAB. [5][6][7][8][9] After the approval of our local institutional ethics board, a systematic EAU scanning of the ascending aorta was adopted only after the implementation of the stroke prevention protocol. Before this, the assessment of atheroma in the ascending aorta was done by digital palpation. Our protocol is as follows: Depending on the severity of ascending aorta disease and the site of the atheroma, a decision is made to choose between using OPCAP (with or without "no touch") or utilizing CPB via the heart-lung machine. Aortic "no touch" revascularization strategy was mainly focused on grafting the LIMA to the left anterior descending and harvesting the RIMA as a free graft to construct a proximal Y anastomosis to graft the next largest target on the left system. A left RA or SVG was used to supplement the left system or the right coronary targets as an end-to-side graft from the mammary. For CPB, the cannulation sites can be in the distal ascending aorta, aortic arch, femoral artery, or axillary artery. If a safe disease-free spot for the aortic cross-clamp is available, then the ascending aorta is cross-clamped and routine CABG is done with cold antegrade cardioplegia for myocardial protection. If the ascending aorta cannot be safely cross-clamped, the surgical team is left to decide between doing FACAB or ARCAB. FACAB is done by cooling the systemic temperature to 28°C, fibrillating the heart by applying a shock using a fibrillatory device, then constructing all the distal Myocardial infarction (MI) was defined as a fatal or nonfatal MI as evidenced by new Q waves on the electrocardiogram or by a peak in creatine kinase isoenzyme MB level greater than 50 IU/L that represented more than 7% of the total creatine kinase.
Echocardiographic corroboration of a new MI was routinely sought but was not necessary for the diagnosis. For the purpose of this manuscript, stroke was defined as signs and symptoms of neurological deficit due to cerebrovascular causes that persist beyond 24 h or are interrupted by death within 24 h. Neurological deficits that resolved completely within 24 h were labeled as transient ischemic attacks (TIAs). Strokes were confirmed by a staff neurologist and CT scans. Renal insufficiency was defined as having a decrease in the calculated GFR to less than 60 ml/min. Completeness of revascularization was determined by successfully grafting all diseased coronary distribution territories. Renal failure was defined as the requirement for dialysis. Smoking was defined as a current history of smoking, or cessation within the 3 months preceding surgery.
disease are referred to medically or surgically treated conditions. As of the first quarter of 2020, the follow-up was 98% complete. Crude survival was determined by matching the unique national identification number for each patient in the series with the national death registry. The cause of death was determined by reviewing the death certificate for those who matched in the registry. Patients who were still alive were directly contacted after obtaining permission at the time of the inquiry. Primary cardiac death was determined if the cause of death was acute coronary syndrome, cardiogenic shock, congestive heart failure, valvular heart disease, death during a cardiac procedure, or sudden cardiac death. History of stroke, TIA, and nonfatal MI were determined at the time of follow-up inquiry by the study team.
Statistical analysis was performed using SPSS 21.0 software (SPSS Inc.). Categorical data were summarized as absolute numbers and percentages. Numeric data were summarized as the mean and standard deviation (SD) or median and interquartile range. The tested variables were grouped in 2 × n tables and the two-group comparisons were made using the chi-square test or Fisher exact test for categorical data. Continuous variables were tested using the Student t-test or Mann-Whitney U-test. The crude odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using univariate logistic regression, and adjusted ORs with 95% CIs were estimated using multiple logistic regression analysis. Crude survival and eventfree survival curve comparisons were done using the log-rank test.
The results were expressed as hazard ratios (HRs), 95% CIs, and p-values. A two-tailed p-value < 0.05 was considered significant for all statistical tests.

| RESULTS
A total of 2100 consecutive patients were referred for isolated CABG within the study time frame (2004-2019). Of those CABG patients, 902 (45%) had CABG before the implementation of the protocol, and 1198 (57%) patients had CABG after implementation. A significantly larger number of patients had a screening with chest CT before surgery and EAU intraoperatively. This resulted in a significantly higher rate of detection of ascending aorta calcification and atheroma after the implementation of the protocol (Supporting Information: Accessory The analysis of how the stroke prevention protocol impacted the use of the six revascularization strategies used in SAA (Table 2)   who had PCI instead of the high-risk surgical revascularization, the outcomes in the 8 years after intervention were: none had stroke/TIA, 30% died due to cardiac causes, and 10% had nonfatal MI. atherosclerotic ascending aorta becomes a pressing priority over achieving complete myocardial revascularization. In essence, this is the logic behind the brain-before-heart strategy, as the spectrum of therapeutic options for ischemic heart disease after incomplete revascularization is wider than the spectrum of therapies available for postoperative stroke. 5 The implementation of a preemptive strategy to detect and modify the revascularization methods over the second half of the study timeline has yielded a greater number of detected cases of SAA and included more patients with a history of stroke, chronic renal dysfunction, and patients with left main coronary stenosis. More importantly, the rate of perioperative strokes under the new protocol was significantly reduced.

| DISCUSSION
One big advantage of the preemptive approach in SAA is the ability to reduce the element of undesirable surprises during surgery.
As with all our B group subjects, Park et al. 10  The late outcomes of PCI as an alternative to surgical revascularization in SAA were not specifically analyzed in this study, due to the small sample size.
In conclusion, this study is an attempt to evaluate practical measures for coping with SAA in the increasing number of patients who need surgical revascularization. Early detection and individualized therapeutic strategies play an important role in reducing the devastating neurologic insults that can result from manipulating a diseased ascending aorta during surgery.

AUTHOR CONTRIBUTIONS
Rakan I. Nazer conceived the study, helped plan the methodology, helped collect the data, and wrote the manuscript. Ali M. Albarrati helped plan the methodology, helped collect the data, did the analysis, and reviewed the manuscript.

ACKNOWLEDGMENTS
The author is very thankful to all the associated personnel in any reference that contributed to the purpose of this study, including the

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.