1. HR.Sanati.MD Interventional Cardiologist Rajaei Cardiovascular Medical & Research Center

2. Introduction To date, no consensus exist for the best approach to manage combined severe carotid and coronary disease. There are several options to revascularize both territories, but the actual risk with contemporary best medical therapy alone is unknown in the absence of RCTs. Extension of the results of RCTs on isolated carotid stenosis to the CABG population, although previous RCTs in this setting excluded severe CAD requiring CABG.

3. Despite this major limitation, carotid revascularization in this setting is common, with the majority (96%) being performed for asymptomatic carotid disease. Recent advances in medical treatment and the low perioperative risk associated with severe unilateral asymptomatic carotid disease have raised the question regarding the role of carotid revascularization in this setting.

5. Peri-CABG stroke The incidence of stroke after CABG ranges from 1.4% to 3.8%, depending on the patient population and the criteria for diagnosis of stroke. 10-fold higher mortality, increased length of hospital stay, overall cost Patient-related risk factors for stroke Advanced age, history of stroke, DM, HTN, female sex Reduced EF, preoperative AF Aortic calcification, atheroma of ascending aorta and arch, mobile protruding arch atheroma, ICA stenosis Preexisting subclinical ischemia and cerebral atherosclerosis on MRA

6. Although off-pump CABG was introduced in large part to reduce stroke and other adverse neurological outcomes associated with CPB, several RCTs comparing on-pump and off-pump CABG have shown no difference in stroke rates. Although macroembolization and microembolization are major sources of stroke, hypoperfusion, perhaps in conjunction with embolization, is a risk factor for postoperative stroke. CABG-specific risk factors for stroke On-pomp CABG with hypothermic circulatory arrest. Combined valve-CABG, double AVR-MVR Cardiopulmonary bypass time

7. How to recognize patients at risk? Routine epiaortic US to evaluate the presence, location, and severity of plaques in the ascending aorta to reduce the incidence of atheroembolic complications. (Class IIa, Level of Evidence: B) (Intraoperative epiaortic US is superior to direct palpation and TEE) and

8. Screening for carotid disease Use of carotid Duplex US in all patients scheduled for CABG?! (extracranial disease of the ICA is a risk factor for adverse neurological events after CABG) Alternatively, the identification of preoperative risk factors known to be associated with the presence of carotid disease to stratify patients into high- and low-risk categories, thereby allowing for a more selective use of noninvasive carotid screening: 40% reduction in preoperative testing, with only a “negligible” impact on surgical management or neurological outcomes.

9. The current 2011 ACCF/AHA guidelines: Class IIa, Level of Evidence C: Carotid duplex US is reasonable before elective CABG in patients aged > 65 years, those with LMCAD, PAD, history of TIA or stroke, HTN, smoking, and DM or carotid bruit. A recent report concluded that age > 70 years may be a more appropriate cut off.

10. Carotid disease in CABG patients Prevalence of severe carotid disease (>80%) in the CABG population: 8-12% Recent data: 7-11% prevalence of severe carotid disease (>70%) in 3VD or LMCAD, carotid stenosis>50% in 20% Stepwise correlation of prevalence and severity of CD with the extent of CAD Bilateral CD in 3%, carotid occlusions in 1-1.5%

11. A systematic review by Naylor et al (2002): asymptomatic unilateral 50-99% CS: 3% bilateral 50-99% CS: 5% carotid occlusion:7-11% STS database (2003-2007): 2% with untreated carotid Doppler stenosis >75% vs. 1% risk without CVD A recent cohort (2008): 7.5% risk with significant CS (1.8% for entire cohort) Significant carotid stenosis and stroke risk in CABG Source of controversy!

12. Extracranial CS >50-60% is an established RF for stroke in general, but in the peri-CABG setting, possibly 60-80% of strokes in patients with significant CS occur in the territory not perfused by the affected carotid, and 50-75% of post-op strokes occur in the absence of significant carotid stenosis. In CABG patients with 50% unilateral carotid stenosis in whom CEA is not performed concomitantly with CABG, the peri-CABG stroke rate is reportedly 3%, rising to 5% in those with bilateral carotid artery stenoses and 11% in those with an occluded carotid artery. More than half of all post-CABG strokes occur after uneventful recovery from CABG (SVTs, low CO, or postoperative hypercoagulability) In patients undergoing CEA, the rates of periprocedural stroke have been reported to be as high as 2.5% in those with asymptomatic CS and 5% in those with previous symptoms

13. The risk posed by asymptomatic nonocclussive and unilateral carotid disease appears to be small and revascularization in this setting is questionable. However, other argue that the evidence is inadequate, citing data on cerebral hemodynamics in severe stenosis, and caution that the individual risk cannot be estimated accurately using carotid stenosis severity alone. Trend toward reduced cerebral perfusion reserve with carotid stenosis > 70% that becomes significant with age at least 70 years. Dynamic MRI revealed altered intracranial hemodynamics and positive correlation with extracranial CS and improvement upon CEA. An incomplete circle of Willis may play a role in cerebral ischemia during carotid cross-clamping and other collateral pathways might be important. Reduced cerebral perfusion may impair clearance of micro-emboli during cardiac surgery and aggravates hypoperfusion-related injury.

14. The high risk patient The current controversy on the causal role of CD in peri-CABG stroke apply only for unilateral asymptomatic CD with 50-90% stenosis. The data so far do suggest that the others are significant risk factor for peri-CABG stroke: 1- Neurological symptoms (stroke/TIA) 2- Bilateral carotid stenosis 80-99% 3-Unilateral or bilateral carotid occlusions 4-Unilateral 50-99% carotid stenosis with contralateral occlusion 5-Asymptomatic 80-99% carotid stenosis with impaired cerebral perfusion reserve.

15. The most critical part in estimating stroke risk with unilateral 50-99% CS is the presence of symptoms that can be localized to the affected carotid territory. Conversely, prior carotid territory infarcts on MRI can identify high risk asymptomatic patients who may have otherwise been categorized as low risk clinically. Symptomatic patients with at least 50% carotid stenosis have a 32% risk of recurrent neurological event at 12 wks without revascularization. Cerebral perfusion reserve or reactivity testing using xenon CT with acetazolamide vasodilator challenge (unilateral occlusion, the elderly, high risk asymptomatic CS)

17. Carotid revascularization in CABG setting Lack of high-quality data in the context of carotid and coronary disease, current guidelines have been framed based on observational data alone. Options: Staged CAS-CABG, Same-day hybrid CAS-CABG, True hybrid CAS-CABG, Staged CEA-CABG, Combined CEA- CABG, Reverse staged CAS-CABG It is difficult to recommend one approach over the other (selection bias by the operator with regard to choice of procedure or staging interval, lack of formal testing for MI, possible noninclusion of patient drop outs or deaths in the staged procedures, and lack of risk- adjusted or propensity-matched analysis in many reports. However, both staged and reversed staged procedures run the risk of interval MI or stroke depending on the territory at risk. Therefore, careful patient selection is paramount and this traditionally rely upon symptom status and disease severity involving the carotid and coronary beds.

18. Results of meta-analyses on staged or combined CEA-CABG: Naylor et al (97 studies, 1972-2002): no significant overall difference in 30- day death, MI, or stroke risk for staged and combined procedures, with the risk being 10-12%. Gopaldas et al (National in patient sample, 22792 pts, 1998-2007): mortality and neurological complications were statistically similar for both the staged and combined procedures. Patients who undergo combined CEA-CABG procedures are more likely to have critical disease in both territories; whether combining CEA and CABG is associated with higher risk is controversial. In a propensity-matched study, Ricotta et al found no increased risk with the addition of CEA to CABG. However, a more recent study using STS database cautions the use of combined procedure: significantly higher neurological complication rate (4.1%, and length of stay in comparison to those with untreated Doppler stenosis >75%). CEA

19. CAS with embolic protection is a less invasive, safe, and durable alternative to CEA in patients considered high risk for CEA. However, CAS appears to be underutilized in this setting based on NIS data. Commonly, CAS is staged several weeks prior to CABG to permit dual antiplatelet therapy. But the limitation is in case of urgent or emergent CABG (bleeding complications). The same day hybrid or true hybrid techniques may help overcome this limitation, but data so far are very limited. In both techniques, CAS is done under aspirin and heparin with the patient receiving a thienopyridine 6-12h after CABG when safe. Van der Heyden et al. (356 pts, CAS for asymptomatic CD followed by CABG): favorable outcome in term of combined death, stroke and MI up to 30 days after CABG (6.7%), comparable to CEA- CABG meta-analysis. CAS

20. Ziada et al. reported no significant difference in 30-day death, stroke, or MI in CAS followed by OHS patients compared with combined CEA and OHS; however, the event rate in the combined CEA-OHS was as high as 21%. Similar findings were noted in the NIS data by Timaran et al. In this study, a comparison of CAS-CABG (n=887) and combined CEA-CABG (n=26 197) patients revealed no significant difference groups. However, an important finding was the 5- fold increased risk of postoperative stroke in symptomatic patients who had CAS-CABG. Similar findings were reported with CAS in contemporary carotid stenosis trials in the symptomatic population.

21. However, some of these trials have been widely criticized for inconsistent use of distal embolic protection devices and operator inexperience. Still, the ultimate impact of such stenting on postoperative stroke rates in CABG patients awaits the results of properly designed trials. Nevertheless, CAS remains an important alternative option in patients deemed to be at high risk for CEA from the cardiac standpoint.

22. Bilateral carotid disease and carotid occlusion Given the limited data, it is generally agreed that patients with asymptomatic bilateral 80–99% carotid stenosis would benefit from carotid revascularization. In selecting the appropriate side to treat, it is desirable to treat the carotid supplying the dominant hemisphere or the side with greater stenosis severity. In the presence of neurological symptoms, the culprit carotid should be treated. When subsequent carotid revascularization on the contralateral side is planned, it is important to reassess stenosis severity to rule out possible artifactual elevation with duplex study in the setting of bilateral carotid disease

23. Patients with unilateral carotid stenosis in the setting of contralateral occlusion need to be revascularized on the side of stenosis if symptomatic with 50– 99% stenosis or asymptomatic with 70–99% stenosis. This group of patients are considered high risk for CEA and CAS may be a superior option in these patients. If CEA is considered, serious consideration should be given for intraoperative shunting, especially in those with impaired collateral circulation. Carotid occlusions are not amenable for CEA or CAS; however, it is important to consider the possibility of a pseudo-occlusion caused by reduced antegrade flow. Carotid duplex in this situation may fail to identify the trickle flow in the internal carotid artery, resulting in misdiagnosis of carotid occlusion.

24. Patency may be confirmed using invasive angiography by the presence of a ‘string sign.’ Although such identification may be worthwhile in the symptomatic patient, it would be better to avoid revascularization in asymptomatic patients with the ‘string sign,’ especially in the absence of reversible perfusion defects on imaging. Even with symptomatic carotid disease, the benefits of CEA for near occlusions appear to be marginal.

25. PCI In the era of drug-eluting stents, PCI is a viable alternative to CABG in selected patients based on data from the SYNTAX trial. A complete endovascular approach consisting of staged CAS followed by PCI could possibly replace staged CAS-CABG in selected patients and may avoid the delay to CABG for reasons of dual antiplatelet therapy

26. Conclusion Management strategies must be individualized and involve the expertise of cardiologists, neurologists, endovascular specialists, and vascular and cardiac surgeons. Additionally, the team approach may play a valuable role in the management of perioperative complications like stroke or MI. At the present time, most patients with asymptomatic unilateral 50–99% carotid stenosis can be treated medically in the perioperative period. Once recovered from CABG, a CEA or CAS revascularization strategy should be adopted. However, neurologically symptomatic patients should all be considered for carotid revascularization. The choice between CAS or CEA depends on the severity of CAD and the urgency for coronary revascularization.

27. In patients with severe CAD requiring simultaneous carotid revascularization and CABG, a hybrid CAS-CABG or combined CEA-CABG should be considered based on local expertise. High-risk asymptomatic patients such as those with contralateral carotid occlusion or severe bilateral carotid stenosis should be further risk stratified by noninvasive imaging modalities such as MRI or by assessment of cerebral perfusion reserve. Additionally, off-pump CABG with aortic ‘no touch’ technique may help to diminish atheroembolism from the aorta.