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a Department of Cardiology, University of Tor Vergata, Rome, Italy
b Department of Cardiac Surgery, University of Tor Vergata, Rome, Italy
c Department of Diagnostic Imaging and Interventional Radiology, University of Tor Vergata, Rome, Italy
Accepted for publication May 21, 2007.
* Address correspondence to Dr Chiariello, Cattedra di Cardiochirurgia, Università di Roma Tor Vergata, Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. (Email: chiariello{at}tiscali.it).
Presented at the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.
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Abstract |
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 Top Abstract IntroductionMaterial and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Methods: The study included 37 patients with severe carotid and coronary artery disease and a European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 5 or higher. Immediately after CAS, patients underwent CABG. The primary end point was the incidence of stroke, myocardial infarction, or death at 30 days. Secondary end points were a combination of transient ischemic attack, major local complications, bleeding, and systemic complications within the 30 days after treatment, and any stroke, acute myocardial infarction, or death from day 31 through to the end of the follow-up. All clinical outcomes were assessed by an independent monitoring board.
Results: The rate of procedural success was 97.3%. The 30-day cumulative incidence of disabling stroke, myocardial infarction, or death was 8.1%: 2 patients (5.4%) died, and 1 patient had a stroke immediately after carotid stenting. Another patient died between day 31 and 6 months after the intervention.
Conclusions: Our findings indicate that in elevated-surgical-risk patients with carotid stenosis and coronary artery disease suitable for CABG, hybrid revascularization by CAS, immediately followed by CABG, is a feasible and promising therapeutic strategy.
Significant atherosclerotic disease affecting both the coronary and carotid arteries is present in a substantial number of patients [1] and has serious implications for surgical management. Among patients undergoing carotid endarterectomy (CEA) in the Veterans Affair Cooperative Study [2] and the Asymptomatic Carotid Atherosclerosis Study (ACAS) [3], 20% and 49%, respectively, of deaths were due to cardiac causes. Similarly, the incidence of perioperative stroke in patients undergoing coronary artery bypass (CABG) is elevated in those with concomitant severe carotid stenosis [4]. Indeed, the incidence of severe carotid stenosis (>75% luminal diameter reduction) in patients undergoing CABG may be as high as 12% [4, 5]. Despite this important association, no clear consensus has been developed for the optimal management of patients with combined carotid and coronary disease.
A combined surgical approach is associated with an increased risk of mortality and morbidity [6–9]. In the staged surgical approach, which addresses the carotid lesion with CEA first, followed several days to several weeks later by CABG, the incidence of perioperative stroke during CABG is reduced; however, the risk of acute myocardial infarction (AMI) during CEA and in the period before CABG is rather high [6–8]. Carotid artery stenting (CAS) using cerebral protection devices is rapidly evolving as an alternative to CEA, mainly for patients with severe carotid stenosis at high surgical risk, as patients with heart disease [10]. A staged CAS-CABG approach has been recently proposed, but the need of an aggressive antiplatelet therapy lasting 3 to 4 weeks after stenting may represent a limitation for CABG [11].
We recently proposed a new therapeutic strategy consisting of a simultaneous hybrid complete revascularization by CAS, immediately followed by CABG. Such an approach has the potential to minimize the incidence of cardiac events in patients at high surgical risk. In a preliminary study, we demonstrated the efficacy and the safety of this therapeutic option [12] and conducted a larger study to demonstrate the potential large-scale applicability of this approach as an alternative to the combined or staged strategies currently adopted.
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Material and Methods |
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A team of physicians composed of 1 neurologist, 1 cardiac surgeon, and 1 interventional physician was assembled. The neurologist was responsible for the initial evaluation and neurologic follow-up of the patients. Only experienced cardiac surgeons (more than 300 bypass interventions) and interventionalists (more than 150 CAS procedures) were involved in the study.
Patients
Patients were considered eligible to be included in the study if they were aged 18 years or older, had concomitant critical disease in both carotid and coronary districts with impossibility to revascularize coronary bed percutaneously, documented myocardial ischemia with coronary artery disease suitable for CABG, surgical risk expressed as standard European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 5 or higher [13, 14], and a stenosis 50% or more in the symptomatic carotid artery disease or 80% or more in asymptomatic carotid stenosis, as determined by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method [15].
The presence of carotid stenosis had to be confirmed by means of catheter angiography or both duplex scanning and magnetic resonance angiography or computed tomography (CT) scan angiography. A CT scan angiography with or without angiographic dye, depending on preprocedural serum levels of creatinine, was performed in all patients to provide the maximum information about the aortic arch and the extent of aortic disease.
Exclusion criteria were coagulopathy, intolerance to heparin, ticlopidine, aspirin, or clopidogrel; ischemic stroke within the previous 6 weeks, presence of intraluminal thrombus, vascular disease precluding use of catheter-based techniques, intracranial aneurism more than 9 mm in diameter, life expectancy of less than 1 year, or pregnancy.
Carotid Stenting and Coronary Bypass Grafting
CAS procedures were performed under local anesthesia through a percutaneous transfemoral access with the use of stents and protection devices approved by the Accreditation Committee. An introducer sheath was positioned in the femoral artery, and heparin (1 mg/kg) was intraarterially administrated. A 7F or 8F guiding catheter was placed in the common carotid artery, proximally to the bifurcation. A "road-mapping" acquisition was used during the stent implantation procedure to reduce the amount of angiographic dye administered. A distal filter protection device was used in all patients. If needed, the lesion was predilated after placement of the protection device. After deployment, stents were postdilated to achieve a residual stenosis of 30% or less.
At the end of the procedure, patients were transferred directly to the operating room for CABG. Surgeons performed the CABG intervention with normothermic cardiopulmonary bypass according to standard practice.
Periprocedural Pharmacologic Protocol
Aspirin (100 mg daily) was started 2 days before CAS. Heparin (1 mg/kg) was administered as a bolus intraarterially immediately before the stent implantation procedure and in the operating room before the cardiopulmonary bypass at the dosage of 2 mg/kg. Activating clotting time (ACT) was checked every 30 minutes and was constantly maintained at 250 seconds or longer until the beginning of the CABG operation and at 480 seconds or longer until the end of cardiopulmonary bypass. Tranexamic acid (10 g) was administrated as antifibrinolytic during the 20 minutes before sternotomy. A 300-mg loading dose of clopidogrel was started in the intensive care unit by nasogastric tube, 6 hours after the end of the CABG procedure, providing that surgical bleeding from the thoracic drainages had definitely stopped, or when it was less than 50 mL/h for 3 consecutive hours from the sixth hour (Fig 1). Clopidogrel was continued at 75 mg/day for 1 month.
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Follow-Up and End Points
A neurologic evaluation was done at 48 hours, 30 days, and 6 months after treatment. Color duplex ultrasonography evaluation and CT brain scan were performed before hospital discharge.
The primary end point was a composite of any stroke, MI, or death occurring within 30 days after the treatment. Secondary outcomes were transient ischemic attack, major local complications, bleeding, and systemic complications within 30 days after treatment; and any stroke, MI, or death from day 31 to the end of the follow-up. The occurrence of stroke, MI, death, and other clinical outcomes was assessed by an independent safety monitoring board that reviewed the data periodically.
Statistical Analysis
Clinical and procedural data were updated on a specific Web site. Analyses of immediate, 30-day, and 6-month outcomes were possible for all patients included in the registry. Continuous variables were presented by their mean ± standard deviation. Statistical analysis was performed according to intention-to-treat analysis. SAS 8.2 software (SAS Inc, Cary, NC) was used for all analyses.
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Results |
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Clinical characteristics of patients are reported in Table 1. The mean EuroSCORE was 8 ± 2.1. Four patients aged older than 80 years underwent simultaneous CABG and aortic valve replacement with aortic bioprostheses, and 1 patient had mitral valve repair. All patients with valvular heart disease were in sinus rhythm. The loading dose of clopidogrel was administrated 6 hours after the end of CABG in 22 (60%) of 37 patients, and 10 hours after CABG in the remaining 15 patients (40%). Procedural data are reported in Table 2.
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The 30-day cumulative incidence of disabling stroke, AMI, or death was 8.1% (Table 3). Two patients (5.4%) died within 30 days. One, who was 82 years old and had EuroSCORE of 10, underwent CABG and aortic valve replacement, had a prolonged stay in postoperative intensive care for pulmonary failure, and died on postoperative day 8 of a severe arrhythmia. The other, who was 72 years old and had diabetes, chronic renal failure, chronic obstructive pulmonary disease, left main disease, low ventricular function, and a EuroSCORE of 8, died 30 days after CABG of multiorgan failure. One patient died during the 31-day to 6-month postoperative period. This patient was 78 years old and had severe stable angina, diabetes mellitus, multivessel atherosclerotic disease, and bilateral carotid stenosis, and had a EuroSCORE of 8. The patient died 90 days after CABG of multiorgan failure.
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The median duration of the postoperative length of stay was 5 days (interquartile range, 3 to 16 days). The median duration in the intensive care unit stay was 2 days (interquartile range, 0 to 12 days), and the median ventilation time was 12 hours (interquartile range, 2 to 24 days). Primary outcome events at 6 months are summarized in Table 4.
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Comment |
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In a previous series of 180 consecutive patients undergoing combined surgical revascularization in our institution between 1991 and 2002, the 30-day mortality was 10% and the stroke rate was 1.1% [16], with a mortality rate of 14.5% when the EuroSCORE was 6 or more and 3.4% when it was lower than 5. A recent single-institution series published during the last 4 years showed that the average rates were 3.8% for the incidence of stroke and transient ischemic attack, 3.1% for AMI, and mortality was 4.6% collectively in more 1500 patients undergoing combined surgical procedure [8, 10, 11].
Compared with combined surgical revascularization, the hybrid strategy requires a shorter surgical time and less extensive surgical trauma, thus reducing cofactors known to increase morbidity and mortality. Compared with CEA, CAS has uncertain efficacy and safety in patients at risk for stroke from atherosclerotic stenosis of the internal carotid artery [17]. However, in high-risk patients for CEA, mainly owing to severe coronary artery disease, the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial showed that CAS was safer than CEA because it lowered the risk of MI within 30 days after CAS compared with surgery [10]. This is likely to be the case mainly in patients with elevated surgical risk such as those involved in our study. In fact, according to inclusion criteria, we enrolled only patients with a EuroSCORE of 5 or more, where mortality rate is elevated. In particular, when the average EuroSCORE is 8, as in our study, the surgical mortality rate may be as high as 14.5% [14, 18, 19].
It is noteworthy that in this high-risk subset of patients, the specific postoperative complications after surgery are also elevated; for example, Fukuda and colleagues [18] reported a morbidity rate 56.5%. In particular, when both carotid arteries are involved with significant stenosis, the risk of stroke after cardiac surgery is particularly high: 25% as reported by Tunio and colleagues [19]. With the percutaneous hybrid approach as in our study, however, the stroke rate was only 2.7% (1 patient), considering that 64% of our patients had bilateral carotid stenosis exceeding 50%. This might also be because our study was at a high-volume center, and all the procedures were performed by experienced interventional physicians.
Another potential advantage of the simultaneous hybrid approach compared with a combined surgical approach is that the neurologic outcome will be known instantly, rather than emerging from general anesthesia. Indeed, this could also be accomplished with a CEA in wakefulness, followed by CABG under general anesthesia. However, our strategy may have some additional advantages compared with staged CEA-CABG or CAS-CABG approaches by reducing the risk of AMI during CEA [10] or in the time elapsing between the two procedures because the interval between them is virtually eliminated [20]. In fact, the MI rate in the time elapsing between procedures was 4.4% when CEA-CABG was performed and 5.8% for CAS-CABG [9–19].
Normothermic cardiopulmonary bypass has been used in our patients. Although hypothermia may be safer from a neurologic standpoint [21], there is also more risk of bleeding due to platelet dysfunction in patients that should undergo aggressive antiplatelet treatment for CAS [22]. It is likely that by using the off-pump technique, the overall stroke risk may be further reduced, especially in patients with aortic wall disease.
Nonetheless, we also demonstrated with our study the efficiency and the efficacy of the periprocedural pharmacologic protocol and the timing of antiplatelet administration proposed: the bleeding rate after surgical intervention was low. This therapeutic strategy was also used in patients with aortic valve disease where bioprostheses were implanted. Only 1 patient had pericardial tamponade requiring pericardiocentesis, and 1 other patient had bleeding after surgery requiring reintervention. In all patients, the need of postoperative transfusions was not different from those after conventional interventions where antiplatelet therapy was stopped before CABG [23]. Moreover, no cardiovascular event, stroke, or TIA occurred between the hospital discharge and the first 30-days of the follow-up. Therefore, in patients with combined carotid and coronary disease at high surgical risk, the proposed hybrid approach seems to be a possible therapeutic strategy.
This study has a number of limitations that should be acknowledged. The study population is small, although highly selected. Furthermore, the presence of patients with combined coronary and valvular heart disease reinforces the representativeness of our study population. Indeed, a larger number of patients with multivessel coronary disease are treated percutaneously, using drug-eluting stent in particular when at high surgical risk.
The use of angiographic dye during CAS procedure might be a major drawback for this approach, in particular in high-risk patients with chronic renal failure. No patient in our study had renal impairment after the procedure. Particular attention was given to the reduction of the amount of angiographic dye in that a road-mapping roentgenogram acquisition was used during the stent implantation, and patients with chronic renal failure underwent a pretreatment with fluid administration and acetylcysteine [24].
In conclusion, our findings indicate that in symptomatic patients suitable for CABG, with combined carotid and coronary arteries disease at high surgical risk, the hybrid revascularization by carotid stenting and coronary artery bypass grafting may be a possible therapeutic strategy.
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Discussion |
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DR ZEITANI: Thank you for your question. In our unit we do use normothermic cardiopulmonary bypass. Your observation is a good point to think of in these kinds of patients.
DR PUSKAS: You reported an incidence of stroke or TIA of 5%, which I guess is a small series, but that number still seems relatively high. Do you have any insights into that?
DR ZEITANI: In our study only 1 patient (2.7%) had a stroke, with transient aphasia and mild hemiparesis immediately after carotid artery stent implantation. In this case the cardiac intervention was performed 2 months later, after a partial functional recovery. However, The incidence of neurological events in our small study is not high. In fact, according to inclusion criteria, we enrolled only patients with EuroSCORE equal or higher than 5, where mortality and morbidity reported in literature are elevated. In particular when EuroSCORE is 8, as in our trial, the morbidity rate is 56.5%. In particular, when both carotid arteries are involved with significant stenosis the risk of stroke after cardiac surgery is particularly high: 25%. On the contrary, using percutaneous hybrid approach as in our study the stroke rate was only 2.7% (1 patient), considering that 64% of our patients had bilateral carotid stenosis of greater than 50%.
DR PUSKAS: Did you see an increased incidence of bleeding complications that you might attribute to the loading of Plavix (Sanofi-Aventis, Bridgewater, NJ) in the intensive care unit after open heart surgery?
DR ZEITANI: In our series 1 patient had postoperative bleeding requiring reintervention and 1 patient had pericardial tamponade requiring pericardiocentesis four days after combined CABG and aortic valve replacement procedure. The incidence of bleeding was not higher than observed in the same subset of patients operated on without antiplatelet therapy. However, surgeons who operated on these patients are more experienced and particular attention should be given to hemostasis. Moreover, the periprocedural pharmacological protocol providing that the loading dosage of clopidogrel was started in the intensive care unit 6 hours after the end of coronary artery bypass surgery, and when blood loss is less than 50 mL/h for 3 consecutive hours.
DR MAHMOOD MIRHOSEINI (Germantown, WI): Carotid surgery is very unforgiving surgery. I would like to know who does carotid surgery in your institution, what training they have?
DR ZEITANI: In our center we have a high volume vascular surgery with very skilled surgeons. However, in accordance with the vascular surgeons, we planned to treat symptomatic patients with combined carotid and coronary arteries disease at high surgical risk with the hybrid revascularization by carotid stenting and coronary artery bypass grafting as we proposed in this trial. This strategy resulted in high immediate and mid-term clinical results. Compared with combined surgical revascularization, this strategy requires a shorter surgical time and less extensive surgical trauma, thus implying a reduction of the high morbidity and mortality observed after the current, combined surgical approach.
DR JOHN R. DOTY (Salt Lake City, UT): Do you have a sense of the additional cost by angiography suite, stent placement and time maybe compared to sort of a standard combined carotid-coronary?
DR ZEITANI: The additional cost of the percutaneous procedure is about 
2000. However, our hybrid strategy requires a shorter surgical time and less extensive surgical trauma, thus implying a significant reduction of the additional cost due to the high morbidity observed after the current, combined surgical approach.
DR GEORGE ECONOMOPOULOS (Athens, Greece): It was not clear to me when these strokes took place, I mean, at what time. The strokes occurred immediately after the stenting of the carotid artery or you discovered the strokes after the coronary artery bypass surgery? This is very important, because if you have a patient who just had a stroke, you have to think twice before you take him back to surgery and put him on bypass.
DR ZEITANI: Thank you. In our study we report only one stroke, with transient aphasia and mild hemiparesis immediately after carotid artery stent implantation. In this case, the cardiac intervention was postponed and performed 2 months later, after a partial functional neurological recovery. In a previous pilot study aimed at evaluating the efficacy and the safety of this procedure, 1 patient had a brief and transient poststenting cerebral ischemia that completely resolved at the end of stent procedure. This patient underwent neurologic evaluation and a computed tomographic scan to rule out hemorrhage before inducing general anesthesia for the surgical procedure. This patient had an uneventful postoperative course and was discharge after 6 days.
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