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Eur J Cardiothorac Surg 2003;24:552-556
© 2003 Elsevier Science NL

Determinants of stroke after coronary artery bypass grafting

Department of Cardiovascular Surgery, Laval Hospital, Quebec Heart Institute, 2725 Chemin Ste-Foy, Sainte-Foy, QC, Canada G1V 4G5

Received 1 April 2003; received in revised form 26 June 2003; accepted 29 June 2003.

^* Corresponding author. Tel.: +1-418-656-4717; fax: +1-418-656-4707
e-mail: rgea{at}hotmail.com

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

 
Objectives: Cerebrovascular accidents (CVA) after CABG are deleterious complications whose prevention remains poorly defined. The aim of this study was to identify the determinants for CVA after CABG. Methods: Nine thousad nine hundred and sixteen patients underwent CABG at our institution from January 1992 to June 2002. Data were prospectively collected and univariate/multivariate analyses conducted. Results: Two hundred and eight patients (2.1%) suffered perioperative CVA. Univariate analysis showed a higher risk profile in the CVA group including advanced age, depressed percent left ventricular ejection fraction (LVEF), unstable angina, diabetes mellitus (DM), chronic renal failure (CRF), redo surgery, peripheral vascular disease (PVD), previous CVA, and higher Parsonnet score (P<0.001). Furthermore, the CVA group had longer myocardial ischemia (CVA 56.2 ±40.9 vs. Control 50.4±20.9 min, P=0.03) and cardiopulmonary bypass (CPB) times (CVA 87.4±30.0 min vs. Control 78.9 ±25.9 min, P<0.0001), and lower off-pump surgery rate (CVA 1.4% vs. Control 4.7%, P=0.01). Multivariable analysis identified seven preoperative and two perioperative determinants for CVA: LVEF<30% (odds ratio (OR)=2.49), previous CVA (OR=2.15), DM (OR=1.78), redo (OR=1.76), PVD (OR=1.66), CRF (OR=1.55), age (OR=1.03), perioperative intra-aortic balloon pump (OR=1.83), and transfusion rate (OR=1.59). Perioperative mortality was higher in the CVA group (CVA 18.6% vs. Control 2.6%, P<0.0001). Conclusions: Although occurrence of CVA seems mainly related to preoperative comorbidities, perioperative surgical variables, such as off-pump surgery, myocardial ischemia and cardiopulmonary bypass time, do not seem to independently influence CVA rate after CABG. In this regard CVA prevention should be performed before posing an indication to CABG, and closer evaluation of patients’ risk profiles and tailored clinical/surgical strategies for those patients at higher risk for CVA occurrence should be included.

Key Words: Cerebrovascular accident determinant • Multivariable analysis • Coronary artery bypass grafting

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

 
Cerebrovascular accident (CVA) after coronary artery bypass grafting (CABG) still remains one of the most deleterious complications. The reported incidence of stroke after CABG ranges from 1 to 6% [1–3]. Its etiology is multifactorial including cerebral embolization from iatrogenic mobilization of atherosclerotic plaques, air/fat embolism, peripheral vascular disease (PVD), hemodynamic fluctuations, cerebral hyperthermia, and systemic inflammatory reaction [1,4]. More importantly, CVAs after CABG account for an increase up to 20% in hospital mortality, in-hospital stay, and costs for hospital and outpatient rehabilitative support. The present change in the referral pattern for CABG is presenting to surgeons the daily challenge of operating on patients with significantly increasing comorbidities that may, directly or indirectly, increase the occurrence of perioperative neurological complications. In this regard some authors have recently focused their analysis on trying to identify the predictors of stroke in the modern era of cardiac surgery [5,6].Moreover, new advances in surgical technique, and particularly the introduction of off-pump coronary artery bypass grafting (OPCAB), have further stimulated researchers to define the importance of perioperative management in preventing stroke occurrence [5–9].

The aim of the present study was to establish, in one of the largest cohorts of CABG patients ever analyzed, the independent determinants for perioperative CVA including preoperative comorbidities, surgical factors, and postoperative management variables.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

 
The present analysis includes all isolate CABGs performed at the Quebec Heart Institute (QHI) from January 1992 to June 2002. Preoperative and perioperative data were prospectively collected by nurse clinicians and entered into our institution database which includes more than 100 variables. Two groups were identified. Cases were defined as those who had suffered a perioperative CVA, and controls comprised all the remaining patients in the cohort.

2.1. Definitions
At the QHI patients with postoperative focal neurological deficits, psychomotor alterations, and confusion are routinely evaluated by staff neurologists and psychiatrists. The diagnosis of CVA is initially made by the surgical team and confirmed by the neurologist on the basis of the clinical findings and independently of the brain imaging pictures. All these patients are, in any case, routinely submitted to control uncontrasted CTs of the head that are, in the majority of the cases, repeated to closely monitor the evolution of the radiographic picture. All imaging studies are read by staff radiologists. Perioperative stroke was defined as any new temporary or permanent, focal or global neurologic deficit, in accordance with published guidelines [10].

2.2. Operative technique
All patients were operated through a mid-sternotomy. Ascending aorta and right atrial cannulation were performed in all patients operated on with cardiopulmonary bypass (CPB). Moderate systemic hypothermia (32 °C) and intermittent antegrade cold blood cardioplegia were used in the majority of the patients. Proximal anastomoses were routinely performed on a side biting clamp. In the OPCAB group, coronary exposure was achieved via deep pericardial traction sutures and coronary stabilization was obtained with a pressure type stabilizer. Distal coronary anastomoses were performed first followed by proximal anastomoses after aortic side clamping. Ascending epiaortic ultrasound scanning was not routinely used. Although ascending aorta palpation was routinely adopted, no information concerning the eventual presence of aortic atherosclerotic plaques was reported in the database.

2.3. Statistical analysis
Univariate analysis was conducted using either the ² test or Fisher's exact test for categorical variables and the Student t-test for continuous variables. Two-tailed P-values of less than 0.05 were considered statistically significant. Multivariable analysis was conducted using stepwise logistic regression (SAS Institute Inc., Cary, NC) and considered all predictors that were significantly associated with CVA in univariate analysis. The logistic regression modeling was conducted initially including only the preoperative variables. In a second instance, operative risk factors were added to the adjusted model containing preoperative predictors. When two or more predictors were strongly correlated, only the variable with the higher significance was retained in the final model.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

 
A total of 9916 patients were included in the cohort. CPB was used in 9455 patients (95.3%) and 461 patients (4.65%) were operated off-pump.

Perioperative CVA occurred in 208 patients (2.1%). Univariate analysis showed a significantly higher risk profile in the CVA group (Table 1). Perioperatively, the CVA group had longer myocardial ischemia and CPB times, and lower off-pump surgery rate (Table 2). As expected, perioperative mortality was significantly higher in the CVA group (CVA 18.6% vs. Control 2.6%; P<0.0001) (Table 2). Multivariable analysis identified only seven preoperative and two perioperative determinants for CVA including: left ventricular ejection fraction (LVEF)<30% (odds ratio (OR)=2.49), previous CVA (OR=2.15), diabetes mellitus (OR=1.78), redo (OR=1.76), PVD (OR=1.66), chronic renal failure (CRF) (OR=1.55), age (OR=1.03), perioperative intra-aortic balloon pump (IABP) (OR=1.83), and transfusion rate (OR=1.59) (Table 3).

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

As documented in the STS National Database, permanent CVAs occur with a frequency of 1.9% after isolated CABG. Because of the rarity of the event, identification of risk factors may be difficult and include mainly those variables that confer a substantial increase in stroke rate. In this regard it is vital to emphasize the importance of investigating CVA determinants in large cohorts of patients to statistically identify the vast majority of variables that have an actual clinical influence towards stroke rate. In this context, we have decided to investigate CVA determinants in our 10-year experience with isolated CABG.

The presence of an atherosclerotic ascending aorta has been reported as the most significant marker for adverse cerebral events in cardiac surgery [1]. Micro- and macroembolization may occur intraoperatively during manipulation of the ascending aorta and heart [4] and following sudden systemic pressure changes. Although in our analysis we did not directly investigate the ascending aorta status, history of previous stroke, carotid disease, and PVD were among the strongest determinants for CVA after CABGs. These findings are in accordance to others’ investigations [4,8,9,11,12] and emphasize the importance of close preoperative assessment of patients with previous CVA and/or suspected carotid disease.

Among the other preoperative variables, advanced age, diabetes mellitus, reoperative surgery, and chronic renal failure were all identified as independent determinants for stroke in our analysis and accordingly to the existing literature [2,5,6,11,13–16].

Moreover, depressed LVEF% (<30%) was the strongest preoperative determinant for CVA with an OR equal to 2.4. This variable has already been identified by Stamou et al. in one of the largest analysis of stroke determinants including more than 16 000 isolated CABGs [2]. Depressed LVEF% may lead to perioperative hemodynamic instability and low-output state directly deranging physiologic brain perfusion and contributing to the neurological events. Furthermore, ventricular hypocontractility may cause intracavitary thrombosis and eventual embolism.

Identification of surgical and postoperative independent determinants for stroke remains difficult and somewhat controversial. In this regard, the recent introduction and popularization of off-pump CABG has galvanized interests about the possible protective effect that this technique may have against perioperative neurological attempts. Avoidance of CPB eliminates the risk of atheroma dislodgement following ascending aortic cannulation and aortic cross-clamping. However, the risks associated with partial aortic side clamping persist in OPCAB surgery and may be even increased when a tense aorta is partially clamped as often happens during off-pump procedures. Furthermore, sudden hemodynamic derangements that may present during OPCAB procedures could, at least theoretically, determine temporary brain hypoperfusion especially in patients with associated cerebrovascular disease.

Small randomized controlled studies have shown a significant reduction in neurocognitive impairment in OPCAB patients [8,17]. In a large multicenter retrospective analysis Cleveland et al. [18] have shown a reduction in the observed/expected ratio of stroke from multivariable analysis of off-pump patients compared with traditional CABG on-pump. More recently, Patel et al. [9] have investigated the independent effect of avoidance of CPB and aortic manipulation on neurological outcomes after CABG. In a total cohort of 2327 patients, Patel identified three subgroups consisting of traditional CABG on CPB, OPCAB with aortic manipulation, and OPCAB without aortic manipulation [9]. The results of the multivariate logistic regression analysis demonstrated that use of CPB was the strongest risk factor for focal neurological deficit with an odds ratio of greater than 3. In contrast, aortic manipulation did not significantly influence neurologic outcome in off-pump patients [9]. In a larger cohort including more than 4000 CABG patients, Ascione et al. [5] have failed to demonstrate, through univariate and multivariate analysis, any significant protective effect of OPCAB against stroke. Moreover they have identified age, unstable angina, preoperative renal failure, previous CVA, preexisting PVD, and salvage operation as the sole independent determinants for perioperative CVA [5].

More recently, Bucerius et al. [6] have investigated determinants of stroke in a large cohort of 16 184 patients including valve surgery, CABG on CPB, OPCAB, and minimally invasive direct coronary artery bypass (MIDCAB).

Multivariable analysis revealed ten variables that were independent predictors of stroke: history of cerebrovascular disease, peripheral vascular disease, diabetes, hypertension, previous cardiac surgery, preoperative infection, urgent operation, CPB time more than 2 h, need for intraoperative hemofiltration, and high transfusion requirement [6].

Interestingly, as emerged in the study by Bucerius et al., at univariate analysis MIDCAB had a significantly lower stroke rate when compared to conventional CABG on CPB and, on the contrary, there was no statistically significant difference between OPCAB and conventional CABG stroke rates. After stepwise logistic regression, off-pump surgery (including the combination between MIDCAB and OPCAB) was identified as the sole protective factor against CVA [6]. In this regard we believe that the MIDCAB and OPCAB variables should be analyzed separately even in the multivariable model to better understand the real independent impact of each technique on CVA occurrence. It is reasonable to believe that patients treated with MIDCAB have lower comorbid profiles including younger age and limited coronary artery and peripheral vascular disease. Furthermore, the limited revascularization performed during MIDCAB allows for no aortic manipulation, minimal hemodynamic derangement, and shorter operating times. All these factors could directly determine a lower occurrence of stroke in this already highly selected group of patients.

The present report includes 461 (4.6%) patients operated off-pump. As shown by our univariate results, OPCAB was significantly less common in patients who developed a perioperative CVA and only 0.6% (3/461) of the OPCAB patients developed a stroke versus 2.2% (205/9455) in the on-CPB group. In spite of this, on multivariable analysis OPCAB failed to achieve a significant protective effect against CVA. We are aware of the fact that results of logistic regression may have been somewhat biased by the relatively small number of OPCABs included in our series and by the rarity of the CVA event. Furthermore, we believe that OPCAB could have a stronger impact in reducing stroke rate in selected high-risk patients (such as, for example, the elderly) where the occurrence of neurological insults is significantly more common. In these patients OPCAB without aortic manipulation or MIDCAB could be advised together with hybrid coronary revascularization.

In our analysis we have also tried to focus on average CPB and myocardial ischemic time as possible independent determinants of perioperative stroke. Although both variables were significantly increased at univariate comparison between CVA versus control patients, no significance was achieved at multivariate analysis. Moreover, after an accurate analysis and division in subgroups, we had to conclude that even myocardial ischemic time longer than 90 min and CPB longer than 120 min did not independently impact on CVA rate. Our results are in contrast with the findings of Bucerius et al. [6] where CPB time had a strong independent relationship with CVA occurrence.

As is shown by our our analysis, the only perioperative determinants for CVA were postoperative use of IABP and transfusion rate. In a multicenter study by Roach et al. [19] IABP has been already identified as a predictor of CVA after cardiac surgery. Requirement for aortic counterpulsation may reflect a state of hemodynamic instability that may lead to brain hypoperfusion. Furthermore, aortic counterpulsation may determine atherosclerotic plaque mobilization and brain embolization. In the light of these findings, insertion of IABP should always be practiced judiciously and after attentive evaluation considering the risks of iatrogenic embolization and cerebral stroke, especially in patients with documented peripheral vasculopathy.

High transfusion requirements have been recently identified by others as independent predictors of CVA after cardiac surgery [6]. Increased transfusions may reflect profuse bleeding, hypotension and consequent cerebral hypoperfusion. Ascione et al. [5] have identified a significantly increased stroke rate in patients receiving more than 3 units of blood, 2 units of platelets, or 1 unit of plasma. Although we were able to identify requirement of any type of transfusion as an independent determinant for CVA after CABG, we could not determine either the quantity or the type of transfusions involved.

Finally, although our analysis was mainly aimed at determining the strongest predictors of CVA after CABG, identification of these variables could guide tailored surgical strategies. Atherosclerosis from the ascending aorta can embolize to the brain with manipulation during surgery and, in this regard, efforts at reducing embolic stroke can involve single cross-clamping of the aorta or no cross-clamp (fibrillatory arrest). In reoperative CABG surgery single cross-clamp, ‘no-touch technique’, and retrograde cardioplegia have been documented to reduce the occurrence of deleterious complications such as perioperative CVAs [20]. Furthermore, intraoperative epiaortic ultrasound can guide the surgeon to an area of reduced aortic plaque where cannulation and proximal anastomoses construction may be performed safely. As documented in our analysis, carotid artery disease and history of previous stroke can result in CVA through intraoperative or perioperative cerebral hypoperfusion. In this context, intraoperative monitoring of perfusion pressures during on-CPB and off-pump CABG, and prevention of perioperative hypotension and low cardiac output state are of crucial importance. Because depressed cardiac output was found to be directly associated with perioperative stroke, appropriate inotropic support should be suggested in patients with reduced LVEF%, and preventive anticoagulation could also be advocated to avoid intracavitary thrombus formation.

	5. Conclusion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

 
Stroke after CABG remains a rare but deleterious complication carrying significant mortality and morbidity rates. Perioperative stroke is mainly related to preoperative comorbidities that should be closely evaluated in each individual patient before posing an indication for CABG. In our logistic regression model perioperative surgical variables, such as off-pump surgery, myocardial ischemia and CPB time, do not seem to independently influence CVA rate after CABG.

The present logistic regression model has allowed us to identify seven preoperative and two operative independent determinants for CVA. We are well aware of the fact that clinically these risk factors present, in the majority of cases, as clustered and their combined effect is not simply additional but may multiply the chances for morbidities such as stroke. As already emphasized herein, the problem is not the presence of a single risk factor, but the combination of more variables in a complex comorbid profile. Although in the present work we have arrived at a final equation expressing the impact of every risk factor when taken singularly, we are still in the process of deriving the concurrent effect of the various risk factors. In this regard we are, for the future, extending a more complex analysis to a larger cohort of patients in the attempt to statistically derive an equation and a downloadable data program that could be used as a means of clinical prevention and patient information.

	Acknowledgments

 
We express our gratitude to Mrs Brigitte Dionne and Serge Simard for their help in the data collection and analysis.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Conclusion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): José Ignacio Saez de Ibarra Richard Baillot Patrick Mathieu Jacques Metras Denis Desaulniers Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by D'Ancona, G. Articles by Dagenais, F. Search for Related Content PubMed PubMed Citation Articles by D'Ancona, G. Articles by Dagenais, F. Related Collections Cerebral protection Coronary disease