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Ann Thorac Surg 2004;77:1241-1244
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Postoperative atrial fibrillation is a major cause of stroke after on-pump coronary artery bypass surgery

^a Division of Cardiothoracic and Vascular Surgery, Department of Surgery, University of Oulu and Oulu University Hospital, Oulu, Finland

Accepted for publication September 22, 2003.

^* Address reprint requests to Dr Biancari, Division of Cardiothoracic and Vascular Surgery, Department of Surgery, Oulu University Hospital, PO Box 21, 90029 OYS, Finland
e-mail: faustobiancari{at}yahoo.it

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
BACKGROUND: Atrial fibrillation, occurring after coronary artery bypass grafting (CABG), has been suggested to be associated with the development of postoperative stroke. However, it is not clear what is the incidence of atrial fibrillation-related postoperative stroke, the timing of its occurrence, and the outcome. These issues have been investigated in a consecutive series of patients who have undergone on-pump coronary artery bypass grafting (ONCAB).

METHODS: Among 2,630 patients who underwent ONCAB, 52 patients (2.0%) experienced postoperative stroke and form the basis of the present study.

RESULTS: Twelve patients (23.1%) died postoperatively. The ischemic cerebral event occurred after a mean of 3.7 days (range, 0 to 33). In 19 patients (36.5%), atrial fibrillation preceded the occurrence of neurologic complication. These patients experienced a mean of 2.5 episodes of atrial fibrillation before the occurrence of neurologic complication. The cerebrovascular event occurred after a mean of 6.0 days in patients in whom atrial fibrillation preceded it, after a mean of 1.2 days in those with calcified ascending aorta, and after a mean of 3.1 days in those without calcified ascending aorta or in whom atrial fibrillation did not precede the cerebrovascular complication (p < 0.0001). Stroke occurred a mean of 21.3 hours after atrial fibrillation.

CONCLUSIONS: This study confirmed that atrial fibrillation, occurring after CABG, is a major determinant of postoperative stroke. Prevention of postoperative atrial fibrillation, and of formation of clots into the left atrium, may dramatically reduce the risk of postoperative stroke.

	Introduction

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Stroke is a major adverse event complicating the immediate outcome of coronary artery bypass grafting (CABG) in about 2% of cases [1]. The severity of such a complication is not only related to the functional sequelae, but also to the increased risk of postoperative death. According to a review of the literature by Naylor and colleagues [1], mortality rate after postoperative stroke is about 23%. Thus, stroke prevention is of foremost importance in improving the results of CABG. Carotid artery disease and calcified ascending aorta have been recognized as the main factors underlying the occurrence of postoperative stroke; thus, carotid endarterectomy and avoidance of aortic manipulation are expected to reduce the risk of such a severe complication.

During the last 15 years, a few studies brought attention to postoperative atrial fibrillation as an important factor associated with the occurrence of postoperative stroke after cardiac surgery [2–8]. Indeed, a recent meta-analysis showed that antiarrhythmic therapy for prevention of postoperative atrial fibrillation is associated with a marked reduction of the incidence of postoperative cerebrovascular accidents (odds ratio: 0.50) [9].

It is not clear what is the incidence of atrial fibrillation-related postoperative stroke, the timing of its occurrence, and the outcome. These issues have been investigated in a consecutive series of patients who developed stroke after isolated on-pump coronary artery bypass grafting (ONCAB).

	Material and methods

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From January 1997 to December 2001, 2,630 patients underwent ONCAB at our institution. All patients underwent CABG under mild hypothermic cardiopulmonary bypass. Intermittent cold blood ante- and retrograde perfusion cardioplegia was used for myocardial protection in almost all cases. Cardiopulmonary bypass rewarming was started on completion of proximal anastomoses and discontinued when pulmonary artery blood temperature reached a temperature of about 36°C. A single aortic cross-clamping technique was used in all cases.

Forty-five (1.7%) patients died during the in-hospital stay. Eighty-five (3.2%) patients experienced neurologic complications ranging from disorientation to unconsciousness. Among these patients, 52 (2.0%) had stroke and form the basis of the present study. Diagnosis of stroke was made on the basis of neurologic signs and symptoms and on imaging findings. In case of negative computed tomography, diagnosis of stroke was made solely on the basis of clinical findings.

Data on these patients were derived from an institutional cardiac surgery registry. However, data on patients having had postoperative cerebrovascular complications were retrospectively collected to include those clinical variables not originally included in the registry, to determine the number of atrial fibrillation events as well as the timing of occurrence of neurologic event.

In our institution, preoperative duplex examination of the carotid arteries is performed only in patients having carotid bruits at preoperative auscultation or history of transient ischemic attacks or stroke. Because of this, only a small number of patients had their carotid arteries investigated preoperatively. Data about other patients who had duplex examination after CABG were retrieved by our hospital, or other regional hospitals' records. The intraoperative finding of calcified ascending aorta has been assessed only by palpation (Table 1).

The type of neurologic deficit and its severity was obtained by reviewing our and neurologists consultations. Because of the retrospective nature of the study, the degree of functional recovery could not be estimated in its real extent, thus it is herein reported just as improving or as stable neurologic conditions.

In our institution, we prefer to use amiodarone in the management of postoperative atrial fibrillation, electrical cardioversion being reserved only in those patients unresponsive to amiodarone treatment. In a few cases included in this series, digoxin, ß-blockers, ibutilide, and quinidine were also used. Our routine practice was to start anticoagulation treatment with enoxaparin only in those patients with prolonged atrial fibrillation. Thus, in only few patients of this series who experienced such a complication, anticoagulation was on-going at the time of neurologic event.

Statistical analysis was performed using the SPSS software (SPSS v. 10.0.5, SPSS Inc., Chicago, IL, USA). Continuous variables are reported as the mean plus range. The ² test and the Fischer's exact test were used for univariate analysis of categorical data. The Mann-Whitney test and the Kruskal-Wallis test were used to assess the distribution of continuous variables in different subgroups. Logistic regression with the help of backward selection was used to identify predictors of outcome. Multivariate analysis included only the variables whose p less than 0.1 at univariate analysis. A p less than 0.05 was considered statistically significant.

	Results

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An ultrasonographic examination of the carotid arteries was performed preoperatively in only 14 patients. Postoperatively, another 16 patients were investigated by duplex ultrasonography. Among these 30 patients, 14 had a stenosis of the internal carotid artery 70%, 8 having had a complete occlusion of at least one internal carotid artery.

Twelve patients (23.1%) died during the in-hospital stay in our institution or in central hospitals. The mean intensive care unit length of stay was 5.0 days . One of these patients had postoperative myocardial infarction and seven experienced low cardiac-output syndrome.

The ischemic cerebral event occurred after a mean of 3.7 days (0–33). Thirty-six patients had hemiplegia, 17 had aphasia/dysphasia, and 17 had unconsciousness. Thirty-seven patients (71.2%) experienced improvements of their neurologic symptoms at discharge from our institution.

Forty-seven patients (90.4%) were evaluated postoperatively by computed tomographic scan. In one patient in whom computed tomography was not performed, the diagnosis of brain infarction was done at autopsy. Another four patients did not undergo computed tomographic scan of the brain in this hospital, and one of them died during the postoperative period, but autopsy was not performed. Among these 47 patients evaluated by computed tomography, 24 patients had focal, unilateral brain infarction, nine patients had multifocal unilateral focal infarctions, 10 had bilateral cerebral infarctions, and in another four there were no signs of brain infarction on imaging. These latter four patients had hemiplegia and three of them also had dysphasia/aphasia. Among those patients with a diagnosis of brain infarction confirmed at autopsy or at computed tomography, bilateral brain infarctions were more frequent than unilateral brain infarction in patients with calcified ascending aorta (p = 0.006) (Table 2)

Twenty patients awoke with signs and symptoms of stroke (Table 2). The cerebrovascular event occurred after a mean of 6.0 days (2–33) in those patients in whom atrial fibrillation preceded it, after 1.2 days (0–3) in those with calcified ascending aorta, and after 3.1 days (1–16) in those without calcified ascending aorta or in whom atrial fibrillation did not precede the cerebrovascular complication (p < 0.0001).

Among those 30 patients in whom the status of the carotid artery was known, a stenosis of the internal carotid artery 70% was more frequently present in those patients without calcified ascending aorta or who did not have postoperative atrial fibrillation (Table 2).

A mean of 2.6 postoperative atrial fibrillations (range, 0 to 20) occurred in the overall series. In 19 patients (36.5%), atrial fibrillation preceded the occurrence of neurologic complication of a mean of 21.3 hours (0–40). These patients experienced a mean of 2.5 episodes (1&ndsh;6) of atrial fibrillation before the occurrence of neurologic complication, while the mean overall number of atrial fibrillations in these 19 patients was 5.1 (1–20). In only eight of these patients, anticoagulation therapy was on-going on the day of occurrence of stroke. Warfarin was on-going in six patients, but only in two of them was the TT-INR value in the therapeutic range (2.04 and 2.32); in one patient the TT-INR value having been far above the therapeutic range (5.70).

At univariate analysis, preoperative serum concentration of C-reactive protein more than 10 mg/dL (in overall 34 patients: 50.0% vs 12.5%, p = 0.02), serum concentration of creatinine on the day of occurrence of neurologic complication (in overall 42 patients: p = 0.002), and cardiopulmonary bypass time (all patients: p = 0.03) were predictive of postoperative death. Multivariate analysis showed that preoperative left ventricular ejection fraction (p = 0.08) and cardiopulmonary bypass time (p = 0.06) tended to be predictors of postoperative death.

	Comment

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Atherosclerotic lesions of the ascending aorta, and of the carotid arteries, have been suggested to be the main sources of embolism after cardiac surgery. No touch technique to prevent dislodgement of plaques from calcified ascending aorta and prophylactic carotid endarterectomy are expected to reduce the risk of postoperative stroke. Major expectations are especially reserved to the role of synchronous or staged carotid endarterectomy and CABG. However, it seems that prophylactic carotid endarterectomy, which by itself carries some further operative risk [10], could prevent only 40% to 50% of postoperative stroke after CABG [1]. A recent population-based study by Brown and colleagues [10] strongly questioned the benefits of combined carotid endarterectomy and CABG. The overall stroke and mortality rate was 17.7% [10], a rate much higher than that calculated by Naylor and colleagues [11] in a systematic review of the literature. It is remarkable that among 226 patients reported by Brown and colleagues [10], 56% were preoperatively asymptomatic and only 9% had a recent transient ischemic attack or stroke, and another 22% of patients had bilateral severe carotid artery disease or contralateral occlusion. In most of the cases, postoperative stroke affected areas not ipsilateral to the carotid endarterectomy or it was multifocal. Certainly, the finding of most interest is that proximal aortic arteriosclerosis was the only independent risk factor for postoperative stroke (adjusted OR: 5.35) [10]. Brown and colleagues [10] observed also that in most of cases stroke after combined carotid endarterectomy and CABG occurred beyond the first 24 postoperative hours, an observation which calls for a mechanism leading to stroke other than arterial embolism.

The occurrence of atrial fibrillation after cardiac surgery has been increasingly recognized as a condition underlying the development of stroke [2–9]. The present study confirmed that atrial fibrillation might cause one third of the postoperative strokes after CABG. This observation may explain why prophylactic endarterectomy provides protection only in a limited number of patients and why in most cases stroke develops later than the first postoperative day [1].

The lack of data on the preoperative status of the carotid arteries is a major limitation of this study, but the finding of an association between atrial fibrillation and postoperative stroke seems to be rather strong and of major clinical importance as it occurs in about one third of patients having undergone CABG and can be potentially prevented. In fact, a reduction of atrial fibrillation-related stroke after CABG can be achieved by strategies effectively preventing postoperative atrial fibrillation as well as by reducing the risk of formation clots into the left atrium by administration of anticoagulants during the postoperative period. Whether the latter strategy can be associated with an increased risk of postoperative bleeding is unknown, but the administration of anticoagulants at least at the onset of atrial fibrillation may be useful in preventing clot formation and in reducing the risk of embolism. The fact that herein a few patients had stroke despite on-going anticoagulation is not conclusive against such a treatment approach. In fact, a mean of 2.5 episodes of atrial fibrillation preceded the occurrence of stroke, thus potentially having reduced the efficacy of anticoagulation therapy not started at the onset of the first arrhythmia episode.

Another prophylactic strategy against atrial fibrillation-related stroke is represented by left atrial appendage occlusion at the time of surgery. A trial designed to evaluate whether atrial appendage occlusion performed during CABG may reduce the long-term risk of stroke and systemic embolism associated with atrial fibrillation is currently on going [12]. It is likely that this study will provide data on the safety of this technique and its potential efficacy in reducing the risk of stroke also during the immediate postoperative period.

In conclusion, this retrospective study confirmed that atrial fibrillation occurring after coronary artery bypass grafting is a major determinant of postoperative stroke. Prevention of postoperative fibrillation and of formation of clots into the left atrium may dramatically reduce the risk of postoperative stroke.

	Acknowledgments

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Doctor Biancari was supported by a grant of the Einar and Karin Stroems Foundation, which is kindly acknowledged.

	References

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1. Naylor A.R., Mehta Z., Rohwell P.M., Bell P.R.F. Carotid artery disease and stroke during coronary artery surgery: a critical review of the literature. Eur J Vasc Endovasc Surg 2002;23:283-294.[Medline]
2. Almassi G.H., Schowalter T., Nicolosi A.C., et al. Atrial fibrillation after cardiac surgery. A major morbid event? Ann Surg 1997;226:501-513.
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9. Zimmer J., Pezzullo J., Choucair W., et al. Meta-analysis of antiarrhythmic therapy in the prevention of postoperative atrial fibrillation, and the effect on hospital length of stay, costs, cerebrovascular accidents, and mortality in patients undergoing cardiac surgery. Am J Cardiol 2003;91:1137-1140.[Medline]
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