Anesth Analg 2004;98:585-589
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000099721.67426.DE
CARDIOVASCULAR ANESTHESIA
The Association of Patent Foramen Ovale and Atrial Fibrillation After Coronary Artery Bypass Graft Surgery
George Djaiani, MD DEAA, FRCA*,
Barbara Phillips-Bute, PhD*,
Mihai Podgoreanu, MD*,
Robert H. Messier, MD
,
Joseph P. Mathew, MD*,
Fiona Clements, MD*, and
Mark F. Newman, MD*
Departments of *Anesthesiology and
Cardiac Surgery, Duke University Medical Center, Durham, North Carolina
Address correspondence and reprint requests to George Djaiani, MD, DEAA, FRCA, Department of Anesthesia, Toronto General Hospital, University Health Network, University of Toronto, 585 University Ave., Toronto, ON, Canada, M5G 2C4. Address e-mail to george.djaiani{at}uhn.on.ca
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Abstract
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Atrial fibrillation (AF) is associated with considerable morbidity and increased resource utilization after coronary artery bypass graft surgery. In this study, we sought to determine whether patent foramen ovale (PFO) and atrial septal aneurysm are associated with an increased risk of postoperative AF in this patient population. We performed a database study on 1008 patients undergoing primary coronary artery bypass graft surgery. All patients were assessed for the development of postoperative AF from the day of surgery to hospital discharge. Atrial septal defects were identified during comprehensive intraoperative transesophageal echocardiographic examination. Postoperative AF was present in 124 (12.3%) patients. Patients with AF were significantly older and had a more frequent incidence of preoperative congestive heart failure, longer cross-clamp time, and prolonged hospital length of stay. PFO was present in 72 (7.1%) and atrial septal aneurysm in 23 (2.3%) patients. In these patients, postoperative AF was present in 14 (19.4%) patients with PFO and 8 (34.8%) patients with atrial septal aneurysm. Multivariate logistic regression analysis identified that PFO (odds ratio [OR], 1.95; 1.007–3.778; P = 0.047), age (OR, 1.03; 1.015–1.053; P = 0.0004), and history of congestive heart failure (OR, 2.55; 1.671–3.900; P < 0.0001) were predictive of postoperative AF.
IMPLICATIONS: The presence of patent foramen ovale is associated with new-onset postoperative atrial fibrillation after coronary artery bypass graft surgery. This finding requires further validation in future prospective trials.
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Introduction
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Atrial fibrillation (AF) is a frequent complication after cardiac surgery and affects 10%–30% of patients undergoing coronary artery bypass graft (CABG) surgery (1–3). AF is associated with considerable morbidity and mortality (4,5). Patients with AF have increased intensive care unit (ICU) and hospital length of stay (LOS), resulting in proportional increases in resource utilization and medical care costs (1,6–8).
Predictors of postoperative AF include advanced age, male sex, congestive heart failure, and a history of AF (6). Surgical practices such as pulmonary vein venting, bicaval venous cannulation, and longer cross-clamp times have also been identified as independent predictors of postoperative AF (6). However, recent data provide evidence that AF occurs with equal frequency in patients undergoing CABG surgery with or without cardiopulmonary bypass (CPB), suggesting a common pathophysiology for the development of AF in these groups of patients (9,10). The suspected factors include increased autonomic imbalance, inflammatory response, pericardial inflammation, and atrial ischemia.
Despite the considerable volume of literature discussing the subject, the etiology of postoperative AF remains unclear. Several recent studies have attempted to identify different echocardiographic variables that may contribute to the development of postoperative AF in patients undergoing coronary revascularization procedures. Shore-Lesserson et al. (11) reported that the left atrial appendage area and the left upper pulmonary vein systolic-to-diastolic velocity ratio, when considered individually, were each associated with an increased risk of developing postoperative AF. Furthermore, Nakai et al. (12) concluded that left atrial enlargement together with advanced age were significant predictors of postoperative AF. Conversely, Skubas et al. (13) found that after adjusting for age and duration of aortic cross-clamping, there were no differences in the transmitral Doppler diastolic filling variables between patients with and without postoperative AF after primary CABG surgery. However, none of the previous studies using intraoperative echocardiography has included atrial septal abnormalities as confounding factors for the development of postoperative AF in the cardiac surgical setting.
Patent foramen ovale (PFO) and atrial septal aneurysm have been associated with paroxysmal AF in patients with ischemic stroke (14). The exact role of atrial septal defects with regard to the risk of perioperative AF in cardiac surgical patients is not known. The objective of this study was to determine whether PFO and atrial septal aneurysm are associated with postoperative AF in patients undergoing conventional CABG surgery.
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Methods
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After IRB approval, we examined data collected prospectively on 1008 patients undergoing primary elective CABG surgery as part of the Duke Intraoperative Transesophageal Echocardiography (TEE) and the Duke Cardiovascular Outcomes Database. Data were collected between February 1999 and March 2000. Patients who were pacemaker dependent, required preoperative inotropic or intraaortic balloon pump support, had preoperative AF, or had any other concomitant surgery were excluded from the analysis. All patients were operated on by the same team of surgeons. Previously described surgical and anesthetic management was used in all patients (15).
Echocardiographic data were acquired by using an Agilent Technologies Sonos 5500 (Andover, MA) ultrasound system equipped with a multiplane transesophageal probe. Systemic TEE examination included two-dimensional, color flow, and pulsed-wave Doppler imaging of the atrial septum from midesophageal four-chamber and modified bicaval views before sternotomy. If the standard TEE examination was inconclusive, an "agitated" saline injection was administered via central venous access (internal jugular or subclavian vein) during the Valsalva maneuver (VM). VM was defined as a sustained positive airway pressure to 30 cm H2O for 10 s before sternotomy. Two injections were performed. The PFO was defined as the presence of "echo dropout" and/or a color jet crossing the atrial septum and/or the appearance of microbubbles in the left atrium within three to five cardiac cycles immediately after the release of VM. An atrial septal aneurysm was defined as bulging and motion of the region of the fossa ovalis >10 mm beyond the plane of the atrial septum. All consecutive CABG patients who met inclusion criteria were included in the study. Eight anesthesiologists performed TEE examinations during the study period. All TEE studies were read initially in the operating room by the fellow, attending anesthesiologist, or both and were subsequently reviewed by a single independent operator (the director of the perioperative echocardiography program, who had >10 yr of experience in TEE).
Preoperative AF was established from patient medical records and 12-lead electrocardiogram (ECG) analysis. All patients were assessed for the development of postoperative AF from the day of surgery to hospital discharge. Patients were monitored with continuous telemetry both in the ICU and in the step-down unit for up to 4 days after surgery. Patients were considered to have postoperative AF if telemetry displayed an irregular rhythm with either absent P waves or the presence of atrial fibrillatory waves that did not resolve spontaneously, and this diagnosis was confirmed by a cardiologist-interpreted 12-lead ECG. If patients developed AF that was confirmed and required treatment after they left the telemetry unit, they were included in the postoperative AF group. All patients received magnesium sulfate 2–4 g and metoprolol 5–10 mg during surgery. After surgery, ß-adrenergic blocker therapy was initiated as tolerated in patients without contraindications as part of the institutional clinical practice. Patients were categorized on the basis of the presence or absence of AF.
Demographic data were analyzed by using the two-tailed Student’s t-test and the 
2 test. Hospital LOS and perioperative mortality were analyzed with Wilcoxon’s ranked sum test and Fisher’s exact test, respectively. Univariate and multivariate logistic regression was performed to assess the relationship between PFO, atrial septal aneurysm, and postoperative AF. Covariates considered for inclusion in the model were age, CPB time, cross-clamp time, congestive heart failure, preoperative ß-adrenergic blockers, sex, and number of distal grafts. Predictors that had a univariate significance level of 
0.05 were included in the multivariate model. Predictors were tested for colinearity, and interactions were investigated for significance. A P value of <0.05 was considered statistically significant. Data are expressed as mean ± SD and median (interquartile range). All initial analyses were performed with SAS version 6.2 (SAS Institute, Cary, NC), and follow-up analysis was performed with SAS version 8.02.
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Results
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Postoperative AF was present in 124 (12.3%) patients. Demographic data and patient characteristics are presented in Table 1.
PFO was present in 72 (7.1%) patients. Atrial septal aneurysm was identified in 23 (2.3%) patients. In these patients, postoperative AF was present in 14 (19.4%) patients with PFO and 8 (34.8%) patients with atrial septal aneurysm. Significant univariate predictors of postoperative AF were included in a multivariate logistic regression model to demonstrate that the presence of PFO, age, and history of congestive heart failure were predictive of postoperative AF (Table 2). Figure 1 shows a predicted probability of AF in patients with and without PFO and atrial septal aneurysm adjusted for age, cross-clamp time, and congestive heart failure.
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Figure 1. Predicted probability model of postoperative atrial fibrillation. PFO = patent foramen ovale; ASA = atrial septal aneurysm; AF = atrial fibrillation.
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Patients with and without PFO had a median hospital LOS of 8.81 days (6–10 days) and 10.18 days (6–11 days), respectively (P = 0.51). There were no perioperative deaths in the PFO group, and the in-hospital mortality in patients without PFO was 2.64% (P = 0.25). Patients with and without AF had a median hospital LOS of 13.22 days (7–15 days) and 9.54 days (6–11 days), respectively (P = 0.0001). The in-hospital mortality was 4.24% in patients with AF and 2.33% in patients without AF (P = 0.21).
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Discussion
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The significance of our report is that it identifies an association between PFO and postoperative AF in the cardiac surgical setting. Furthermore, our findings are consistent with several previous reports (6,7,16) confirming that age and congestive heart failure are two major predictors for postoperative AF.
When adjusted for well known confounding factors such as age, history of congestive heart failure, and cross-clamp time, the odds of developing AF are 1.95 times as great in patients with PFO than in patients without this defect. Our data indicate that, even though the incidence of AF increases proportionally with the increase in age, patients with PFO or atrial septal aneurysm have a considerably higher predicted probability of developing postoperative AF at any given age. For example, given our predicted probability model, at the age of 50 years, the prevalence of postoperative AF is 8% in patients without atrial septal abnormalities, and this increases to 13% in patients with PFO and further to 18% in patients with atrial septal aneurysm. Similarly, at the age of 75 years, the prevalence of postoperative AF is 16%, 25%, and 35%, respectively.
Large-scale longitudinal studies have shown that AF is the most common arrhythmia in the general population (17,18). The incidence of AF almost doubles with each decade of adult life and ranges from 2 or 3 new cases per 1000 population per year between the ages 55 and 64 years to 35 new cases per 1000 population per year between the ages of 85 and 94 years (19). Furthermore, AF has been identified as an independent risk factor for death in the general population, with a relative risk of approximately 1.5 for men and 1.9 for women after adjustment for known risk factors (20). Although a substantial number of patients develop AF after cardiac surgery, there appears to be no difference in early in-hospital mortality between patients with and without postoperative AF. The presence of PFO and AF did not affect perioperative mortality in our study.
Previously, we reported the association between postoperative AF and neurocognitive decline after cardiac surgery (21). This study presents another association between PFO and postoperative AF in cardiac surgical patients. Is there a common pathophysiologic pathway or link between atrial septal abnormalities, postoperative AF, and neurocognitive decline? Although evidence for paradoxical embolism exists (22), the role of PFO as a mechanism for cerebral embolization remains controversial. It has been suggested that atrial vulnerability is associated with atrial septal abnormalities in patients with ischemic stroke (14). This result raises the question of the potential role of transient atrial arrhythmias and formation of thrombi in the presence of PFO and atrial septal aneurysm. Furthermore, the redundant septum provides an area of stasis and a potential for thrombus formation. Although these possibilities are intriguing, the causal relationships between PFO, atrial septal aneurysm, cognitive dysfunction, and postoperative AF are not established. Although different treatment potentials are open to these patients, including medical (antiplatelet or anticoagulant therapy), radiological (transcatheter closure of PFO), and surgical (open heart surgery with CPB for correction of atrial septal defects) treatments, the exact mechanisms and prognostic implications of these atrial septal abnormalities with respect to postoperative AF in cardiac surgical patients remain to be determined in future studies (23).
Limitations of our study include the retrospective design to evaluate the association between atrial septal abnormalities and postoperative AF. However, the Duke Intraoperative TEE and Cardiovascular Outcomes Databases contain a prospectively collected complete data set that provides an appropriate tool for analyzing the association between PFO and postoperative AF. Another limitation is in the measurement of postoperative AF. Data were collected only for the period of the hospital stay. Although it is likely that some patients developed AF after hospital discharge, the peak of postoperative AF is usually between postoperative Days 2 and 5, i.e., well within the duration of hospital stay. In addition, all patients received magnesium sulfate 2–4 g and metoprolol 5–10 mg during surgery, which may account for the overall reduction of postoperative AF in our study. Furthermore, ß-adrenergic blocker drug therapy was initiated as tolerated after surgery in patients without contraindications.
With respect to detection of atrial septal abnormalities, one can argue that the prevalence of patients with PFO in our study (7.1%) was rather small. In fact, the incidence of PFO in the general population, as well as in patients undergoing cardiac surgery, is reported to vary between 8% and 53% (24–29). Detection of PFO by contrast echocardiography is based on transient inversion of the interatrial pressure gradient. A contrast TEE (with IV administration of "agitated" saline) has a sensitivity of 89% and a specificity of 100% (30,31). It is noteworthy that the presence of left-sided heart disease with a potential increase of left atrial pressure may obscure the diagnosis of PFO, reducing its observed prevalence to as small as 5% (32). Furthermore, in patients with chronic obstructive pulmonary disease, the right-sided cardiac pressures may be increased, and the detection of PFO with color flow imaging can be problematic. In these patients, the patency of the foramen ovale may be missed even by contrast TEE, thereby increasing the number of false negatives. Although the application of provocative maneuvers would likely increase the sensitivity of the method to detect PFO, in this study only one in five patients received agitated saline and VM. Even if the prevalence of PFO in our study was underestimated, the group differences would only have worked against finding support for our hypothesis. Also, multivariate logistic regression analysis revealed an effect of PFO on postoperative AF that was independent of age, cross-clamp time, and congestive heart failure.
Finally, although the prevalence of patients with atrial septal aneurysm and AF was more frequent when compared with PFO, the overall number of patients with atrial septal aneurysm was too small to detect significance even in the cohort of more than 1000 patients. In the current scenario, one would likely require doubling or tripling the sample size to make definitive conclusions with respect to the predictive risks of postoperative AF in patients with atrial septal aneurysm.
In summary, we have demonstrated that the presence of PFO is associated with new-onset postoperative AF after conventional CABG surgery. Future studies should include PFO as a potential confounding factor for the development of AF after CABG surgery. Further trials are needed to determine whether preemptive therapy reduces the incidence of postoperative AF in patients with PFO.
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Acknowledgments
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Funding for this study was provided by the Division of Cardiothoracic Anesthesiology, Duke University Medical Center.
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References
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- Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993; 56: 539–49.[Abstract]
- Crosby LH, Pifalo WB, Woll KR, Burkholder JA. Risk factors for atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 1990; 66: 1520–2.[ISI][Medline]
- Lowe JE, Hendry PJ, Hendrickson SC, Wells R. Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation. Ann Surg 1991; 213: 388–92.[ISI][Medline]
- Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials—Studies of Left Ventricular Dysfunction. J Am Coll Cardiol 1998; 32: 695–703.[Abstract/Free Full Text]
- Chugh SS, Blackshear JL, Shen WK, et al. Epidemiology and natural history of atrial fibrillation: clinical implications. J Am Coll Cardiol 2001; 37: 371–8.[Abstract/Free Full Text]
- Mathew JP, Parks R, Savino JS, et al. Atrial fibrillation following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization—MultiCenter Study of Perioperative Ischemia Research Group. JAMA 1996; 276: 300–6.[Abstract]
- Almassi GH, Schowalter T, Nicolosi AC, et al. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg 1997; 226: 501–11.[ISI][Medline]
- Wong DT, Cheng DC, Kustra R, et al. Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing coronary artery bypass graft with fast-track cardiac anesthesia: a new cardiac risk score. Anesthesiology 1999; 91: 936–44.[ISI][Medline]
- Place DG, Peragallo RA, Carroll J, et al. Postoperative atrial fibrillation: a comparison of off-pump coronary artery bypass surgery and conventional coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2002; 16: 144–8.[ISI][Medline]
- Mueller XM, Tevaearai HT, Ruchat P, et al. Did the introduction of a minimally invasive technique change the incidence of atrial fibrillation after single internal thoracic artery-left anterior descending artery grafting? J Thorac Cardiovasc Surg 2001; 121: 683–8.[Abstract/Free Full Text]
- Shore-Lesserson L, Moskowitz D, Hametz C, et al. Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting. Anesthesiology 2001; 95: 652–8.[ISI][Medline]
- Nakai T, Lee RJ, Schiller NB, et al. The relative importance of left atrial function versus dimension in predicting atrial fibrillation after coronary artery bypass graft surgery. Am Heart J 2002; 143: 181–6.[ISI][Medline]
- Skubas NJ, Barzilai B, Hogue CW Jr. Atrial fibrillation after coronary artery bypass graft surgery is unrelated to cardiac abnormalities detected by transesophageal echocardiography. Anesth Analg 2001; 93: 14–9.[Abstract/Free Full Text]
- Berthet K, Lavergne T, Cohen A, et al. Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause. Stroke 2000; 31: 398–403.[Abstract/Free Full Text]
- Newman MF, Croughwell ND, Blumenthal JA, et al. Effect of aging on cerebral autoregulation during cardiopulmonary bypass: association with postoperative cognitive dysfunction. Circulation 1994; 90: II243–9.
- Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med 1997; 336: 1429–34.[Free Full Text]
- Benjamin EJ, Levy D, Vaziri SM, et al. Independent risk factors for atrial fibrillation in a population-based cohort. JAMA 1994; 271: 840–4.[Abstract]
- Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995; 115: 469–73.
- Falk RH. Atrial fibrillation. N Engl J Med 2001; 344: 1067–78.[Free Full Text]
- Benjamin EJ, Wolf PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998; 98: 946–52.[Abstract/Free Full Text]
- Stanley TO, Mackensen GB, Grocott HP, et al. The impact of postoperative atrial fibrillation on neurocognitive outcome after coronary artery bypass graft surgery. Anesth Analg 2002; 94: 290–5.[Abstract/Free Full Text]
- Knauth M, Ries S, Pohimann S, et al. Cohort study of multiple brain lesions in sport divers: role of a patent foramen ovale. BMJ 1997; 314: 701–5.[Abstract/Free Full Text]
- Sukernik MR, Mets B, Bennett-Guerrero E. Patent foramen ovale and its significance in the perioperative period. Anesth Analg 2001; 93: 1137–46.[Free Full Text]
- Cabanes L, Mas JL, Cohen A, et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age: a study using transesophageal echocardiography. Stroke 1993; 24: 1865–73.[Abstract/Free Full Text]
- Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988; 318: 1148–52.[Abstract]
- Di Tullio M, Sacco RL, Gopal A, et al. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992; 117: 461–5.
- DeRook FA, Comess KA, Albers GW, Popp RL. Transesophageal echocardiography in the evaluation of stroke. Ann Intern Med 1992; 117: 922–32.
- Webster MW, Chancellor AM, Smith HJ, et al. Patent foramen ovale in young stroke patients. Lancet 1988; 2: 11–2.[ISI][Medline]
- Konstadt SN, Louie EK, Black S, et al. Intraoperative detection of patent foramen ovale by transesophageal echocardiography. Anesthesiology 1991; 74: 212–6.[ISI][Medline]
- Chen WJ, Kuan P, Lien WP, Lin FY. Detection of patent foramen ovale by contrast transesophageal echocardiography. Chest 1992; 101: 1515–20.[Abstract/Free Full Text]
- Schneider B, Zienkiewicz T, Jansen V, et al. Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings. Am J Cardiol 1996; 77: 1202–9.[ISI][Medline]
- Siostrzonek P, Lang W, Zangeneh M, et al. Significance of left-sided heart disease for the detection of patent foramen ovale by transesophageal contrast echocardiography. J Am Coll Cardiol 1992; 19: 1192–6.[Abstract]
Accepted for publication September 16, 2003.
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Abstract
Introduction
