Published online before print June 21, 2004, doi: 10.1161/01.CIR.0000134481.24511.BC
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(Circulation. 2004;110:124-127.)
© 2004 American Heart Association, Inc.
Original Articles |
Plasma B-Type Natriuretic Peptide Levels Predict Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery
From the Center for Atrial Fibrillation, The Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to Andrea Natale, MD, Co-Head, Section of Pacing and Electrophysiology, Director Electrophysiology Laboratory, Co-Director Center for Atrial Fibrillation, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Desk F 15, 9500 Euclid Ave, Cleveland, OH 44195. E-mail natale{at}ccf.org
Received December 29, 2003; revision received March 16, 2004; accepted March 22, 2004.
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Abstract |
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Background— Postoperative (postop) atrial fibrillation (AF) occurs in up to 60% of patients after cardiac surgery, leading to longer hospital stays and increased healthcare costs. Recently, B-type natriuretic peptide (BNP) has been reported to predict occurrence of nonpostoperative AF. This study evaluates whether elevated preoperative (preop) plasma BNP levels predict the occurrence of postop AF.
Methods and Results— One hundred eighty-seven patients with no history of atrial arrhythmia who had a preoperative BNP level and had undergone cardiac surgery were identified. Their records were reviewed, and postoperative ECG and telemetry strips were analyzed for AF until the time of discharge. Postop AF was documented in 80 patients (42.8%). AF patients were older (68±11 versus 64±14 years, P=0.04), but there was no difference in sex distribution, hypertension, left ventricular (LV) function, LV hypertrophy (LVH), left atrial size, history of coronary artery disease (CAD), or ß-blocker use. Preop plasma BNP levels were higher in the postop AF patients (615 versus 444 pg/mL, P=0.005). After adjustment for age, sex, type of surgery, hypertension, LV function, LVH, left atrial size, CAD, and ß-blocker use, the odds ratios of postop AF according to increasing quartiles, compared with patients with lowest quartile, were 1.8, 2.5, and 3.7 (Ptrend=0.03).
Conclusions— An elevated preop plasma BNP level is a strong and independent predictor of postop AF. This finding has important implications for identifying patients at higher risk of postop AF who could be considered for prophylactic antiarrhythmic or ß-blocker therapy.
Key Words: atrial fibrillation • peptides • cardiac surgery
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Introduction |
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Postoperative atrial fibrillation (postop AF) has been reported to occur in up to 60% of patients after cardiac surgery, occurring in most patients within 72 hours.1–3 In this setting, most episodes are self-limiting but can increase the risk of postoperative stroke.4 Even uncomplicated postop AF requires medical and nursing time and can prolong hospital stay.1–6 Certain risk factors that are associated with the development of postop AF include older age, low ejection fraction, and presence of electrolyte imbalance. However, only older age has consistently been associated with postop AF.7,8
Various studies have failed to establish a reliable method to predict the occurrence of postop AF. An elevated B-type natriuretic peptide (BNP) level has been shown in some studies to be associated with AF.9–12 Furthermore, recent studies have demonstrated that BNP levels can predict recurrence of AF after direct current (DC) cardioversion in patients with mild heart failure.13,14 It has also been shown to predict occurrence of AF in patients with pacemakers for sick sinus syndrome.15 The aim of our study was to evaluate the potential use of BNP as a preoperative predictor of the occurrence of postop AF.
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Methods |
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Patients for whom a preoperative plasma BNP level was available after their referral for cardiac surgery (coronary artery bypass and/or valve surgery) through the Cardiology Department at the Cleveland Clinic Foundation from January 1, 2002, to December 31, 2002, were eligible for inclusion. Their records were reviewed, and postoperative ECGs and telemetry strips were analyzed for AF within the postop period until discharge. Blood samples for plasma BNP and routine chemistry were drawn in all these patients before surgery. All patients had presurgical ECGs and transthoracic echocardiograms. Exclusion criteria included decompensated heart failure within 60 days, an acute coronary syndrome within 60 days, history of atrial arrhythmia, preoperative antiarrhythmic medications, presence of a permanent pacemaker, and emergency surgery.
Patients were placed on continuous cardiac monitoring during the hospital stay, and 12-lead ECGs were obtained when necessary to confirm rhythm abnormalities. ECG and rhythm strips were checked daily. AF was defined as absent P wave before the QRS complex together with irregular ventricular rhythm on the rhythm strips. ECGs were performed to confirm the diagnosis. The occurrence of the first documented AF episode was the study end point. Plasma BNP levels were determined by use of the Biosite Diagnostics assay.
For statistical analysis, an independent-samples t test was used when comparing approximately normally distributed variables between 2 groups. Categorical variables were compared by the 
2 test. The relationship between the occurrence of AF and baseline predictors was assessed by use of logistic regression modeling. For regression modeling, BNP was dichotomized at the median value, and odds ratios were computed for the upper versus lower 50th percentiles of BNP. We also divided the population data into increasing quartiles with respect to BNP. The odds ratios of postoperative AF were computed for quartiles 2 through 4 compared with the lowest quartile in unadjusted and adjusted analyses. Results with a value of P<0.05 were considered statistically significant. All analyses were performed with SPSS version 9.0 (SPSS Inc). Unless noted otherwise, results are presented as mean±SD. The Institutional Review Board of our institution approved the investigation.
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Results |
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Baseline characteristics are presented in Table 1. Patients were divided into 2 groups based on whether or not they developed postop AF. Postop AF was documented in 80 patients (42.8%). AF patients were significantly older (68±11 versus 64±14 years, P=0.04). More patients in the AF group had undergone valve surgery (75% versus 52%, P=0.03). There were no statistically significant differences in sex distribution, hypertension, left ventricular (LV) function, LV hypertrophy (LVH), left atrial size, or history of coronary artery disease (CAD). The use of ß-blockers and ACE inhibitors was comparable in both groups, with a higher trend of ß-blocker and ACE inhibitor use in the nonpostop AF population (84% versus 73%, P=0.07, and 41% versus 37%, P=0.6, respectively). Preop plasma BNP level was higher in patients who developed postop AF (615 versus 444 pg/mL, P=0.005). More patients in the group that developed postop AF had a BNP level in the upper 50th percentile.
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Characteristics of study subjects and AF occurrence according to plasma BNP level dichotomized into upper and lower 50th percentiles are presented in Table 2. There was no statistically significant difference in sex, left atrial size, or LVH between the 2 groups. More patients in the postop AF group had a preop plasma BNP level >50th percentile (63% versus 40%, P<0.05). Patients with a plasma BNP level >50th percentile were older and more likely to have a history of hypertension and lower LV ejection fraction (LVEF). LVH was more prevalent in the group of patients with plasma BNP >50th percentile, but this was not statistically significant.
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In a multivariable logistic regression model that adjusted for sex, age, type of surgery (CABG only versus valve surgery), hypertension, LV function, LVH, left atrial size, presence of coronary artery disease, use of ß-blockers, and plasma BNP, only a BNP level in the upper 50th percentile was associated with a higher risk of postop AF (odds ratio, 2.5; 95% CI, 1.121 to 5.390; P=0.025) (Table 3).). Furthermore, after adjustment for age, sex, hypertension, LV function, LVH, left atrial size, CAD, ß-blocker use, and type of surgery, the odds ratios of postop AF according to increasing quartiles of BNP compared with patients with the lowest quartile were 1.8, 2.5, and 3.7 (Ptrend=0.03), see Figure.
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Discussion |
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In this study, an elevated plasma BNP level obtained before cardiac surgery was the strongest independent predictor of the occurrence of postop AF. There was a "dose-response" relationship in that the risk of postoperative AF increased as plasma BNP levels increased after adjustment for several factors, most notably age, LVEF, and type of surgery. Importantly, elevated plasma BNP was a stronger predictor than age, which has been the most consistent risk factor associated with postop AF in previous investigations.
The incidence of AF in our patient population was 42.8%, which is well within the range reported in the literature and suggests that the study subjects were typical of patients undergoing cardiac surgery. In line with evidence from previous studies, a higher level of BNP was associated with older age, history of hypertension, and depressed LV function.16
BNP is a member of the natriuretic peptide family. The natriuretic peptide family has both regulatory and modulatory roles in the cardiovascular system.17 Moreover, elevated BNP levels have been used as diagnostic and prognostic factor in various cardiovascular diseases.17 Pathological changes such as hypertrophy, fibrosis, and inflammation have been demonstrated in patients with long-standing hypertension and isolated diastolic dysfunction and may be associated with elevation of BNP levels.16,18–20
Levels of BNP have been shown to be increased in patients with lone AF and idiopathic bilateral atrial dilatation.10,12 Recently, BNP has been demonstrated to predict occurrence of AF in patients with pacemakers implanted for sick sinus syndrome and recurrence of AF after cardioversion in patients with mild heart failure.13,15 Moreover, BNP levels have been shown by various studies to decrease after direct current cardioversion of AF and restoration of normal sinus rhythm.9,12,21
The common pathological and physiological changes associated with both AF and increased BNP in various clinical settings include age, atrial fibrosis, and increased cardiac chamber wall stress. Clearly, left atrial pressure can increase at the time of surgery, which may be the inciting factor. If the left atrial pressure is increased preoperatively, plasma BNP may also be increased, thus marking the patients destined to develop postop AF.
Clinical Implications
In our patient population, an elevated plasma BNP level above the 50th percentile was the major determinant of postop AF. There was a stepwise increase in risk of AF with increasing BNP levels in that the risk of postoperative AF increased as BNP levels increased after adjustment for several factors, most notably age, LVEF, and type of surgery. This observation has important clinical implications. Accurately identifying patients at higher risk of developing postop AF will enable the treating physicians to initiate aggressive prophylactic therapy either before surgery or, perhaps, by using intraoperative ablation techniques. This will decrease the incidence in this high-risk group and reduce the length of stay, overall healthcare costs, and the morbidity associated with AF. In addition, healthcare costs may also be decreased by not initiating prophylactic therapies in patients at low risk of postop AF.
Limitations
Although BNP and other preoperative studies were collected prospectively in patients, the incidence of AF was assessed retrospectively by chart review. However, this was performed by a physician blinded to the respective BNP values. It is possible that the patients in whom a preop BNP level was obtained were perceived to be at higher risk for perioperative complications. However, this would not alter the conclusion that in this cohort, a high plasma BNP level is predictive of postop AF. It is possible that some patients may have had very transient episodes of AF that were not documented by an ECG or mentioned in the chart. These episodes would not have had any important clinical significance. It is also possible that a subset of this study population had episodes of undocumented preoperative atrial arrhythmias. Other factors not accounted for in this analysis, such as thyroid function, and postop complications and management parameters may have affected the propensity to develop AF.
Conclusions
Preoperative BNP levels predict postop AF in patients undergoing cardiac surgery. BNP levels could be used to better stratify patients in this respect. Larger prospective studies are needed to validate our findings.
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Acknowledgments |
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Disclosure
Dr Mills has received an educational research grant from Scios Inc. Dr Francis serves on the advisory board committee of Biosite Diagnostics.
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References |
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