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(Circulation. 2000;101:1403.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Atrial Fibrillation After Coronary Artery Bypass Surgery
A Model for Preoperative Risk Stratification
From the Department of Cardiology (A.G.Z.), University Hospital of Wales, Cardiff, Wales; the Cardiovascular Institute (G.H.), Mount Sinai Medical Center, New York, NY; the Department of Cardiology (R.A.A., N.P.C., P.G.M.), London Chest Hospital; and the Department of Environmental and Preventive Medicine (E.A.P.), St Bartholomew’s and The Royal London School of Medicine, London, UK.
Correspondence to Dr Zaman, Department of Cardiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14-4XN, UK. E-mail azfarzaman{at}hotmail.com
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Abstract |
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Background—Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG. Identification of patients vulnerable for arrhythmia will allow targeting of those most likely to benefit from prophylactic therapy. The aim of the present study was to evaluate accuracy of a prospectively defined signal-averaged P-wave duration (SAPD) cutoff and additional preoperative characteristics for the prediction of AF after CABG.
Methods and Results—Patients undergoing elective isolated CABG
were recruited to the present prospective study. SAPD was
recorded in all patients. Filtered signals from 3 orthogonal leads
were combined in a vector analysis, and total SAPD was measured
preoperatively. Postoperative in-hospital AF occurred in 92 (28.2%) of
326 patients. Patients who developed AF were older (65.9 versus 61.7
years of age; P<0.0005) and had longer SAPD (158 versus
145 ms; P<0.0005) than non-AF patients. Incidence of AF
increased in patients 
75 years of age and increased progressively
throughout the range of SAPD. Stepwise logistic regression
analysis of preoperative variables identified that SAPD
>155 ms (odds ratio, 5.37; 95% CI, 3.10 to 9.30;
P<0.0005), advanced age (odds ratio, 1.53; 95% CI,
1.26 to 1.86 per 5-year increase in age; P<0.0005), and
male sex (odds ratio, 2.88; 95% CI, 1.30 to 6.40;
P<0.01) independently predicted AF. Prospectively
defined SAPD >155 ms predicted AF with positive and negative
predictive accuracy of 49% and 84%, respectively.
Conclusions—A combination of prolonged SAPD, advanced age, and male sex identifies patients at high risk for development of AF after CABG.
Key Words: fibrillation • arrhythmia • surgery • men • sex • aging
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Introduction |
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TopAbstractIntroductionResultsDiscussionMethodsReferences |
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Atrial fibrillation (AF) occurs in 20% to 40% of patients after CABG.1 2 3 Incidence of arrhythmia has not changed, despite improvements in anesthetic and surgical techniques, and evidence suggests its incidence may be increasing.1
AF after CABG is self-limiting in most cases. However, even when AF is uncomplicated, its treatment requires additional medical and nursing time and a prolonged hospital stay.1 2 3 4 5 6 In a minority of cases, arrhythmia can cause hemodynamic compromise and increase risk of postoperative stroke.1 7 8 Consequently, AF after CABG leads to increased use of resources.2 3 4
Numerous studies have sought to identify predictors of AF after CABG. Their number is testament to the failure to prevent arrhythmia by prophylactic measures in unselected patients. Only increased age has consistently been associated with AF after CABG.1 2 3 9 10 11 Several workers, including those in our group, have demonstrated that prolonged preoperative signal-averaged P-wave duration (SAPD) is associated with AF after CABG.12 13 14 15
The present study was designed to evaluate prospectively accuracy of predefined SAPD for prediction of AF after CABG. The cutoff figure of 155 ms was derived from a previous study of 102 patients who underwent CABG.12 A secondary aim of the present study was to stratify patients at risk of AF on the basis of simple preoperative variables.
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Results |
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Of 358 eligible patients, 30 (8.4%) were excluded as a result of signal interference or high noise levels on SAPD recordings. Two patients who died within 72 hours of surgery were excluded. The remaining 326 patients form the basis of our results. Of these, 3 died before discharge: 1 each on postoperative days 8, 11, and 25. All 3 developed AF, on days 6, 1, and 2, respectively. Mean patient age was 63 years, and 268 (82%) were male. Preoperatively, 218 (67%) were taking ß-blockers. After surgery, 8 (2.5%) returned to theater for sternal rewiring and 7 (2.1%) for bleeding.
Ninety-two (28.2%) patients developed AF, at 2.8±1.7 (mean; range, 0
to 11) days after operation. Five patients were noted to have
brief (<30-s) episodes of irregular rhythm on Holter monitor; these
episodes were not recorded on 12-lead ECG, and these patients were
not included in the AF group. These patients did not develop AF during
hospital stay, and their postoperative course was unremarkable.
Demographic data are presented in Table 1
, and distribution of AF is illustrated
in Figure 1.
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Low serum magnesium on the first postoperative day was not associated with AF. Levels <0.7 mmol/L were seen in 57% of patients who received cross-clamp fibrillation for myocardial protection, 22% who received cold-crystalloid cardioplegia, 14% who received whole blood, and 0% after CABG on the beating heart.
Univariate Predictors
No differences were seen between AF and non-AF patients in left
ventricular ejection fraction, Q waves on preoperative ECG,
and left atrial diameter. Surgical techniques were similar between
groups.
With univariate analysis, preoperative variables significantly associated with development of postoperative AF were age and SAPD. Use of preoperative ß-blockers was more prevalent (70% versus 59%; P<0.05) in younger patients and those who remained in sinus rhythm. Weaker associations were noted between perioperative and postoperative variables of cardiopulmonary bypass time, units of blood transfused, and elevated postoperative plasma urea (>7 mmol/L) and creatinine (>125 µmol/L) concentrations. No difference was seen between groups in preoperative or postoperative magnesium concentrations. Postoperative ß-blockers were used less commonly (26% versus 44%; P<0.005) in those who developed AF. ß-Blocker withdrawal was significantly different (35% in the AF group versus 29% in those without AF; P=0.03). Postoperative hospital stay was significantly longer in patients with AF than in those without (9.2 versus 7.3 days; P<0.0005).
Age
Advanced age was strongly associated with postoperative AF. Mean
age was 65.9 years in the AF group compared with 61.7 years in the
non-AF group (P<0.0005). Incidence of AF increased
progressively in patients aged 
75 years (Figure 2), such that 1 of 29 (3.4%) patients
aged 50 to 54 years versus 19 of 45 (42.2%) aged 70 to 74 years
developed AF. Odds of developing AF increased 1.48 (95% CI, 1.24 to
1.77)-fold for each 5-year increase in age and 3.80 (2.00 to 7.23)-fold
for those aged 60 years compared with patients <60 years of age.
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No correlation existed between age and SAPD (R2=0.1; P=0.9). When incidence of SAPD >155 ms was documented within each 5-year age band, a small, nonsignificant difference was seen between groups. Those in the 55–to-69–years age band had lowest incidence of prolonged SAPD, 25.4%, and those in the 70-to-74-years age band, highest, 44.4% (P=NS).
Signal-Averaged P-Wave Duration
Mean SAPD was significantly longer (158 versus 145 ms;
P<0.0005) in patients who developed AF after CABG.
Incidence of AF increased progressively with increases in SAPD (Figure 3), such that 3 of 50 (6%) patients with
SAPD 130 ms developed AF compared with 8 of 13 (61.5%) with SAPD
>175 ms. Odds ratio (OR) for AF was 2.11 (95% CI, 1.62 to 2.74) per
15-ms increase in SAPD and 4.95 (2.96 to 8.28) for SAPD >155 ms.
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In the 64 patients in whom preoperative echocardiograms were recorded (18 developed postoperative AF), no association existed between left atrial size (measured at the level of the aortic valve leaflets in the parasternal long-axis view) and AF. Furthermore, no significant difference was seen between AF and non-AF groups in mean body weight (82.2 and 77.6 kg, respectively) or body mass index (27.7 and 26.5 kg/m2, respectively). We found no association between SAPD and either body weight or body mass index or with left atrial diameter. No significant difference was seen between the sexes in SAPD (148.9 ms for men versus 147.9 ms for women) and no significant difference in percentage of males (35.4%) versus females (39.7%) with SAPD >155 ms.
Multivariate Analysis
Stepwise logistic regression analysis of preoperative
variables showed that age (P<0.0005), SAPD
(P<0.0005), and male sex (P<0.01) were
independently associated with development of AF (Table 2). When all (preoperative and
postoperative) variables were entered into analysis, >3
grafts (OR, 2.22; 95% CI, 1.17 to 4.21; P<0.02) and
elevated postoperative plasma creatinine concentration (OR,
1.93; 95% CI, 1.04 to 3.60; P<0.04) were additionally
associated with AF. ß-Blockade use was not associated with AF
preoperatively (P=0.098) or postoperatively
(P=0.057).
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Predictive Accuracy of Preoperative Variables
SAPD >155 ms predicted AF with a sensitivity of 63%, specificity
of 74%, and positive and negative predictive accuracy of 49% and
84%, respectively. The combination of SAPD >155 ms and age 60 years
increased positive predictive accuracy to 57%, with a negative
predictive accuracy of 82%. Age of 60 years alone had a positive and
negative predictive accuracy of 35% and 87%, respectively. When
combined with male sex, respective values were 39% and 87%.
Risk Profile
Table 3 stratifies patients by
SAPD >155 ms and aged 60 years. Table 3 shows that the
incidence of AF after CABG for patients aged <60 years with SAPD 155
ms was 6.8%, versus 56.8% for patients aged 60 years with SAPD
>155 ms.
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Similarly, Table 4 is a risk
stratification table that includes gender. Interestingly, 0 of 35 women
with SAPD 155 ms developed AF, irrespective of age, whereas 11 of 23
(47.8%) women with SAPD >155 ms developed AF. Highest incidence was
in males 60 years with SAPD >155 ms, who had a 58.8% chance of AF
after CABG.
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Discussion |
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TopAbstractIntroductionResultsDiscussionMethodsReferences |
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The present study confirms both high incidence of AF after CABG and its strong association with increases in age and SAPD. The present study is the largest to evaluate SAPD for the prediction of AF after CABG and the first to validate a cutoff value prospectively defined from a study of patients undergoing CABG. We have described incidence of AF in a population undergoing elective, isolated CABG and quantified the risk from SAPD, age, and sex, thereby to allow preoperative identification of vulnerable patients.
Despite improvements in surgical and anesthetic techniques, incidence of AF after CABG remains stubbornly unchanged. Little doubt exists that this is, at least in part, a reflection of increased age of patients undergoing surgical revascularization,1 16 itself a consequence of the aforementioned improvements.
Patients who develop AF have a prolonged postoperative hospital stay compared with patients who remain in sinus rhythm; this finding was confirmed in the present study. Recent evidence shows that prolonged hospitalization is attributable to arrhythmia rather than clinical characteristics of AF patients.6 The financial burden that results from prolonged hospitalization is considerable.2 3 4
We failed to confirm our previously reported association of AF with postoperative hypomagnesemia. One reason could be the different strategies of myocardial protection used in the 2 studies. In the earlier study12 post hoc analysis revealed 59% of patients received cross-clamp fibrillation and 41% cold-crystalloid cardioplegia. Patients in the former group had a significantly lower serum magnesium level on the first postoperative day (P<0.005; unpublished data). In the present study, although cross-clamp fibrillation was again associated with postoperative hypomagnesemia, most patients received whole-blood cardioplegia supplemented with magnesium. However, prevalence of AF in the 2 studies was similar, which suggests that postoperative magnesium is not causally related to arrhythmia development.
Age
Advanced age increases risk of AF in the general
population.17 18 Therefore, it is not surprising that
incidence of AF after CABG also increases with age. Dilatation and
fibrosis of the atria have been shown to increase with
age,19 with a loss of side-to-side electrical coupling
between groups of atrial muscle fibers.20 Consequent
slowing of electrical conduction within the atria provides a substrate
for arrhythmogenesis. Of interest, the increase in AF was not sustained
in patients >75 years of age, a finding previously reported in
patients >80 years of age.3 Mathew et al postulated that
the increase in atrial connective tissue with age and resulting
nonuniform anisotropic conduction could be maximal by the eighth decade
of life in humans. Although numbers of patients within this age group
were relatively small, the finding is important, given that the mean
age of patients undergoing CABG continues to
increase.1 16
SAPD Duration
AF is generally accepted to be reentrant in
origin.21 22 23 Therefore, sustained AF requires that the
depolarizing wave fronts continuously encounter excitable tissue, a
circumstance favored by slow atrial conduction and a short atrial
refractory period.24 SAPD has been established to be
prolonged in patients who develop AF after CABG, and this is thought to
reflect slow atrial conduction in patients with the arrhythmia
substrate.25 26 27 28 29 Absence of a relation between SAPD and
age or body weight in the present study suggests that the former is
an independent marker of the arrhythmia substrate.
Prolonged SAPD merely identifies patients with the arrhythmia substrate. The trigger for development of AF is probably multifactorial. Cox proposed that vulnerability to development of AF after cardiac surgery is increased by nonuniformity of local refractory period distribution within the atrium.30 This dispersion of atrial refractoriness may be promoted by perioperative factors such as atrial ischemia, imbalance in autonomic tone, or electrolyte imbalance. That an additional trigger is necessary to initiate AF in those with the arrhythmia substrate is a possible explanation for the moderate positive predictive accuracy of SAPD. Those without the arrhythmia substrate and, hence, at low risk for AF after CABG are identified more accurately.
Gender
Several studies have found an increased incidence among
males,1 2 3 9 whereas others have reported no
difference.6 31 32 In our study, the number of women was
small, and any conclusion should be treated with caution. We found no
differences on univariate analysis, but male sex
was an independent predictor of AF after CABG on
multivariate analysis and improved the accuracy
of SAPD in identification of vulnerable patients.
Left Atrial Size
We did not find a relation between AF and left atrial size or
between SAPD and left atrial size in a subset of patients. This is
consistent with results from other studies.3 33
Given the strong association between left atrial size and AF in the
general population, this result is surprising and may indicate that a
different mechanism underlies arrhythmia induction in the
postoperative group.
ß-Blocker Therapy
Use of ß-blockers preoperatively protected against
arrhythmia on univariate analysis, but this
effect was lost when stepwise logistic regression with other
significant preoperative variables was performed. Previous reports
suggest that ß-blockers suppress AF after surgery.34 35
However, in our study, ß-blocker use was confounded by age in
multivariate analysis. Younger patients were
given ß-blockers more commonly than older patients, and age was more
strongly associated with AF. We emphasize that the present study
was not designed to establish drug efficacy. Our sole aim was to
identify preoperative variables in risk stratification.
Clinical Relevance
Pharmacological intervention to reduce AF incidence in unselected
patients has proved disappointing. Daoud et al36 reported
amiodarone to be of benefit, but the study had major
limitations and the in-hospital benefit was marginal.37
The ability to identify patients at increased risk for AF after CABG
will increase the statistical power of studies to detect a meaningful
reduction in AF in the treated group. Conversely, recognition of
low-risk patients indicates those who will not benefit from preventive
therapy and allows better planning of hospital resources in patient
management after cardiac surgery. Given that the additional cost of AF
after CABG in the United States is estimated to be $153
million,3 information on likely risk and possible
increased hospital stay is useful to both providers and purchasers of
health care.
Signal-averaged ECG is a noninvasive test that takes 20 minutes to record. The machine is portable and allows bedside recording, and it is thus suitable for outpatient use. By use of additional preoperative clinical variables, we have significantly improved the ability of high-resolution ECG to identify patients at risk of AF after CABG.
Study Limitations
As with all similar studies, one limitation of the present
study is the method used to record arrhythmias. We
continuously monitored rhythm on all patients for 72 hours and
recorded 12-lead ECGs if arrhythmia was suspected
clinically. Our AF prevalence of 28% is within the 25% to 30% range
reported in the majority of such studies.
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Methods |
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TopAbstractIntroductionResultsDiscussionMethodsReferences |
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Population
The present study is a prospective study of patients undergoing elective CABG at 2 regional cardiac centers in the United Kingdom. Patients participating in other trials were excluded, as were those undergoing concomitant valve surgery, in AF or with a history of AF, or receiving class I or III antiarrhythmic agents. All patients gave informed consent, and the study was approved by the local ethics committee for each of the participating centers.
Patient Assessment
Preoperative SAPD was measured in all patients. In addition, the
following data were recorded prospectively. Preoperative data
included age, sex, medications, presence of Q waves on 12-lead ECG,
coronary anatomy, left ventricular ejection
fraction on angiogram, hemoglobin, urea, electrolytes, and magnesium
concentration. Echocardiograms were performed when possible (n=64) to
assess left atrial size. Perioperative data included
number of distal anastomoses, use of internal mammary artery graft,
aortic cross-clamp time, cardiopulmonary bypass time, method of
myocardial protection, and operator status. Postoperative data included
units of blood transfused, hemoglobin, urea, electrolytes, and
magnesium concentration on first postoperative day; duration of
postoperative hospital stay; and drugs at discharge.
Signal-Averaged ECG
The method of recording and analyzing P-wave
signal-averaged ECG has previously been described.12 38
ECGs were recorded and analyzed by a single individual at
each center using a Predictor IIc signal averaging system
(Arrhythmia Research Technology Inc). After preparation of the
skin, silver-silver chloride electrodes were applied in an orthogonal
arrangement. QRS was used as the trigger for the signal-averaging
process. To expose the P wave and PR segment, the fiducial point was
shifted to the extreme right of the 300-ms window. A P-wave template
was manually selected, and P-wave complexes that did not match the
template with a 99% correlation coefficient were rejected. This
ensured that any variation in the P-wave complex due to surface noise,
ectopic activity, or autonomic activity was not averaged.
Recordings were terminated when 500 beats had been accepted for
averaging. If noise exceeded 0.5 mV, the recording was repeated
until the criterion was met. A least-squares-fit filter with a window
width of 100 ms (high-pass cutoff, 29 Hz) was applied for data
analysis. P-wave complexes of the X, Y, and Z bipolar leads
were combined into a vector magnitude with the root-mean-square of each
lead. P-wave onset and offset were determined manually in the spatial
magnitude, and P-wave duration was calculated preoperatively. P-wave
onset was defined as the first atrial deflection from baseline noise
level and offset as return of the atrial signal to baseline or onset of
the QRS complex, whichever was earlier.38
Reproducibility was assessed by blinded remeasurement of 20 randomly
selected P waves by the original investigator (for intraobserver
reproducibility) and by a second investigator (for interobserver
reproducibility). Mean intraobserver difference in the absolute SAPD
measurement was +1.2±6.7 ms, which represented a
coefficient of reproducibility of 13.4, or 8.7% when expressed as
percentage of mean value for 2 measurements.39
Interobserver values were +3.0±10.8 ms, or 21.5% and 14%.
Intraobserver agreement for greater than or less than the 155-ms cutoff
occurred in 18 of 20 cases (90%; 
=0.8; P<0.0005), and
agreement between observers occurred in 17 of 20 cases (85%; =0.7;
P=0.002).
Surgical Procedure
All patients underwent isolated elective CABG. Material for vein
grafts was harvested from saphenous vein. Internal mammary artery
grafts were used when appropriate. Four patients underwent CABG surgery
performed on a beating heart. Myocardial protection was achieved with
blood cardioplegia supplemented with magnesium (n=243),
cold-crystalloid cardioplegia (n=9), or intermittent cross-clamp
fibrillation (n=72) according to operator preference. Core temperature
was allowed to decrease to 28°C to 32°C. Each patient was rewarmed
to 37°C as cardiopulmonary bypass was discontinued.
Postoperative Management
Postoperatively, patients were managed in the intensive care
unit before transfer to the high-dependency unit and main ward. ECG was
monitored continuously by bedside monitor. Patients transferred to the
main ward before the third day underwent telemetry or ambulatory ECG to
allow continuous monitoring for 72 hours postoperatively. Thereafter,
patients were examined daily, and an ECG was performed whenever AF was
suspected clinically. Nursing staff members were asked to record
tachycardias noted during monitoring by 12-lead ECG. Study
end point was any episode of documented (on 12-lead ECG) postoperative
in-hospital AF, defined as an irregular rhythm with no identifiable P
waves. Prophylaxis against postoperative AF was not used routinely, and
its occurrence was managed by the attending physician. Prescription of
drugs was not influenced by study investigators.
Statistical Analysis
Data were stored electronically and analyzed by use of
SPSS for Windows statistical software. Univariate
analysis by Student’s unpaired t test was performed
for continuous data with a normal distribution, by Mann-Whitney
U test for nonnormal data, and by 
2
test for categorical variables. Stepwise logistic regression was
performed to investigate the effect of possible confounders on SAPD.
Variables with univariate significance 0.1 were
entered into the regression. Preoperative variables were considered
before a separate analysis of all variables. For purposes
of stepwise logistic regression, nonnormal data were dichotomized.
Predictive accuracy of the prospectively defined SAPD >155 ms was
determined. ORs for AF were calculated for these preoperative
variables: SAPD, age, and male sex. Risk tables were generated from
incidence of AF in different patient groups.
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Acknowledgments |
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The present study was supported by a British Heart Foundation project grant (No. 96/188). Dr Zaman was a Fulbright Scholar supported by an International Fellowship from the British Heart Foundation.
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Footnotes |
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The Methods section of this article can be found at http://www.circulationaha.org
Received July 8, 1999; revision received October 12, 1999; accepted October 19, 1999.
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