International Journal ofCardiology, 36 (1992) 253-261 0 1992 Elsevier Science Publishers B.V. All rights reserved
CARD10
253 0167.5273/92/$05.00
01519
Review
Atria1 fibrillation and flutter after coronary artery bypass surgery: epidemiology, risk factors and preventive trials Lars Frost ‘, Henning Mfllgaard ‘, Evald H@j Christiansen ‘, Kirsten Hjortholm j, Peter K. Paulsen 4 and Poul Erik Bloch Thomsen ’ Departments of ’ Cardiology, .’Anaesthesiology and ’ Thoracic and Cardio~~ascular Surgery, Skejby Hospital, lJnic,ersity Hospital Aarhus, Aarhus. and ’ Institute of Pharmacology. Unilvrsity of Aarhus. Aarhus, Denmark (Received
16 December
1991; revision
accepted
20 April 1992)
Frost L, Mslgaard H, Christiansen EH, Hjortholm K, Paulsen PK, Thomsen PEB. Atria1 fibrillation and flutter after coronary artery bypass surgery: epidemiology, risk factors and preventive trials. Int J Cardiol 1992:36:253-261. Atria1 fibrillation and atria1 flutter are common arrhythmias after coronary artery bypass grafting. Although the consequences of the arrhythmia are generally not life-threatening, it constitutes a major clinical problem often requiring conversion to sinus rhythm. Atria1 fibrillation or flutter can result in hypotension, heart failure, pneumonia, and stroke. This article reviews the literature on epidemiology, electrophysiology, risk factors, and preventive trials. The major conclusions are: (11 In patients undergoing coronary artery bypass surgery, the incidence of postoperative atria1 fibrillation or flutter is 20-30%, the peak incidence being on the second or third postoperative day. (2) The strongest independent preoperative predictor for atria1 fibrillation or flutter is the patients’ age. (3) Intra-atria1 conduction delay recorded pre and peroperatively may predict development of atria1 fibrillation. (4) Peroperative inducibility of atria1 fibrillation by pacing the right atrium may identify patients at risk for postoperative atria1 fibrillation. (5) Development of postoperative atria1 fibrillation or flutter has not been associated with peroperative or postoperative events. (6) The specificity and sensitivity of age and other possible relevant factors for prediction of atria1 fibrillation or flutter after coronary artery bypass grafting is low. (7) No effective prophylactic regimen has yet been established. Key words: Atria1 fibrillation; Atria1 flutter; Coronary artery bypass surgery
Introduction Globally 200,000 patients undergo coronary artery bypass surgery each year for angina pec-
Correspondence to: L. Frost, M.D., Dept. of Cardiology, Skejby Hospital, University Hospital Aarhus, DK-8200 Aarhus N, Denmark. Tel. +45 86 784511. Fax +45 86 784533.
toris 111. Twenty to 30% (40,000-60,000) of the patients develop atria1 fibrillation or atria1 flutter during the postoperative in-hospital period [3,4]. Although the consequences of the arrhythmia are generally not life-threatening, it constitutes a major clinical problem as conversion to sinus rhythm is often mandatory. The results of the atria1 fibrillation or flutter can be hypotension, heart failure, pneumonia, stroke, and postponement of dis-
254 TABLE
1
Incidence
of atrial
fibrillation
Ref. + year
or flutter
99 1666 100 5 807 418
COM = continuous
oscilloscopic
artery
bypass
Pts. developing atrial fibrillation or flutter
No. of patients studied
[7]. 1981 [4], 1989 [13]. 1990 [3], 1990 [ll], 1990
Buxton Fuller Yousif Leitch Crosby
after coronary
monitoring;
No.
%
29 473 19 999 115
29 28 19 17 27
Electrocardiographic documentation
2
Factors
associated
or flutter
No. of patients studied
Significant
Epidemiology The incidence of atria1 fibrillation after coronary artery bypass grafting siderably in different reports (Table mainly due to the varying quality of surveillance and to differences in the
after coronary predictive
artery
bypass
Statistics
99 1666 1666 100 5 807 5 807 5 807 5 807 5 807 5 807 5 807 5 807 418
Peroperatke factors Capucci [8]. 1987 Yousif [13], 1990 Yousif 1131, 1990 Leitch [3], 1990 Lowe [9], 1991
100 100 5 807 50
Atrial conduction delay Adjunctive coronary endarterectomy Topical cardiac cooling More than three distal anastomosis Pace inducibility of atrial fibrillation
Postoperative factors Fuller [4], 1989 Fuller [4], 1989
1666 1666
Postoperative Stroke
P-wave duration Age Preoperative digoxin treatment Myocardial ischemia (ST-segment
monitoring)
Age Chronic airflow limitation Chronic renal failure Hypertension Preoperative diuretic treatment Preoperative beta-blocker treatment Cardiothoracic ratio > 0.5 Three-vessel or left main disease Age
beta-blocker
and flutter varies con1). This is arrhythmic duration of
surgery.
factor
Pre0peratii.e factors Buxton [7], 1981 Fuller [4], 1989 Fuller 141, 1989 Yousif [l3], 1990 Leitch [3], 1990 Leitch [3], 1990 Leitch [3], 1990 Leitch [3], 1990 Leitch 131. 1990 Leitch [3]. 1990 Leitch [3], 1990 Leitch [3], 1990 Crosby [ 111. 1990
50
3 2 15 mmHg and this had no significant influence on development of atria1 fibrillation. Factors such as left atria1 dimension measured by echocardiography, previous myocardial infarction and unstable angina have no significance for development of atria1 fibrillation/flutter [3,4,6]. From this it can be concluded, that age of the patient is the strongest preoperative predictor for development of atria1 fibrillation and flutter after aortocoronary artery bypass grafting and that no heart related factor has been isolated that is
of atrial
fibrillation
control
#
Trials started postoperatil’ely Stephenson [26], 1979 Propranolol vs. control propranolol control # Digoxin vs control Csicsko [15], 1981 digoxin control Silverman [24], 1982 Propranolol vs propranolol withdrawal propranolol propranolol withdrawal Williams [32], 1982 Propranolol vs control propranolol control # Abel [23], 1983 Propranolol vs propranolol withdrawal propranolol propranolol withdrawal Timolol vs placebo White (271, 1984 timolol placebo # Ormerod [17], 1984 Propranolol vs digoxin vs control propranolol digoxin #
Trials started preoperaticely Johnson [16], 1976 Digoxin vs control digoxin control Martinussen [31], 1988 Propranolol vs placebo propranolol placebo # Lamb [28], 1988 Atenolol vs control atenolol control #
Drug(s)
Results
Ref. + year
3
of trials for prevention
TABLE
100 41 50 41 21 20 90 27 30
R, NB
R, NB
R, DB
R, NB
33
100 50 50 60 28 32
R, NB
R. NB
223 87 136 407 137 270
120 54 66 75 35 40 60 30 30
(Holter
4th postoperative 1(4%)
3 (6%)
3 (2%)
7 (8%)
1(3%)
5 (14%)
3 (6%)
Treated
(7 days)
Not reported
Holter
4 (15%) 10 (33%)
3 (14%)
9 (27%)
7 (35%)
22 (44%)
6 (19%)
14 (28%) day)
33 (12%)
24 (18%)
10 (33%)
5 (13%)
10 (15%)
Untreated/ placebo
n (%) with arrhythmia
COM (3 days), ECG, Holter 9 (22%)
Not reported
COM (2 days), ECG
COM (3 days), ECG
Not reported
COM (3 days), ECG
COM (4 days)
COM (4 days), ECG
Electrocardiographic documentation
bypass surgery.
No. of pts.
artery
coronary
after
R, NB
R, NB
R. DB
R, NB
Design
and flutter
0.52 1.22
0.41
0.50
0.19
0.60
0.18
0.46
0.10
1.14
0.37
group(s)
Relative risk in treatment
0.19-1.57 0.58-2.59
0.12-1.36
0.26-0.96
0.02-1.49
0.07-0.70
0.06-0.57
0.21-1.01
0.01-0.73
0.36-3.62
0.11-1.27
95% confidence interval
0.27
0.24
0.05
0.15
0.006
0.0005
0.06
0.006
1.00
0.16
‘p value
P d
independently associated with development postoperative atria1 fibrillation or flutter.
of
Electrophysiology. Buxton and Josephson [7] studied total P-wave duration measured from leads I, II and III and concluded, that an intraatria1 conduction defect measured by P-wave prolongation preoperatively is a sensitive but nonspecific predictor of postoperative atria1 fibrillation in patients undergoing coronary bypass grafting. An Italian group [81 looked into this by making peroperative electrophysiologic studies in 50 patients who later underwent cardioplegia and bypass grafting in order to determine the possible mechanism explaining the frequent postoperative episodes of atria1 fibrillation. The patients developing atria1 fibrillation had a high percentage of splitting of the atria1 electrogram (77% vs 5%, p < 0.0002) during atria1 premature stimulation suggesting that patients with intra-atrial conduction defects were at greater risk of developing atria1 fibrillation after coronary artery bypass grafting. By stimulating the mid-right atria1 free wall with incremental stimuli, before the initiation of cardiopulmonary bypass, Lowe and coworkers [9] demonstrated that peroperative pace inducibility of atria1 fibrillation may predict development of postoperative atria1 fibrillation. From these studies it can be concluded that atria1 vulnerability expressed by splitting of the atria1 electrogram during premature stimulation and pace inducibility of atria1 fibrillation are factors of importance for development of postoperative atria1 fibrillation. It remains to be determined which pacing protocol is most informative, and to which degree the data generated from pacing are age associated.
Peroperative predictors Many factors i.e. number and type of grafts, type of cardioplegia, volume of cardioplegia solution, aortic cross-clamping time, time of extracorporeal circulation and acid-base balance, have been analyzed with negative results [3,4]. In a recent study [lo] the duration of cardioplegic
arrest was isolated as an independent predictor of atria1 fibrillation. The mean duration of the clamp time was long, exceeding 1.5 h, and this may explain that duration of clamping time was of no importance in other studies [4,11,12]. An interesting finding is the more frequent occurrence of atria1 fibrillation after topical atria1 cooling to secure complete atria1 plegia [131, as it has been documented that atria1 electrical activity can be present during conventional cardioplegia technique [ 141. Postoperative predictors One would expect postoperative hemodynamic deterioration to dispose to atria1 fibrillation. Indirect evidence against a hemodynamic provocation of atria1 fibrillation is available, as atria1 fibrillation has not been associated with myocardial infarction or death [3], which in many cases must have been preceded by a low cardiac output syndrome. No association between postoperative bleeding or infection and atria1 fibrillation has been found [4] and no particular activity of the patient or nurse has been associated with the onset of atria1 fibrillation or flutter [.51. Preventive trials Several preventive trials with a small number of patients included have been performed using digoxin, verapamil and/or beta-blockers. In Table 3 data from these studies are shown. Studies were only included in this table if they were done in coronary artery bypass grafting patient populations and only episodes of atria1 fibrillation or flutter were counted. Furthermore, electrocardiographic documentation was critically evaluated. All data were retested by a two-tailed Fisher’s exact test, if data were presented in 2 X 2 tables or chi-square test, if the data were presented in N x 2 tables, and the results appear in Table 3. Digoxin Several studies have been performed using digoxin [12,15-171 and no beneficial effect has been documented (Table 3).
Verapamil
No beneficial prophylactic demonstrated [19-211.
effect
has been
Amiodarone
A study involving 77 patients randomized to amiodarone or placebo treatment has been done. No significant prophylactic effect was demonstrated [22]. Beta-blockers
Several beta-blocker trials [12,17,23-361 have been carried out (Table 3). In general these studies are invalidated by the fact that a large proportion (median 70%; range: 47-93%) of the patients randomized to placebo treatment or no treatment actually were randomized to betablocker withdrawal, as they were treated with beta-blockers up to the time of operation. Two studies [23,24] have looked into that specific problem, and a significant increase in the incidence of atria1 fibrilllation was documented in the beta-blocker withdrawal group. Furthermore, some of the beta-blocker studies (Table 3) are biased by the fact that atria1 fibrillation occurring after the second postoperative day was only counted if the patient developed symptoms suggesting atria1 fibrillation and an ECG was recorded. One would expect atria1 fibrillation to be less symptomatic in patients on beta-blocker treatment. Finally it should be kept in mind, that the beta-blocker studies have been performed in selected patient populations with exclusion of patients with contraindications for beta-blocker treatment. Recently three studies on sotalol, a betablocker with class III antiarrhythmic properties, have been published [29,30,34]. The results from these studies are conflicting. Low- and high-dose sotalol was compared with low- and high-dose propranolol [29]. No difference in incidence of atria1 fibrillation and flutter between the groups were seen. In another study, so far only published in abstract [30], sotalol was superior to other beta-blocking agents in reducing risk for supra-
ventricular arrhythmias after aortocoronary bypass grafting. The main conclusion to be drawn from the beta-blocker studies is that preoperative betablocker treatment should be continued for an unknown time period after coronary bypass surgery. This has been confirmed by the study done by Leitch and coworkers [3] in a consecutive series of 5807 patients undergoing aortocoronary artery bypass grafting in which beta-adrenergic blocking drugs were stopped on the day before the operation and not recommenced. Preoperative beta-blocker treatment was isolated as an independent significant predictor of postoperative atria1 fibrillation in multivariate analysis (p = 0.011). If postoperative beta-blocker prophylaxis has an effect, it is inferior to the age effect [4], and even in prediction models taking into account both age and beta-blocker treatment, only a smaller fraction of the patients developing atria1 fibrillation can be predicted. Fuller and coworkers [4] constructed a prediction model using the three variables gender, age and postoperative beta-blocker treatment, and the median probability of predicting atria1 fibrillation was 0.34 (range 0.0075-0.581 for those patients who actually had postoperative atria1 fibrillation and 0.28 (range 0.025 to 0.56) for those patients without atria1 fibrillation. A reduced effectiveness of postoperative beta-blockers was found in the patients at highest risk; i.e. the eldest patients. A properly designed prospective study with sufficient statistical power on beta-blocker effects - beneficial and/or adverse - in conjunction with coronary artery bypass grafting has yet to be performed. Conclusions
(1) In patients undergoing coronary artery bypass grafting the incidence of postoperative atria1 fibrillation or flutter is 20-30%, the peak incidence being on the second or third postoperative day. (2) Increasing age of the patient is independently associated with increased risk for development of atria1 fibrillation. (3) Intra-atria1 conduction delay and inducibility of atria1 fibrillation
260
recorded peroperatively may predict development of atria1 fibrillation. (4) Development of postoperative atria1 fibrillation or flutter is not associated with peroperative or postoperative events. (5) Specificity and sensitivity of predictive models for development of atria1 fibrillation/flutter after coronary bypass grafting is low. (6) No effective prophylactic regimen has been established. Acknowledgement Michael Vzeth, Ph. D., Department of Theoretical Statistics, University of Aarhus, made important contributions to statistical evaluation of data. References Force T, Hibberd P, Weeks G et al. Perioperative myocardial infarction after coronary artery bypass surgery. Clinical significance and approach to risk stratification. Circulation 1990:82:903-912. Lauer MS, Eagle KA, Buckley MJ, DeSanctis RW. Atrial fibrillation following coronary artery bypass surgery. Prog Cardiovasc Dis.1989:31:367-378. Leitch JW, Thomson D, Baird DK. Harris PJ. The importance of age as a predictor of atrial fibrillation and flutter after coronary bypass grafting. J Thorac Cardiovasc Surg 1990;100:338-342. Fuller JA, Adams GG, Buxton B. Atrial fibrillation after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1989;97:821-825. Crosby LH, Woll KR, Wood KL, Pifalo WB. Effect of activity on supraventricular tachyarrhythmias after coronary artery bypass surgery. Heart Lung 1990;19:666-670. Hashimoto K, Ilstrup DM. Hartzell VS. Influence of clinical and hemodynamic variables on risk of supraventricular tachycardia after coronary artery bypass. J Thorac Cardiovast Surg 1991;101:56-65. Buxton AE, Josephson ME. The role of P wave duration as a predictor of postoperative atrial arrhythmias. Chest 1981;80:68-73. Capucci A, Frabetti L, Turinetto B. Pierangeli A, Magnani B. Fibrillazione atriale nei post operati de by-pass aortocoronarica. G Ital Cardiol 1987;17:575-582. Lowe JE, Hendry PJ, Hendrickson SC, Weells R. Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation. Ann Surg 1991; 231:338392. 10 Caretta Q, Mercanti CA, De Nardo D et al. Ventricular conduction defects and atrial fibrillation after coronary artery bypass grafting. Multivariate analysis of preoperative and postoperative variables, Eur Heart J 1991;12: 1107-1111.
11 Crosby LH, Pifalo WB, Woll KR, Burkholder JA. Risk factors for atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 1990;66:1520-22. I2 Rubin DA, Nieminski KE. Reed GE, Herman MV. Predictors, prevention, and long-term prognosis of atrial fibrillation after coronary artery bypass graft operations. J Thorac Cardiovasc Surg 1987;94:331-35. 13 Yousif H, Davies G, Oakley CM. Peri-operative supraventricular arrhythmias in coronary bypass surgery. Int J Cardiol 1990:26:313-18. 14 Lolk A. Martinussen HJ, Madsen T. Alstrup P, Szczepanski C. Right atrial temperature and electrical activity during cardioplegic cardiac arrest, J Cardiovasc Surg 1989;30: 682-86. 15 Csicsko JF, Schatzlein MH, King RD. Immediate postoperative digitalization in the prophylaxis of supraventricular arrhythmias following coronary artery bypass. J Thorac Cardiovasc Surg 1981;81:419-422. 16 Johnson LW, Fickstein RA, Fruehan T et al. Prophylactic digitalization for coronary artery bypass surgery. Circulation 1976:53:819-822. 17 Ormerod OJM, McGregor CGA, Stone DL. Wisbey C, Petch MC. Arrhythmias after coronary bypass surgery. Br Heart J 1984;51:618-621. HF, Decker EL, Cleveland RJ. 18 Weiner B. Rheinlander Digoxin prophylaxis following coronary artery bypass surgery. Clin Pharm 1986;5:55-58. P 19 Davison R, Hartz R. Kaplan K, Parker M, Feiereisel Michaelis L. Prophylaxis of supraventricular tachyarrhythmia after coronary bypass surgery with oral verapamil: A randomized, double-blind trial. Ann Thorac Surg 1985;39: 336-339. 20 Smith EEJ, Shore DF, Monro JL, Ross JK. Oral verapamil fails to prevent supraventricular tachycardia following coronary artery surgery. Int J Cardiol 1985;9:37-44. GA. Kruse AP. Ivey TD. Oral 21 Williams DB, Misbach verapamil for prophylaxis of supraventricular tachycardia after myocardial infarction. J Thorac Cardiovasc Surg 1985;90:592-596. SH, Meinertz T, Dammbacher T et al. Electro22 Hohnloser cardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study. Am Heart J 1991;121:89-95. 23 Abel RM, Van Gelder HM, Pores IH, Liguori J, Gielchinsky I, Personnet V. Continued propranolol administration following coronary bypass surgery. Arch Surg 1983;118: 727-731. 24 Silverman NA, Wright R. Levitsky S. Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias. Ann Surg 1982;196:194-197. I, Levasseur JP, Cabrol 25 Daudon P. Corcos T, Gandjbakhch A, Cabrol C. Prevention of atrial fibrillation or flutter by acebutolol after coronary bypass grafting. Am J Cardiol 1986;58:933-936. 26 Stephenson LW, MacVaugh H. Tomasello DN. Josephson ME. Propranolol for prevention of postoperative cardiac arrhythmias: A randomized study. Ann Thorac Surg 1980;29:113-116.
261 27 White HD, Antman EM, Glynn MA et al. Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery. Circulation 1984:70:479-484. 28 Lamb RK, Prabhakar G, Thorpe JAC, Smith S. Norton R, Dyde JA. The use of atenolol in the prevention of supraventricular arrhythmias following coronary artery surgery. Eur Heart J 1988;9:32-36. 29 Suttorp MJ. Kingma JH, Gin MTJ et al. Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. J Thorac Cardiovast Surg 1990;100:921-926. 30 Peels HOJ. Suttorp MJ. Koomen EM et al. Supraventricular tachyarrhythmias early after coronary artery bypass graft surgery: Analysis of risk factors (abstract). JACC 1991;17:211A. 31 Martinussen HJ. Lolk A, Szczepanski C, Alstrup P. Supraventricular tachyarrhythmias after coronary bypass surgery - a double blind randomized trial of prophylactic low dose propranolol. Thorac Cardiovasc Surg 198836: 206-207.
32 Williams JB, Stephenson LW, Holford FD. Langer TL, Dunkman B, Josephson ME. Arrhythmia prophylaxis using propranolol after coronary artery surgery. Ann Thorac Surg 1982;34:435-438. 33 Materne P. Larbuisson R. Collignon P. Limet R, Kulbertus H. Prevention by acebutolol of rhythm disorders following coronary bypass surgery. Int J Cardiol 1985:8:275283. 34 Janssen J, Loomans L, Harink J et al. Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial. Angiology 1986:37:601-609. 35 Vecht RJ, Nicolaides EP, Ikweuke JK. Liassides C, Cleary J, Cooper WB. Incidence and prevention of supraventricular tachyarrhythmias after coronary bypass surgery. Int J Cardiol 1986;13:125-143. 36 Khuri SF, Okike ON, Josa M et al. Efficacy of nadolol in preventing supraventricular tachycardia after coronary artery bypass grafting. Am J Cardiol 1987:60:5lD-58D.
CARD10
253 0167.5273/92/$05.00
01519
Review
Atria1 fibrillation and flutter after coronary artery bypass surgery: epidemiology, risk factors and preventive trials Lars Frost ‘, Henning Mfllgaard ‘, Evald H@j Christiansen ‘, Kirsten Hjortholm j, Peter K. Paulsen 4 and Poul Erik Bloch Thomsen ’ Departments of ’ Cardiology, .’Anaesthesiology and ’ Thoracic and Cardio~~ascular Surgery, Skejby Hospital, lJnic,ersity Hospital Aarhus, Aarhus. and ’ Institute of Pharmacology. Unilvrsity of Aarhus. Aarhus, Denmark (Received
16 December
1991; revision
accepted
20 April 1992)
Frost L, Mslgaard H, Christiansen EH, Hjortholm K, Paulsen PK, Thomsen PEB. Atria1 fibrillation and flutter after coronary artery bypass surgery: epidemiology, risk factors and preventive trials. Int J Cardiol 1992:36:253-261. Atria1 fibrillation and atria1 flutter are common arrhythmias after coronary artery bypass grafting. Although the consequences of the arrhythmia are generally not life-threatening, it constitutes a major clinical problem often requiring conversion to sinus rhythm. Atria1 fibrillation or flutter can result in hypotension, heart failure, pneumonia, and stroke. This article reviews the literature on epidemiology, electrophysiology, risk factors, and preventive trials. The major conclusions are: (11 In patients undergoing coronary artery bypass surgery, the incidence of postoperative atria1 fibrillation or flutter is 20-30%, the peak incidence being on the second or third postoperative day. (2) The strongest independent preoperative predictor for atria1 fibrillation or flutter is the patients’ age. (3) Intra-atria1 conduction delay recorded pre and peroperatively may predict development of atria1 fibrillation. (4) Peroperative inducibility of atria1 fibrillation by pacing the right atrium may identify patients at risk for postoperative atria1 fibrillation. (5) Development of postoperative atria1 fibrillation or flutter has not been associated with peroperative or postoperative events. (6) The specificity and sensitivity of age and other possible relevant factors for prediction of atria1 fibrillation or flutter after coronary artery bypass grafting is low. (7) No effective prophylactic regimen has yet been established. Key words: Atria1 fibrillation; Atria1 flutter; Coronary artery bypass surgery
Introduction Globally 200,000 patients undergo coronary artery bypass surgery each year for angina pec-
Correspondence to: L. Frost, M.D., Dept. of Cardiology, Skejby Hospital, University Hospital Aarhus, DK-8200 Aarhus N, Denmark. Tel. +45 86 784511. Fax +45 86 784533.
toris 111. Twenty to 30% (40,000-60,000) of the patients develop atria1 fibrillation or atria1 flutter during the postoperative in-hospital period [3,4]. Although the consequences of the arrhythmia are generally not life-threatening, it constitutes a major clinical problem as conversion to sinus rhythm is often mandatory. The results of the atria1 fibrillation or flutter can be hypotension, heart failure, pneumonia, stroke, and postponement of dis-
254 TABLE
1
Incidence
of atrial
fibrillation
Ref. + year
or flutter
99 1666 100 5 807 418
COM = continuous
oscilloscopic
artery
bypass
Pts. developing atrial fibrillation or flutter
No. of patients studied
[7]. 1981 [4], 1989 [13]. 1990 [3], 1990 [ll], 1990
Buxton Fuller Yousif Leitch Crosby
after coronary
monitoring;
No.
%
29 473 19 999 115
29 28 19 17 27
Electrocardiographic documentation
2
Factors
associated
or flutter
No. of patients studied
Significant
Epidemiology The incidence of atria1 fibrillation after coronary artery bypass grafting siderably in different reports (Table mainly due to the varying quality of surveillance and to differences in the
after coronary predictive
artery
bypass
Statistics
99 1666 1666 100 5 807 5 807 5 807 5 807 5 807 5 807 5 807 5 807 418
Peroperatke factors Capucci [8]. 1987 Yousif [13], 1990 Yousif 1131, 1990 Leitch [3], 1990 Lowe [9], 1991
100 100 5 807 50
Atrial conduction delay Adjunctive coronary endarterectomy Topical cardiac cooling More than three distal anastomosis Pace inducibility of atrial fibrillation
Postoperative factors Fuller [4], 1989 Fuller [4], 1989
1666 1666
Postoperative Stroke
P-wave duration Age Preoperative digoxin treatment Myocardial ischemia (ST-segment
monitoring)
Age Chronic airflow limitation Chronic renal failure Hypertension Preoperative diuretic treatment Preoperative beta-blocker treatment Cardiothoracic ratio > 0.5 Three-vessel or left main disease Age
beta-blocker
and flutter varies con1). This is arrhythmic duration of
surgery.
factor
Pre0peratii.e factors Buxton [7], 1981 Fuller [4], 1989 Fuller 141, 1989 Yousif [l3], 1990 Leitch [3], 1990 Leitch [3], 1990 Leitch [3], 1990 Leitch [3], 1990 Leitch 131. 1990 Leitch [3]. 1990 Leitch [3], 1990 Leitch [3], 1990 Crosby [ 111. 1990
50
3 2 15 mmHg and this had no significant influence on development of atria1 fibrillation. Factors such as left atria1 dimension measured by echocardiography, previous myocardial infarction and unstable angina have no significance for development of atria1 fibrillation/flutter [3,4,6]. From this it can be concluded, that age of the patient is the strongest preoperative predictor for development of atria1 fibrillation and flutter after aortocoronary artery bypass grafting and that no heart related factor has been isolated that is
of atrial
fibrillation
control
#
Trials started postoperatil’ely Stephenson [26], 1979 Propranolol vs. control propranolol control # Digoxin vs control Csicsko [15], 1981 digoxin control Silverman [24], 1982 Propranolol vs propranolol withdrawal propranolol propranolol withdrawal Williams [32], 1982 Propranolol vs control propranolol control # Abel [23], 1983 Propranolol vs propranolol withdrawal propranolol propranolol withdrawal Timolol vs placebo White (271, 1984 timolol placebo # Ormerod [17], 1984 Propranolol vs digoxin vs control propranolol digoxin #
Trials started preoperaticely Johnson [16], 1976 Digoxin vs control digoxin control Martinussen [31], 1988 Propranolol vs placebo propranolol placebo # Lamb [28], 1988 Atenolol vs control atenolol control #
Drug(s)
Results
Ref. + year
3
of trials for prevention
TABLE
100 41 50 41 21 20 90 27 30
R, NB
R, NB
R, DB
R, NB
33
100 50 50 60 28 32
R, NB
R. NB
223 87 136 407 137 270
120 54 66 75 35 40 60 30 30
(Holter
4th postoperative 1(4%)
3 (6%)
3 (2%)
7 (8%)
1(3%)
5 (14%)
3 (6%)
Treated
(7 days)
Not reported
Holter
4 (15%) 10 (33%)
3 (14%)
9 (27%)
7 (35%)
22 (44%)
6 (19%)
14 (28%) day)
33 (12%)
24 (18%)
10 (33%)
5 (13%)
10 (15%)
Untreated/ placebo
n (%) with arrhythmia
COM (3 days), ECG, Holter 9 (22%)
Not reported
COM (2 days), ECG
COM (3 days), ECG
Not reported
COM (3 days), ECG
COM (4 days)
COM (4 days), ECG
Electrocardiographic documentation
bypass surgery.
No. of pts.
artery
coronary
after
R, NB
R, NB
R. DB
R, NB
Design
and flutter
0.52 1.22
0.41
0.50
0.19
0.60
0.18
0.46
0.10
1.14
0.37
group(s)
Relative risk in treatment
0.19-1.57 0.58-2.59
0.12-1.36
0.26-0.96
0.02-1.49
0.07-0.70
0.06-0.57
0.21-1.01
0.01-0.73
0.36-3.62
0.11-1.27
95% confidence interval
0.27
0.24
0.05
0.15
0.006
0.0005
0.06
0.006
1.00
0.16
‘p value
P d
independently associated with development postoperative atria1 fibrillation or flutter.
of
Electrophysiology. Buxton and Josephson [7] studied total P-wave duration measured from leads I, II and III and concluded, that an intraatria1 conduction defect measured by P-wave prolongation preoperatively is a sensitive but nonspecific predictor of postoperative atria1 fibrillation in patients undergoing coronary bypass grafting. An Italian group [81 looked into this by making peroperative electrophysiologic studies in 50 patients who later underwent cardioplegia and bypass grafting in order to determine the possible mechanism explaining the frequent postoperative episodes of atria1 fibrillation. The patients developing atria1 fibrillation had a high percentage of splitting of the atria1 electrogram (77% vs 5%, p < 0.0002) during atria1 premature stimulation suggesting that patients with intra-atrial conduction defects were at greater risk of developing atria1 fibrillation after coronary artery bypass grafting. By stimulating the mid-right atria1 free wall with incremental stimuli, before the initiation of cardiopulmonary bypass, Lowe and coworkers [9] demonstrated that peroperative pace inducibility of atria1 fibrillation may predict development of postoperative atria1 fibrillation. From these studies it can be concluded that atria1 vulnerability expressed by splitting of the atria1 electrogram during premature stimulation and pace inducibility of atria1 fibrillation are factors of importance for development of postoperative atria1 fibrillation. It remains to be determined which pacing protocol is most informative, and to which degree the data generated from pacing are age associated.
Peroperative predictors Many factors i.e. number and type of grafts, type of cardioplegia, volume of cardioplegia solution, aortic cross-clamping time, time of extracorporeal circulation and acid-base balance, have been analyzed with negative results [3,4]. In a recent study [lo] the duration of cardioplegic
arrest was isolated as an independent predictor of atria1 fibrillation. The mean duration of the clamp time was long, exceeding 1.5 h, and this may explain that duration of clamping time was of no importance in other studies [4,11,12]. An interesting finding is the more frequent occurrence of atria1 fibrillation after topical atria1 cooling to secure complete atria1 plegia [131, as it has been documented that atria1 electrical activity can be present during conventional cardioplegia technique [ 141. Postoperative predictors One would expect postoperative hemodynamic deterioration to dispose to atria1 fibrillation. Indirect evidence against a hemodynamic provocation of atria1 fibrillation is available, as atria1 fibrillation has not been associated with myocardial infarction or death [3], which in many cases must have been preceded by a low cardiac output syndrome. No association between postoperative bleeding or infection and atria1 fibrillation has been found [4] and no particular activity of the patient or nurse has been associated with the onset of atria1 fibrillation or flutter [.51. Preventive trials Several preventive trials with a small number of patients included have been performed using digoxin, verapamil and/or beta-blockers. In Table 3 data from these studies are shown. Studies were only included in this table if they were done in coronary artery bypass grafting patient populations and only episodes of atria1 fibrillation or flutter were counted. Furthermore, electrocardiographic documentation was critically evaluated. All data were retested by a two-tailed Fisher’s exact test, if data were presented in 2 X 2 tables or chi-square test, if the data were presented in N x 2 tables, and the results appear in Table 3. Digoxin Several studies have been performed using digoxin [12,15-171 and no beneficial effect has been documented (Table 3).
Verapamil
No beneficial prophylactic demonstrated [19-211.
effect
has been
Amiodarone
A study involving 77 patients randomized to amiodarone or placebo treatment has been done. No significant prophylactic effect was demonstrated [22]. Beta-blockers
Several beta-blocker trials [12,17,23-361 have been carried out (Table 3). In general these studies are invalidated by the fact that a large proportion (median 70%; range: 47-93%) of the patients randomized to placebo treatment or no treatment actually were randomized to betablocker withdrawal, as they were treated with beta-blockers up to the time of operation. Two studies [23,24] have looked into that specific problem, and a significant increase in the incidence of atria1 fibrilllation was documented in the beta-blocker withdrawal group. Furthermore, some of the beta-blocker studies (Table 3) are biased by the fact that atria1 fibrillation occurring after the second postoperative day was only counted if the patient developed symptoms suggesting atria1 fibrillation and an ECG was recorded. One would expect atria1 fibrillation to be less symptomatic in patients on beta-blocker treatment. Finally it should be kept in mind, that the beta-blocker studies have been performed in selected patient populations with exclusion of patients with contraindications for beta-blocker treatment. Recently three studies on sotalol, a betablocker with class III antiarrhythmic properties, have been published [29,30,34]. The results from these studies are conflicting. Low- and high-dose sotalol was compared with low- and high-dose propranolol [29]. No difference in incidence of atria1 fibrillation and flutter between the groups were seen. In another study, so far only published in abstract [30], sotalol was superior to other beta-blocking agents in reducing risk for supra-
ventricular arrhythmias after aortocoronary bypass grafting. The main conclusion to be drawn from the beta-blocker studies is that preoperative betablocker treatment should be continued for an unknown time period after coronary bypass surgery. This has been confirmed by the study done by Leitch and coworkers [3] in a consecutive series of 5807 patients undergoing aortocoronary artery bypass grafting in which beta-adrenergic blocking drugs were stopped on the day before the operation and not recommenced. Preoperative beta-blocker treatment was isolated as an independent significant predictor of postoperative atria1 fibrillation in multivariate analysis (p = 0.011). If postoperative beta-blocker prophylaxis has an effect, it is inferior to the age effect [4], and even in prediction models taking into account both age and beta-blocker treatment, only a smaller fraction of the patients developing atria1 fibrillation can be predicted. Fuller and coworkers [4] constructed a prediction model using the three variables gender, age and postoperative beta-blocker treatment, and the median probability of predicting atria1 fibrillation was 0.34 (range 0.0075-0.581 for those patients who actually had postoperative atria1 fibrillation and 0.28 (range 0.025 to 0.56) for those patients without atria1 fibrillation. A reduced effectiveness of postoperative beta-blockers was found in the patients at highest risk; i.e. the eldest patients. A properly designed prospective study with sufficient statistical power on beta-blocker effects - beneficial and/or adverse - in conjunction with coronary artery bypass grafting has yet to be performed. Conclusions
(1) In patients undergoing coronary artery bypass grafting the incidence of postoperative atria1 fibrillation or flutter is 20-30%, the peak incidence being on the second or third postoperative day. (2) Increasing age of the patient is independently associated with increased risk for development of atria1 fibrillation. (3) Intra-atria1 conduction delay and inducibility of atria1 fibrillation
260
recorded peroperatively may predict development of atria1 fibrillation. (4) Development of postoperative atria1 fibrillation or flutter is not associated with peroperative or postoperative events. (5) Specificity and sensitivity of predictive models for development of atria1 fibrillation/flutter after coronary bypass grafting is low. (6) No effective prophylactic regimen has been established. Acknowledgement Michael Vzeth, Ph. D., Department of Theoretical Statistics, University of Aarhus, made important contributions to statistical evaluation of data. References Force T, Hibberd P, Weeks G et al. Perioperative myocardial infarction after coronary artery bypass surgery. Clinical significance and approach to risk stratification. Circulation 1990:82:903-912. Lauer MS, Eagle KA, Buckley MJ, DeSanctis RW. Atrial fibrillation following coronary artery bypass surgery. Prog Cardiovasc Dis.1989:31:367-378. Leitch JW, Thomson D, Baird DK. Harris PJ. The importance of age as a predictor of atrial fibrillation and flutter after coronary bypass grafting. J Thorac Cardiovasc Surg 1990;100:338-342. Fuller JA, Adams GG, Buxton B. Atrial fibrillation after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1989;97:821-825. Crosby LH, Woll KR, Wood KL, Pifalo WB. Effect of activity on supraventricular tachyarrhythmias after coronary artery bypass surgery. Heart Lung 1990;19:666-670. Hashimoto K, Ilstrup DM. Hartzell VS. Influence of clinical and hemodynamic variables on risk of supraventricular tachycardia after coronary artery bypass. J Thorac Cardiovast Surg 1991;101:56-65. Buxton AE, Josephson ME. The role of P wave duration as a predictor of postoperative atrial arrhythmias. Chest 1981;80:68-73. Capucci A, Frabetti L, Turinetto B. Pierangeli A, Magnani B. Fibrillazione atriale nei post operati de by-pass aortocoronarica. G Ital Cardiol 1987;17:575-582. Lowe JE, Hendry PJ, Hendrickson SC, Weells R. Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation. Ann Surg 1991; 231:338392. 10 Caretta Q, Mercanti CA, De Nardo D et al. Ventricular conduction defects and atrial fibrillation after coronary artery bypass grafting. Multivariate analysis of preoperative and postoperative variables, Eur Heart J 1991;12: 1107-1111.
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