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Eur J Cardiothorac Surg 2004;25:415-418
© 2004 Elsevier Science NL

Cardioplegic arrest does not increase the risk of atrial fibrillation after coronary artery bypass surgery

Tapio Hakalaa*, Otto Pitkanenb, Juha Hartikainenc

a Department of Surgery, Kuopio University Hospital and Kuopio University, P.O. Box 1777, FIN-70211 Kuopio, Finland
b Department of Anesthesiology and Intensive Care, Kuopio University Hospital and Kuopio University, Kuopio, Finland
c Department of Medicine, Kuopio University Hospital and Kuopio University, Kuopio, Finland

Received 27 September 2003; received in revised form 10 December 2003; accepted 15 December 2003.

* Corresponding author. Tel.: +358-17-173-311; fax: +358-17-173-746
e-mail: tapio.hakala{at}kuh.fi


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Objective: Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass grafting (CABG). It is a considerable source of morbidity, prolongs hospital stay and increases costs of treatment. Atrial cannulation, cardiopulmonary bypass and cardioplegic arrest have been suggested to play a role in the development of AF after CABG. The aim of this case-control study was to evaluate the role of cardiopulmonary bypass and cardioplegic arrest in the development of postoperative AF. Methods: Data from 114 patients undergoing CABG without cardiopulmonary bypass and cardioplegic arrest (off-pump) between October, 1998 and December, 2002 were evaluated for the occurrence of postoperative AF. Each patient was individually matched by gender, age (±3 years), left ventricle ejection fraction (±5%), history of myocardial infarction, unstable angina, and ß-blocker medication with patients undergoing CABG with cardiopulmonary bypass and cardioplegic arrest (on-pump) during the same period. The data from off-pump and on-pump groups were compared. Results: Off-pump and on-pump groups had similar preoperative characteristics. The number of distal anastomoses was lower in the off-pump (2.3±0.9) than in the on-pump (3.9±1.1, P<0.001) group. However, the incidence of postoperative AF in the off-pump (36.8%) and the on-pump groups (36.0%) did not differ from each other. Old age was the only independent predictor of AF after CABG. Conclusions: Neither cardiopulmonary bypass nor cardioplegic arrest increases the risk of postoperative AF after CABG.

Key Words: Atrial fibrillation • Off-pump coronary artery bypass grafting • On-pump coronary artery bypass grafting


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 References
 
Atrial fibrillation (AF) has been recognized as the most common arrhythmia to occur after coronary artery bypass grafting (CABG). Studies have reported an incidence ranging from 20 to 40%, with a peak incidence occurring between the second and fourth postoperative days [1–4]. AF is associated with postoperative complications including increased risk of stroke, gastrointestinal complications, patient discomfort, and need of additional treatment, as well as prolonged hospital stay and increased costs [4–6]. The pathophysiology of AF after CABG is not clear. It has been proposed that atrial cannulation, cardiopulmonary bypass and cardioplegic arrest might play an important role in the development of AF after CABG. However, several studies have reported contrasting results regarding the role of cardiopulmonary bypass and cardioplegic arrest in the development of AF after CABG [7–14].

This case-control study was designed to compare the incidence of postoperative AF after CABG performed with (on-pump) and without (off-pump) cardiopulmonary bypass and cross clamping.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 References
 
This study was approved by Kuopio University Ethical Committee. From October 1998 to December 2002, 146 patients underwent off-pump CABG at our institution. Eighteen patients were operated through a left thoracotomy. One patient underwent a redo operation and seven patients presented with a history of preoperative paroxysmal AF. In addition, five patients died within 30 days of the operation. All these patients were excluded from the study and therefore, 115 patients were taken into the final analysis. The CABG procedures were performed through a median sternotomy approach. The bypasses were performed with beating heart using CTS stabilization system (Guidant, Santa Clara, CA). Intra-coronary shunts were not used. ß-Blocking medication (metoprolol) was continued in every patient starting on the first postoperative day and the dosage was titrated for the resting heart rate of 60–90 beats/min.

During the same period 2909 patients underwent isolated (no additional procedures) on-pump CABG. After a median sternotomy, the ascending aorta was cannulated for the arterial line and a single-stage venous cannula was inserted through the right atrial appendix. Aortic root venting was used and cold crystalloid cardioplegia was administrated through the antegrade route. Twenty-five patients died within 30 days from the operation and 71 patients were found to have a history of AF and thus, were not suitable for matching.

The 115 off-pump CABG patients were individually matched to on-pump CABG patients. The matching characteristics were gender, age (±3 years), ejection fraction (±5%), history of previous myocardial infarction and presence of unstable angina. Because all the patients in the off-pump group had ß-blocking medication for arrhythmia prophylaxis postoperatively, also all the controls were selected from patients, who had ß-blockers postoperatively. ß-Blockers were administered from the first postoperative day. The individual matching process was performed by a single investigator blinded to the occurrence of postoperative AF or other complications. Controls were randomly selected from the entire pool of suitable patients. At the end of the matching process, no suitable match was found for one off-pump patient. Thus, 114 pairs formed the final study population for the analysis.

All the patients were connected to ward monitors for continuous ECG monitoring to the third postoperative day. The ward monitor stored the ECG recordings for subsequent analysis. The recordings were analyzed off-line. After the third day, 12-lead ECG recording was done daily and if necessary to detect the AF episodes in both off-pump and on-pump groups.

The relevant preoperative, perioperative and postoperative data of the patients in the off-pump and on-pump groups were retrospectively reviewed from our cardiac surgical database. All the data had been prospectively collected by cardiologists and stored in the database. The cardiac rhythm was defined as AF when there were no consistent P waves before each QRS complex and the ventricular rhythm was irregular. Only AF episodes lasting longer than 5 min were counted. Perioperative myocardial infarction was defined as a development of new Q waves. A stroke was defined as a new neurological symptom verified by correlative changes in the computer tomograph.

2.1. Statistical analysis
The difference in the continuous variables was analyzed by paired-samples Student's t-test. Ordinal variables were analyzed by paired-samples Wilcoxon test and dichotomized variables by McNemar test. An approximate standard error (SE) for the difference in the incidence between the groups was calculated by the formula

where n is the number of case-control pairs, s and t are numbers of different positive/negative incidence findings in each pairs [15]. The continuous variables are presented as mean±standard deviation in tables. P-values <0.05 were regarded as statistically significant. All statistical procedures were performed with SPSS 9.0 statistical package (SPSS Inc., Chicago, IL, USA).


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 References
 
The adequacy of the matching process was confirmed by the lack of difference between the groups with respect to matching characteristics. Preoperative and perioperative data are presented in Table 1. In addition to matching characteristics there was no difference between the groups concerning the presence of diabetes, CCS class, the presence of three-vessel disease or a history of either stroke or transient ischemic attack. History of claudication and chronic obstructive pulmonary disease (COPD) were more common in the off-pump group than in the on-pump group. In the off-pump group the number of distal anastomoses was lower compared to the on-pump group (2.3±0.9 vs. 3.9±1.1, P<0.001, respectively).


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  		Table 1. Preoperative matched patient characteristics and operative data

 
Postoperative data are presented in Table 2. We found no difference in the incidence of postoperative AF between the off-pump (36.8%, 95% confidence interval (CI) 28.7–46.7%) and the on-pump (36.0%, 95% CI 29.5–47.7%) groups. SE for the difference in the incidence between the groups was 7% (95% CI -12 to 14%). Neither was any difference found between the groups with respect to the occurrence of perioperative myocardial infarction, conduction disturbances, length of stay in the intensive care unit (ICU) or in the hospital, readmission to ICU, or return to operation theatre due to bleeding. Two patients in the on-pump group developed postoperative stroke.


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  		Table 2. Morbidity and postoperative data

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
References
 
The main result of our study is that off-pump myocardial revascularization did not decrease the risk of AF after CABG. The results of our study are in agreement with some recently published studies [7–10]. Those studies also found no difference in the incidence of AF after CABG between the off-pump and the on-pump groups. Tamis-Holland et al. [11] reported lower incidence of AF after off-pump CABG than on-pump CABG surgery. However, in their study the lower incidence of AF was due to different clinical characteristics of the patients rather than the use of off-pump technique per se. Abrey et al. [13] also reported a trend towards a lower incidence of AF after off-pump CABG compared to on-pump CABG. However, their study was retrospective and there were only 34 patients in the off-pump group. Buffolo et al. [14] reported significantly fewer arrhythmias among patients who underwent off-pump CABG. Their study was also retrospective. In addition, the goal of the study was to assess the feasibility of off-pump CABG rather than compare off-pump and on-pump procedures with each other. Thus, off-pump and on-pump patients were not matched with each other and were not comparable according to preoperative characteristics. The only published prospective, randomized trial of 200 patients comparing arrhythmia incidences after off-pump and on-pump surgery by Ascione et al. [12] showed significantly lower incidence of AF after off-pump CABG compared to on-pump CABG. However, the use of ß-blockers was not uniform and the incidence of AF after on-pump CABG was exceptionally high, at 49%.

One could argue that although in our study the incidence of AF did not differ between the groups, this does not necessarily mean that there is no difference, but that we were not able to demonstrate it. However, the confidence intervals for the AF incidence and SE for the difference in the AF incidence between the groups demonstrated that clinically relevant differences could be excluded.

The number of distal anastomoses was lower in the off-pump CABG group than in the on-pump group. The lesser number of grafts in the off-pump group is probably accounted for by the greater technical challenge, as the severity of disease was uniform between the groups.

It has been believed that atrial ischemia plays an important role in the development of underlying substrate and triggering factors of AF. Atrial tissue is warmer than ventricular tissue during cardioplegic arrest and often persistent electrical activity is considered as a sign of inadequate atrial protection [16,17]. In fact, a correlation between persistent electrical activity and postoperative atrial arrhythmias has been reported [16]. Yet, atrial hypothermia during cardioplegic arrest has not been found to influence the atrial effective refractory period or the inducibility of AF in canine heart [18]. In line with this, also our study suggests that atrial ischemia or mechanical manipulation of the atrium does not play an important role in the development of postoperative AF after CABG.

The incidence of postoperative AF after CABG in our study was rather high (36.4%), despite ß-blocker medication being used for arrhythmia prophylaxis in all patients. Because of continuous ECG monitoring, all AF episodes, not only those causing clinical symptoms, were recognized. This is probably the explanation for the high incidence of AF in our study.

History of COPD was more common in off-pump group. There are reports that has found COPD to be independent risk factor for AF after CABG [5,6]. However, as the number of patients in the off-pump group with COPD is small, the influence of this difference between the groups is only minor.

History of claudication was more common in off-pump than in on-pump group. This might reflect more universal and diffuse atherosclerosis in off-pump group and thus might have an influence for the postoperative incidence of AF.

Our patients had relatively good ejection fraction and the incidence of comorbidities was low. Thus, our patient population is not very representative of patients generally seen in current practice.

We conclude that cardiopulmonary bypass and cardioplegic arrest are not causal factors for the development of postoperative AF. Thus, compared to off-pump CABG, on-pump CABG does not increase the risk of postoperative AF.


   Footnotes
 
This study was presented at The International Society of Cardio-Thoracic Surgeons 13th World Congress in San Diego, CA, 3rd November 2003.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 

  1. Aranki S.F., Shaw D.P., Adams D.H., Rizzo R.J., Couper G.S., Vander Vliet M., Collins J.J., Cohn L.H., Burstin H.R. Predictors of atrial fibrillation after coronary artery surgery. Circulation 1996;94:390-397.[Abstract/Free Full Text]
  2. Svedjeholm R., Hkanson E. Predictors of atrial fibrillation in patients undergoing surgery for ischemic heart disease. Scand Cardiovasc J 2000;34:516-521.[CrossRef][Medline]
  3. Mahoney E.M., Thompson T.D., Veledar E., Williams J., Weintraub W.C. Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy with intravenous amiodarone to prevent atrial fibrillation. J Am Coll Cardiol 2002;40:737-745.[Abstract/Free Full Text]
  4. Hakala T., Pitkänen O., Hippelainen M. Feasibility of predicting the risk of atrial fibrillation after coronary artery bypass surgery with logistic regression model. Scand J Surg 2002;91:339-344.[Medline]
  5. Creswell L.L., Schuessler R.B., Rosenbloom M., Cox J.L. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993;56:539-549.[Abstract]
  6. Almassi G.H., Schowalter T., Nicolosi A.C., Aggarwal A., Moritz T.E., Henderson W.G., Tarazi R., Shoyer A.L., Sethi G.K., Grover F.L. Atrial fibrillation after cardiac surgery. A major morbid event?. Ann Surg 1997;4:501-513.
  7. Cohn W.E., Sirois C.A., Johnson R.G. Atrial fibrillation after minimally invasive coronary artery bypass grafting: a retrospective, matched study. J Thorac Cardiovasc Surg 1999;117:298-301.[Abstract/Free Full Text]
  8. Siebert J., Rogowski J., Jagielak D., Anisimowich L., Lango R., Narkiewich M. Atrial fibrillation after coronary artery bypass grafting without cardiopulmonary bypass. Eur J Cardiothorac Surg 2000;17:520-523.[Abstract/Free Full Text]
  9. Saatvedt K., Fiane A.E., Sellevold O., Nordstrand K. Is atrial fibrillation caused by extracorporeal circulation. Ann Thorac Surg 1999;68:931-933.[Abstract/Free Full Text]
  10. Salamon T., Michler R.E., Knott K.M., Brown D.A. Off-pump coronary artery bypass grafting does not decrease the incidence of atrial fibrillation. Ann Thorac Surg 2003;75:505-507.[Abstract/Free Full Text]
  11. Tamis-Holland J.E., Homel P., Durani M., Iqbal M., Sutandar A., Mindich B.P., Steinberg J.S. Atrial fibrillation after minimally invasive direct coronary artery bypass surgery. J Am Coll Cardiol 2000;36:1884-1888.[Abstract/Free Full Text]
  12. Ascione R., Caputo M., Calori G., Lloyd C.T., Underwood M.J., Angelini G.D. Predictors of atrial fibrillation after conventional and beating heart coronary surgery. Circulation 2000;102:1530-1535.[Abstract/Free Full Text]
  13. Abrey J.E., Reilly J., Salzano R.P., Khachane V.B., Jekel J.F., Clyne C.A. Comparison of frequencies of atrial fibrillation after coronary artery bypass grafting with and without the use of cardiopulmonary bypass. Am J Cardiol 1999;83:775-776.[CrossRef][Medline]
  14. Buffolo E., de Andrade J.C.S., Branco J.N.R., Teles C.A., Aguiar L.F., Gomes W.J. Coronary artery bypass grafting without cardiopulmonary bypass. Ann Thorac Surg 1996;61:63-66.[Abstract/Free Full Text]
  15. Gardner M.J., Altman D.G. Statistics with confidence. Confidence intervals and statistical guidelines. . London: British Medical Journal, 1989.
  16. Tchervenkov C.I., Wynands J.E., Symes J.F., Malcolm I.D., Dobell A.R., Morin J.E. Persistent atrial activity during cardioplegic arrest: a possible factor in the etiology of postoperative supraventricular tachyarrhythmias. Ann Thorac Surg 1983;36:437-443.[Abstract]
  17. Chen X.Z., Newman M., Rosenfeldt F.L. Internal cardiac cooling improves atrial preservation: electrophysiological and biochemical assessment. Ann Thorac Surg 1988;46:406-411.[Abstract]
  18. Sato S., Yamauchi S., Schuessler R.B., Boineau J.P., Matsunaga Y., Cox J.L. The effect of augmented atrial hypothermia on atrial refractory period, conduction, and atrial flutter/fibrillation in the canine heart. J Thorac Cardiovasc Surg 1992;104(2):297-306.[Abstract]



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