Prevention of atrial fibrillation after cardiac surgery

Abstract

Atrial fibrillation is the most common arrhythmia occurring after heart surgery. Its prevalence after coronary artery bypass surgery is 17 – 33%. Atrial fibrillation requires additional treatment, lengthens hospitalization and increases the overall expenses of cardiac surgery. Atrial fibrillation can cause hemodynamic problems, predispose to congestive heart failure and increase the risk of stroke. Beta-blockers have been shown to effectively prevent atrial fibrillation, and beta-blockers should be a part of the medication of every patient undergoing cardiac surgery, if there are no contraindications. Amiodarone therapy can also be considered for especially high-risk patients.

• Cardiac surgery
• arrhythmia
• atrial fibrillation
• prophylaxis

Pathophysiology

The pathophysiology of atrial fibrillation (AF) occurring after heart surgery is not precisely known, but its etiology is thought to be multifactorial. The abnormal electrophysiological state of the atria, the unequal shortening of the refractory period of the atrial myocytes and variable conduction speed through the atrial tissue predispose to the development of AF. It is also thought that ischemia of the atrial tissue is a triggering factor for atrial fibrillation 1–3. During cardioplegy the temperature of the atrial tissue is higher than that of the ventricles, and therefore more sensitive to ischemia intraoperatively 4–6. However, according to some reports the incidence of AF is not lower after off-pump than on-pump surgery 7, 8, suggesting that ischemia does not play a major role.

Increased sympathetic activation is also considered to predispose to AF. Postoperatively noradrenaline concentrations, a marker of sympathetic activation, have been found to be higher in patients who develop atrial fibrillation than in those who do not 9. It has also been shown that terminating long-term beta-blocker therapy results in a so-called withdrawal effect. This is characterized by an increase in the heart rate, blood pressure and catecholamine concentrations, and a further increased susceptibility to AF 9, 10. Exaggerated inflammatory response may also play a role in the development of postoperative AF 11.

Incidence and risk factors

AF is the most common arrhythmia occurring after cardiac surgery. Its incidence after surgery has ranged from 17 – 33%, Table I, 12–23. The incidence of AF is greater in patients who undergo combined valve and bypass operations than in those who undergo just bypass surgery 18, 24. The incidence of AF is highest between the second and fourth postoperative days. In the first postoperative day its incidence is less than 10% 17.

Table I.  Incidence and independent preoperative risk factors of atrial fibrillation after cardiac surgery. Studies with at least 300 patients.

Study	Number of Patients	Incidence of atrial fibrillation, %	Risk factors
Fuller et al. 1989	473	28	High age, male sex
Leitch et al. 1990	5 807	17	High age, COPD, renal insufficiency, use of a beta-blocker before surgery
Hashimoto et al. 1991	800	23	High age, previous atrial arrhythmias, high left ventricular pressure before surgery
Cresswell et al.1993	2 833	32	High age, male sex, use of digoxin prior to surgery, COPD, PVD, smoking
Matthew et al. 1996	2 048	26	High age, congestive heart failure, heart rate > 100
Aranki et al. 1996	570	33	High age, male sex, hypertension
Almassi et al. 1997	3 126	28	High age, COPD, use of digoxin prior to surgery, heart rate < 80
Svedjeholm et al. 2000	775	29	High age, hypertension, previous atrial fibrillation
Zaman et al. 2000	326	28	High age, male sex, SAPD > 155 ms
Mahoney et al. 2002	8 709	18	High age, male sex, previous myocardial infarction
Majahalme et al. 2002	586	32	High age, use of the radial artery as a graft
Hakala et al. 2002	3 676	31	High age, decreased ejection fraction, use of digoxin prior to surgery, large body surface area

COPD = chronic obstructive pulmonary disease, PVD = peripheral vascular disease, SAPD = signal-average duration of the P-wave

The risk factors for postsurgical AF are presented in Table I. The most important risk factor is age. The incidence of AF increases with age by at least 50% for every decade 13, 16, 18, 21. The increase in risk with age is thought to be changes in tissues related to aging. These changes include degeneration of the cardiac myocardium, slowed conduction velocity, increase in the size of the atria and increased content of connective tissue 25, 26.

Prevention of atrial fibrillation after surgery

Beta-Blockers

The effectiveness of beta-blockers in the prevention of AF after surgery has been demonstrated in numerous studies. In a meta-analysis published in 1991 the incidence of atrial fibrillation decreased from 34% to 8.7% 27. In another meta-analysis the decrease in incidence was from 20% to 8.7% 28. The type of beta-blocker or the dose has not influenced the effectiveness of the prevention. In a meta-analysis published in 2002, 27 randomized trials with altogether 3 840 patients were included. In this meta-analysis, beta-blockers decreased the incidence of AF from 33% to 19% 29. The type or dose of beta-blocker did not influence the effectiveness of beta-blocker therapy. Yaziciolglu and co-workers have found that combining digoxin with atenolol is more effective than atenolol alone 30. Intravenous esmolol has also been investigated 31. The study showed that the tolerance to esmolol was poor, and that its effectiveness in the prevention of atrial fibrillation was not better than oral beta-blockers. We compared the efficacy of intravenous metoprolol to oral metoprolol in the prevention of AF after cardiac surgery in prospective, randomized trial 32. The results revealed that intravenous metoprolol is well tolerated and the incidence of AF was significantly lower in intravenous group compared to oral group (14.5% vs. 31.0%, respectively, p = 0.005).

Sotalol is a betablocker that also has Class III antiarrhytmic characteristics. The effectiveness of sotalol has been demonstrated in placebo-controlled trials 33–35. The effectiveness of sotalol has also been compared to other beta-blockers in three randomized trials 36–38. In the trial by Parikka and coworkers sotalol 75 mg/d was compared with metoprolol 120 mg/d in 191 patients who underwent coronary artery bypass surgery. AF occurred in 32% of the metoprolol group and 16% of the sotalol group (p < 0.01). No proarrhythmic effects of sotalol were found during the study. Similarly, Janssen and co-workers and Suttorp and co-workers found that sotalol was more effective than metoprolol 37 or propanolol 38 in the prevention of AF. In addition to these studies, sotalol has been found in a randomized trial to possibly decrease the incidence of AF in patients who were at especially high risk to develop AF postoperatively 39. Sotalol can be proarrhythmic. In non-surgical patients the proarrhythmic risk has been reported to be 4.3 – 5.9% 40. Because of the proarrhythmic effects of sotalol, ordinary beta-blockers are a safer alternative to sotalol in the prevention of AF after surgery.

Based on the current evidence for safety and effectiveness, it has been concluded that only beta-blockers can be recommended for the prevention of atrial fibrillation after heart surgery 41. Nowadays beta-blockers should be part of the routine medication to prevent atrial fibrillation in all patients undergoing heart surgery, if there are no contra-indications to their use. Further studies are needed to evaluate the feasibility of intravenous administration of beta-blocker in the prevention of AF after cardiac surgery.

Amiodarone

Amiodarone has been shown to be useful in the prevention of postoperative AF. In a study in which patients received amiodarone at least 7 days before cardiac surgery up until they were discharged from the hospital, the incidence of atrial AF decreased by 53% in patients who underwent coronary artery bypass and valvular surgery 42. The duration and dosage of amiodarone has also been evaluated. In a group in which 7 g amiodarone was given over a 10 days period beginning 5 days before surgery, the incidence and duration of asymptomatic and symptomatic atrial fibrillation decreased. If 6 g of amiodarone was given over a 6 days period beginning 1 day before surgery, symptomatic AF and fibrillation lasting at least 24 h decreased, but the decrease in the overall incidence of AF was not significant 43. In a randomized trial with 220 patients over 60 years of age, amiodarone was given per orally (p.o.) beginning either 1 day (6 g over 6 days) or 5 days (7 g over 10 days) before surgery. In addition 90% of the patients received a beta-blocker. In both amiodarone groups the incidence of AF was 22.5%, whereas the incidence in the control group was 38% 44.

The effect of intravenous (i.v.) amiodarone therapy has also been evaluated. In a study in which patients received i.v. amiodarone 2 days following surgery, the incidence of AF was significantly lower in the amiodarone group (5% vs. 21%) 45. In another study, the incidence of AF in the group receiving i.v. amiodarone for 2 days following surgery was 35% vs. 47% in the placebo group 46. Butler and co-workers found that patients who were given i.v. amiodarone (15 mg/kg) for 24 h following surgery and then p.o. 600 mg/days for the following 5 days did not have a lower incidence of supraventricular tachyarrhythmias than the placebo group. The need for treatment of rhythm disturbances was less, but the incidence of bradycardia was greater in the amiodarone group 47. Lee et al. began i.v. amiodarone 3 days before coronary artery bypass surgery and continued it for 5 days after surgery. The incidence of AF and heart rate during atrial fibrillation was lower and the duration shorter in the amiodarone group than in the placebo group (12% vs. 34%), respectively 48.

The effectiveness of amiodarone has not been confirmed in all studies, however. In a trial in which 150 patients were randomized into amiodarone or placebo groups, amiodarone given i.v. for 3 days following surgery did not decrease the incidence of AF 49. In a randomized controlled double-blind trial in which patients received amiodarone postoperatively (900 g/days for 72 h), the decrease in AF was not statistically significant. Circulatory instability lasted longer for patients receiving amiodarone, and they needed more time in the intensive care unit 50. Redle and co-workers found that amiodarone 2 g/days for 1 – 4 days before surgery and 400 mg/days for 7 days following surgery decreased AF by 25%, but the decrease was not significant 51.

A meta-analysis of nine randomized trials showed that amiodarone therapy decreased the incidence of AF from 37% to 22.5% 29. However, amiodarone was not found to be a cost-effective alternative for all patients after coronary artery bypass surgery. In contrast, for elderly patients, patients with chronic obstructive pulmonary disease and patients undergoing both bypass and valvular surgery possibly benefit from amiodarone 21. No studies have compared the efficacy and safety of amiodarone and beta-blockers in the prevention of AF after cardiac surgery.

Amiodarone cannot be recommended to be given routinely to all patients undergoing heart surgery. On the other hand, amiodarone therapy can be considered for patients who are at an especially high risk (old patient, previous episodes of AF, valve surgery) for developing AF postoperatively.

Magnesium

Low serum magnesium levels after cardiac surgery is common 52, 53. Low magnesium concentrations are also independent determinants of AF after coronary artery bypass surgery 50, 54. Moreover, this association has been noted even though serum magnesium concentrations do not correlate with intracellular or myocardial magnesium concentrations 55.

Administration of magnesium has decreased the incidence of AF after cardiac surgery 52, 56–59. In a randomized study in which patients received either magnesium 178 mEq or placebo for 4 days following surgery, the incidence of AF was lower in the magnesium group 52. In the study by Wistbacka and co-workers, in which the dosage of magnesium in the prevention of AF was assessed, the highest dose of magnesium (4.2 g before surgery, 11.9 g infusion by the morning of the first postoperative day and 5.5 g on the following day) decreased the incidence of AF more than lower doses (4.2 g, 2.9 g, 1.4 g). Magnesium concentration was also normal in patients receiving the lower dose of magnesium 57. In a trial in which 200 coronary artery bypass patients were randomized to receive 6 mmol/days of magnesium or placebo on the day before surgery and the first four days after surgery, the incidence of AF was only 2% in the magnesium group, but 21% in the placebo group 58. Jensen and co-workers instead found that magnesium decreased the duration of AF and flutter, but did not decrease the incidence of AF 60. In a retrospective study patients undergoing beating heart bypass surgery who received magnesium were less likely to experience postoperative AF than other patients (12% vs. 29%) 61.

Negative studies about the preventive effect of magnesium on postoperative AF have also been published. In a study in which 70 mmol of magnesium was given in the first 48 h after surgery, no effect on the incidence of atrial AF was seen, and a high serum magnesium level increased the incidence of AF 62. Another study in which 14.4 g of magnesium was given during the first 24 h postoperatively, no effect of magnesium on the incidence of supraventricular tachycardias was found 63.

In a meta-analysis of 20 studies with 2 490 patients, magnesium decreased atrial fibrillation from 28% to 18% 64. The effectiveness of magnesium has been shown also in other meta-analysis 65, 66. At the present there is no evidence that magnesium would be of benefit for patients who already are on beta-blocker medication.

Other pharmacological prevention

Digoxin has not been found effective in the prevention of postoperative AF 27, 28, 67. Also verapamil is ineffective 27.

Intravenous diltiazem has been compared with i.v. nitrate in the prevention of AF in four different studies 68–71. In these studies diltiazem was more effective than nitrates. Placebo-controlled trials with diltiazem have not been carried out.

In one randomized controlled trial triiodothyronine was found to decrease postoperative atrial fibrillation in patients who had a low left ventricular ejection fraction 72.

The effect of corticosteroids has been examined in a randomized controlled trial in which patients were given methyl prednisolone before surgery and one day after surgery. Methyl prednisolone was shown to decrease the postoperative incidence of atrial fibrillation, but it also caused more complications 73.

Prevention by atrial pacing

The effectiveness of atrial pacing in the prevention of AF occurring after heart surgery has been investigated in many studies. Gerstenfeld and co-workers demonstrated that biatrial and right atrial pacing was well tolerated and safe 74. In another study they found that biatrial pacing combined with beta-blockers decreased the incidence of postoperative AF. Especially patients older than 70 years seemed to benefit from the combination treatment 75. In a randomized trial with 154 patients, dynamic right, left and biatrial pacing decreased the incidence of AF compared with the control group 76. In one study dynamic right atrial overpacing decreased postoperative AF 77. In a study comparing the location of atrial pacing, biatrial pacing was more effective than right or left atrial pacing 78. The effectiveness of biatrial pacing in the prevention of postoperative AF has also been shown in another controlled study 79. In a prospective study with 118 patients, biatrial pacing, but not right or left atrial pacing, decreased AF 80. In a randomized trial with 100 patients, AAI pacing (pacing cut-off 10 beats above the normal pulse rate) was compared with no pacing, and no difference was found between groups. Instead, more atrial premature contractions were found in the pacing group 81. In another study, biatrial pacing was compared with pharmacological treatment in the prevention of atrial fibrillation. The trial was terminated early because of proarrhythmias in the pacing group 82. In our study dynamic right atrial overpacing or prevention of bradycardia did not decrease the incidence of postoperative atrial fibrillation 83.

In a meta-analysis comprised of 10 studies with 1 473 patients, three different methods of atrial pacing (right, left and biatrial) were compared. Only biatrial pacing was shown to decrease the incidence of postoperative atrial AF 29.

Posterior pericardiotomy

The concept of opening the posterior pericardium to prevent atrial fibrillation is based on the assumption that this would decrease the accumulation of pericardial fluid postoperatively. The posterior pericardium has been opened with a 4 cm longitudinal incision. Mulay and colleagues were the first to report on the effectiveness of this procedure in the prevention of AF 84. They found that the occurrence of significant accumulation of pericardial fluid on echocardiogram decreased from 40% in the control group to 8% in the intervention group. At the same time, the incidence of supraventricular tachyarrhythmias decreased from 36% to 8%. Two other randomized trials have also found that posterior pericardiotomy decreases the incidence of postoperative AF 85, 86.

In contrast, in a prospective, controlled trial of 100 patients, posterior pericardiotomy had no effect on postoperative atrial fibrillation 87. Thus, the role of posterior pericardiotomy in the prevention of AF remains unclear.

Conclusions

AF occurring after heart surgery is a major problem that requires additional treatment and increases costs. Beta-blocker therapy has been shown in many studies to be safe and effective, and can be used in most patients. Therefore, beta-blockers should be administered postoperatively to all patients for whom there are no contraindications. Amiodarone can be used in patients who are at an especially high risk for AF. At the present there is no evidence that routine magnesium administration or atrial pacing would be of benefit for patients who already are on beta-blocker medication.