Abciximab

The recommendations put forth in these guidelines for the management and prevention of atrial fibrillation (AF) after cardiac surgery are based on information available at the time of the final literature review. As a result, they will become dated as new information and results from new trials becomes available. The maintenance of clinical practice guidelines is an evolving process requiring the alteration of recommendations over time, based on new studies and new results. The current set of guidelines attempts not only to identify new therapeutic options for AF after cardiac surgery but also to develop a strategy to indicate how and when to update the guidelines themselves.

Key words: atrial fibrillation; coronary artery bypass graft; maze procedure; off-pump coronary artery bypass

Abbreviations: AF = atrial fibrillation; CABG = coronary artery bypass graft; OPCAB = off-pump coronary artery bypass graft

**********

The management and prevention of atrial fibrillation (AF) following cardiac surgery poses a significant challenge. The currently available evidence offers important insight and direction for the management of this common condition, but even with > 100 clinical trials relevant to the problem, the numbers of specific and well-supported recommendations are relatively few. Reviews such as this bring to light not only the available information and evidence but also gaps in our knowledge base, and the need for future research in this area.

NEW DRUGS

New drugs may become available in the near future to selectively treat and prevent AF. Newer class III antiarrhythmic agents that are likely to find clinical application include azimilide, a type III potassium channel blocker that blocks the rapid I(kr) current like amiodarone, sotalol, and ibutilide but is unique in blocking the slow I(ks) current as well. Dronedarone, a new drug that is similar to amiodarone, is currently undergoing clinical trials along with the other agents listed above. (1-3)

SURGICAL TECHNIQUES

Elective surgical ablation for AF has been well-established. (4) While the maze procedure is fairly complicated and is unlikely to become a routine part of standard coronary artery bypass graft (CABG) surgery, alternative surgical ablation procedures may be beneficial in the high-risk patient with valvular lesions or preexisting AF. (5) These procedures have been refined for minimally invasive surgery and are applicable to off-pump techniques. (6,7) This approach could find widespread application and may even become a part of standard coronary artery bypass procedures for those patients who are at high risk for postoperative AF. A better understanding of the role of pulmonary vein activity in AF may allow for a more limited surgical approach, which then might lower the threshold for a concomitant procedure, even in the realm of prophylaxis for postoperative AF. (8,9) Pulmonary vein stenosis remains a potential risk for most of these procedures. (10) Further studies in the future may be able to determine which modality of ablation (eg, radiofrequency, cryoablation, or microwave, and unipolar vs bipolar) is better in which circumstances.

In one prospective randomized trial, (11) partial cardiac denervation, when used as an adjunct to coronary bypass, was shown to be effective in preventing AF. This limited ventral cardiac denervation is a relatively simple procedure adding only 5 min to the operation with minimal excess morbidity, and it could find widespread application if the results are readily reproducible by other investigators. (11) In the study by Melo and colleagues, (11) the incidence of AF was reduced from 9.7% in the control group to 7% in the study population using this technique.

INFLAMMATORY RESPONSE AND CARDIOPULMONARY BYPASS

The advantages and disadvantages of the off-pump CABG (OPCAB) are currently being debated. Theoretically, there should be less inflammatory response and fewer neurologic, hematologic, and arrhythmic sequelae; however, further study is required to assess the potential benefits of OPCAB compared to traditional CABG surgery using cardiopulmonary bypass. Early evidence (12-14) has suggested that differences, if present, may be small. The Department of Veterans Affairs has instituted a multicenter prospective trial (CSP517) to compare OPCAB surgery with on-pump CABG surgery using the end points of neurocognitive outcomes, infection, bleeding, and graft patency. However, the rates of postoperative AF will not be available for several years until the data are tabulated.

The role of inflammation as an etiologic factor in postoperative arrhythmia should be more fully examined. In addition to direct myocardial electrical influences, inflammatory mediators such as bradykinin may evoke proarrhythmic hemodynamic effects in patients receiving cardiopulmonary bypass. (12) Because cardiopulmonary bypass techniques continue to evolve, the use of closed collection systems and heparin-bonded circuits may reduce the number of cytokines produced and may lessen the systemic inflammatory response, but this requires further study. Despite early suggestions to the contrary,(13) some evidence (14) has suggested that the inflammatory response occurs in patients undergoing OPCAB surgery as well. In addition, more work is needed to determine whether the systemic inflammatory response influences the incidence of postoperative arrhythmias. If inflammatory mediators contribute to postoperative arrhythmias, a question could be posed about whether antiinflammatory agents or cytokine blockers are potentially prophylactic. However, current research (150 suggests that corticosteroids do not appear to be beneficial and, in fact, may be detrimental. Therefore, further research is needed to understand the mechanisms of the inflammatory response and the contribution of this response to the genesis of postoperative atrial arrhythmias.

INVASIVE NONOPERATIVE TECHNIQUES

Advances in radiofrequency ablation and other nonoperative techniques are likely to become a part of the armamentarium of those treating postoperative AF. (16) Radiofrequency ablation appears to have distinct advantages over direct-current countershock methods, but both techniques require the insertion of a permanent pacemaker. (17) AV-node ablation is generally reserved for patients in whom pharmacologic control of ventricular rate cannot be achieved or is poorly tolerated. Transcatheter ablation with the insertion of a rate-responsive pacemaker offers symptomatic improvement, and transcatheter AV node modification without full ablation may become an alternative that does not require permanent pacing. Unfortunately, clinical success rates do not yet warrant the widespread application for these techniques in patients with postoperative AF. (16,18)

The Dual Site Atrial Pacing for Prevention of Atrial Fibrillation trial (19,20) demonstrated the relative effectiveness of dual-site right atrial pacing in reducing the frequency of paroxysmal AF when compared to no pacing or single-site pacing, although it did not eliminate the need for antiarrhythmic drug therapy in most patients. However, it is not clear whether these invasive techniques have application in the postoperative patient since they are currently more suited to the patient with chronic paroxysmal AF. There are a few studies (21-24) that have provided some evidence on the effects of biatrial pacing for the prevention of postoperative AF after coronary artery bypass surgery.

A third area in this category of invasive, nonoperative techniques is that of synchronized direct-current cardioversion, which is often required in patients with AF, particularly in the presence of hemodynamic instability or when attempts at pharmacologic conversion fail. New biphasic defibrillators that are effective at lower energy levels are now available, (25) and implantable atrial defibrillators are another innovation that may be suitable for patients with recurrent episodic AF. (26)

ANTICOAGULATION THERAPY

The recommendations for anticoagulation therapy in post-cardiac surgery patients are largely based on studies in nonsurgical patients. It is known that the risk for postoperative bleeding that is associated with anticoagulation therapy may be compounded in older surgical patients and, even in nonsurgical patients, anticoagulation therapy has attendant risks, especially when the international normalized ratio is > 3.0. (27) It is not clear what role fractionated low-molecular-weight heparin or the newer pentasaccharide, fondaparinux, may play. These agents appear to be more efficacious than unfractionated heparin in many situations and, in the case of fondaparinux, can be administered subcutaneously once a day. Another 10a inhibitor, idraparinux, has the potential for once-a-week dosing. Studies (AMADEUS) are ongoing to see whether these agents are suitable alternatives to warfarin. They still require a subcutaneous injection. (28) Unfortunately, measuring efficacy is difficult, and if bleeding occurs, reversal treatment may be more difficult in patients receiving these drugs than in patients receiving heparin or warfarin. (29)

There are newer antiplatelet agents that should be assessed as substitutes for warfarin in the postoperative patient with AF since currently there are few studies. The Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events trial, (30) which compared clopidogrel to aspirin in patients who were at risk of ischemic events, did not show differences between aspirin (325 mg/d) and clopidogrel (75 mg/d) for myocardial infarction or stroke but did show a modest reduction in vascular death. Although this trial was not designed to assess the effectiveness of clopidogrel in patients with AF, it appears that clopidogrel offers little advantage over aspirin. (30) One study (31) has looked at the GpIIb/IIIa antibody, abciximab, for the reduction of postangioplasty restenosis, but antigenicity and bleeding complications remain concerns that may make this drug unsuitable for the postoperative patient.

Oral direct thrombin inhibitors look promising as a safe alternative to vitamin K antagonists such as warfarin. Fixed-dose ximelagatran (36 mg bid) without monitoring, has been shown to be as safe and effective as monitored warfarin and was better tolerated. (31-33)

SLEEP APNEA AS A RISK FACTOR FOR POSTOPERATIVE AF

Undiagnosed sleep apnea is a risk factor for postoperative AF as well as for heart disease in general. (34) Some studies (35-38) have shown that therapy with continuous positive airway pressure can reduce cardiac arrhythmias in patients who have sleep apnea. Thus, screening for and treating sleep-disordered breathing as part of the routine preoperative evaluation of cardiac surgical patients may be a useful strategy for preventing post-cardiac surgery AF.

CONCLUSION

Evidence-based medicine and clinical practice guidelines constitute a continuously evolving science. New studies constantly add to the information we use to create clinical practice guidelines, necessitating the update and review of guidelines on an ongoing basis. For the treatment of AF following cardiac surgery, invasive and noninvasive procedures as well as the use of new pharmacologic agents will alter clinical approaches to prevention and management. In addition, these procedural and pharmacologic developments will also mandate periodic updating of these current clinical practice guidelines.

REFERENCES

(1) Tran HT. Azimilide dihydrochloride: a unique class III antiarrhythmic agent. Heart Dis 1999; 1:114-116

(2) Bril A. Recent advances in arrhythmia therapy: treatment and prevention of atrial fibrillation. Curr Opin Pharmacol 2002; 2:154-159

(3) Conway DS, Lip GY. New antiarrhythmic agents for atrial fibrillation. Curr Opin Investig Drugs 2001; 2:87-89

(4) Cox JL, Shuessler RB, D'Agostino HJ Jr., et al. The surgical treatment of atrial fibrillation: III. Development of a definitive surgical procedure J Thorac Cardiovasc Surg 1991; 101:569-583

(5) Izumoto H, Kawazoe K, Eishi K, et al. Medium-term results of the modified Cox/Maze procedure combined with other cardiac surgery. Eur J Cardiothorac Surg 2000; 17:25-29

(6) Cox JL. Minimally invasive Maze procedure [abstract]. Circulation 1999; 100:(suppl):I 778

(7) Lee R, Nitta T, Shuessler RB, et al. The closed heart MAZE: a nonbypass surgical technique. Ann Thorac Surg 1999; 67:1696-1702

(8) Kahn R. Identifying and understanding the role of pulmonary vein activity in atrial fibrillation. Cardiovasc Res 2004 1; 64:387-394

(9) Kubota H, Takamoto S, Ohtsuka T, et al. Epicardial pulmonary vein isolation with a hook-shaped cryoprobe to treat atrial fibrillation. Ann Thorac Surg 2004; 78:1056-1059

(10) Nilsson B, Chen X, Pehrson S, et al. Acute fatal pulmonary vein occlusion after catheter ablation of atrial fibrillation. J Interv Card Electrophysiol 2004; 11:127-130

(11) Melo J, Ferreira MM, Abecassis M, et al. Partial cardiac denervation reduces the incidence of atrial fibrillation after coronary revascularization. Paper presented at The American Association for Thoracic Surgery 82nd Annual Meeting; May 5-8, 2002; Washington, DC; abstract 9

(12) Cugno M, Nussberger J, Biglioli P, et al. Increase of bradykinin in plasma of patients undergoing cardiopulmonary bypass: the importance of lung exclusion. Chest 2001; 120: 1776-1782

(13) Ascione R, Lloyd CT, Underwood MJ, et al. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg 2000; 69:1198-1204

(14) Diegeler A, Doll N, Rauch T, et al. Humoral immune response during coronary artery bypass grafting; a comparison of limited approach "off-pump" technique and conventional cardiopulmonary bypass. Circulation 2000; 102(suppl): III95-III100

(15) Chang MA. Corticosteroids and cardiopulmonary bypass: a review of clinical investigations. Chest 2002; 121:921-931

(16) Iskos D, Fahey GJ, Lurie KG, et al. Nonpharmacologic treatment of atrial fibrillation: current and evolving strategies. Chest 1997; 112:1079-1090

(17) Morady F, Calkins H, Langberg JJ, et al. A prospective randomized comparison of direct current and radiofrequency ablation of the atrioventricular junction. J Am Coll Cardiol 1993; 21:102-109

(18) Wellens HJ. Atrial fibrillation--the last big hurdle in treating supraventricular tachycardia. N Engl J Med 1994; 331:943-945

(19) Sakensa S. DAPPAF trial data. Paper presented at the American College of Cardiology Meeting; March 18, 2001; Orlando, FL

(20) Kusumoto FM, Goldschlager N. Device therapy for cardiac arrhythmias. JAMA 2002; 287:1848-1852

(21) Daoud EG, Dabir R, Archambeau M, et al. Randomized, double-blind trial of simultaneous right and left atrial epicardial pacing for prevention of post-open heart surgery atrial fibrillation. Circulation 2000; 102:761-765

(22) Fan K, Lee KL, Chiu CS, et al. Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery. Circulation 2000; 102:755-760

(23) Greenberg MD, Katz NM, Iuliano S, et al. Atrial pacing for the prevention of atrial fibrillation after cardiovascular surgery. J Am Coll Cardiol 2000; 35:1416-1422

(24) Levy T, Fotopoulos G, Walker S, et al. Randomized controlled study investigating the effect of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass grafting. Circulation 2000; 102:1382-1387

(25) Mittal S, Ayati S, Stein KM, et al. Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks. Circulation 2000; 101:1282-1287

(26) Tse HF, Lau CP, Yomtov BM, et al. Implantable atrial defibrillator with a single-pass dual-electrode lead. J Am Coll Cardiol 1999; 33:1974-1980

(27) Cheesbro JH, Wiebers DO, Holland AE, et al. Bleeding during antithrombotic therapy inpatients with atrial fibrillation. Arch Intern Med 1996; 156:409-416

(28) Donnan GA, Dewey HM, Chambers BR. Warfarin for atrial fibrillation: the end of an era? Lancet Neurol 2004; 3:305-308

(29) Bauer KA, Eriksson BI, Lassen MR, et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med 2001; 345:1305-1310

(30) CAPRIE Steering Committee. A randomized, blinded, trial of Clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348:1329 1339

(31) EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty: The EPIC Investigation. N Engl J Med 1994; 330:956-961

(32) Olsson SB, Executive Steering Committee on behalf of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomized controlled trial. Lancet 2003; 362:1691-1698

(33) Reiffel JA. Will direct thrombin inhibitors replace warfarin for preventing embolic events in atrial fibrillation? Curr Opin Cardiol 2004; 19:58-63

(34) Mooe T, Gullsby S, Rabben T, et al. Sleep-disordered breathing: a novel predictor of atrial fibrillation after coronary artery bypass surgery. Coron Artery Dis 1996; 7:475-478

(35) Jahaveri S, Parker TJ, Liming JD, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure: types and their prevalences, consequences, and presentations. Circulation 1998; 97:2154-2159

(36) Fietze I, Rottig J, Quispe-Bravo S, et al. Sleep apnea syndrome in patients with a cardiac pacemaker. Respiration 2000; 67:268-271

(37) Sin DD, Fitzgerald F, Parker JD, et al. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med 1999; 160:1101-1106

(38) Kanedo Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003; 348:1233-1241

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml).

Correspondence to: Peter McKeown, MBBS, MPH, FCCP, Department of Surgery, VAMC, 1100 Tunnel Rd, Asheville, NC 28805; e-mail: peter.mckeown@med.va.gov

* From the Asheville Veterans Affairs Medical Center (Dr. Mc Keown), Asheville, NC; the University of Alabama (Dr. Epstein), Birmingham, AL.

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group