Early Cardioversion of Atrial Fibrillation Guided by Transesophageal Echocardiography

Login or register to view PDF.

Atrial fibrillation (AF) is the most commonly sustained arrhythmia with a prevalence of 0.4% in the general population1-4 affecting 2.3 million people in the US.5 The prevalence increases with age being <1% in persons younger than 60 years of age to >8% in those older than 80 years.1,5-8 The incidence ranges from 0.2% per year for men 30 to 39 years of age to 2.3% per year in men 80 to 89 years of age.6,9 Men are twice as likely to have AF with age as women.10 Most patients with AF have symptomatic AF ranging from irregular palpitations to fatigue. Patients with structural heart disease may present with decompensated heart failure.

Risk of Stroke with AF

Patients with AF have an increased risk for thromboembolism. The relative risk for stroke is increased two- to seven-fold in patients with non-rheumatic AF when compared with age-matched controls.6,8,9,11,12 The absolute risk for stroke ranges between 1% and 5% per year-depending mainly on age, the presence of structural heart disease, and other clinical characteristics.6,8,11,12 Electrical cardioversion is usually used in an attempt to restore sinus rhythm in patients with AF especially in those with symptoms. This procedure, however, is associated with an increased risk of stroke that may result if left atrial thrombi are dislodged when sinus rhythm is restored.13-15 It is estimated that the risk for thromboembolism after cardioversion is about 0.33% in those who received anticoagulation before cardioversion and 5.00% in those who did not.16,17 This risk was similar in both pharmacologic cardioversion or DCC18. There are two proposed mechanisms responsible for the thromboembolic risk associated with cardioversion of AF;

  • Embolization of thrombi in the left atrium or the left atrial appendage that are present before conversion once atrial contraction is restored.
  • Left atrial stunning after conversion, with thrombi developing after conversion and embolizing as the atrium recovers contractility.19-22

The current ACCP conventional guidelines for anticoagulation in patients with AF for >2 days requires three weeks of empirical anticoagulation before cardioversion followed by four weeks of warfarin therapy after cardioversion.23,24 Pathophysiologically, such a strategy could stabilize preexisting thrombi, prevent new thrombus formation, and enhance the resorption and elimination of preexisting thrombi. No clinical trials have directly compared this strategy without anticoagulation or with other strategies of anticoagulation involving varying intensities or duration.

Use of Transesophageal Echocardiography to Guide Cardioversion

Transesophageal echocardiography (TEE) can reliably detect left atrial and left atrial appendage thrombi.25-27 This procedure could be used to risk stratify patients before cardioversion. The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study, a randomized clinical trial comparing a TEEguided strategy with the conventional strategy in patients with atrial fibrillation lasting >2 days18,28 showed that the use of TEE was safe and facilitated early cardioversion. In the TEE-guided group of this study, thrombus in the left atrium, left atrial appendage, or right atrium was identified in 14% of patients (76/619). The patients at high risk for stroke received at least four weeks of anticoagulation before any cardioversion attempts. Patients without thrombus identified on TEE were converted immediately and received anticoagulation for at least four weeks after cardioversion. The composite primary end-point of stroke, transient ischemic attack, or peripheral embolism did not differ between the TEE-guided group and the conventional group that was treated with three weeks pre- and four weeks post-cardioversion (0.81% versus 0.50%, respectively; P>0.2). However, there was a significant difference in the composite end-point of major and minor bleeding (2.9% for the TEE-guided group and 5.5% for the conventional group; P = 0.02).

Furthermore, the length of anticoagulation therapy is an established determinant of bleeding.18 In the ACUTE study, the TEE-guided group had a much shorter length of anticoagulation therapy before cardioversion compared with the conventional group.28 Thus, the difference in the composite bleeding rate between the two treatment groups appears to be a result of the difference in length of anticoagulation therapy over the eight-week follow-up period. Recently, the Observational Cardioversion Study by Seidl et al. showed similar results with low embolic rates and no difference between patients treated with the TEE-guided approach and patients treated conventionally (0.8% for both groups), and underscored the importance of well-monitored anticoagulation regimens especially in post-cardioversion period regardless of strategy.29 Overall, the literature suggests that TEE-guided conversion using short-term pre-cardioversion anticoagulation, and at least three weeks of appropriate post-conversion anticoagulation may be an effective and safe alternative to the conventional approach.

On a pathophysiologic level, early cardioversion using the TEE approach could prevent electrophysiologic and structural remodeling in the atria that can lead to persistent or recurrent AF after successful cardioversion30 as the duration of AF is a strong determinant of the of atrial remodeling.31 Hence the concept of 'atrial fibrillation begets atrial fibrillation.ÔÇÖ32

Quality of Life

Quality of life is an important consideration for patients. Anticoagulation therapy also affects quality of life due to frequent blood testing for adequate anticoagulation and patient concerns regarding limitation of some activities. Protheroe et al. and others33,34 have estimated that only 61% of patients who meet the requirements for anticoagulation prefer anticoagulation to no treatment. Furthermore, in clinical practice, conventional guidelines for anticoagulation are not routinely followed in as many as 40% of the patients undergoing cardioversion, particularly elderly patients.35,36 Therefore, a strategy that would help limit anticoagulation to only the four weeks post-cardioversion and circumvent the need for a long pre-cardioversion period of anticoagulation in most patients would be more desirable with also decreased exposure to the risks associate with anticoagulation.

Facilitation of treatment and better convenience for physicians and patients in most cases has become the most compelling reason to use the TEE facilitated approach. In the ACUTE study,28 the mean time to cardioversion was substantially reduced from 31 days in the conventional arm to just three days in the TEE. The ability to perform both TEE and cardioversion during a single visit eliminates the need for a second visit for cardioversion and protects patients from the potential for wide fluctuations in the INR (when warfarin therapy is initiated) and antecedent complications.28

Cost-effectiveness

The cost-effectiveness of TEE-facilitated cardioversion has recently been studied in the ACUTE cost-effectiveness study.37 The results of the economic study showed that a TEE-guided approach is slightly more costly than the conventional approach but outcome costs tended to be higher for the conventional strategy, resulting in no significant cost difference between the two strategies. The cost of the TEE procedure itself (US$277 using Medicare reimbursement) is a small portion of the estimated US$6,400 total eight-week management cost for patients undergoing cardioversion for AF37.

Selection of Patients for TEE-guided Versus Conventional Therapy

It is important to select the appropriate candidates for the TEE guided approach because the ACUTE trial and most other studies do not reflect most patients with AF who generally have a more prolonged duration of AF and have more structural disease.

Patients ideal for the TEE approach usually have one or more of the following characteristics:

  • new onset AF;
  • uncertain anticoagulation status, symptoms;
  • higher risk for bleeding;
  • potential noncompliance with anticoagulation; and
  • high risk for left atrial thrombus. See Table 1.38,39

 

Future Directions

 

There is current investigation into more practical and economic alternatives to intravenous heparin therapy in patients considered for cardioversion. The ACUTE II study will compare the enoxaparin (low molecular heparin) with unfractionated heparin as an antithrombotic strategy in patients with atrial fibrillation and cardioversion. The use of the oral thrombin inhibitor Ximegaltran (without the need for monitoring INR) may hold promise as well in these patients.

Conclusion

In patients with AF,TEE-guided early cardioversion is a safe and convenient alternative to the conventional anticoagulant approach. Ôûá

References
  1. Ostrander Jr L D, Brandt R L, Kjelsberg M O et al., "Electrocardiographic Findings among the Adult Population of a Total Natural Community,Tecumseh, Michigan", Circulation (1965);31: pp. 888-898.
    Crossref | PubMed
  2. Prystowsky E N, Benson Jr D W, Fuster V et al., "Management of Patients with Atrial Fibrillation. A Statement for Healthcare Professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association", Circulation (1996);93: pp. 1,262-1,277.
    Crossref | PubMed
  3. Feinberg W M, Blackshear J L, Laupacis A et al.,"Prevalence, Age Distribution, and Gender of Patients with Atrial Fibrillation. Analysis and Implications", Arch. Intern. Med. (1995);155: pp. 469-473.
    Crossref | PubMed
  4. Kannel W B,Abbott R D, Savage D D et al.,"Coronary Heart Disease and Atrial Fibrillation:The Framingham Study", Am. Heart J. (1983);106: pp. 389-396.
    Crossref | PubMed
  5. Go A S, Hylek E M, Phillips K A et al.,"Prevalence of Diagnosed Atrial Fibrillation in Adults: National Implications for Rhythm Management and Stroke Prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study", JAMA (2001);285: pp. 2,370-2,375.
    Crossref | PubMed
  6. Wolf P A, Kannel W B, McGee D L et al.,"Duration of Atrial Fibrillation and Imminence of Stroke: the Framingham Study", Stroke (1983);14: pp. 664-667.
    Crossref | PubMed
  7. Furberg C D, Psaty B M, Manolio T A et al., "Prevalence of Atrial Fibrillation in Elderly Subjects (The Cardiovascular Health Study)", Am. J. Cardiol. (1994);74: pp. 236-241.
    Crossref | PubMed
  8. Flegel K M, Shipley M J and Rose G,"Risk of Stroke in Non-Rheumatic Atrial Fibrillation", Lancet (1987);1: pp. 526-529.
    Crossref | PubMed
  9. Krahn A D, Manfreda J,Tate R B et al., "The Natural History of Atrial Fibrillation: Incidence, Risk Factors, and Prognosis in the Manitoba Follow-Up Study", Am. J. Med. (1995);98: pp. 476-484.
    Crossref | PubMed
  10. Psaty B M, Manolio T A, Kuller L H et al.,"Incidence of and Risk Factors for Atrial Fibrillation in Older Adults", Circulation (1997);96: pp. 2,455-2,461.
    Crossref | PubMed
  11. Levy S, Maarek M, Coumel P et al.,"Characterization of Different Subsets of Atrial Fibrillation in General Practice in France: The ALFA Study. The College of French Cardiologists", Circulation (1999);99: pp. 3,028-3,035.
    Crossref | PubMed
  12. Hart R G, Pearce L A, Rothbart R M et al., Stroke with Intermittent Atrial Fibrillation: Incidence and Predictors During Aspirin Therapy. Stroke Prevention in Atrial Fibrillation Investigators", J.Am. Coll. Cardiol. (2000);35: pp. 183-187.
    Crossref | PubMed
  13. Grimm R A, Stewart W J, Black I W et al., "Should all Patients Undergo Transesophageal Echocardiography Before Electrical Cardioversion of Atrial Fibrillation?", J.Am. Coll. Cardiol. (1994);23: pp. 533-541.
    Crossref | PubMed
  14. Lown B, "Electrical Reversion of Cardiac Arrhythmias", Br. Heart J. (1967);29: pp. 469-489.
    Crossref | PubMed
  15. Stein B, Halperin J L and Fuster V,"Should Patients with Atrial Fibrillation be Anticoagulated Prior to and Chronically Following Cardioversion?", Cardiovasc. Clin. (1990);21: pp. 231-247, Discussion, pp. 248-249.
    PubMed
  16. Bjerkelund C J and Orning O M, "The Efficacy of Anticoagulant Therapy in Preventing Embolism Related to D.C. Electrical Conversion of Atrial Fibrillation", Am. J. Cardiol. (1969);23: pp. 208-216.
    Crossref | PubMed
  17. Moreyra E, Finkelhor R S and Cebul R D,"Limitations of Transesophageal Echocardiography in the Risk Assessment of Patients Before Nonanticoagulated Cardioversion from Atrial Fibrillation and Flutter: An Analysis of Pooled Trials", Am. Heart J. (1995);129: pp. 71-75.
    Crossref | PubMed
  18. Klein A L, Murray R D and Grimm R A, "Role of Transesophageal Echocardiography-Guided Cardioversion of Patients with Atrial Fibrillation", J.Am. Coll. Cardiol. (2001);37: pp. 691-704.
    Crossref | PubMed
  19. Leung D Y, Grimm R A and Klein A L, "Transesophageal Echocardiography-Guided Approach to Cardioversion of Atrial Fibrillation", Prog. Cardiovasc. Dis. (1996);39: pp. 21-32.
    Crossref | PubMed
  20. Harjai K, Mobarek S,Abi-Samra F et al.,"Mechanical Dysfunction of the Left Atrium and the Left Atrial Appendage Following Cardioversion of Atrial Fibrillation and its Relation to Total Electrical Energy Used for Cardioversion", Am. J. Cardiol. (1998);81: pp. 1,125-1,129.
    Crossref | PubMed
  21. Fatkin D, Kuchar D L, Thorburn C W et al., "Transesophageal Echocardiography Before and During Direct Current Cardioversion of Atrial Fibrillation: Evidence for "Atrial Stunning" as a Mechanism of Thromboembolic Complications", J.Am. Coll. Cardiol. (1994);23: pp. 307-316.
    Crossref | PubMed
  22. Stoddard M F, Dawkins P R, Prince C R et al.,"Transesophageal Echocardiographic Guidance of Cardioversion in patients with Atrial Fibrillation", Am. Heart J. (1995);29: pp. 1,204-1,215.
    Crossref | PubMed
  23. Albers G W, Dalen J E, Laupacis A et al.,"Antithrombotic Therapy in Atrial Fibrillation", Chest (2001);119: pp. 194S-206S.
    Crossref | PubMed
  24. Laupacis A,Albers G, Dalen J et al., "Antithrombotic therapy in Atrial Fibrillation", Chest (1998);114: pp. 579S-589S.
    Crossref | PubMed
  25. JHwang J J, Chen J J, Lin S C et al., "Diagnostic Accuracy of Transesophageal Echocardiography for Detecting Left Atrial Thrombi in Patients with Rheumatic Heart Disease Having Undergone Mitral Valve Operations",Am. J. Cardiol. (1993);72: pp. 677-681.
    Crossref | PubMed
  26. Manning W J,Weintraub R M,Waksmonski C A et al.,"Accuracy of Transesophageal Echocardiography for Identifying Left Atrial Thrombi. A Prospective, Intraoperative Study", Ann. Intern. Med. (1995);123: pp. 817-822.
    Crossref | PubMed
  27. Fatkin D, Scalia G, Jacobs N et al.,"Accuracy of Biplane Transesophageal Echocardiography in Detecting Left Atrial Thrombus", Am. J. Cardiol. (1996);77: pp. 321-323.
    Crossref | PubMed
  28. Klein A L, Grimm R A, Murray R D et al.,"Use of Transesophageal Echocardiography to Guide Cardioversion in Patients with Atrial Fibrillation", N. Engl. J. Med. (2001);344: pp. 1,411-1,420.
    Crossref | PubMed
  29. Seidl K, Rameken M, Drogemuller A et al., "Embolic Events in Patients with Atrial Fibrillation and Effective Anticoagulation: Value of Transesophageal Echocardiography to Guide Direct-Current Cardioversion. Final Results of the Ludwigshafen Observational Cardioversion Study", J.Am. Coll. Cardiol. (2002);39: pp. 1,436-1,442.
    Crossref | PubMed
  30. Tieleman R G,Van Gelder I C, Crijns H J et al., "Early Recurrences of Atrial Fibrillation After Electrical Cardioversion:A Result of Fibrillation-Induced Electrical Remodeling of the Atria?", J.Am. Coll. Cardiol. (1998);31: pp. 167-173.
    Crossref | PubMed
  31. Verhorst P M, Kamp O,Welling R C et al.,"Transesophageal Echocardiographic Predictors for Maintenance of Sinus Rhythm After Electrical Cardioversion of Atrial Fibrillation", Am. J. Cardiol. (1997);79: pp. 1,355-1,359.
    Crossref | PubMed
  32. Pandozi C and Santini M, "Update on Atrial Remodelling Owing to Rate; Does Atrial Fibrillation Always 'Beget' Atrial Fibrillation?", Eur. Heart J. (2001);22: pp. 541-553.
    Crossref | PubMed
  33. Hamer M E, Blumenthal J A, McCarthy E A et al.,"Quality-of-Life Assessment in Patients with Paroxysmal Atrial Fibrillation or Paroxysmal Supraventricular Tachycardia", Am. J. Cardiol. (1994);74: pp. 826-829.
    Crossref | PubMed
  34. Protheroe J, Fahey T, Montgomery A A et al., "The Impact of Patients' Preferences on the Treatment of Atrial Fibrillation: Observational Study of Patient Based Decision Analysis", BMJ (2000);320: pp. 1,380-1,384.
    Crossref | PubMed
  35. Carlsson J,Tebbe U, Rox J et al.,"Cardioversion of Atrial Fibrillation in the Elderly.ALKK-Study Group. Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausaerzte", Am. J. Cardiol. (1996);78: pp. 1,380-1,384.
    Crossref | PubMed
  36. Schlicht J R, Davis R C, Naqi K et al.,"Physician Practices Regarding Anticoagulation and Cardioversion of Atrial Fibrillation", Arch. Intern. Med. (1996);156: pp. 290-294.
    Crossref | PubMed
  37. Klein A L, Murray R D, Becker E R et al., "Economic Analysis of a Transesophageal Echocardiography-Guided Approach to Cardioversion of Patients with Atrial Fibrillation: The ACUTE Economic Data at Eight Weeks", J. Am. Coll. Cardiol. (2004);43: pp. 1,217-1,224.
    Crossref | PubMed
  38. Asher C R and Klein A L, "The ACUTE Trial. Transesophageal Echocardiography to Guide Electrical Cardioversion in Atrial Fibrillation. Assessment of Cardioversion Using Transesophageal Echocardiography", Cleve Clin. J. Med. (2002);69: pp. 713-718.
    Crossref | PubMed
  39. Asher C R and Klein A L, "Transesophageal Echocardiography in Patients with Atrial Fibrillation", Pacing Clin. Electrophysiol. (2003);26: pp. 1,597-1,603.
    Crossref