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.'32
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.