Correspondence
Transesophageal Echocardiography to Guide Cardioversion in Patients with Atrial Fibrillation
N Engl J Med 2001; 345:837-839September 13, 2001
- Article
To the Editor:
The findings of Klein et al. (May 10 issue)1 compel reexamination of fast-track cardioversion with the use of transesophageal echocardiography. Is it safe? The mortality rate was 2.5 times as high in the transesophageal-echocardiography group as in the conventional-treatment group (15 vs. 6 patients). The low probability that this difference was due to chance (P=0.06) should not be ignored. Is it beneficial? Sinus rhythm was not more likely at eight weeks, and functional capacity was not increased. Although fewer major hemorrhages occurred in the transesophageal-echocardiography group (5 vs. 9 patients), the clinical significance of this result is doubtful. First, the deaths in the transesophageal-echocardiography group may have eliminated a group at high risk for major hemorrhage. Second, except in one patient, the international normalized ratio at the time of hemorrhage in the conventional-treatment group was either excessively high (3.8 to 12.0) or too low to be the cause. Third, if anticoagulation is continued beyond four weeks in some patients, as recommended,2 reducing the period of anticoagulation by three weeks is unlikely to affect the outcome. What is the incremental value of transesophageal echocardiography in the patient treated with adequate anticoagulation? No patient with thrombus detected by transesophageal echocardiography had an embolic event. The findings on transesophageal echocardiography were negative in all five patients in the transesophageal-echocardiography group who had embolic events (anticoagulation was subtherapeutic in three of the five). Alternatively, transesophageal echocardiography might have prevented the three embolic events in the conventional-treatment group. In conclusion, the trial by Klein et al. reemphasizes the need for meticulous control of anticoagulation. More important, it raises questions about the safety and benefit of fast-track cardioversion.
2 ReferencesKelley P. Anderson, M.D.
Marshfield Clinic, Marshfield, WI 54449-5777
anderskp@mfldclin.edu 1
Klein AL ,Grimm RA ,Murray RD , et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411-1420
Full Text | Web of Science | Medline2
Albers GW ,Dalen JE ,Laupacis A ,Manning WJ ,Petersen P ,Singer DE . Antithrombotic therapy in atrial fibrillation. Chest 2001;119:Suppl 1:194S-206S
CrossRef | Web of Science | Medline
To the Editor:
We compliment Klein and colleagues for undertaking such an important clinical trial. We are concerned, however, that the conclusion that “the strategy of using transesophageal echocardiography to guide treatment may be considered . . . safe” is not substantiated.
The study was designed as a superiority trial to demonstrate the efficacy of a management plan guided by transesophageal echocardiography as compared with conventional treatment in 3000 patients with atrial fibrillation of more than two days' duration. However, the study was terminated after 1222 patients were enrolled on the basis of an interim analysis that indicated that the rates of enrollment and events were too low to provide adequate statistical power to detect the differences the study was originally designed to identify. Unfortunately, because the study was stopped early, there was inadequate power to demonstrate convincingly the equivalency of the two treatment strategies for safety. Despite this consideration, the results of the study are disconcerting. According to the data provided in Table 2, it appears that there were 19 strokes or deaths in the transesophageal-echocardiography group as compared with 8 in the conventional-treatment group (relative risk, 2.31; 95 percent confidence interval, 1.02 to 5.24; P=0.04). Furthermore, in the Assessment of Cardioversion Using Transesophageal Echocardiography pilot study of 126 patients, the conventional-treatment group had no deaths, whereas the transesophageal-echocardiography group had two deaths.1 These data call into question the safety of therapy guided by transesophageal echocardiography and emphasize the need for more data before this strategy is accepted as part of routine clinical practice.
1 ReferencesP.J. Devereaux, M.D.
Salim Yusuf, D.Phil.
McMaster University, Hamilton, ON L8N 3Z5, Canada1
Klein AL ,Grimm RA ,Black IW , et al. Cardioversion guided by transesophageal echocardiography: the ACUTE pilot study. Ann Intern Med 1997;126:200-209
Web of Science | Medline
To the Editor:
As emergency physicians, we are very interested in defining the safest and most effective strategy for anticoagulation in patients with persistent atrial fibrillation before an attempt at cardioversion.1 However, we are surprised that the group of patients assigned by Klein et al. to receive the conventional treatment did not undergo transesophageal echocardiography after three weeks of warfarin therapy, in order to exclude the presence of thrombi or morphologic and functional cardiac alterations (e.g., valvular disease, ventricular or atrial dilatation, or low ejection fraction) that can contraindicate direct-current shock because of the high risk of early recurrence of the arrhythmia after the cardioversion procedure. Thrombi can be detected in the atrial cavities even after three weeks of anticoagulant therapy, especially in patients who have been affected by persistent atrial fibrillation for a longer period.1 Echocardiographic findings may suggest prolongation of anticoagulation. Furthermore, positive echocardiographic findings may lead to a decision not to undertake cardioversion2 and thus a decrease in the incidence of systemic thromboembolism after reestablishment of the sinus rhythm.
2 ReferencesGiuseppe Barbaro, M.D.
Maurizio Soldini, M.D.
Giuseppe Giancaspro, M.D.
University La Sapienza, 00161 Rome, Italy
g.barbaro@tin. it 1
Giancaspro G ,Soldini M ,Lorenzo GD ,Bonaffini N ,Barbaro G . Classification of atrial fibrillation as a model of decisional analysis for the treatment of patients with current atrial fibrillation observed in the emergency department. Eur J Emerg Med 2000;7:99-109
CrossRef | Medline2
Gallagher MM ,Camm AJ . Classification of atrial fibrillation. Pacing Clin Electrophysiol 1997;20:1603-1605
CrossRef | Web of Science | Medline
To the Editor:
The study by Klein et al. suggests that cardioversion of atrial fibrillation guided by transesophageal echocardiography may be an effective, and even preferable, alternative to the conventional approach. With conventional therapy, spontaneous cardioversion occurred twice as frequently as with transesophageal echocardiography (21 percent vs. 10 percent), probably because of the much longer delay to cardioversion with conventional therapy (31 days vs. 3 days). Thus, it seems likely that about 1 in 10 additional patients in the transesophageal-echocardiography group would have had spontaneous conversion had the time to electrical cardioversion been longer. From the perspective of the patient, spontaneous conversion is a highly desirable outcome, since it eliminates the need for both transesophageal echocardiography and electrical cardioversion. The conventional approach thus would probably be favored by most patients.
John R. Stratton, M.D.
University of Washington School of Medicine, Seattle, WA 98108
jrs@u.washington. edu Author/Editor Response
The authors reply:
To the Editor: Dr. Anderson and Drs. Devereaux and Yusuf question the safety of the transesophageal-echocardiography–guided strategy, given the trend in death rates from all causes. Clearly, there was no statistically significant difference between the two treatment groups in terms of death from cardiac or noncardiac causes. The data safety and monitoring board found no relation between treatment and death. It is important to note that 95 percent of the deaths were in patients with serious coexisting conditions, and only one death resulted from embolism. Also, there was no relation between the transesophageal-echocardiography procedure and death. The original analysis plan of the study dictated that death and embolism be treated as separate end points, and we appropriately adhered to the study design.1 An increase in the probability of a type I error could result from unplanned combining of the underpowered primary composite rate of embolism with death. We plan to explore this issue more in ancillary analyses and in the analysis of six-month follow-up data.
The trial showed that the incidence of the composite bleeding end point was lower in the transesophageal-echocardiography group, mainly because the duration of anticoagulant therapy in the conventional-treatment group was nearly double that in the transesophageal-echocardiography group over the eight-week period and thus allowed more opportunity for bleeding. The Assessment of Cardioversion Using Transesophageal Echocardiography protocol did not mandate discontinuation of anticoagulation at four weeks.1 Clinical decisions dictated whether or not patients received anticoagulation therapy beyond the four-week period.1
Anderson questions the incremental value of transesophageal echocardiography in patients treated with adequate anticoagulation. The study showed that the transesophageal-echocardiography–guided strategy with short-term anticoagulation is a safe and clinically effective alternative in patients for whom an early cardioversion is deemed to be clinically beneficial.2 It is ideal for inpatients with atrial fibrillation of recent onset or patients who have an increased risk of bleeding complications during prolonged anticoagulation therapy.2,3 The study does not address the use of the strategy in patients receiving long-term anticoagulation therapy who have persistent atrial fibrillation and are undergoing cardioversion. We also agree about the importance of therapeutic anticoagulation for four weeks after cardioversion, because three patients with no evidence of thrombus on transesophageal echocardiography later had embolic events with the anticoagulant at subtherapeutic levels.
Stratton states that the conventional approach may be favored because of its associated higher rate of spontaneous conversions. However, more than half (53 percent) of the patients who never had a cardioversion in the conventional group did not undergo cardioversion because of bleeding, surgery, patient or physician decisions, or medical complications. Thus, for every patient who “benefited” from spontaneous conversion in the conventional group, at least one other patient did not undergo conversion for other reasons. The net effect is the higher relative number of patients in the transesophageal-echocardiography group who achieved sinus rhythm during the study period.
Barbaro et al. note that transesophageal echocardiography may be diagnostically beneficial for all patients even in the conventional-treatment group, especially after three weeks of anticoagulant therapy because of unresolved thrombi. However, the protocol for the conventional-therapy group was that recommended by the American College of Chest Physicians and therefore did not include transesophageal echocardiography.1,4 We agree that transesophageal echocardiography can help stratify high-risk patients with atrial fibrillation, but further work is needed to assess its incremental value with regard to the standard clinical and transthoracic risk factors.2,4
4 ReferencesAllan L. Klein, M.D.
R. Daniel Murray, Ph.D.
Richard A. Grimm, D.O.
Cleveland Clinic Foundation, Cleveland, OH 441951
Design of a clinical trial for the assessment of cardioversion using transesophageal echocardiography (The ACUTE Multicenter Study). Am J Cardiol 1998;81:877-883
CrossRef | Web of Science | Medline2
Klein AL ,Murray RD ,Grimm RA . Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation. J Am Coll Cardiol 2001;37:691-704
CrossRef | Web of Science | Medline3
Silverman DI ,Manning WJ . Strategies for cardioversion of atrial fibrillation -- time for a change? N Engl J Med 2001;344:1468-1470
Full Text | Web of Science | Medline4
Laupacis A ,Albers G ,Dalen J ,Dunn MI ,Jacobson AK ,Singer DE . Antithrombotic therapy in atrial fibrillation. Chest 1998;114:Suppl 5:579S-589S
CrossRef | Web of Science | Medline
