The Acute Trial: Six-month Follow-up on Patients undergoing a Transesophageal Echocardiography Guided Cardioversion from Atrial Fibrillation

Six-month Follow-up on Patients undergoing a Transesophageal Echocardiography Guided Cardioversion from Atrial Fibrillation: The ACUTE Trial

Allan L. Klein, Richard A. Grimm, R. Daniel Murray, Carolyn Apperson-Hansen, Richard W. Asinger, Ian W. Black, Ravin Davidoff, Raimund Erbel, Jonathan L. Halperin, David A. Orsinelli, Thomas R. Porter, Marcus F. Stoddard for the ACUTE Investigators

Background

Electrical cardioversion of patients with atrial fibrillation (AF) to normal sinus rhythm is frequently performed to relieve symptoms, improve cardiac performance and reduce the risk of stroke. If the patient has a preexisting thrombus (clot) inside the left atrial appendage of the heart, there is a risk of stroke during the procedure. In order to decrease the risk of stroke, patients undergoing electrical cardioversion are usually treated with anticoagulation medications ("blood-thinners") for three weeks before and four weeks after the procedure.

A transesophageal echocardiography (TEE) guided approach, with short-term anticoagulation, has been proposed as an alternative strategy to lower the risk of stroke and bleeding for these patients. This strategy may have several advantages over conventional care:

• The TEE should be able to detect any thrombi (clots) in the left atrial appendage (these are the clots thought to be responsible for stroke after cardioversion). Patients with thrombi would have a postponed cardioversion following anticoagulation.
• Patients without a thrombus could undergo a shorter anticoagulation period, thus decreasing the risk of bleeding complications.
• Earlier cardioversion may increase the successful return to normal sinus rhythm (NSR).

Left atrial appendage thrombus by TEE

Objective this study : To prospectively compare a TEE (transesophageal echo) guided approach with short term anticoagulation to a conventional anticoagulation strategy for patients in atrial fibrillation undergoing cardioversion over a 6 month follow-up period

Methods:

The ACUTE study was a controlled, randomized prospective, multicenter trial, conducted in 70 hospitals worldwide over a five year period. Patients were randomly assigned to conventional care, following standard guidelines for anticoagulation, or a TEE guided arm. Those in the TEE guided approach, received anticoagulation and then received a TEE. Those who did not have a left atrial thrombus were cardioverted and then, anticoagulated with warfarin for 4 weeks post procedure. If a thrombus was detected, the patients received warfarin for 3 weeks, after which a repeat TEE was conducted.

Inclusion criteria:

• Patients greater than 18 years with AF greater than 2 days' duration who were candidates for DCC
• Atrial flutter with document history of AF

Exclusion criteria:

• Chronic (>7 days) anticoagulation
• Hemodynamic instability or contraindications to TEE or warfarin
• Anticipated need to discontinue anticoagulation

Primary endpoints included composite embolism, such as stroke, transient ischemic attack or peripheral embolism. Secondary endpoints included mortality, bleeding, functional status and success and maintenance of sinus rhythm. The data was analyzed on an intention to treat basis. The study period lasted eight weeks with six-month follow-up.

Results

The groups included a total of 1222 patients, 619 in the TEE guided group, and 603 patients in the conventional therapy group.

At 8 weeks:

• Rate of embolic events: not significantly different between the TEE-guided and conventional therapies (0.8% vs. 0.5%, p = 0.50).
• Rate of hemorrhagic events: reduced significantly with TEE-guided cardioversion compared with the conventional-treatment group (2.9% vs. 5.5%, p = 0.03). Most bleeding events at 8 weeks were minor.
• Successful restoration of sinus rhythm: not different between the two groups (80.3% vs. 79.9%; p = 0.90). Although, initially, the TEE guided arm had more patients with successful cardioversion (p = 0.03), at 8 weeks, the proportion of patients in whom sinus rhythm was maintained was not significantly different between the two groups (52.7% vs. 50.4%; p = 0.43).

At 6 months:

Between eight weeks and six-months, 94 patients were lost to follow-up in each group, bringing the TEE guided group to 525 patients and the conventional group to 509 patients.

• Rate of embolic events: no significant difference between the TEE-guided and conventional therapies (p = 0.23).
• Rate of hemorrhagic events:composite hemorrhagic rates were the most significant outcome between the groups, 4.4% in the TEE-guided group and 7.5% in the conventional group (p = 0.04). Major bleeds occurred less in the TEE-guided group (1.0% vs. 2.0% ,p=0.17). Minor hemorrhagic events were also less in the TEE group (3.6% vs. 5.5%, p=0.15).

• Successful restoration of sinus rhythm: There was a trend toward improved maintenance of sinus rhythm with the TEE-guided approach (305/490 (62.3%) in the TEE-guided arm, vs. 280/482 (58.2%) in the conventional treatment group, however this was not statistically significant (p = 0.19) .

• All-cause mortality & cardiac death : There were no differences in all cause or cardiac related deaths in the two groups.

Limitations:

• Under-funded: The ACUTE study was funded primarily by small grants and site investigator dedication.
• Low enrollment rate over the five year period
• Under-powered for primary endpoint
• Difference in cardioversion timing for the two groups; embolism, death and sinus rhythm were compared at an average of 43 days post-cardioversion in the TEE group vs. 25 days post cardioversion in the conventional group. This may have favored the conventional approach.
• 15 percent of patients were lost to 6-month follow-up.

Six month conclusions:

• Aggregate embolic events were lower than expected (1.4%) and bleeding was higher than expected (5.9%) in both the TEE guided and conventional groups over 6 months
• There were no differences in embolic rate between the TEE guided and conventional strategies.
• The TEE-guided strategy with short term anticoagulation allowed for early cardioversion and continued lower bleeding through 6 months
• At 6 months, there were no differences between the 2 study groups for sinus rhythm outcome or death.

TEE guided electrical cardioversion with short term anticoagulation had significantly less bleeding complications than the conventional therapy, as well as a trend toward improved maintenance of sinus rhythm at six weeks of follow-up. This approach may be considered as a safe and effective alternative in the management of patients with atrial fibrillation undergoing cardioversion.

Clinical Practice :

The conventional approach to electrical cardioversion is still most widely used, however the TEE-guided strategy is increasing. At the Cleveland Clinic Heart Center, approximately 30 percent of all electrical cardioversions use this approach. ² From the evidence available, certain patient populations may benefit more from the TEE-guided strategy. These include:

• the inpatient with new-onset atrial fibrillation (AF), especially in high risk patients. These include those with heart failure, previous embolism or hemodynamic instability, in whom early cardioversion would be beneficial.
• the high risk patient who may benefit from further risk stratification via TEE
• those whom the likelihood of thrombus is low, ruling out of thrombus by TEE allows for early cardioversion and avoidance of the risks of longer term anticoagulation.

On the other hand, those patients who are on life-long anticoagulation therapy have more limited benefits by using the TEE guided strategy.

Future Studies:

Studies are on-going to increase the safety, comfort, and effectiveness of electrical cardioversion for AF. Current studies are looking at low molecular weight heparin (which would allow for outpatient anticoagulation), and other pharmacologic agents, such as thrombin inhibitors and chemical cardioversion.

References:

1. Klein AL, Murray RD. Six-Month Follow-Up on Patients Undergoing a Transesophageal Echocardiography Guided Cardioversion from Atrial Fibrillation: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE Trial). Presented at American Heart Association's Scientific Sessions 2001 on Tuesday, November 13, 2001. See American Heart Association sponsored Sessions on Line at http://www.sessionsonline.org/( a new browser window will open with this link. The inclusion of links to other web sites does not imply any endorsement of the material on the web sites or any association with their operators)
2. Klein AL, Murray RD, Grimm RA. Role of transesophageal guided cardioversion of patients with atrial fibrillation (Review). J Am Coll Cardiol 2001;37:691-704.
3. 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;344:1411-9.
4. Murray RD, Shah A, Jasper SE, et al. for the ACUTE II Pilot Study Investigators. Design of a Pilot Study to Test the Feasibility, General Safety, and Economics of a Transesophageal Echocardiography Guided Low Molecular Weight Heparin (Enoxaparin) Approach to Cardioversion of Patients in Atrial Fibrillation: The ACUTE II Study. Am Heart J 2000; 139: E5