The presence of intra-atrial thrombi or their precursors with their propensity for systemic embolism or the presence of interatrial septal defects are major concerns for patients with atrial fibrillation (AF) undergoing cardioversion. Transesophageal echocardiography (TEE) has been demonstrated to be a sensitive tool to detect septal defects, left atrial thrombi and spontaneous echo contrast (1, 2,3). The ACUTE trial documented that TEE based exclusion of intra cardiac thrombi, smoke or spontaneous echo contrast can facilitate safe immediate cardioversion in patients with AF. (4) This trial demonstrated comparable risk of embolic events with a TEE- based strategy to identify low risk patients for immediate cardioversion when compared to a conventional strategy of 3 weeks of anticoagulation before cardioversion.
The recognition of systemic thromboembolism as a significant potential complication of cardioversion during interventional cardiology procedures in patients with AF has stimulated interest in the clinical evaluation of catheter based intra cardiac echocardiography (ICE). Initial experience with intra cardiac phased -array imaging has demonstrated the efficacy and feasibility of this technology for intracardiac application and its capability in high resolution imaging of endocardial structures. (5) In the recent times, the utility of this imaging modality in various interventional procedures has been investigated and its effectiveness in visualizing left atrial thrombi during ablative procedures has been demonstrated in observational studies. (6 -11) However, a prospective multicenter comparative study of these two imaging techniques is unavailable. Should ICE provide comparable imaging capabilities to TEE, the value of ICE guided cardioversion during invasive procedures can also then be systematically studied during a prospective multicenter clinical study.
The ICE CHIP study is a prospective open label randomized multi-center investigation performed in two phases designed to initially compare two distinct imaging modalities (Phase 1) and subsequently two different strategies (ICE guided Cardioversion and Conventional) in the management of AF in patients undergoing invasive cardiac procedures in whom electrical cardioversion is indicated (Phase 2).
In Phase I, each patient will be imaged by TEE \& ICE and a core echo laboratory will perform a blinded comparison of the two imaging modalities.
In Phase II, patients will be randomized to one of the two treatment groups. Investigators will be blinded to the method of management for each patient prior to their enrollment into the study. The composite incidence rate of major cardiac and bleeding complications (stroke, TIA, peripheral embolism, major hemorrhagic event) will be compared between the two treatment groups over the duration of the study.
In Phase 1, 100 patients will be enrolled at up to 12 investigational centers in USA \& Europe. Study patients will have clinically indicated a TEE procedure as well as an invasive cardiac procedure. Recordings from both imaging methods will be analyzed in an independent and blinded manner at the core laboratory. It is estimated that enrollment will take 3 months.
In Phase 2, a total of 300 patients (3:2 randomization) will be enrolled in the study at up to 15 investigational sites in USA and Europe. Patients with AF who require electrical cardioversion will be enrolled into the study. The study will last for 8 weeks for each subject, with an estimated overall duration of 12 months (8 months enrollment period, 2 months follow-up period, remaining time for close-out) for the study.
The pilot study design was selected in order to evaluate the comparative accuracy of ICE imaging and TEE as well as the feasibility of ICE guided management of AF. In Phase 1, the design will ensure that ICE imaging is not inferior to standard TEE for detection of left atrial pathology. In Phase 2, ICE imaging will be performed in patients prior to immediate electrical cardioversion to determine if it is equivalent to the conventional management strategy of electrical cardioversion after anticoagulation for 3 weeks prior to cardioversion.
Both the Phase I and Phase II studies will be open label. An open label study design is proposed because it is not possible to blind the clinicians, patients or the sponsor to the identity of the diagnostic technique in Phase I (ICE vs. TEE) and to management strategy in Phase II (ICE vs. Conventional Strategy). The ICE and TEE data analysis in the Phase I component by the core lab will be blinded in so far as the identity of the patient, investigator and center. In the Phase II study, patient randomization to the treatment groups will minimize the chance of patient selection bias. An 8-week study duration was chosen for the Phase II component because most major cardiac and bleeding complications occur within this period.
