Proposed Implementation of a Phase II Study

The goal of the development of this multimodal imaging system is not to replace electrical mapping as the gold standard for confirming block. Rather, ARFI imaging is meant to augment the procedure by monitoring lesion growth for safety and completeness and providing a visual means for assessing lesion continuity. This would reduce the number of times mapping would be required and should reduce the number of repeat procedures due to post-ablation electrical reconnection. We would envision ARFI being used to monitor lesion extent at some or all ablation sites. The sites that would be of particular importance would around the left inferior pulmonary vein. Sites here are particularly close to the esophagus where there are severe implications for over burning. ARFI would then be us ed to confirm line continuity and transmurality after the ablations have been completed.

A phase II application would propose a clinical study of ICE based ARFI image guided ablation therapy and would proceed with two clinical studies.

The first study would be very much like the study described in section D.4. It would be designed to not impact patient care by adding no time to procedures and by not changing the procedure normally used to determine lesion line continuity.

Consecutive patients undergoing ablation for atrial fibrillation would be enrolled. Circumferential pulmonary vein ablations would be performed guided by CARTO with ICE assistance placing the transseptal catheters. ARFI imaging would be used during any waiting periods during the procedure to characterize lesion lines. Each pair of lesions will imaged and graded as either incomplete or complete by an observer blinded to the mapping procedure. Once the lesions have been imaged, electrical pace mapping will be used to characterize conduction as is normally the case. As gaps are located and ablated their location will be noted as an incomplete gap. This process will be repeated until full electrical isolation has been achieved. Similar statistical evaluation of the lesions will be applied as described in D.4. This study will result in the sensitivity and specificity of ARFI for identifying incomplete lesion lines in patients compared to electrical mapping.

Providing the results of the first study indicate a high sensitivity and specificity, a second study would be performed in which procedure for care would be altered. It is thought this would be a multi-center trial. AF patients that are candidates for circumferential pulmonary vein ablations would be enrolled in the study and randomly assigned to a control or ARFI imaging arm. The patients would be followed for a period of a year following their procedure. In the control arm the ablation procedure would use current methods for creating and evaluating lesions. In the ARFI arm, lesions would be made with real time ARFI imaging and lines would be evaluated using ARFI imaging. Electrical mapping demonstrating complete block would be the procedure endpoint in both arms of the study.

All patients would follow the normal course of treatment for complications and post ablation care. Patients would be assessed at 6 weeks, 6 months and 1 y ear for the symptoms of AF. Procedure times and peri-ablation complications, and long term success (determined by alleviation of symptoms) will be compared between the two arms.