Experimental Design: Milestone 4

Milestone 4: Development of Ablation Procedures using ICE based ARFI imaging

The goal of these experiments are 1) to develop the in vivo procedures for visually characterizing lines of block using the combined ARFI imaging and CARTO systems, 2) to measure how frequently electrical block determined by pace mapping corresponds with ARFI image determinations of contiguous and transmural lesions, and 3) to show that gaps in an ablation line visualized with ARFI correspond anatomically with sites of electrical breakthrough that are in need of repair.

Twelve sheep will be prepped as described above. A 12 fr sheath will be inserted into each femoral vein and each external jugular for catheter access. Under fluoroscopic guidance, a 10 fr ICE imaging catheter (AcuNav, Seimens Medical) will be inserted and advanced to the level of the right atrium (RA). A 6 fr CARTO mapping and ablation catheter will be advanced to RA and approximately 50 position and electrical measurements made to characterize the shape and the conduction pattern of the RA. A 6 fr pacing catheter will be advance to the RA and positioned on the antero-lateral wall of the RA in the IVC-SVC junction. Pace mapping of the lateral wall will be conducted at a basic cycle length 2/3 of the normal sinus interval and at twice diastolic threshold. A line of ablation lesions will be made approximately 1.5 cm from the pacing lead and extending from the IVC to the SVC. Ablations will be performed at 55º C thermal controlled lesions for one minute. Lesions will be made at approximately 5 mm spacing. We will position the ICE catheter using the CARTO guidance of the image plane to image a cross section of the tissue below the ablation tip. Real time ARFI images of the ablations will be acquired and stored. These images will help us to assess the ability to characterize the lesions in real time. After the initial lesion is created, as each sequential lesion is made, a real time assessment of quality will be made by the person performing the procedure.

Immediately after the ablations have been completed, the ICE catheter will be used to again scan the lesions one segment at a time. The CARTO system will be used to align the imaging plane sequentially between each pair of lesions. B-mode and ARFI images will be made of each lesion and gap and an observer will assign a category of transmural or not transmural for each lesion and complete or incomplete for each pair of lesions. After the imaging is complete and at least 30 minutes after the lesions were made, pace mapping of the line will be conducted with the pacing and CARTO catheters. A second observer blinded to the ARFI results will assess the continuity of each pair of lesions based on the results of the maps. In our experience, electrical gaps or incomplete lesions will be identified in the line; however, if after one animal no gaps are found, the ablation lesion spacing will be increased by 1 mm. Each electrical gap or incomplete lesion demonstrated by electrical mapping will be repaired as it is located. This will simplify pace mapping of other gaps. The creation, ARFI imaging, pace mapping sequence will be repeated until the line shows complete electrical block.

This procedure will be repeated for an isthmus burn between the tricuspid annulus and the IVC. Following the isthmus burns, the ICE catheter will be used to guide the placement of a trans-septal sheath and the ablation and pacing catheter advanced to the left atrium. The imaging catheter will be placed in the coronary sinus and advanced to image the left atrium. A line of lesions will be made on the roof of the left atrium following the protocol described above.

At the end of the procedure, the animal will be euthanized and the heart removed and dissected to expose the lesions. The tissue will be labeled with clips to retain orientation. The lesions will be photographed on both sides and cut longitudinally bisecting the lesions. The cut surfaces will be labeled and photographed. The tissue will be fixed in formalin, stained and again photographed. A third observer blinded to the results of the ablations and mapping will assign a score to each lesion and gap. The sections will then be stored in formalin.

A contingency table will be made of the results of the rtARFI vs. mapping determinations of lesion assessment and a second of the ARFI and histological determinations. A Chi-Square analysis will be performed to determine if the frequency of concurrent determinations is significant (p<.05). Specificity and sensitivity of the ARFI determination of transmurality and continuity will be made using pace mapping as the gold standard.

All ARFI images and pace maps of lesions will be saved as will photographs of the lesions, a second blinded assessment will be made of each lesion and the analysis repeated and checked for consistency.