Modifying PVI Lines to Incorporate Non-PV Targets Identified by Pre-Ablation Mapping with the AcQMap System: Update on the UNCOVER-AF Trial

We recently enrolled the first patient in the Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation (UNCOVER-AF) trial, being conducted in Europe and Canada. UNCOVER-AF is a prospective, single-arm, multicenter trial evaluating the safety and effectiveness (at 6 and 12 months) of the AcQMap^® High Resolution Imaging and Mapping System (Acutus Medical) for ablation of persistent atrial fibrillation (AF).

Introduction

Ablation strategies in AF, regardless of disease state, are moving toward a ‘pulmonary vein isolation (PVI) only’ approach. The results of the recent STAR AF II trial demonstrated that patients with persistent AF who only underwent PVI had better outcomes (59%) than patients who received either the addition of a set of linear lesions (46%) or complex fractionated electrogram ablation (49%).¹ Rotor mapping and body surface mapping methods have recently been introduced to identify targets beyond the pulmonary veins to guide ablation strategies. However, results for rotor mapping have been mixed, reporting that 12-70.6%^2-4 were AF free at one year. A single-center study reported 64.4% were AF free at one year with body surface mapping.⁵

While regularly used during AF ablation procedures, sequential voltage-based mapping systems are indeterminate of AF mechanisms and unable to display the continuous activation that is characteristic of AF. We herein report on the use of a global, instantaneous non-contact imaging and mapping system that uses dipole density to identify activation in the myocardium for the purpose of mapping all atrial arrhythmias, including atrial fibrillation, and guiding ablation therapy. 

About the System 

The AcQMap High Resolution Imaging and Mapping System (Acutus Medical) provides heart chamber reconstruction using 3D ultrasound overlaid with high-resolution maps of electrical activation either as dipole density or voltage. Cardiac voltage arises as a spatially broad summation of local, dipolar charge sources generated by the action of cellular ion channels throughout the myocardium. Dipole density mapping (µCoulombs/cm) represents the magnitude of these sources on the endocardial surface of the chamber with a view of cardiac activity that is at least four times sharper and narrower than voltage.⁶ (Figure 1) The AcQMap System derives dipole density from non-contact sensing of cardiac voltage within the chamber cavity. The result is an instantaneous, global view that captures the conduction pattern of every activation cycle and enables mapping of both stable and unstable arrhythmias. 

The diagnostic recording catheter (AcQMap 3D Imaging and Mapping Catheter, Acutus Medical) is deployed by the user as a spheroid with six splines. Each spline is populated with eight ultrasound transducers and eight biopotential electrodes, resulting in a total of 48 of each type of sensor. The entire endocardial surface is sampled by the ultrasound sub-system at a rate of up to 115,000 surface points per minute. The 3D surface is algorithmically reconstructed from the ultrasound point-set. The reconstructed atrial chamber is a surface mesh composed of more than 3,600 triangles. Cavitary unipolar voltage is sampled at a rate of 150,000 per second to map cardiac activity. 

Inverse and forward algorithms are applied to the intracardiac voltage to derive and display 3D maps of dipole density and voltage, respectively. The calculated data is spatially and temporally applied to the final processed surface anatomy as a propagation-history map, in which the red band represents the leading edge of the activation wavefront and the trailing color bands retain earlier locations of the wavefront over a set period of time. (Figure 2)

Sample Case 

A 70-year-old male with documented hypertension, polymyalgia rheumatica, and chronic renal disease, developed highly symptomatic persistent AF. He had undergone 5 electrical cardioversions between 2011 and 2016. His visually estimated left ventricular ejection fraction was 55-60%, with a normal left atrial (LA) dimension of 3.8 cm and LA volume indexed biplane of 32.1 ml/m². At the time of the procedure, the patient was receiving a number of drugs, including warfarin for thromboprophylaxis and sotalol 80 mg b.d. for both rhythm and rate control, and had recently reverted to AF. The patient was consented for the UNCOVER-AF study and presented for the procedure in AF.

The predefined study protocol procedural flow was as follows: 

• Build ultrasound-based anatomy;
• Map AF prior to any ablation;
• Identify sites of interest/AF patterns;
• Customize PVI to include targets within ~1 cm of the anatomic ‘standard’ position;
• Perform PVI and confirm isolation in AF. If patient converts to sinus rhythm during PVI, re-induce AF; 
• Remap, identify, and ablate any new or remaining targets;
• Remap until the AF converts or organizes with CL prolongation, or AcQMap remap shows no additional targets.

The initial map clearly showed on the posterior wall inferior to the left inferior pulmonary vein (LIPV) a single dominant localized irregular activation (LIA) that occasionally alternated into a rotational conduction pattern through the same site. (Figure 3). It was determined that the central point of the LIA was sufficiently close to be incorporated within a somewhat modified PVI line. An irrigated bi-directional D-F curve ablation catheter was localized and visualized on the AcQMap System. Standard protocol at the hospital is to deliver 25 watts to the posterior wall and 30 watts elsewhere in the left atrium. A circular mapping catheter was also visualized and later used to confirm pulmonary vein isolation.

PVI, using an irrigated bi-directional D-F curve ablation catheter, was started at the posterior roof aspect of the left superior pulmonary vein (LSPV). Contiguous ablation lesions were placed down the posterior wall and as per protocol, took a ~1.5 cm wider deviation below the LIPV. (Figure 4) Approximately 45 seconds after passing through the center of the AcQMap-identified LIA target, the patient converted into sinus rhythm. Rapid burst pacing was used to re-induce, but only resulted in non-sustained AF of <15 seconds’ duration. The remaining veins were subsequently isolated, and pacing was used to verify entrance and exit block. 

The patient recovered well from the procedure, and was in sinus rhythm at 3-month follow-up. 

Discussion

Pulmonary vein isolation, whether accomplished point-by-point or by single-shot devices such as the cryoballoon, is an anatomically based ablation strategy. In the case described above, we demonstrate how mapping with the AcQMap System, prior to ablating, led to adjusting the PVI line to incorporate an identified LIA target, resulting in termination to sinus rhythm during energy delivery. The ability to visualize the location of the non-PV target prior to ablation ensured that the target was incorporated as part of the PVI strategy. Without AcQMap guidance, chance alone could still have possibly provided the same outcome. 

For this very reason, when coupled with the clinical results from STAR AF II, it is not surprising that the most recent clinical update on catheter ablation in patients with persistent AF states that “Pulmonary vein isolation is a reasonable and often sufficiently effective ablation strategy in patients undergoing a first catheter ablation of persistent AF. Additional ablation targets should in our view not routinely be pursued in the first procedure.”⁷ However, this case provides a compelling example where a precise knowledge of a target outside the pulmonary veins and proactive adjustment of the PVI can quite clearly obviate the need for additional ablation procedures. 

Initial mapping studies with the AcQMap System have shown that most persistent AF patients have more than one site of interest located beyond the pulmonary veins. The most frequently mapped activation patterns have included focal sites, localized rotational activation (LRA) sites, and LIA sites (Figure 5). These sites were located throughout the left atrium, with the highest incidence in and around the LSPV and right inferior pulmonary vein and adjacent posterior wall. (Figure 6)

The UNCOVER-AF study is designed to evaluate the safety and effectiveness of the AcQMap System to identify and guide ablation of targets outside the pulmonary veins in persistent AF patients. The trial is rigorously designed with inclusion/exclusion criteria common to other important ongoing studies in Europe and the United States. The procedural protocol requires an initial mapping in AF, followed by PVI and then remapping and ablation of any remaining identified targets. The ability of the system to efficiently and repetitively acquire activation data, enables a map, ablate, and remap procedural flow that breaks down the spatial complexity of conduction and allows sequential assessment of therapy effectiveness. Patients in the study will be followed for 12 months post ablation, inclusive of a 3-month blanking period, and outcomes will be assessed both on and off antiarrhythmic drugs. Outcomes will be compared to the results of all relevant published patient cohorts treated with PVI only. Study results will be available in mid 2018.

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Disclosure: Dr. Grace has no conflicts of interest to report regarding the content herein. Outside the submitted work, he discloses he is a member of the Scientific Advisory Board of Acutus Medical Inc. He is also a member of the Patient Safety Advisory Board of Boston Scientific and the Translational Awards Committee of the British Heart Foundation. 

References

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