In a late breaking session at the 2019 AF Symposium in Boston, USA (24–26 January), it was announced that a dipole density (DD) mapping and ultrasound imaging system to identify non-pulmonary vein (PV) targets in persistent atrial fibrillation (AF) performed safely and effectively, and with higher success rates than historical AF ablation trials. Results of the UNCOVER AF trial were presented by Atul Verma of Southlake Regional Health Centre (Newmarket, Canada).
“Based on initial results,” Verma comments, “mapping dynamic patterns during atrial fibrillation and ablating them, in addition to traditional pulmonary vein isolation, can produce higher success rates in persistent AF patients.” He continues that the AcQMap system (Acutus Medical) used in the investigation, and an iterative, patient-specific treatment approach “warrants additional investigation.”
The investigators describe how use of the AcQMap system with an iterative mapping, adaptive therapy approach resulted in 72.5% AF free, single procedure effectiveness at 12 months, and over 80% of subjects in this persistent AF patient population having no AF burden recorded over the total duration of 24-hour continuous monitoring at 12 months. Furthermore, they note that a decrease in arrhythmia burden was associated with symptom improvement, the ability to perform daily activities, and increased treatment satisfaction based on AFEQT scores.
Verma and colleagues continue comment that sinus rhythm at the end of the procedure was achieved in 98% of the patient cohort. The time to create atrial anatomy was 4.3 ± 2 minutes and the mean total procedure time was 4.1 ± 1.1 hours, they note, and on average, 5 ± 3.4 focal, localised rotational activity (LRA) and/or localised irregular activity (LIA) patterns were identified per patients with 4.2 ± 2.8 patterns ablated.
In addition, the investigators remark that AF freedom after one or two procedures was 93% (95% CI 97%–87.1%) at 12-months, and of the 96 patients who underwent a single procedure, 89.6% had zero episodes of AF lasting >30 seconds. After one or two procedures, 82.4% of patients experienced zero episodes of AF >30 seconds. Predictors of 12-month AF free success included ablating >3 focal, LRA or LIA patterns, with an odds ratio of 9.39 (2–44.1) and a p-value of 0.004, while ablation termination to SR predicted a three times greater likelihood of SR at 12 months (odds ratio 2.97 [1.06–8.29], p=0.3).
According to the authors, safety events were adjudicated by an independent clinical events committee (one European and two US physicians). They comment that “no major adverse events (MAEs) were adjudicated to be related to use of the AcQMap system,” however a total of three MAEs were adjudicated to be “probably related” to the procedure, including two instances of cardiac tamponade, and one of stroke, which was resolved after five days.
Verma and colleagues describe acute efficacy as the procedural conversion to sinus rhythm within 12 hours of index procedures. Safety outcome was defined as freedom from device or procedure related MAEs within 24 hours of the ablation procedures. Chronic effectiveness was defined as freedom from AF >30 seconds, on or off antiarrhythmic drugs (AADs) with single procedure and multiple procedures, or freedom from AF, atrial flutter (AFL), or atrial tachycardia (AT) > 30 seconds, on or off AADs with single procedure and multiple procedures.
According to the authors, this was the first use of the AcQMap system combining ultrasound-based anatomy and high-definition charge density non-contact maps to guide iterative ablation therapy in a prospective, single-arm, multicentre study in patients with persistent AF.
They describe the system as a “high resolution imaging and mapping system,” incorporating “a non-contact 3D electro-anatomic system capable of mapping all types of complex atrial arrhythmias; ultrasound anatomy reconstruction in as little as two minutes; full-chamber mapping, providing a clear view of cardiac activation; charge density mapping revealing conduction patterns in the substrate; and rapid re-mapping (1–2 minutes) allowing for a quick assessment of ablation effectiveness.” The system has received FDA clearance and CE mark approval.
All 127 patients in the UNCOVER AF trial presented with persistent AF, defined as lasting longer than seven days, but less than one year. In 13 centres across Europe and Canada, these patients underwent atrial mapping prior to PVI. The investigators describe how an imaging and mapping catheter reconstructed atrial anatomy and mapped the atria. High-resolution DD maps then identified localised focal, LRA and LIA conduction patterns, before PVI was performed using irrigated RF. Re-map and ablation continued until termination or elimination of all targets. Freedom from >30 second AF was measured at three, six, nine and 12 months using a continuous 24-hour electrocardiogram (ECG) recording, and AF burden was calculated as the total percentage of time in AF across total ECG monitoring time for all follow-up visits.
The authors hypothesised that “identification and elimination of non-PV targets may improve outcomes in patients with persistent AF.” The purpose of the UNCOVER AF trial was therefore to evaluate the safety and effectiveness of a non-contact ultrasound imaging and DD mapping system to identify non-PV sources during persistent AF ablation. The investigators also set out to demonstrate the value of real-time iterative mapping to guide an adaptive patient-specific therapeutic strategy.
Talking to Cardiac Rhythm News, Verma comments that “success rates in historical AF ablation trials were about 50 to 60% compared to the 70% demonstrated after one procedure in this trial.” Indeed, in the STAR AF II pulmonary vein isolation (PVI) trial, freedom from >30 second AF after one procedure, with or without AAD was 61% compared to 73% in the present trial, and freedom from >30 second atrial arrhythmias after one procedure, without AAD was 52% compared to 69%. A similar trend can be detected in the results for multiple procedures.
On the limitations of the results, he notes that “this was a non-randomised, single-arm trial” and that “head-to-head randomised comparison will be required for future studies to fully assess efficacy”.