Atrial fibrillation (AF), the most common cardiac arrhythmia, significantly increases the risk of stroke. Catheter ablation is an effective treatment, but outcomes are suboptimal in patients with persistent AF due to challenges in creating durable lesions. Conventional radiofrequency ablation uses a mapping catheter and a separate ablation catheter, resulting in a point-by-point approach that is time-consuming and may leave gaps in lesion sets, leading to recurrence. This necessitates creating contiguous lesions without gaps, a technically challenging task. Large-tip catheters, capable of creating wide-footprint lesions, aim to increase ablation effectiveness and efficiency. This study investigated a novel dual-energy lattice-tip catheter that integrates high-density electro-anatomical mapping with both radiofrequency and pulsed field ablation (PFA) energies in a single catheter. PFA, a non-thermal ablation method, offers the potential for minimizing damage to adjacent non-cardiac structures. Preclinical and initial human studies suggested superior lesion creation and faster PVI with this technology. This randomized trial aimed to evaluate the safety and effectiveness of this dual-energy system compared to standard radiofrequency ablation in patients with drug-refractory persistent AF.

Numerous studies have shown the effectiveness of catheter ablation in treating atrial fibrillation, particularly paroxysmal AF. However, treating persistent AF presents greater challenges due to a more complex arrhythmogenic substrate. Conventional radiofrequency ablation, while effective in some patients, suffers from limitations such as the difficulty of creating contiguous lesions, leading to conduction gaps and recurrence. The technical challenges of achieving complete pulmonary vein isolation (PVI) and the risk of complications such as atrio-esophageal fistula and phrenic nerve injury further limit success rates. The use of two catheters (one for mapping and one for ablation) adds to the procedural complexity and cost. 'Single-shot' ablation catheters have been developed to simplify PVI, but they often fall short in addressing the more extensive ablation needs of persistent AF. The development of new technologies, such as pulsed field ablation (PFA), aims to address these limitations. PFA's non-thermal mechanism is thought to preferentially affect myocardial tissue while minimizing damage to adjacent structures. Previous studies have indicated the potential benefits of PFA in creating larger, more durable lesions.

SPHERE Per-AF (NCT05120193) was a prospective, multicenter, randomized, single-blind, non-inferiority trial. 469 patients with symptomatic, drug-refractory persistent AF were screened, and 432 were randomized (1:1) to receive ablation with either the investigational dual-energy lattice-tip catheter system (Sphere-9 catheter with Affera Mapping and Ablation System, Medtronic) or a conventional radiofrequency ablation system (Carto3 system with THERMOCOOL SMARTTOUCH catheter, Biosense Webster). After accounting for dropouts, 420 patients (212 investigational, 208 control) underwent ablation. Baseline characteristics were similar between groups. The investigational system used a single catheter for both mapping and ablation, employing either radiofrequency or pulsed field energy as determined by the operator. The control group used standard mapping and ablation catheters. The primary effectiveness endpoint was a composite of freedom from acute procedural failure, repeat ablation, arrhythmia recurrence, drug initiation/escalation, or cardioversion after a 3-month blanking period. The primary safety endpoint was freedom from serious procedure-related or device-related adverse events. Patients were followed for 1 year with regular clinical visits and remote monitoring. Statistical analysis used the Farrington-Manning method for non-inferiority testing.

The primary effectiveness endpoint was met, with a success rate of 73.8% in the investigational arm versus 65.8% in the control arm (P<0.0001 for non-inferiority). The 1-year Kaplan-Meier estimates were 73.5% and 65.2%, respectively. The difference in the primary effectiveness endpoint was 8.0% (95% CI: -0.9% to 16.8%). The primary safety endpoint showed non-inferiority, with a low rate of major complications in both arms (1.4% investigational, 1.0% control, P<0.0001 for non-inferiority). There were no cases of atrio-esophageal fistula, PV stenosis, tamponade, or permanent phrenic nerve paralysis in either arm. Secondary analyses showed significant superiority for the investigational system in procedural efficiency, with shorter total energy application time (7.1 ± 2.0 min vs 36.4 ± 17.7 min, P<0.0001), shorter transpired ablation time (46.7 ± 20.0 min vs 73.5 ± 34.4 min, P<0.0001), and shorter skin-to-skin procedural time (100.9 ± 30.8 min vs 126.1 ± 49.2 min, P<0.0001). The investigational arm also demonstrated lower fluoroscopy use and fluid delivery. A post-hoc analysis of PVI durability showed superior results with the investigational device. A neurological substudy revealed a low rate of FLAIR-hyperintense acute lesions (8%).

This study demonstrates the non-inferiority of a novel dual-energy lattice-tip catheter ablation system compared to standard radiofrequency ablation in patients with persistent AF. The significantly shorter procedural times and the low rate of major complications suggest improved efficiency and safety. While the study did not demonstrate superiority in the primary effectiveness endpoint, the observed trend toward improved effectiveness, combined with the significant gains in procedural efficiency, supports further investigation of this technology. The results are promising given the historically suboptimal outcomes observed in trials of persistent AF ablation. The superior procedural efficiency offers several potential benefits: reduced patient exposure to fluoroscopy and radiation, decreased procedural costs, and potentially increased patient comfort. The ability to toggle between radiofrequency and pulsed field ablation offers flexibility in lesion creation and may contribute to improved safety, especially in sensitive areas such as the posterior left atrium. The lower rate of complications compared to some previous studies may reflect the experience of the operators and the intuitive design of the investigational device.

The SPHERE Per-AF trial demonstrated the non-inferior safety and effectiveness of the dual-energy lattice-tip catheter for the treatment of persistent atrial fibrillation, with significant advantages in procedural efficiency. Further large-scale, real-world studies are needed to confirm these findings and assess the long-term impact of this technology on patient outcomes. Future studies should also focus on optimizing ablation strategies and exploring the potential of this system in different AF patient populations.

Several limitations should be considered. The study lacked continuous invasive monitoring, potentially underdetecting asymptomatic atrial tachyarrhythmias. While the randomization should mitigate the effect on the study results, the possibility of underdetection exists. Although the ablation protocol was standardized, the high rate of additional ablation lines, especially in the investigational arm, introduces some heterogeneity. The study was not powered to assess the impact of additional lines on outcomes, so further investigation on that aspect is warranted. The relatively small number of centers participating might also limit the generalizability of findings. Finally, longer-term follow-up is needed to assess the durability of the ablation results over time.