The PROMPT-AF trial, published in JAMA, reveals that a comprehensive ablation strategy, incorporating pulmonary vein isolation (PVI) with optimized linear ablation, significantly improves outcomes for patients with persistent atrial fibrillation (AF). The study, led by Sang et al., randomized 498 patients to either PVI alone or PVI plus linear lesions, including mitral isthmus ablation with ethanol infusion in the vein of Marshall (EIVOM), left atrial roof, and cavotricuspid isthmus ablation.
The trial demonstrated a 9.2% absolute risk reduction in the recurrence of atrial arrhythmia lasting 30 seconds or more in the comprehensive ablation group (hazard ratio 0.73, 95% CI, 0.54-0.99). While several secondary endpoints favored the linear lesion group, these differences did not reach statistical significance.
The Role of EIVOM
The PROMPT-AF trial underscores the value of EIVOM in enhancing the outcomes of persistent AF ablation. While EIVOM-specific mechanisms, such as parasympathetic denervation, may play a role, the results conceptually support the idea that improving the reliability of a lesion set—as EIVOM does for the mitral isthmus—can lead to better outcomes. This is particularly relevant given that previous trials, such as STAR-AF II, which tested similar lesion sets without EIVOM, yielded negative results. The addition of EIVOM and improved catheter technologies, like contact force sensing, appears to have improved the implementation and efficacy of the ablation strategy.
Limitations and Future Directions
Despite the promising results, the PROMPT-AF trial has limitations. The effects of the linear lesion set, while clinically relevant, were modest. Rhythm monitoring was conducted using a wearable single-lead monitor for 24 hours weekly, along with periodic Holter monitoring, but adherence was not universal. The study also employed an unconventional definition of persistent AF (AF of 3-month duration), and a higher proportion of patients in the lines group had long-standing persistent AF. The use of freedom from atrial arrhythmias lasting 30 seconds or more as the primary endpoint may only partially capture the clinically relevant effects of the procedure.
It remains unclear whether further advancements in ablation technologies will lead to continued improvements in outcomes for persistent AF. Pulsed field ablation, which uses nonthermal irreversible electroporation, has the potential to enhance ablative efficacy and may reduce risks associated with PVI. However, whether this will translate into better outcomes remains to be seen. EIVOM requires specialized technical expertise and is not universally available, and pulsed field ablation may offer an alternative for effective mitral isthmus ablation without the technical demands of EIVOM.
Implications for Clinical Practice
Ultimately, therapeutic success depends on the lesion set, not just the technology used to create it. A fixed lesion set, whether PVI alone or with add-ons, is unlikely to achieve universal AF cure unless mechanistically guided, individualized approaches are developed. As Miguel Valderrábano, MD, PhD, of Houston Methodist Hospital, notes, "Unless a more complete, individualized, mechanistic understanding of persistent AF guides our therapies, we will continue to be limited by the success ceiling of PVI and its add-ons."
