PVI Add-Ons Provide Better Control of Persistent AF

The addition of linear ablation plus ethanol infusion to pulmonary vein isolation (PVI) improves control of persistent atrial fibrillation (AF) better than PVI alone, a multicenter randomized trial shows.

With the two add-ons to PVI, “freedom from AF recurrences without anti-arrhythmia drugs was achieved in 70.7% of patients, compared to 61.5% assigned to PVI alone,” said Chenyang Jiang, MD, deputy director of the Cardiology Department at Sir Run Run Shaw Hospital at Zhejiang University in Hangzhou, China.

PVI is the “cornerstone” of catheter ablation for AF, but the benefits are substantially lower in patients with persistent AF than in those with paroxysmal AF, he explained during his presentation of the PROMPT-AF results in a latebreaker at the American Heart Association (AHA) Scientific Sessions in Chicago, which were simultaneously published online in JAMA. 

The strategy with the two add-ons showed greater efficacy with only a small potential cost in adverse events.

In the open-label PROMPT-AF trial, 498 patients from 12 participating hospitals in China were randomized to PVI alone or PVI plus linear ablation and ethanol infusion of the vein of Marshall. The primary endpoint was freedom from any atrial arrhythmias without the use of antiarrhythmic drugs for 12 months. 

Endpoint: No AF at 12 Months

Enrollment was open to patients with persistent AF, defined as lasting at least 3 months, that was refractory to at least one antiarrhythmic drug. Patients were excluded if they had previously undergone catheter ablation, had a left ejection fraction of ≤ 30%, and had a life expectancy of less than 1 year.

For participants randomized to receive the add-ons, the ethanol infusion procedure was performed first, followed by bilateral PVI and linear ablation at the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The PVI protocol was the same in both treatment groups and was performed with the same anatomical mapping system and devices.

When the add-ons were combined with PVI, there was a 27% risk reduction in the primary endpoint at 12 months compared with PVI alone (hazard ratio, 0.73; P = .045).

As an isolated secondary outcome, freedom from atrial arrhythmias at 12 months just missed statistical significance (73.2% vs 64.7%; P = .06). Other secondary outcomes — such as AF as a standalone endpoint (76.4% vs 69.9%; P = .14) and freedom from atrial arrhythmias irrespective of the number of ablations (77.6% vs 72.6%; P = .31) — favored the add-on group over the PVI-alone group numerically but not statistically. 

The overall incidence of procedure-related adverse events was higher in the add-on group than in the PVI-alone group (5.2% vs 2.4%). Although this difference was not significant, seven patients in the add-on group but no patients in the PVI-alone group experienced pericarditis or pericardial effusion. The overall rate of serious adverse events of any kind between the two groups did not differ significantly (P = .36).

PROMPT-AF Builds on Research

The PROMPT-AF trial builds on a series of previous studies that evaluated strategies to improve on PVI alone in patients with persistent AF. Although several studies have suggested that linear lesions modify the AF substrate and might be additive to PVI, a clinical benefit has not yet been demonstrated in a randomized trial. The failure of linear ablation to achieve a mitral isthmus block is one suspected explanation, Jiang explained.

Ethanol infusion, which involves creating chemical lesions that affect both the epicardial and endocardial mitral isthmus, did show a benefit over catheter ablation alone in the 2020 VENUS trial. The effect was modest (49.2% vs 38.0%; P = .04), but it provided the rationale for exploring how the combination of linear ablation and ethanol infusion could optimize the effect of PVI for persistent AF in the PROMPT-AF trial.

Overall, PROMPT-AF “validates the findings from VENUS” and might change the status of ethanol infusion alone or with linear ablation as add-ons to PVI in persistent AF, said to Jonathan P. Piccini, MD, director of cardiac electrophysiology at the Duke University Medical Center in Durham, North Carolina. 

The value of ethanol infusion is listed as an “area of uncertainty” in the joint 2023 guidelines from American College of Cardiology, AHA, American College of Clinical Pharmacy, and Heart Rhythm Society. But the PROMPT-AF results are meaningful and suggest that the linear ablation and ethanol infusion add-ons are an “important treatment option” for persistent AF, Piccini said.

However, the PROMPT-AF population was at relatively low risk for stroke, no data were provided on the effect of treatment on quality of life, and the rates of procedural complications were higher in the add-on group than in the PVI-alone group. All of these limitations should be considered when evaluating add-ons for PVI in specific patients, he pointed out. 

Some of the same points were made by Miguel Valderrábano, MD, PhD, chair of the Houston Methodist DeBakey Heart and Vascular Center, in an editorial that accompanied the publication of PROMPT-AF. 

He characterizes the improved control of persistent AF as incremental and “far from curative.” Despite recent technological advances that have improved the precision of fixed lesions for attenuating the AF substrate, a universal cure for persistent AF with this approach is unlikely, he explains.

“Even with improved lesion reliability, we are still facing the humbling fact that the mechanistic foundation of ablative strategies for persistent AF is speculative, simplistic, and incomplete,” Valderrábano notes.