Afib Ablation Falls in New Sham-Controlled Trial

Some techniques of catheter ablation for atrial fibrillation (Afib) did not hold up under scrutiny in new randomized trials, researchers reported at the European Society of Cardiology (ESC) Congress.

For one, the fundamental strategy of pulmonary vein isolation (PVI) had a stumble in the sham-controlled PVI-SHAM-AF trial.

Among people with symptomatic paroxysmal or persistent Afib, the Atrial Fibrillation Effect on the Quality-of-life Questionnaire (AFEQT) summary score increased from a mean 61.3 points at baseline to 81.1 points at 6 months after PVI, and from 59.2 points to 74.9 points in the sham control group. The between-group difference in these increases was not enough to indicate superiority for the ablation group (P=0.36), according to Rolf Wachter, MD, from University Hospital Leipzig in Germany.

In defense of catheter ablation, the trialists had cardioverted participants during either study procedure if they were in Afib, and several other factors are suggested to explain the trial’s departure from prior, more positive sham-controlled studies in this population.

In separate reports also presented at the ESC meeting, researchers explored other adjunctive strategies to catheter ablation in people with persistent Afib.

Low-voltage zone ablation had a win by safely improving rhythm outcomes and quality of life in IDEAL-AF, whereas posterior left atrial wall isolation (PWI) using pulsed field ablation failed to reduce atrial tachyarrhythmias in the PIFPAF-PFA trial.

Together the PIFPAF-PFA and IDEAL-AF trials “provide important insights” into improving outcomes with catheter ablation in persistent Afib, commented Peter Kistler, MBBS, PhD, and David Chieng, MBBS, PhD, both from the University of Melbourne and Monash University in Australia.

“Ultimately, the jury remains out on whether a tailored or empirical ablation strategy will improve outcomes in patients with persistent atrial fibrillation, but with better, more detailed mapping and large-footprint dual-energy technology, the future is bright,” they concluded in an editorial published in JAMA.

PVI-SHAM-AF

PVI-based catheter ablation failed to significantly improve Afib-related quality-of-life measures over a sham procedure in the PVI-SHAM-AF trial, which was simultaneously published in The Lancet.

However, the procedure did significantly reduce the likelihood of Afib recurrence detected on 7-day Holter electrocardiography (ECG; 21% vs 41%; adjusted difference 20.1%, 95% CI -32.6 to -7.7) and the Afib burden at 6 months (average 11.6% vs 23.6% of time in Afib, adjusted difference -11.9%, 95% CI -21.0 to -2.8).

“Symptomatic improvement observed after ablation and improvement in [Afib] recurrences and burden are distinct, and symptomatic improvement cannot necessarily be attributed entirely to the ablation procedure,” Wachter said. “Sham-controlled trials for well-established cardiovascular procedures are feasible, and I think they provide important information.”

The PVI-SHAM-AF findings differ from previous sham-controlled catheter ablation studies, SHAM-PVI and PFA-SHAM, both of which showed greater improvement in Afib-related quality of life with ablation than with the sham procedure.

“However, the trials were small and differed in patient selection, ablation method, masking, endpoint hierarchy, and rhythm-monitoring methods,” Wachter’s group noted in their manuscript.

ESC session discussant Harry Crijns, MD, from the Cardiovascular Research Institute Maastricht in The Netherlands, also suggested placebo effects, regression to the mean, and low baseline symptom burden, as factors that would tend to favor the sham procedure and explain PVI-SHAM-AF’s divergent findings.

Importantly, baseline AFEQT scores were significantly higher in PVI-SHAM-AF than in the previous trials, “and this relatively preserved quality of life at baseline may have precluded the differential effect” of ablation compared to sham, Crijns pointed out.

In the end, Kistler and Louise Segan, MBBS, PhD, of the same institutions, suggested that PVI-SHAM-AF does not challenge the efficacy of PVI by catheter ablation.

Of note, both patient groups had been cardioverted during the study procedure if they were in Afib. Thus, unlike sham procedures in other interventional trials, the comparator in PVI-SHAM-AF included an active rhythm-control intervention. “The study therefore estimates the incremental benefit of atrial fibrillation ablation beyond temporary rhythm control, not simply beyond placebo,” Segan and Kistler wrote in a separate accompanying comment.

“The weight of evidence and efficacy in rhythm restoration including sham-controlled trials supports the role of catheter ablation to improve symptoms and quality of life in appropriately selected patients with atrial fibrillation,” the duo concluded.

PVI-SHAM-AF was a double-blind, randomized trial conducted at nine sites in Germany and Poland. A total of 262 patients with symptomatic paroxysmal or persistent Afib were randomized in a 2:1 ratio to PVI by catheter ablation or a sham procedure.

One death occurred in each group; neither was considered related to the study procedure.

IDEAL-AF

IDEAL-AF, simultaneously published in JAMA, assessed whether adding individualized low-voltage zone ablation to PVI would improve arrhythmia outcomes and quality of life for patients with persistent Afib and significant low-voltage zones.

In this multicenter, randomized trial of 209 patients with low-voltage zones on voltage mapping, freedom from documented arrhythmia at 12 months was seen in 67.6% of patients treated with adjunctive low-voltage zone ablation and 37.4% of those treated with PVI alone (P<0.001).

For these patients, “adjunctive low-voltage zone ablation improves rhythm outcomes and quality of life without increasing serious adverse events, and should be considered as an adjunctive ablation strategy,” Astrid Paul Nordin, MD, PhD, from Karolinska Institutet in Stockholm, said during her presentation.

Paul Nordin noted that in current practice, while ablation outcomes in patients with persistent Afib remain “suboptimal” with about 60% remaining free of atrial arrhythmia after the procedure, outcomes are “even worse” for patients with low-voltage zones — considered a surrogate marker for atrial fibrosis — where only 27% to 43% remain arrhythmia-free after PVI.

PIFPAF-PFA

Another trial looked at whether adding PWI to PVI using pulsed field ablation would reduce atrial tachyarrhythmias in patients with persistent Afib.

However, the results of PIFPAF-PFA (also published in JAMA) ultimately showed adding PWI did not significantly reduce atrial tachyarrhythmia recurrence lasting 30 seconds or longer (50.6% vs 60.6%, P=0.13), the primary endpoint of the 206-person trial.

Investigators did see a lower arrhythmia burden and fewer recurrences of longer duration with treatment, both secondary endpoints, but these findings “are hypothesis generating, and warrant further evaluation in a larger trial,” Laurent Roten, MD, of Inselspital Kardiologie in Bern, Switzerland, and colleagues concluded.

The PIFPAF-PFA trial, “may temper the enthusiasm for PWI by some electrophysiologists given that the primary endpoint of recurrence was not significantly different, while others may choose to embrace the increasingly accepted secondary endpoint of atrial fibrillation burden,” Kistler and Chieng wrote in their editorial. “IDEAL-AF, with its stricter trial design, shifts support toward atrial mapping and individualized adjunctive low-voltage zone ablation, present in a minority of patients.”