REMEDIAL: AF Ablation Eases Anxiety, Depression

The randomized trial reinforces what many in the field had already believed based on clinical experience, one expert says.

REMEDIAL: AF Ablation Eases Anxiety, Depression

Performing catheter ablation for symptomatic atrial fibrillation (AF) has additional benefits beyond improving symptoms and lowering arrhythmia burden, according to the small REMEDIAL trial, which demonstrated reductions in anxiety and depression as well.

The average score on the Hospital Anxiety and Depression Scale (HADS), the primary endpoint, was significantly lower in the patients treated with ablation versus medical therapy alone by 6 months, a difference that was maintained out to 12 months, lead author Ahmed Al-Kaisey, MBChB (Royal Melbourne Hospital, Australia), and colleagues report in a study published online this week in JAMA.

At the same time, ablation was associated with reductions in AF burden and symptoms and in use of antiarrhythmic drugs (AADs) and beta-blockers.

“We weren’t terribly surprised by the results,” senior author Jonathan Kalman, MBBS, PhD (Royal Melbourne Hospital), told TCTMD, noting that patients referred for management of AF, as well as their spouses, often use words like anxious and depressed to describe the everyday impact of the arrhythmia. In fact, a 2018 study by his group found 35% of patients with symptomatic AF had severe psychological distress and one-fifth reported suicidal ideation.

Observational studies had hinted that AF ablation could mitigate some of these issues, but REMEDIAL was the first randomized test of the concept with psychological distress as a primary endpoint.

The benefit observed here is “strongly related to reduction in AF burden and improvement in physical quality of life and reduction in antiarrhythmic drugs with side effects,” Kalman said.

Commenting for TCTMD, Michael Shehata, MD (Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA), said he was impressed by the study, which “echoes the sentiment and the observations that many of us in the arrhythmia world have had for quite some time—that atrial fib does have a huge impact on psychological distress and mental health factors and that treating it, and treating it in a way potentially in which you eliminate some need for medication, has a big impact on people’s quality of life and their overall mental health.”


REMEDIAL, conducted at two Australian centers, enrolled 100 patients with symptomatic AF (mean age 59 years; 32% women), roughly half of whom (49%) had persistent AF. Patients randomized to ablation were treated with radiofrequency catheters, with successful pulmonary vein isolation achieved in all who underwent the procedure.

During the 12-month follow-up period, patients who underwent ablation were significantly less likely than those treated with medical therapy alone to have documented AF on monitoring (47% vs 96%) and had a lower median AF burden (0 vs 15.5%; P < 0.001 for both). Moreover, ablation-treated patients were less likely than controls to be taking an AAD (30% vs 85%) or a beta-blocker (4% vs 30%) at 12 months.

For the primary endpoint, the mean HADS score at 12 months was significantly lower in the ablation arm (7.6 vs 11.8; P = 0.005), with a difference observed for both the anxiety and depression components.

Secondary outcomes also favored ablation—there was a lower proportion of patients reporting severe psychological distress (10.2% vs 31.9%) as well as a lower mean Beck Depression Inventory-II score and University of Toronto AF symptom severity score.

“The REMEDIAL trial nicely demonstrates what happens when AF symptom burden is reduced: depression and anxiety symptoms concomitantly decrease while measures of quality of life significantly improve, promoting the freedom of patients to engage in physical and social activities,” Julia Lurz, MD (Heart Center Leipzig, Germany), and Karl-Heinz Ladwig, MD, PhD (Technical University Munich, Germany), write in an accompanying editorial.

Impact of Placebo Effect?

Lurz and Ladwig note, however, that the impacts on AF recurrence and quality of life observed in REMEDIAL are greater than what has been seen in prior trials like CABANA and CAPTAF, hinting that some of that could have been due to the open-label design of REMEDIAL.

“Potential disappointment about treatment assignment in the medical therapy group and high expectations for the benefits of the invasive procedure in the intervention (ablation) group could have fueled the success of catheter ablation also in terms of mental health criteria,” they write. “In line with this, it not surprising that depression and anxiety improved after catheter ablation irrespective of AF recurrences.”

Kalman acknowledged that there could have been a bit of a placebo effect at play since the trial was open-label, but said, “I think those of us in the field have seen the impact of this procedure on patients over time and that the impact is maintained over time and is very closely correlated with AF burden.”

Shehata, too, did not think that a placebo effect could fully explain the REMEDIAL findings, stating that the reductions in anxiety and depression were probably due to the combined impact of lessening AF burden and use of medications known to have mood-related side effects. He said the open-label design is a limitation of the study, though he added that “in an evidence-based, randomized way, they’re able to show that psychological distress as a primary outcome was significantly different. I still think there’s weight to that.”

Informing Clinical Decision-Making

Shehata said that when considering AF ablation, these results will provide “more evidence to give patients that over the long term that potentially the decreased use of antiarrhythmic drugs, the decreased use of oral anticoagulants, and the reduction in AF burden can lead them to have a better quality of life.”

The study may also help convince referring physicians to send their patients for specialty AF care earlier when they describe mental health issues related to their condition, Shehata added.

For Kalman, the findings have led the authors to talk about symptoms more holistically with patients. “We talk to them about the physical impact. We talk to them about the psychological and the emotional impact. And patients by and large are very grateful to have that conversation,” he said. Then, when considering whether a patient is feeling sufficiently symptomatic to warrant an interventional procedure, “we factor that in as an important part of that decision-making process.”

Lurz and Ladwig highlight the need for individualized treatment strategies in their editorial, urging physicians to be more attuned to “frequently concomitant depression, stress, and anxiety in patients with AF; to implement screening and assessment; and to initiate comprehensive and collaborative care,” they write. “This includes psychotherapeutic interventions, such as mind and body interventions with the prospect of releasing stress and balancing the autonomic system.”

Trials evaluating these types of approaches are not common, and “given the importance of comorbid mental health conditions for the long-term clinical course of AF, there is a need to prioritize this issue in future AF research,” they argue.

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • Al-Kaisey reports support from a National Health and Medical Research Council (NHMRC) research scholarship.
  • Kalman reports receiving support from a practitioner fellowship and grants from the NHMRC; having received research support from Biosense Webster and Medtronic; and having received grants unrelated to the current study from Medtronic, Mooney, and Biosense Webster.
  • Lurz and Ladwig report no relevant conflicts of interest.