Successful catheter ablation in a recent study may have helped alleviate anxiety or depression in patients with atrial fibrillation (AF) who had initially tested high for such psychological distress.
The finding, say researchers, may point to an overlooked potential benefit of ablation that can be discussed with patients considering whether to have the procedure.
Importantly, the 100 adults with symptomatic paroxysmal or persistent AF in the randomized trial weren’t blinded to treatment assignment, which was either ablation or continued medical therapy.
That leaves open the possibility that psychological distress improved in the ablation group not from any unique effect of ablation itself but because patients expected to benefit from the procedure.
The investigators acknowledge that their trial, called REMEDIAL, can’t rule out a placebo effect as part of the observed benefit. Indeed, studies suggest that there is a substantial placebo component of AF ablation — which, notably, is usually done to make patients feel better.
But the current findings are more consistent with the conventional view that patients feel better primarily because ablation reduces the AF causing their symptoms, the group says.
Psychological stress in the study started to fall early after the procedure and continued to decline consistently over the next 6 months (P = .006) and 12 months (P = .005), not a typical pattern for placebo, they observe.
Moreover, the mental health benefits “correlated very strongly” with less recurrent AF, reduced AF burden, and withdrawal of beta-blockers and anti-arrhythmic agents, outcomes that might be expected from ablation, said Jonathan M. Kalman, MBBS, PhD.
“Of course, I cannot say there is no placebo effect from having had the procedure, and maybe that something to consider,” but it’s probably not the main driver of benefit, he told theheart.org | Medscape Cardiology. The relationship between successful AF ablation “and improvements in physical and now mental health is overwhelming.”
Kalman, who is affiliated with Royal Melbourne Hospital, Parkville, Victoria, Australia, is senior author on the study, published September 12 in JAMA. The study’s lead author is Ahmed M. Al-Kaisey, MBChB, of the same institution.
The findings add to “strong, reproducible evidence that ablation is the best way to tackle rhythm control in atrial-fib populations” regardless of age, mental-health status, or AF burden, said Auroa Badin, MD, who wasn’t involved in REMEDIAL but has studied the psychological effects of arrhythmia ablation.
For example, there is “very good evidence” from CABANA and other trials that AF ablation “considerably improves quality of life,” Badin, of OhioHealth Heart & Vascular Physicians, Columbus, told theheart.org | Medscape Cardiology. The current study “just emphasizes that there’s also a psychological effect.”
Some of that response could be a placebo or even a nocebo effect. Most of the patients assigned to the medical arm had already been on medications that failed at rhythm control. And their management in the trial, he said, “even if you optimize it, was still drug therapy.”
Patients in the control group, therefore, could have been “disappointed” at the prospect of continued ineffective therapy in a way that influenced their outcomes. “That is another confounding factor,” Badin said.
But if the psychological results of ablation in the trial were predominantly a placebo effect, early differences in psychological test scores would not have persisted for long, certainly not for a year, he observed. Moreover, the ablation group had better test scores at 12 months than at 6 months, “indicating a likelihood of improvement over time.”
Differences between the groups would probably have been less pronounced if the control group had received a sham procedure, Badin proposed. That would potentially differentiate ablation’s clinical and placebo contributions to the outcomes.
Still, he said, any observed placebo effect in a sham-controlled trial would probably have been limited. “I think it still would have been a positive trial. It may not show the same difference, but I don’t think you would have a neutral trial just by doing a sham.”
REMEDIAL has “good data,” and its conclusions about ablation’s potential psychological benefits are “reasonable” and worth bringing up when discussing the procedure with patients, Badin said.
Indeed, psychological distress is “important and often overlooked” in patients with AF, Kalman observed. “The dominant indication for atrial fibrillation ablation is symptomatic impact on quality of life. We should think about that broadly, about not just the physical symptoms but the impact on their mental health.”
The trial was conducted at two centers in Australia. It enrolled patients, one third of whom were women, who were on medical management for AF. Patients receiving treatment for severe depression were excluded. The included patients were randomly assigned to undergo catheter ablation or to continue on closely managed rhythm-control meds, with cardioversion as indicated.
Psychological distress was measured at baseline and throughout follow-up by a battery of self-administered, validated questionnaires. Baseline test scores for the two groups were similar.
Recurrence and burden of AF were tracked primarily by daily KardiaMobile (AliveCor) ECG monitoring. A few patients were followed using already implanted cardiac rhythm devices or by 24-hour Holter monitor every 3 months, Kalman said.
Composite scores on the Hospital Anxiety and Depression Scale (HADS) at 12 months, the primary endpoint, were 7.6 and 11.8 (P = .005) for the ablation and medical groups, respectively. They were 8.2 and 11.9 (P = .006), respectively, at 6 months.
The prevalence of severe psychological distress, defined as a HADS score > 15, was lower in the ablation group at 6 months (14.2% vs 34%; P = .02) and 12 months (10.2% vs 31.9%; P = .01).
Scores on the Beck Depression Inventory-II questionnaire were also consistently and significantly better for the ablation group at 6 and at 12 months (P = .01 for both).
Monitoring picked up AF in 47% of the ablation group and 96% of the control group (P < .001) over 12 months. Their median AF burdens were 0% (interquartile range [IQR], 0%-3.2%) and 15.5% (IQR, 1%-46%), respectively (P < .001).
Antiarrhythmic drug use fell from a baseline of 90% to 53% 3 months after ablation and 30% at 12 months (P = .003). Use of these drugs in the control group was 89% at baseline and remained essentially the same, 85%, at 12 months.
AF symptom severity scores were significantly lower after ablation compared with medical management at 3, 6, and 12 months.
The observed effect of ablation on psychological stress “clearly speaks in favor of effective rhythm control, and moreover catheter ablation” and is a “novel argument” in support of catheter ablation for AF, states an editorial accompanying publication of REMEDIAL.
But the findings also “raise the question of why rhythm control was so ineffective in the medical treatment group,” write Julia Lurz, MD, Heart Center Leipzig at University Leipzig, and Karl-Heinz Ladwig, MD, PhD, Technical University Munich, Germany.
They agreed that the randomization process itself may have had its own psychological effects. “Potential disappointment” in the medical group and “high expectations” among patients who received ablation “could have fueled the success of catheter ablation” with respect to mental health endpoints.
Kalman reports receiving grants from the National Health and Medical Research Council of Australia, Medtronic, Mooney, and Biosense Webster; disclosures for the other authors are in the report. Badin has recently declared no conflicts. Lurz and Ladwig report no conflicts of interest.
JAMA. Published online September 12, 2023. Full text; Editorial
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