By Michael H. Crawford, MD, Editor
SYNOPSIS: A randomized trial of catheter ablation vs. medical therapy for atrial fibrillation (AF) patients has shown that anxiety and depression scores are significantly reduced by catheter ablation and are associated with decreases in AF burden and improved physical symptoms.
SOURCE: Al-Kaisey AM, Parameswaran R, Bryant C, et al. Atrial fibrillation catheter ablation vs medical therapy and psychological distress: A randomized clinical trial. JAMA 2023;330:925-933.
Catheter ablation for atrial fibrillation (AF) has been shown to be superior to medical therapy for relieving physical symptoms and improving quality of life, but less is known about its effect on psychological distress, such as anxiety and depression. Thus, Al-Kaisey and colleagues conducted the Randomized Evaluation of the Impact of Catheter Ablation on Psychological Distress in Atrial Fibrillation (REMEDIAL) trial from 2018-2021.
REMEDIAL was a randomized trial with a blinded evaluation of outcomes conducted in two centers in Australia. Entry criteria included paroxysmal or persistent AF, eligibility for receipt of at least two antiarrhythmic drugs, and no severe depression. Radiofrequency ablation was performed within one month of randomization. Oral anticoagulation was mandated for a minimum of three months post-ablation. Antiarrhythmic drugs were continued during this period, then stopped. Rhythm monitoring was done twice daily by the KardiaMobile device, an implanted loop recorder, or 24-hour Holter monitoring at three, six, and 12 months. AF recurrence was defined as > 30 seconds in duration, and AF burden was expressed as the estimated percentage of time the patient had AF for 24 hours during the monitoring period.
Psychological distress was measured by self-administered questionnaires at three, six, and 12 months using the Hospital Anxiety and Depression Scales (HADS) and the Beck Depression Inventory-II (BDI-II) score. A HADS score ≥ 7 indicates psychological distress (range 0-42) and a score ≥ 15 indicates severe distress. The minimal HADS score for a clinically significant difference is 1.7. In the BDI-II score for depression, a score > 13 is mild depression, > 19 is moderate, and > 28 is severe (range 0-63). Also, the University of Toronto AF symptom severity score (AFSSS) was assessed. The primary outcome of the study was the HADS score at 12 months.
Of the 100 patients enrolled in the study, four were lost to follow-up or withdrew, resulting in 49 patients in the ablation group and 47 patients in the medical therapy group. Also, five patients crossed over study groups, but the trial analysis was on the intention-to-treat basis. The mean age of the patients was 59 years, 32% were women, and 49% had persistent AF. Ablation was successful in 100% of the assigned patients. The median AF burden in the ablation group was significantly less than that in the medical group (0% vs. 15.5%, P < 0.001). At baseline, the HADS scores were identical (12) for the ablation group and the medical group. At 12 months, HADS was significantly lower in the ablation group (7.6 vs. 11.8, P = 0.005), as were both components of the HADS, anxiety (4.5 vs. 6.6, P = 0.01) and depression (3.1 vs. 5.2, P = 0.004).
Also, the BDI-II score was not significantly different between the two groups (11 vs. 12.7), but at 12 months it was lower in the ablation group (6.6 vs. 10.9, P = 0.01). In addition, the AFSSS was not significantly different between the two groups (14 vs. 16) but was at 12 months (8.1 vs. 12.7, P = 0.005). The authors concluded that catheter ablation, but not medical therapy, significantly reduced psychological distress in patients with symptomatic AF.
COMMENTARY
Even though patients with severe depression were excluded, the mean baseline psychological distress score (HADS for anxiety plus depression) was severe in 32%. It is not clear whether the researchers targeted patients with psychological distress or if this represents the usual psychological state of patients with AF. Regardless, significant improvements in psychological distress were observed in the ablation group compared to the medical therapy group by six months and persisted for 12 months. This difference was associated with a reduction in AF and its physical symptoms.
However, other factors also could have played a role. The use of beta-blockers and antiarrhythmic drugs decreased in the ablation group but not in the medical therapy group, where beta-blocker use actually increased. These drugs are known to have adverse psychological effects in some patients. Also, the reduction in the physical symptoms of AF may have allowed the ablation patients to exercise more. In addition, these improvements were observed despite fixed personality-based traits that make patients vulnerable to anxiety and depression.
There are limitations to this study. It was not blinded but blinding would require a larger study with a sham procedure, which would be challenging. Although rhythm monitoring was intense, it may not have captured all asymptomatic AF events. The seasons during which the study was conducted are not described, and it is possible that seasonal affective disorder could have skewed the results. Finally, it was conducted in Australia, and no description of the ethnic and racial characteristics of the study group is provided. Presumably it was mainly white Australians and, if so, the results may not apply to other groups.
The REMEDIAL study highlights the negative mental health effects of AF and supports the conclusion that ablation is a better approach to relieving symptoms of anxiety and depression associated with AF than medical therapy alone. Interestingly, in the current guidelines, medical therapy is a class IA recommendation for maintaining sinus rhythm in AF. Perhaps this study will help stimulate a reevaluation of the optimal therapy for AF.
