Atrial Fibrillation and Dementia: New Findings in Risk of Dementia in AF Patients Undergoing Catheter Ablation vs Antiarrhythmic Drug Therapy

In this interview, EP Lab Digest speaks with Emily P. Zeitler, MD, MHS, about new research¹ comparing the risk of dementia in patients with atrial fibrillation (AF) who were treated with catheter ablation vs antiarrhythmic drugs, showing that catheter ablation was associated with a significantly lower risk of dementia in AF patients compared to treatment with antiarrhythmic drugs alone. Dr Zeitler is an Assistant Professor of Medicine at the Geisel School of Medicine at Dartmouth and The Dartmouth Institute.

Please introduce yourself and the focus of your work.

I am Emily Zeitler, an assistant professor of medicine at Dartmouth in New Hampshire. I also have an appointment at the Dartmouth Institute, which is where I do a lot of my outcomes-based research related to electrophysiology (EP) questions.

Describe key findings and take-home points of your research.  

My work in the past has focused on a variety of topics within EP, mostly related to outcomes-type questions, including clinical outcomes in groups that either are not well represented in clinical trials or questions that are not well answered in clinical trials, ever or yet. So, the work that we will talk about today falls into that latter category, which is a clinical outcomes question in the field of EP that a lot of people are interested in for good reason, and we do not yet have definitive answers, or even nearly definitive answers, from randomized clinical trials. Hopefully, those will be coming. But this work was designed to try to further the discussion and help generate additional hypotheses that may be answerable with randomized trials in the future.

We took a population of all comers from a claims database and identified patients with the diagnosis of AF, and we did so quite carefully to make sure that these patients had all at least attempted one antiarrhythmic drug. Of that population who had attempted to control AF with an antiarrhythmic drug, some of them went on to try a second antiarrhythmic drug and some of them went on to have an AF ablation. We identified those 2 groups and compared their relative risk of developing dementia over the course of follow-up. What we found was consistent with prior work, which showed that those patients who had a catheter ablation following failure of an antiarrhythmic drug were significantly less likely to develop dementia when compared to those patients who failed an antiarrhythmic drug and went on to try another. And the difference was quite dramatic. There was a 41 percent difference in this risk of dementia between the 2 groups. We prespecified that we would do a similar assessment within the subgroups of females and males. So we were not comparing females to males, but we did compare females who were in the antiarrhythmic drug group to females in the catheter ablation group, and we did the same for the male population, and we rematched using propensity score matching. We rematched within these sex subgroups, and found that both males and females in the ablation group were significantly less likely to develop dementia. We thought it was important to do a sex subgroup analysis because of the differential risks of dementia in the 2 groups, along with differential life expectancy, and a well-appreciated disparity in the likelihood between males and females of having catheter ablation, with females significantly less likely to undergo catheter ablation compared with males. 

What is the potential impact of these findings on clinical practice?

I think the findings from this analysis are really interesting. They are consistent with prior work in different populations, both American and global populations. Primarily, these findings should be considered in 2 ways: first, in the context of informed decision-making with patients at the point of care. In fact, this was part of the reason that we did the subgroup analyses by sex, because at the point of care, a patient is either a male or female—it is a nonmodifiable risk factor for both AF and dementia and for risks and benefits that might be associated with drugs or ablation. So the findings from this analysis in the context of others like it can contribute to that conversation when discussing the risks and benefits of an intervention that is not exclusively designed to address quality of life, but does have a significant quality of life component. We felt like these findings would add to that conversation in a meaningful way, if there is a possibility—again, we cannot say definitively—but if there is a possibility that catheter ablation can reduce the risk of dementia compared with antiarrhythmic drugs in the context of a known close relationship between AF and dementia, then that is worthwhile to contribute to conversations with patients at the point of care. So that is one clinical implication of these findings, but it is really important, and I have already incorporated this into my practice. Second, I do think that these findings add to the growing body of literature to help us continue to refine our understanding of the relationship between AF and dementia. As we already discussed, this is an area of significant interest in the EP and neurology communities. Thankfully, there are some clinical studies under way to try and sort this out with a little more clarity. So, what we found helps contribute to developing those hypotheses, so that we can run the most informative, helpful, and well-powered clinical trials that we can as a field.

What questions remain unanswered, and where do you see future research in this area heading?

We need randomized clinical trials. We know that there are a lot of ways that AF can be connected to dementia. Traditionally, we thought this relationship was primarily related to multiple strokes, thrombotic strokes, and hemorrhagic strokes in the context of chronic anticoagulation use. But we know now that that model is incomplete. It is oversimplified. There are a lot of ways that AF and dementia are connected. For example, in AF, there are changes to cerebral blood flow that can be corrected with restoration of sinus rhythm. So it would follow that the most effective way of achieving and maintaining sinus rhythm would give the best chance at improving cerebral blood flow, and thus, reducing the risk of dementia. There are a lot of questions, so I think clinical trials are important to understand the relationship between AF and dementia. How much do each of these hypotheses actually contribute to the risk? I also think that with emerging energy sources for AF ablation, we still have a lot to learn. At the time of ablation, we know from serial magnetic resonance imaging studies that there can be multiple small thrombotic events immediately during or following an AF ablation, and I think we still have a lot to learn about that process in the context of new energy sources for ablation and whether or not that contributes to risk of dementia over time. So, I am excited to see what we learn in this field and for the emerging trials designed to try and answer this question.

Reference

1. Zeitler EP, Bunch JT, Khanna R, Fan X, Iglesias M, Russo AM. Comparative risk of dementia among patients with atrial fibrillation treated with catheter ablation versus anti-arrhythmic drugs. Am Heart J. 2022;254:194-202. doi:10.1016/j.ahj.2022.09.007

Disclosures: Dr Zeitler has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. She discloses analytic support from Biosense Webster; a research grant from Boston Scientific; consulting fees from Biosense Webster and Medtronic; payment or honoraria for speaking engagements for Abbott, Biosense Webster, and Medtronic; support for attending meetings and/or travel from Abbott, Heart Rhythm Society (HRS), and Medtronic; is a board of trustees member for HRS; and assistance with analytics and medical writing for scientific purposes for Sanofi.