Is There an Under-Referral of Women for Atrial Fibrillation Ablation?

At this year’s ACC meeting, Dr. Russo et al presented research on the under-referral of women for atrial fibrillation (AF) ablation. Andrea M. Russo, MD is the Electrophysiology Laboratory Director and Clinical Associate Professor of Medicine at Penn Presbyterian Medical Center at the University of Pennsylvania. Tell us about your research. What population of patients were studied? When were the patients studied? We had been performing AF ablations, primarily pulmonary vein isolation procedures, since 1999, so our data included over 1,100 cases of men and women who underwent AF ablation from November 2000 to July 2007 at the University of Pennsylvania. However, since only 23% of our cohort were women, we were interested to see if there were different clinical characteristics or outcome measures that might help us determine why there was such a low percentage of women with AF who had undergone ablation. If you look at previously published data, you’ll see that although at any given age men are more likely to have AF than women, actually 53-55% of patients who have atrial fibrillation in the population are women — the reason for this is related to women living longer than men, and as we get older there is a higher chance for developing AF. In general, women tend to be older at the time of presentation with AF. Therefore, we tried to see why women represent such a small percentage of patients undergoing ablation, and see if this may be because women just don’t do as well, and to examine any gender differences in baseline characteristics that may help us to explain these differences. What percentage of women patients were referred for AF ablation? What was often their first line or method of treatment? I should first mention that once patients were sent to us in the EP section, we referred the male and female patients equally for ablation. However, this is a retrospective analysis, and we don’t have any specific information regarding referral practices and decisions made by their primary care physicians or general cardiologists before patients get to us. As more men than women are referred to electrophysiologists at our center, bias cannot be excluded. Alternatively, it is certainly possible that women may elect not to undergo invasive procedures, and are therefore not given the referral. If we compare the men and women who underwent ablation, we can see that women were more likely to be placed on antiarrhythmic drugs than men prior to undergoing ablation, and they failed more drugs. That was an average of 2.5 versus 2.2 in the cohort, but it was statistically significant. There are other characteristics that are different between men and women who undergo ablation. For example, women tended to be a little older, with an average age of 58, compared to men, who were 54 years old on the average. Women tended to have slightly better ejection fractions than men. In addition, women were more likely to have paroxysmal AF as opposed to persistent AF, which is interesting because you would think that physicians would then refer more of these women. Lastly, we did not see any difference in the duration of AF prior to ablation. Were you surprised by the findings? Why do you think women are less often referred for AF ablation? I was surprised, because it does look like men and women are being treated differently. It seems that women are being offered ablation later in terms of trying more drugs first. We do not know if this is referral bias, or if women themselves are refusing the ablation procedure. All of this would have to be evaluated prospectively, to find out why women aren’t getting to us. Previous studies have shown that women are more symptomatic than men, so it’s not because they’re not symptomatic that we don’t see them. Women are perhaps a little bit older at the time of referral — so it is possible they may not be felt to be as good candidates for an invasive procedure. However, if you look at our data, there was no difference in complication rates between men and women, so complications wouldn’t justify not referring women. One possibility is that women may be too busy taking care of everyone else in their families and are not interested in being away from home or out of work for a few days to undergo an invasive procedure. However, since the success rates are similar and because antiarrhythmic drugs are not very efficacious, we need to figure out the reason for this under-referral and what can be done. In general, are women under-represented in clinical trials in this area? Yes, there have been other studies that have reported an under-representation of women. However, if you look at clinical trials for coronary disease and bypass surgery, there was initial data that women are less likely to undergo invasive procedures. There also may be under-representation of women in some of the more recent trials. For example, in the Multicenter Unsustained Tachycardia Trial (MUSTT), only 10% of the randomized group were women. If you look at the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), women were a little better represented at 23%. There are certainly a lot of questions to be answered! Do you think women are also less likely to receive other EP treatments, such as ICDs? If you look at ICD trial data, there does seem to be a discrepancy in the women versus men who receive ICDs. However, it is difficult to ascertain the reason for this, since women are less likely to have coronary disease and they present at a later age with coronary disease. I actually just presented at the ACC on the topic of ventricular arrhythmias and gender differences. Some of the larger beta blocker trials show that between 20-23% of women are enrolled. However, if you look at a population of patients that present to a heart failure unit, about 37-53% of those patients are women. Of course, it is important to note that women are also more likely to have diastolic heart failure than men, so they may not be candidates for an ICD. Therefore, it may be a combination of the fact that women have a different type of heart failure or that some heart failure patients aren’t referred for ICDs because they’re not candidates. I do think part of it may also be patient preference, and part of it may be because of bias — maybe it also matters which physician sees them. However, this is all speculation, so these are things we need to learn out more about. Is there a need for better clinical research in this area, such as more women-centric clinical trials? Yes, definitely. We need to not only increase the number of NIH trials, but also encourage the enrollment of women in clinical trials. In addition, we need to pay more attention to spreading education and awareness about these diseases — many still think heart disease is primarily a man’s illness. However, most importantly, we need to make a special effort to focus more on women in clinical trials. What was the reaction to your research at the ACC? Was it supported or was there a general consensus that women as treated equally? It was well received — both at the poster and at the other presentation I gave on gender differences in arrhythmias. There are clear physiological differences between men and women, and I think people now accept that fact. The more I learn about it, I believe innate differences, including hormonal, autonomic, ion channel and cellular differences likely influence arrhythmias. I suspect this goes beyond under-referral; there are simply just some physiologic differences that make us intrinsically different. We need to make sure everyone pays attention to this when designing future clinical trials. What can be done to improve upon AF referrals in women? Does it start with an educated patient or with the clinician? I think both. Some patients are referred by their primary care physician, but most are referred from cardiologists, and either way, we need patients to recognize that no matter what their gender, body size, or age, they are still potentially a candidate for an invasive procedure. We also need to educate doctors and make them more aware of these gender differences and potential bias with respect to referrals, because bringing topics like this to the surface can make such a difference. In addition, patients need to be educated about arrhythmias and the different treatments available, so even if their general practitioner doesn't know very much about ablation, they can inquire further. At our clinic, many of our patients look online for information about their condition — of course, what they find online is not always accurate, but at least they have a basic awareness that this procedure is out there. Ultimately, patient education is best served through some of the big societies and medical groups, such as the ACC, AHA, or HRS, which can help raise awareness and foster education.