Dr. Christina Adams outlines how bias, conscious or unconscious, can affect cardiac care and treatment as well as how gender effects epidemiology, management, and prognosis in cardiac electrophysiology.
DR Adams, a good friend and colleague of mine, we've been working together for years. She's an integrative cardiologist with expertise and integrative medicine, cardiac rehab. Women's heart disease, nutrition and exercise. Of course. She was one of the co founders of the Women's Heart Center that she and DR Kim and I established here at Scripps Clinic. DR Adams believes in um completing assessments to compile individual risk profile and set specific cardiac goals for each patient's. She has a particular interest in athletes with heart disease and she always, I know she's always uh kind of encourages exercise therapy, cardiac rehab. She's very big on getting people to reach their health potential in that way. Prior to entering medical school, DR Adams actually spent two years in South Africa, working with organizations emphasizing improved health outcomes through education and sports. It was this work that prompted her to become a physician. She completed national research at the Centre for human nutrition at the University of Colorado and field research in Peru Guatemala and oh gosh, I don't know what this other one is. DR Adams. Okay, cardiovascular fellowship at Scripps Clinic. She was selected as Brave Well fellow and completed a two year Integrative Fellowship under the direction of DR Andrew Wheel at the University of Arizona Integrated Fellowship. DR Adams also served as chief resident at the University of Colorado. We're very excited to hear more about her take on this issue with Ativan women and some of these gender disparities today. Dr Adam. Thank you. Okay, thank you, paulina and Doug. That was just the perfect segue because we're going to actually address everything you had mentioned. So, um women in atrial fibrillation, you know, obviously a fib is the most common arrhythmia that we see, but there are some unique gender. Um there are some unique gender differences that come up between women and men. And I'm going to highlight those today. Um let's see, I have no disclosures. So again, I want to echo uh paul Lena's introduction from a historical perspective. We really still need to have more conferences emphasizing women because there are so many differences between the sexes and this does affect outcomes. Um It was not too long ago that women were not even part of um for example, the physicians health study, and only at the turn of the century was it recognized that Physicians were not referring women for coronary angioplasty or bypass or balloon valvular plasticky. Now, in 2021, we're finding um and we'll speak about this. Um and I should be happy. We're not we we need to be referring women more for a fib ablation. We're going to talk about why that's probably the same reason why there was a delay in coronary artery disease referrals, because women typically tend to be older with a fib and have more comorbidities. Again, going back to the historical perspectives of why it's so important that we identify women is that only recently in the early two thousands did the H. A. And the NIH really start to say we need specific guidelines on women. So, as paulina reiterated several times throughout her talk a lot is unknown, but we know that there are differences every time we have see a randomized controlled trial or some type of landmark research trial. I'm always curious to see the percentage of women that are included in these trials and they tend to be underrepresented um in regards to arrhythmias itself. So we now are very much aware of the difference in presentation and symptoms, in regards to coronary artery disease, atherosclerotic disease and heart failure. But gender differences in arrhythmias has received much less attention than coronary disease. We know that a gender differences are there within the cardiac maya sites and therefore cardiac electrophysiology differences is going to affect epidemiology management, decision making as well as prognosis. So the biggest key take away from my talk today is that with this later onset of arrhythmia, just like with coronary artery disease, potentially this is why we don't refer women. They're diagnosed later. They have more comorbidities. Perhaps we think they're at increased risk for the procedure and just like paulina had mentioned, she spot on, we kind of attribute the symptoms to a different co morbidity that they have. So one of the arguments that I would like to make today is that we should be more proactive in screening people for a fib and potentially be more aggressive in choosing a rhythm control strategy to see if that helps with symptomatic changes and better quality of life. So one last slide on gender disparity. There's it's not just about conscious or unconscious bias from physicians. When we look at things such as cardiac rehabilitation, women are referred less likely to cardiac rehab, but women are less likely actually even to participate in cardiac rehab. So maybe it's not just the procedure itself, but really the importance of identifying why do women not go forward with more aggressive therapies? Where is our me being physician's responsibility for bias? Um, and are the differences in treatment really related to the differences in the disease ideology itself? Okay, so onto a fib. So even into the deep polarization of a cardiac maya site, there's already been well understood differences between men and women, and this is just highlighted here in this quick slide and the cardiac maya sites have receptors for estrogen's and androgens. And I'm going to show a slide later on that yes, hormones matter, But it's kind of a not it's not good of us to talk about hormones. Is this giant kind of bucket? It becomes this kind of dark space because it's far more complicated of course, than just saying estrogen or testosterone effects on the cardiac maya sites. Why we need to talk about a fib. Well, the prevalence of a fib is increasing. As we know, this is the most common type of sustained arrhythmia in north America. This is a huge, huge health care expenditure in our country associated with morbidity, mortality, hospital admission. I just came off the inpatient service and you know, we have On our 20 patient census each day, you know, probably 50 of our patients have a fib. We also know that the strokes coming from a fib are important strokes and asterix there because strokes are probably underrepresented from a fib, meaning there's probably more a fib. We just haven't found it. Thanks to the technology such as link and the subcutaneous monitors were able to identify more strokes with strokes from a fib typically result in worse outcomes more disability and greater mortality. So this arrhythmia is so critical in our care and treatment. And again, what I'm gonna emphasizes since prevalence is increasing, shouldn't we be screening more? Shouldn't we be identifying patients who are at risk for developing a fib and being more aggressive early on as a prevention ist You're going to hear me kind of talked about this throughout my talk. So diving into the epidemiology, most of our data behind uh Women in A fib comes from Medicare data. The Framingham studies the atria, study art data. Certainly we understand that the risk with a fib and women is age. So the incidence and prevalence of a fib is actually uh more common in men. But the absolute number of A fib in women increases solely because of life expectancy. And as as Dr Gibson pointed out, yes, women have worse and very atypical symptoms and Paulino is correct. So if we're attributing the atypical symptoms to her heart failure, the A fib kind of gets put into the back burner. And I'm going to argue today that we should probably be more aggressive in treating the A. Fib and potentially giving women a chance at a rhythm control strategy to see if that affects their quality of life, because women do have worse quality life. And I'll talk about that moment. So I should actually put up here a fib. Men and women, the risks overall are the same. So one of the next future slides you'll see is another option. That I'm going to argue that we start talking about is the type of a fib. The risk that you see here are associated with what we consider kind of the co morbid A fib, the A fib that comes from age long standing hypertension, obesity. In fact, body mass index for both sexes is one of the most important risk factors for the development of a fib. We'll touch on genetics. That's not really in prime time for the average clinician. Um, but sedentary behavior, high alcohol intake for both men and women. Um, Actually moderate intake and alcohol increases a fib risk in men and of course sleep apnea, thyroid issues. Some of the other risk factors come to bring up that are more unique just to women is on the next slide, but that includes valvular heart disease and heart failure. So, you know, if you see these, these are most of these other than genetics and age, these are all modifiable risk factors. And so when pauline and I were looking at the participants of the conference, we are really excited to see some internal medicine docs and family medicine docs. This is an opportunity to screen early for people and if they're hitting these different risk factors, alright, post menopausal body mass index is elevated, high blood pressure is not under optimal control. Um, looks like a positive screen for sleep apnea. You can bet that the pretest probability of that woman developing a fib is very high. So I feel like we can do a much better job at screening for women and saying, let's get on top of that hypertension, let's screen you for sleep apnea. Let's moderate that alcohol intake so uniquely to women. Women are older at the time of diagnosis, The incidents skyrockets after menopause, women have more high blood pressure and heart failure. And this goes into the symptomatic kind of prevalence of how are we, how are we able to say this is a heart failure, exacerbation admission versus no, this is symptomatic a fib and I think that's where it gets a little muddy because women have far more comorbidities. By the time they're diagnosed, women also have more associated valvular heart disease, even though rheumatic heart disease such as mitral stenosis and rheumatic heart heart failure is on the decline, We do still see it. And it's more incidents with a fib with women. Interestingly, men develop more post op a fib after, after cabbage and men's a fib is more associated with coronary disease. Womens a fib is associated with that hef hef and poorly controlled hypertension. Pregnancy was talked about during Polina says, talk, I'm only going to mention it briefly. It's very rare during pregnancy. Actually, the prevalence is very low and usually it's associated with valvular disease or underlying structural heart disease or peri partum cardio myopathy. But increasing priority does actually increase your overall a fib risk. We do always talk about pregnancy is a woman's first stress test and that's an important Delia nation in regards to a woman's overall cardiac risk in her lifetime. So, we know gestational diabetes, preeclampsia and eclampsia increase the risk of coronary disease for a fib hypertension during pregnancy does increase the overall lifetime risk. Well, women who get hypertensive during pregnancy tend to get hypertension and of course hypertension is a risk factor for a fib. So you can see it all kind of kind of rolls in on itself and we see this increased risk of a fib. So just to compare men and women, women, it's heart failure, high blood pressure that left ventricular hypertrophy, valvular heart disease and for both sexes, high body mass index. Now, I'm gonna have I'm going to talk about exercise again, if we subtype a fib, there is some data out there. Um and actually our own dr natalia has has actually published some of this data about the difference and exercise and the risk in a fib for both sexes. Sedentary behaviour is a risk factor for the development of a fib and for both sexes, moderate exercise decreases the risk of a fib. So again, there's so many opportunities for us as clinicians to prevent a fib and to help decrease the incidence and the severity. Um, you know, paulina had kind of talked about a little bit of testosterone. I completely concur really weird numbers and data and conflicting evidence about what does testosterone actually do for the heart because men have more if it bit younger ages there is some thought that it does affect the A. P. D. And facilitates the mechanism of a fib which is re entry. And then there's lots of interesting mice models about what happens to that atrium and the fiber optic modeling. We're going to get into that a little bit later on. So as I mentioned before and we talk about a fib maybe we should actually start talking about different types of a fib. So with idiopathic a. Fib and looking at are there any differences with men and women? Lots of controversial data on sex differences with those idiopathic cases with genetic A. Fib. Well again this is still ambiguous data. We certainly know that there are a couple of genes and these are X links genes. Both the K. Cny five gene which confers we think a protective effect. Um an alternative AMG dilation which affects a fib risk. But again no clear genetic apartment, no clear gender differences in regards to genetic a. Fib. So exercise a definite sex differences. So we see an elite athletes and again this is where I really caution uh patients um you really have to be the elite athlete to develop the exercise. A fib and I have a whole slide. We're going to talk about that. But again sedentary behaviour increases a fib risk. But an exercise associated a fib with elite athletes. Men tend to have more marked concentric and atrial remodeling. Um So so vigorous exercise and men tends to actually increase their a fit risk and this is more of a vagal tone. Again, we'll talk about that when I get to my exercise slides, other types of a fit, autonomic atrial fibrillation, no real known gender differences. Although interestingly with women being more commonly having pots and men have been more commonly having um Parkinson's disease. The autonomic nervous system does play a part in a fib but it's not been elucidated if there are gender differences. In regards to this type of a fib. The most common a. Fib we see is the co morbid co morbidity associated with a fib. These are the usual risk factors, hypertension, age, body mass index. So anyone at Scripps clinic who goes and does their T. E. T. T. E. S in the afternoons, down in the in the cloud. Hey, these are the people that were cardioverter and then we're treating for their resistant a. Fib. They all have sleep apnea. They're obese their sedentary. Um This is the most common type of a fib and these are similar risk factors. And men and women again, body mass index seems to be one of the highest predictors. Women again though, are older at the time of their diagnosis and I can't emphasize enough that we need to be better at really addressing the obesity epidemic here in America because it is a risk factor. Um hormonally related a fib. Again, we do see peri partum um we do see peri partum cardiomyopathy and that increases the risk of a fib. So if we think about the co morbid sex differences, this this speaks directly to what to what dr Gibson was bringing up. This is why symptoms tend to be more atypical because at the time of diagnosis women tend to have more hefty f women have worse hypertension. Women are more likely to have an and stem E. A. Type two and steamy associated with that LV. Hypertrophy and rapid A. Fib rates than men. So the thought always when women are presenting and we're going to get to symptoms. But they do present with a typical symptoms, they're fatigued, they're short of breath, there have general malaise, they have more depression associated with the A. Fib, their quality of life is poor and we tend I think too put too much emphasis on the other comorbidities instead of addressing saying, well perhaps they're actually symptomatic from there. A fib. Unfortunately that delay in diagnosis from a fib then makes the A fib worse more difficult to treat. And perhaps that's why we're less likely to follow a rhythm control strategy and we opt for the rate control strategy. So again throughout this talk, we want to roll in the prevention of a fib with then the development of the other comorbidities and then the presentation of a fib is different in women and that may affect how we treat women. And whether or not we're really recognizing those symptoms because just like with coronary disease women have a typical symptoms and they're typically not. Oh my heart is racing. I'm in a fib. It is more general malaise and fatigue shortness of breath. So first back to exercise poor Tokyo. Hopefully it'll go through this year. Um So in both sexes very important. Sedentary behaviour increases risk, moderate and vigorous exercise lowers risk in women. So this is something where we should be able to give our patients exercise prescriptions in the outpatient setting. Now vigorous exercise in many is associated with an increased risk. This is a U. Shaped model. So again sedentary behavior, increased risk and then at really high levels of exertion. So we're talking excessive endurance sports. This is 1500 hours of sports per year, that's about four hours a day. So most of our patients aren't doing this. So I don't really think the general male population in America has to worry about exercising too much to increase their risk. But the thought is that in athletes they have male athletes specifically the atrial remodeling is different. They have more changes to their atrial. And athletes tend to get their paroxysmal a. Fib during high vagal tone situations. This isn't exercised induced a fib. This is during rest sleep and kind of postprandial episodes. So when we talk about these mechanisms let's let's break it down into four main types the hormones that scary black box that nobody really understands the differences in the atrial anatomy which then goes on to affect stroke risk. So even though women have smaller atrial volumes and lower stroke volumes, the left atrial appendage tends to be larger and the left atrial appendage velocity also tends to be larger. Which is why some theories are that why women have more stroke risk, but that's also much more complicated. Um hormone function on atrial function itself. Remember there are cardiac myo sites located apart. Cardiac maya sites all hold receptors for both androgens and estrogens and then just gender differences in autonomic and neuro hormonal modulation we'll talk about. So first hormones that black box, it's so complicated. Um And that's why whenever you do uh bench research, the first thing you do with the rats and the mice is that you over optimize the females because it does have effects is paulina started mentioning. So let's talk about what happens again. Remember with women developing a fib at older ages, they are already going through changes. Menopause um has other important changes which increase a fib risk. So the question is if the incidence of a fib in premenopausal women is low and then increases after menopause. Is that the loss of the beneficial effects of estrogen? Or is it actually the harmful effects of post menopausal changes? To review what happens after menopause? Women's blood pressure increases their LDL increases their HDL drops and their body mass index increases. So increase in body mass index increase in hypertension, increase their risk factors for a fib. So I don't think we can just say it's the lack of the beneficial, effective estrogen. Now, when I say estrogen, let's also be more clear about, we're talking about endogenous estrogen. So endogenous estrogen is known to have empathy, legal effects. And it promotes vaso dilatation and increased blood flow. Uh this is through direct effects with nitric oxide and prostate cycling. And we understand this because of spontaneous coronary artery dissection. So those fluctuations in estrogen when they go away, we lose that beneficial endogenous estrogen of inhibiting platelet aggregation and adhesion. Now, if we think about extra dial and the exogenous or the conjugated estrogens that we do with hormone replacement therapy, well, there is some evidence that that actually increases the markers for hypercritical ability. Specifically Factor seven A. This goes back to the HRT HRT studies. So you can see how this is complex. It's not just estrogen. We need to be clear about our we just losing the endogenous estrogen and what truly are the effects of exogenous estrogen? Or is it just that after menopause women tend to gain weight, their blood pressure goes up and those are your risk factors for a fib similarity with men. The average American male gains 1-2 lbs every year beginning at age 40 and never stops. Therefore we can see how at their ages edge age 50 they're usually 10 to £20. Overweight, 60 years old. 20 to £40 overweight. So again this goes back to what can clinicians do to really improve that. So this is just a wonderful little cartoon showing the the receptors of of sex hormones um estrogen here and kind of that pink red and testosterone there in the blue. Look at how it actually changes um thus the deep polarization on these iron channel. So a very complicated background and for example the best and most well understood is the prolonged Q. T. Yes we understand that that has an effect and that's why our our choice of anti arrhythmic as paulina pointed out is so important. So again um we do know so as as paulina pointed out when people go through menopause and we start hormone replacement therapy. That certainly does not decrease a woman's risk of a fib. Um And there's some evidence that it increases the risk of stroke. So again, the hormone story is more to come overall the differences between men and women. I love this slide because it really brings in everything we're talking about the hormonal influences, the endogenous factors such as physical activity, lifestyle, the genetics. Probably we're going to learn a lot more about those in the future. Maybe we should test for them and how those, how all of those epigenetic factors than affect genomic regulation and the presentation of a fib. So as as dr Gibson brought up, there are a typical and they come in later effort intolerance, dysosmia, fatigue, weakness and those are signs of heart failure. So again, we're treating a lot of women I think for their hefty f and not necessarily for the A. Fib. This leads to delay diagnosis. This leads to women presenting with more persistent a fib, making it harder to treat. And then does that result in us referring women less for ablation? Um Again, women report more functional impairment, worst quality of life, later presentation. They're more likely hospitalized and they're more prone to recurrences. And so my argument again is we should be more active and proactive in treating a fib and screening for a fib. If we look at this overall at the increased age of diagnosis, they present already with the underlying comorbidities that all of these things also increase their risk of stroke, leading to these worse outcomes. You can see how it's all interrelated. And again, should we be more proactive and following a rhythm control strategy and referring to ablation That is yet to be seen. And as Polina pointed out, this is important because after the age of 75 yes, the mortality for women a fib goes up. So this needs some more attention. I think we need to be a little bit more aggressive and treatment. So speaking of management, like we had mentioned on the first slide, you know, it's not just treatment bias but it's also patient patient preference and how to be treated. But women we know are less likely to receive a rhythm control strategy. But maybe that's because again, they're already presenting and persistent a fib and we have to follow that rate control strategy rather than a rhythm control strategy, but they are less likely to refer for electrical cardioversion and capital ablation. Now in orbit af there was no difference in anti arrhythmic therapy, but interestingly they didn't undergo as much cardioversion. Um And just like this week this is real world when we're on impatient I think on monday we had four women going for an A. V. Notable ation with a micro pacemaker implantation. So again is this age at presentation? Is this because we're more worried about their comorbidities um resulting in more complications. I think we should just do more from a prevention standpoint. If we look at a firm data and the diamond chf trial, looking at those again confirm uh anti arrhythmic therapies. Women are just as much to convert with defeat allied but torso odds is going to occur more frequently in women. So when we decide to initiate soda all, for example a lot of my colleagues we kind of debate whether or not we need to bring patients into the hospital for E. K. G. Surveillance. Um And it's kind of 50 50. Some people are initiating soda in the outpatient setting. And other people are opting for uh telemetry monitoring even just with something like soda also. But we do see because of that long Q. T. In women more torso odds, more QT prolongation. I know Dr Gibson is going to talk about this at length. But there are several registry studies in addition to just the german ablation registry, um We've got the Gloria the refer registry, the orbit A. F. Registry. So when we look at these abrasions and stroke risk, possibly some venus and vascular complications. What's really important? The cabana trial showed that ablation was effective for women and the complication rate was very similar. So that's that again. So I feel maybe we should be a little bit more aggressive and proactive and trying to dealing. Eight is she symptomatic from a fib And should we consider catheter ablation for more women stroke risk increased in women. And that's why the chad score has evolved to the chads vast score chads two Ds two vast score. Again based off of Garfield af. The german registry, the orbit af the Gloria and the prefer registry looking at stroke with is well documented that women stroke risk is increased in a fib. Why though? Well, the atrial mechanics and even though the atria are smaller, we believe the velocities are decreased. We believe the left atrial appendage appendage appendices are are increased in area. If we go back to the Atria, study the annual thrombosis embolism rate was 3.5 in women and at 1.8 in men. And these are people who are not being treated with anti coagulation. And this goes down to is there a hormonal effect? Is it actually the appearance of the a tree itself? Um or is it that by the time that women are diagnosed with a fib, they've had longstanding hypertension and now they're atria are dilated and they have even decreased left atrial velocities and they have that more stiff left atrial syndrome. Unfortunately, even in all the No Act trials, women were underrepresented, Accounting for about only 37 of patients in over 42,000 participants overall, but similar efficacy and safety in the no axe. So again, women with a fib worse outcomes, more disability, greater mortality. So in closing, when we talk about increased stroke risk, it's not just hormones, It's not just one thing or the other. It's this huge interplay. So perhaps the left atrial appendage size is larger, but the atrial size is smaller, but there's more atrial fibrosis. In women, we see the same thing with women and aortic stenosis. We know that women referred for tavern have more left ventricular hypertrophy. So is it that women are older? They then have higher blood pressure. Now they've got atrial fibrosis, they have more comorbidities such as heart failure. So we are perceiving that their um that their symptoms are more prone to the other comorbidities they present. Later. We follow less of a rhythm control strategy. We don't give them as much chance to follow. Maybe get a cardioversion or an ablation. These are all these social factors. I want to just point out this does confound the diagnosis and delays treatment significantly. Um Here's a fun fact. Women with a fib were also more likely to receive antidepressant medication. So are we treating these other comorbidities when really this is symptomatic a fib and we should be more aggressive with treatment um quickly with men women are more less likely to have coronary disease with a fib but men do. But that's also the thought why women have less intracranial hemorrhage compared to just overall traumatic risk compared to men. Because men are more likely to be on something like Plavix as well as their no act. So in conclusion for a fib treatment, I argue that for clinicians on the front line for us, general cardiologist and for our internal medicine colleagues we need to be much more proactive and aggressive and risk factor management. Consider screening earlier. Um The risk factors for a fib remain the biggest risk factors remain hypertension, obesity, sleep apnea and sedentary behavior. These are all modifiable. So consider an order set right that exercise prescription. Put up a weight loss referral, get contact with you know uh your other colleagues to get patients to lose the weight and do closer blood pressure. Follow up consider early treatment for cardioversion and rhythm control before the significant remodeling begins. And of course we need more studies. But remember women have more symptoms and more atypical symptoms and worse quality of life. I think that in the future we're going to see that we should be a little bit more aggressive with women and a fib. And this is a great segue for doug to start talking about the efficacy of ablation. Thank you Dr Adams you finished perfectly in time. That was really amazing. And I'm really glad you brought up that point about the antidepressants in women, because it's just one of those points. Are we a little biased? Are we calling everything about women emotional rather than physical or physiological? So it's a really interesting point you brought up
