2021 Virtual Cardiovascular Evening Symposium: Prevention & EP Updates
Originally Broadcast: Thursday, February 25th, 6:00 - 7:15 PM CST
Expiration Date: February 25, 2022
We invite you to join your fellow clinicians to learn about cutting-edge best practices in cardiovascular care. Minneapolis Heart Institute® providers discuss topics in prevention, diagnosis, managements, and treatment of cardiovascular conditions.
Allina Health, Learning & Development intends to provide balance, independence, objectivity and scientific rigor in all of its sponsored educational activities. All speakers and planning committee members participating in educational activities are required to disclose to the activity audience any real or apparent conflict(s) of interest related to the content of this conference. The ACCME defines a commercial interest as “any entity” producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. The ACCME does not consider providers of clinical service directly to patients to be commercial interests - unless the provider of clinical service is owned, or controlled by, an ACCME-defined commercial interest.
Michael Miedema, MD, MPH and Manju Pai, MD have disclosed that they DO NOT have any real or apparent conflicts with any commercial interest as it relates to presenting their content in this 1-hour activity.
Retu Saxena, MD, Christopher Leighton, and Michael Berger have disclosed that they DO NOT have any real or apparent conflicts with any commercial interest as it relates to the planning of this 1- hour activity.
Good evening, everyone. Thanks for joining us. I'm coming. You to you from the confines of my bedroom upstairs. I thought this was the safest place to make. Sure you can hear my dog if he freaks out, which on occasion he does. So hopefully this works out. So tonight we're gonna talk about fish oil and cardiovascular prevention, and I think this is a really fascinating topic, and typically for supplements. Um, we often have a lot of preliminary information, which makes it intriguing. But we don't have those big, large randomized trials which tell us the actual truth, The truth about it, whether or not it works. And so this is really fascinating topic. We have really good data, and so hopefully you find it up some value. Mm. So if you go back to cardiovascular death rates in the 20th century from about the 19 twenties, all the way up until the 19 sixties, there was a substantial increase in rates of cardiovascular death. We have an epidemic of coronary heart disease. And so around the 19 forties fifties sixties, there was this push to say, Hey, we need to figure out how to treat this disease And first of all, we need to figure out what causes it. And so that's really what led to the Framingham Heart study and these other studies looking into what causes 40 heart disease. And part of that was nutrition. What about what we eat could potentially cause heart disease? And so one of the studies that came out of that was the seven country study, which looked at total fat intake and rates of death from coronary heart disease and one of their initial take homes was that the countries that seem to be eating more fat seem to have more deaths from heart disease. And so this kind of was intuitive, right? The plaques under a microscope seemed to be fatty. They're full of cholesterol, and so the thought was, Well, we eat more fat, and then we get more heart disease, and so this really took off in terms of research. But also there are some people that pushed back, and so one of the people that push back were a couple of researchers in Denmark who were researching the Inuit used to be called Eskimos. This is on the western coast of Greenland, and they said we have this population of people that were studying, they seem to take in a fair amount of fat. They take in a high amount of fat, yet they don't seem to have any heart disease. And so we better be a little careful when we talk about fat and heart disease. There might be more to the story, and so we're gonna take a step back and go into kind of chemistry 1 to 1 for a second. And really, the research has been into do different types of fat potentially have different health implications? The answer clearly is yes. And so on the left here is a molecule of saturated fat, And so when we say it's saturated, we're saying that for every carbon, uh, it's saturated with hydrogen. There's no double bonds. There's no lack of hydrogen, so it's a saturated fat, which tends to make a linear molecule. And so linear molecules can pack very densely when they pack very densely, they tend to be a solid at room temperature, so that's why butter and animal fats tend to be solid. And that's very different than unsaturated fats, which don't have saturation of hydrogen. And so they form some double bonds. When they form those double bonds, they become irregular, and so they are more likely to be liquid at room temperature. And it turns out that changes some of the properties of the fat, and it changes the health implications. And so when they're naming these fats, you have the acid end of the fat, which they call the alpha, and and they have the methylene, which they call the omega. And and so, depending on where that double bond is, that changes the name of the unsaturated fatty acids. So if you have multiple double bonds, you become a poly unsaturated fatty acid. And for several polyunsaturated fatty acids, they have their double bond in the third space. The third carbon has that first oh, bond, and so those become omega three fatty acids. And so, in nutrition, we have really three main omega threes. We have alpha linolenic acid, which is a plant based omega three, which we mainly find in nuts and seeds. And then we have two marine based fatty acids, which are I Costa Penton, OIC acid and Darko Hexen, OIC acid. So e. P. A. And D. H. A so those are what you find in fish oil. These are what you basically say. Omega three fatty acids you're talking about E P. A. And D H A. And not all fish are created equal. We know very clearly. Um, certain fish seem to have more. Official. They seem to have more fatty acids, and so it's mainly cold water, larger saltwater fish. And so it's salmon and herring and trout, anchovies and sardines, which aren't as big but seem to have more official mackerel and tuna. Those are mainly your oily fish or fish that have more official in them and have more D H A and E P A. And so the American heart recommends around 2 g of fish oil per week. 2 g will make three fatty acids, and so a serving of salmon has around 1000 mg, and so that's variable, depending on what type of salmon reading and whether it's farm raised or wild. But in general, two servings of salmon will get you towards that 2000 mg that will make it threes. And so some of the initial studies simply looked at fish intake and risk for coronary heart disease. And what they found was, is that as people taking fish, their risk of coronary heart disease, death goes down, but it doesn't go down in a linear fashion. It goes down in more of a threshold fashion. And so this is data from the Physicians Health Study, and they found that 1 to 2 servings of fish per week seem to reduce the risk of coronary heart disease death. But taking in more than that didn't seem to change. It seemed to be a threshold seem to be a threshold for coronary risk reduction. And in 2000 and six they published a pooled analysis of basically all the studies that have been done. The prospective studies looking at fish intake and coronary heart disease risk. And what they found was that same kind of threshold relationship where, when people took in fish 1 to 2 servings a week, they reduce the risk of sudden cardiac death. And that's really seems to be the main benefit here. People who've taken fish you have more stable cardiovascular are more stable Maya site membranes. They seem to eat less likely to have death from arrhythmias from sudden cardiac death. But when people take in. More than that, they don't seem to see as much of a reduction in risk. And so it's a threshold relationship where about 250 mg a week of fish sorry, 200 mg a day, about 2 g a week of fish seems to reduce your risk of coronary heart disease, and more than that doesn't seem to provide an incremental benefit. And so this is the basis for the H A recommendation to take in about 2 g of omega three days a week. We also had some randomized data early on, and this is in the setting of of, you know, this isn't in the modern era. This is in a lack of statins and not very good. Blood pressure control. Not very good. Diabetic control, higher rates of smoking. But in that context, um, intake of Omega three seem to be a benefit. And so the dark trial was simply a dietary advice trial, Um, and so they didn't provide food for people providing a supplement. They simply said, This is what you should focus on eating. And so these were 2000 people who have just had an Emmy and they split them into three groups. One group, they said. Try and minimize your fat intake. One group, they said, Try and increase your fiber intake and one group they said, try and increase your intake of fatty fish And that really seemed to be the group that benefit the most. The people that took in more fatty fish seem to have lower rates of death from heart disease. And shortly after that, there was the G C study, which looked at a fish oil supplement, 1 g of DHL and EPA and in over 11,000 people, the people that took in the fish oil had lower rates of CHD mortality. And so from early on we had some evidence that people who took in Omega three seem to do better from a cardiovascular standpoint. And so the question is, what's the mechanism? Why are why are Omega threes beneficial? And so There's been a lot of basic science studies looking at this, and there seems to be quite a few mechanisms by which this could be beneficial. There's anti inflammatory effects where people that take in more omega three seem to have lower inflammatory levels. There's plaque stabilization where people that take in more Omega three seem to have lower rates of plaque development. There's less foam cells and less plaque volume. Several different mechanistic studies showing benefit there in terms of lipids, we know very clearly this is probably one of the most consistent effects is that people that take in omega threes have lower triglycerides. Very clearly, they don't affect the other lipids as much. But people who take them in have lower trade. This rights. There's an anti serum biotic effect where people that taking Omega three seem to have reduced platelet activity. And so, you know, part of the heart attack processes a platform ng and so people that taking Omega three seem to be less likely to have that or that platform. And then finally, the one that's a little bit harder to understand is that people that take in more omega threes seem to have a more stable cardiac membrane, a mile site membrane. And we know that anti arrhythmic effect is through stabilization of that membrane. But also we see that cholesterol oxidation involves that membrane, and so this is the one area where we see a difference between E. P A and D. H. A, where people have taken more, EPA seem to have a more stable membrane, and they seem to be less likely to oxidize their fats. They're less likely to have those. LDL is turned into oxidized LDL, which are then plaque forming. Whereas DHS seems to be less stable, they seem to have more cholesterol issues, and so they seem to potentially be more prone to plaque formation. And so in splitting the two out from a food standpoint, Um, anytime you have fish, you're gonna have both E. P A and D H A. But from a supplement standpoint, they can separate them. And so there's one study looking at is EPA or D H A better? And really, from an inflammatory marker standpoint, they seem to be kind of the same. From a lipid standpoint, they seem to be relatively similar. The one difference that comes out is that with D. H. A. We do seem to see an increase in LDL cholesterol levels. We see more bad cholesterol and people that take in D. H. A. It's not a substantial increase by any means. It's a pretty small increase. Yeah, that's something that obviously raises a little bit of concern. And so, for people that take in seafood, we see benefit. But obviously there's other ways to take in omega threes as well. And so we have over the counter fish oil, of which there are numerous types. There literally are hundreds, Um, and the dose of fish oil in each capsule is different. The ratio of e p. A. To D. H. A is different, and the issue is that this is considered a food. This is not considered a medicine. And so this is not under FDA regulation. Um, and so there are certain studies showing that some of these fish oils have fish oil that has been oxidized kind of rancid fish oil, which is not something you want, obviously, and like he doesn't have much benefit. There's some fish oil studies showing that some of these pills have a lot of saturated fat, not actually the Omega threes that are said to be in there. There's other studies showing there's a fair amount of mercury in some of these, and so I think most official that we get has in it what we think is in it. But we aren't guaranteed to that. And I have some patients say, Well, you know, that's why I'm concerned. That's why buy the expensive stuff. Well, the expensive stuff isn't any more regulated than the cheap stuff. And so we got to be a little bit careful with where we get these fish oil tablets. From there are prescription fish oils, which are FDA regulated. And so there's really three combinations of E. P. A and D. H A. That's a Panova and Lavazza and on trig vases, probably one we're most familiar with in Midwest. And all three of these have FDA approval to lower triglycerides. They've been pretty well studied, and they've shown that very clearly. When people take them, they're triplets. Rides go down. The downside is that all the studies also show that a slight bump in LDL, so you're trading off a lower triglycerides for a slightly higher bad cholesterol. Conversely, we have I, Costa Pen Ethel, which is a derivative, and Esther and Ethyl Ester of Purified E P. A. So this has no D. H. And it's just purified E p A, which potentially is somewhat of a healthier substance, and we're gonna show a few trials looking at that. And if we we're talking about most supplements, um, this is where the talk would end. This is where we say, boy, we have this nutrient. It looks to be pretty healthy. We have some preliminary data which suggests that might be healthy, but we don't really just don't know. We don't know beyond that what we're gonna find. And so the nice thing about officials, we have really large, well done randomized trials. Looking at the benefit from a cardiovascular standpoint, you don't care if the fish oil lipids or triglycerides you care if you're less likely to have heart attacks or strokes or death from coronary heart disease. And so, luckily, we have six different trials looking at this. So the first trial comes back in 2012. And again, these are our official states from the modern era. So this is in the setting of good statin therapy. Good little during therapy, good blood pressure control, lower rates of smoking. So, in the modern era, what exactly does special supplementation do? And so this is the origin trial, and it's a well done study. 12,000 patients at high cardiovascular risk They either had known cardiovascular disease or diabetes, simply randomized to 1 g official today. So relatively low dose but 900 mg of E P. A and D. H A. There followed for over six years and looked at an outcome of cardiovascular death, and they found really no significant benefit. There was no reduction in cardiovascular death in here. In the secondary outcome, there's no reduction in heart attack or stroke or dying from cardiovascular disease, really no significant benefit that they could find despite triglycerides coming down a little bit and despite inflammatory markers coming down a little bit just a year later, we have the study from the Risk and Prevention Study Group and a very similar design to the origin trial. Over 12,000 individuals at high cardiovascular risk so multiple risk factors are known a theocratic cardiovascular disease. But they could not have a prior m I. They want to exclude that group. And so same design of 1 g of fish oil versus uh, no fish oil minimum of 850 D H. A and E p. A. So similar to the prior study, followed for five years with outcome of death from cardiovascular disease or hospitalization due to cardiovascular is a little bit of a broader outcome and still no significant benefit. Um, didn't seem to reduce the rate of those things. Despite a pretty large study. This is an adequate sample size to figure out if this should be a benefit, and they really didn't see any benefit. And then the other trial that recently came out was the vital try. And I think this is really informative. And so there's a study out of Boston. Um, this is over 25,000 people, almost 26,000 individuals, and this is really more of a primary prevention study. So this is I'm 55 years old. I want to do whatever I can to reduce my cardiovascular risk. I wanna be as healthy as I can be. I'm eating a healthy diet. The question is, should I take a fish oil supplement on top of that? And so it was. 1 g of fish oil versus placebo followed for five years, similar cardiovascular outcomes, and again they just didn't see any reduction in cardiovascular events, an 8% reduction that was not statistically significant. And so overall, a negative study. It's a large enough study that I can look at other outcomes. Um, official is proposed to be anti inflammatory, so potentially that could be cancer reducing. Um, in this trial, there was no reduction in cancer, didn't see any cardiovascular, any cardiovascular benefit or any cancer benefit in terms of the secondary outcomes. Um, there was a reduction in total am I? And so we get a little hint that maybe there's something there that maybe there is something beneficial. There was less heart attacks at 28% reduction. Um, and people randomized, official and overall rates of M I were low, but potentially a hint of of a benefit there. And the nice thing about these large studies is that you can do subgroup analysis. You can look at different groups and see if one group is more likely to benefit than the other. And their subgroup analysis really didn't show anything except for one area. So look at if you look at it by baseline fish consumption. The people that average less than 1.5 servings of fish per week had a significant 90% reduction in cardiovascular death. Am I in stroke Where is the people that averaged more than that had no reduction. And so if this were just a random finding, I don't know if we put much stock in it, but this really fits with what the science has shown before and that this is a threshold relationship. If you don't have any seafood, your diet, getting some seafood helps. And if you're not taking seafood, fish oil might be able to take that place. And so, for people that average a very low intake of fish, taking that daily fish oil pill seem to be of cardiovascular benefits. So this fits with the prior science. And so I talked about this with patients a lot, Um, and they say, you know well, with different supplements, I say we have pretty good evidence that these don't seem to work very well, and they said, Well, maybe they weren't taking enough. And so the answer to that in this situation is that we have the strength trial. They took what they were doing before, and they cranked it up. They said, Well, let's look at 4 g of fish oil a day, and so this is 13,000 people with high triglycerides and low HDL and elevated cardiovascular risk group. That should be ideal for an intervention if there if the intervention works. And so this is 4 g official versus a placebo, which is corn oil and again similar cardiovascular outcomes for the primary outcome. And unfortunately, after 3.5 years, the Data and Safety Committee said. Boy, we don't see anything here. We think this is really unlikely to show a benefit. And so they stopped due to futility. And so, after 3.5 years earlier, was no benefit with taking a high dose of a balance of E. P A and D H A um, they really didn't see any evidence of any benefit, even in subgroup analyses. And so, from a standpoint of a combined pill that has E. P A and D. H A, the evidence is pretty weak. We don't seem to have any benefit for people benefiting from taking that even in high risk individuals. Unless potentially you don't have any seafood in your diet, then it might make a little bit of sense. However, that's a little bit different from purified EPA, as we talked about. If we look at EPA versus D. H A. It seems like the EPA potentially is the one that has more cardiovascular benefit. And so we have two trials looking at EPA alone. Um, and again, from a food standpoint, you're not going to get that in a food. This has to be in a supplement form and really in a medication for, um And so in 2000 and seven, the jealous study was was published. And so this is 18,000 people in Japan. Um, it's about 70% women, uh, 45 to 75 years old with Hyperloop anemia. And so this was a mixed group. This was primary and secondary prevention, and the interventions were either a Staten plus 1800 mg of E p a. Some kind of a moderate dose of e p a versus a statin oil. And it was a pretty low dose that I think it was five of simvastatin and so followed for almost five years. Primary outcome was a major coronary event. And if you look at the changes in lipids again, the control group is getting a statin. So when the control group cholesterol went down and it went down pretty similarly, and the people who got e p. A with the statin. Same thing for LDL. Same thing for HDL. The only thing that changed from a lipid standpoint was triglycerides. The trigger sides were reduced and people who got additionally P A in comparison to the statin. But overall, the reduction with triglycerides was relatively modest. And yet, despite that modest reduction, we see a decrease in cardiovascular events, and so the rate of any major corner event was decreased, the rate of myocardial infarction was decreased and the rate of death from cardiovascular disease was decreased. And so here we see a benefit with puree pH that we haven't been seeing with the combined G p a. D. H a pill. And then, more recently, we have to reduce it trial. And so this was kind of increasing the dose even further. So vast people, which is the medication studied, uh, is a purified dose of e p. A. And this was looked at 4 g, so 2 mg or 2 g B I d. And so this is pounds of salmon a day. This is not a nutritional study. This is a medicinal study. And so this is 8000 people at high cardiovascular risk. They had to have high triglycerides as well, but then a normal LDL. So people that are adequately treated with lipid lowering therapy The question is, Does adding masipa further reduce their risk again followed for five years? Like the other studies similar end point to the other studies. And here we see a pretty substantial reduction in cardiovascular risk at 25% relative risk reduction. But overall, the event rates in this trial work quite high, and so you get a 5% overall reduction in absolute risk for cardiovascular disease, and so that equates to a number need to treat of 21. So you need to treat 21 people for five years with the CEPA in this setting to reduce an event. And so for a preventive medication that's actually pretty low, most the other ones come out as 40 to 50 or even higher, quite a bit higher, and so a pretty substantial benefit from taking high dose E. P. A. And in the subgroup analysis, whether you're old or young or different races or different genders or different diabetic status, it really didn't seem to matter, including by lipid status. I think this is important, the people that high triglycerides seem to benefit quite a bit and the people that have low triglycerides and I should say people had moderately elevated triglycerides seem to benefit quite a bit, and this is very similar to what we see with the status where the relationship is probably linear. Wherever your triglycerides are lowering, it lowers your risk. Mhm couple Other points worth mentioning there was a slight increase and reduce it in the LDL group are in the placebo group. Um, so mineral oil might inhibit absorption of your status a little bit. And so we saw a slight bump in LDL in the placebo group, which they weren't expecting, so this was controversial when it came out. But the FDA review this pretty intensely and said, You know what? We feel pretty confident that this really didn't impact the results. This probably shouldn't factor in our decision to use a pacifier or not. There was an increase in atrial fibrillation, slash atrial flutter in both those arrhythmias, and so a little bit over a 1% increase or not a huge increase. But given that we talked about, you know, e p A and D H having a membrane stabilization, a decrease in arrhythmias sort of thing. This is a little bit surprising. And if we're the only study that showed it to be one thing but in strength, which was the high dose? E p a. D h A study, we just looked a little bit ago. There also is a slight increase in a fib. This seems to be something that's real, its modest and increase. But it's probably something worth discussing with our patients, and they already have a predisposition to field, but something that we might want to factor in. Um, also, we saw a slight increase in bleeding. This was not statistically significant, but about a 0.5% increase in serious bleeding. Given that it has some anti platelet effects, that's something probably again worth factoring in. But there was no fatal bleeding in either group, and so a pretty small increase overall. And so one of the questions is that we have these multiple trials with a combination of D h A N E p A. That don't seem to show any benefit. Why does hired O. C. p a. Have a benefit. Um, I showed this. Reduce the trial here. They measured up a level, and there's about a 300% increase in pay levels and the people that got the real thing and people that get placebo. But in the strength trial, that combination high dose one, there's like a 250% increase in pay levels. And so the question is, is, does D. H a somehow negate the benefit of EPA, that slight increase in LDL and that membrane instability that causes more cholesterol coming? Does that negate the benefit of EPA, which then raises the question? What exactly is the mechanism of benefit for EPA? Is there something else beyond decreasing, setting cardiac death that makes EPA beneficial? And so we do have a mechanistic study here, which I think does shed some light on that. And so this was just recently published its 80 patients who had a CT coronary angiogram that showed plaque and they were on statin therapy, and they had high triglycerides, and they simply got randomized to via SEPA versus a placebo again. And then they underwent a repeat c t. A 18 months later, and looking mainly at plac progression. How does the Vespa affect plaque progression? And pretty clearly it seems to be a beneficial thing in terms of plaque progression. These red bars here are your placebo group, and the people that got the placebo had plaque progression over time, and this is total plaque and calcified plaque. But the main thing we really care about is this low attenuation back. This is the soft plaque, the plaque that's most likely to be associate with an acute coronary syndrome, people that were on the placebo. It very clearly progressed over time and progress by a fair amount. Conversely, the people that got the bicep a actually had a regression and soft attenuation plaque. So it seems to be beneficial and regressing black not only in stabilizing it but making it go backwards a little bit. And so we seem to have this mechanism that with high dose C p A. We not only see a reduction in maybe sudden cardiac death that we see with normal, efficient take, we also see an anti pathogenic component. It seems to reduce plaque over time, which is likely the main mechanism of benefit. So overall I think it's pretty clear that polyunsaturated fats, including omega three fatty acids, are essential nutrients that improve cardiovascular function. Seafood, especially fish high in EPA and DHA, are an important part of a heart healthy diet. That being said, routine fish oil supplementation is not really supported by the large randomized trials. It's just way better to eat the real thing. And we see this again and again in the supplement world. We have all these foods that are very, clearly very healthy for us, and for some reason we want to be smarter than food. We want to try to figure out what about that Food is healthy. Let's take it out of that food and put it in a pill, and that will be even better. And yet we have trial and trial and trial again. That shows that that's not the case. It's just way better to eat the real thing. If you don't like seafood or if you don't have access to it, then taking official supplement is probably a reasonable option for people that are at high risk and have higher triglycerides be. Super Height is moderately elevated despite a healthy diet and despite good little going therapy, then Masipa is very clearly an evidence based option to reduce the risk, and it's very important. Masipa is not fish oil, right? What's 4 g VP? A. Like I said, that's not a natural thing at all. Necessarily. Sometimes I talk about the steeple of patients. They all take official instead. No, that's not how this works is very different. And so if you're at high risk, you wanna reduce it further. The CMP is potentially a reasonable option. So I hope that was informative. I'm gonna hang around later for questions. If you have any questions, please send them to our, um, to our moderator, Dr Saxena and Dr Monju. Pie is going to talk now. He's a great colleague and a good friend, and he gets great talks. And so I hope you enjoy that as well. Thanks. Hello, everyone. Thank you for having me. I don't have a dog, but I have two young kids who love to freak out. So I think I'm in a safe space as well. Um, so I understand that electrophysiology is the esoteric field in the corner. And the goal of my talk today was to discuss some of the newer data articles and technologies which are relevant for the non EP for for primary care for emergency medicine. Etcetera. Um, and so we'll be discussing some data with atrial fibrillation and just some technology with device management, and I thought would be more fun to talk about it in a case presentation format. So the first case is I, 65 year old female who was diagnosed with symptomatic atrial fibrillation about four months ago. And at that time she underwent cardioversion and she had appropriate therapy. Uh, modifiable risk factors were addressed. She was diagnosed with sleep apnea. She's been wearing her CPAP Um, she reduced her alcohol intake. She's been exercising, and she's lost about £15. However, despite all of this, she now presents with a recurrence of her symptomatic atrial fibrillation. Her rates are not well controlled. Um, and so the question goes back to rate control versus rhythm control. Should we should we try a beta blockers? Should we attempt rhythm management? And we all know there's a number of trials that have addressed this in the past, most popularly affirmed, and the general consensus was that there wasn't an improvement in hard endpoints such as mortality screen, ischemic stroke, etcetera. So there were some post hoc analyses, firm etcetera, that suggested maybe a lower mortality with Sinus rhythm. And oftentimes, rate control is often chosen In situations like these, rate control medications are easy to use. They don't require as much monitoring unless there's something outside of the ordinary. So why do we have such poor results with rhythm control? You would think, at least intuitively, by being in Sinus rhythm, people would do better. Um, it would be more effective, et cetera. Um, one problem is that our anti arrhythmic just aren't very good. The efficacy is sub optimal, even infirm. The crossover rate was just a little below 40% from going from rhythm control to rate control. And there is a plethora of adverse associated events, including pro arrhythmia, um, and more minor things that are just that make it more difficult to take the medication, such as fatigue or dizziness, etcetera in the interim. And the reason why there have been more studies recently is that there have been advances in atrial fibrillation ablation our ethics. He has improved. There is a decreased risk of complications as we recognize how to handle them. And I believe that we now have a better understanding of who the more appropriate patients are for this type of procedure. Um, this was a study published in The New England Journal about the end of last year called East F. Net Ford. And it was a randomized, multi center trial. And it had about a little under 3000 patients with atrial fibrillation who these weren't lone atrial fibrillation to Chad's basket two or greater. And the important thing that I really want to point out And the crux of the study is that these were patients who are diagnosed with atrial fibrillation less than one year ago. So these were newer diagnoses, and a third of the patients in the study had one episode of atrial fibrillation before enrollment, and they were randomized to rhythm control, where 20% of them received ablation in two years versus usual care, which is really control, with about 15% crossing over. And the primary outcome was a composite of cardiovascular death, stroke, cardiovascular hospitalization, and this was a positive study, and we saw that those undergoing rhythm control, um, had a decrease in the primary outcome. So much so that was stopped for efficacy. Um, and just as importantly, um, when dealing with the violation, the primary safety outcome was similar between the two groups Are not statist statistically significant? Uh, there was a slightly higher risk of adverse events in the rhythm control group, but that was felt to be due to bradycardia from some of the medications. Um, I thought this was interesting that the nights spent in the hospital he per year between the two groups was not statistically significant as well. I I presumed, intuitively that by putting someone on a rate control medication, they'd be in the hospital less. You weren't starting anti arrhythmic. You won't bring them in for an inflation, et cetera, But that wasn't necessarily the case in the study. So the question is, why is there a difference between this trial and some of the prior rate and rhythm control studies that we know about? Um, one anti arrhythmic therapy still hasn't progressed markedly over the last couple of decades. Ablation therapy has gotten better, but I think the main key, uh, take away from this trial is that patient selection may be key, and that earlier intervention may actually improve outcomes. Um, this is kind of our rudimentary classification of atrial fibrillation. Paroxysmal, persistent, longstanding, persistent, which really just defines it based on how long someone stays in atrial fibrillation. But what is getting at is the longer that someone can stay in atrial fibrillation, that there's progressive atrial remodeling, fibrosis and eventually atrial fibrillation begets atrial fibrillation. This is just one MRI study where it shows that people with uh longer histories of atrial fibrillation have more atrial scar is seen by the green areas on the MRI of the left atrium here. Additionally, there is maybe some evidence that when choosing a rhythm control strategy, early ablation may be better than anti arrhythmic therapy, and it may be safe. There were two articles published in the New England Journal over the last month, called Earlier and Stop, which were fairly similar trials. Um, but just to go over one of them briefly. Earlier, it was a randomized trial with paroxysmal atrial fib, and the key thing to note here is all of the people enrolled in this trial were previously untreated in any fashion for the atrial fibrillation. They were randomized to anti arrhythmic drug therapy versus cryo ablation. And what was interesting is they were monitored for a year and they actually had a loop recorder and planted to evaluate for recurrence of atrial fibrillation. And again, this was a positive study favoring the ablation group. And they had a lower incidence of documented arrhythmias, and it was also felt to be, uh, to be safe. So, um, we'll jump to our next case and, uh, slightly similar, slightly different. So this is a 60 year old gentleman with no past medical history. He comes in with a new diagnosis of atrial fibrillation with rapid ventricular rates. And he's in heart failure. Um, he has an ejection fraction of 35%. Uh, doesn't appear to be ischemic, and he's initiated a guideline, directed medical therapy, anti coagulation, and he undergoes a cardioversion and amiodarone was initiated a few months later. He's doing well. He's maintaining Sinus rhythm, and his ejection fraction is normalized. This looks like a attack of cardiac mediated cardiomyopathy. So the question is, what do we do now for the long term management in regards to his atrial fibrillation? One. Do we stop the amiodarone. Do we continue the beta blocker and just monitor the recurrence? It's not the wrong answer. Um, there's probably a 50% percent chance or greater that he will have some recurrence of atrial fibrillation in the future. To do we switch his anti arrhythmic, since he's young to an anti arrhythmic that has less potential for long term toxicities than and deodorant such as settled law. This is a very reasonable option or three. Do we consider capital revelation? So Castle AF was a study published in The New England Journal about 2.5 years ago. Now it was a smaller study about 360 patients multi center randomized, um, with people with atrial fibrillation with heart failure. Today a functional class 2 to 4 and an ejection fraction less than 35%. They were randomized to capital ablation or some type of medical therapy, either rate or rhythm control. Um, and the primary endpoint was a composite of all cause death or heart failure. Hospitalization. This is a busy table, one slide, but all I want to point out is that this was a very niche demographic, and so these were all primarily middle aged men, and they were on the healthier side of six. So they were closer to N Y H A two rather than four. Um, their ejection fraction was closer to 35% rather than 20%. All of these people had I C. D s and the majority were implanted for primary prevention rather than secondary prevention. So they were on the healthier side of sick, and this was again a positive study favoring ablation and the composite endpoint of death or cardiovascular hospitalization favored the ablation arm. But when you took these apart and you looked at both death as well as heart failure, it again favored the ablation groups. So you saw that about five years in this small study, there appeared to be a mortality benefit for proceeding with ablation in those otherwise healthy people who had atrial fibrillation and atrial fibrillation potentially lead to articular. That's what the hypothesis is from this study. Um, what's also interesting from this study is that even the people who benefited from this ablation, which are from from intervention, still have some recurrence of atrial fibrillation, less so than medical therapy. But they still have some recurrence. And so the question that can also be asked is, Can success of atrial fibrillation ablation be defined more by a reduction in the atrial fibrillation burden rather than, um, complete complete success of not having any kind of recurrence? Um, there have been some other heart failure trials that have possibly suggested this as well. The largest trial we have this cabana, which was about 2200 patients. Um, and there was a lot of controversy about this trial, Um, one, because the primary outcome was to change midway through because they weren't able to achieve sufficient power. Two, there was a lot of crossover, and so depending on how the statistics were performed, it was either a positive or negative study. But at least in the subgroup analysis, um, it also showed benefit for those undergoing ablation in regards to a positive death, stroke, bleeding, cardiac arrest, or all cause Kaz mortality. And this was primarily people with half path where people with a preserved ejection fraction in about 20% at an ejection fraction less than percent in that in that subgroup analysis, and there's been multiple studies that have favorite ablation for soft and points like improved quality of life, improved ejection fraction, decreased heart failure, hospitalizations, etcetera. So again, the question is, why is there a discrepancy between this trial and prior trials? Um, one again. There may be a benefit at an earlier stage of disease, but to there may be a benefit in the heart failure population as well. Um, more so than someone with a preserved ejection fraction anti arrhythmic drug therapy or beta blockers. Calcium channel blockers can be much more difficult to take. So, um, we'll switch gears again and go to another case. And this is a 90 year old female with diabetes and hypertension, and during an exam. She's an incidentally, found to be in atrial fibrillation. The rate is well controlled. She's asymptomatic and, appropriately, a rate control strategy or permanent A s strategy is is undertaken. So the question is, does the choice of oral anti coagulation matter? Um, I would say most likely not. But I wanted to point out that in the New York focused update from the H A. C C that there's now a class one, a recommendation for no acts above warfarin. And the reason for this is there has been now for randomized trials, comparing no explore fair in that have shown non inferiority to warfarin for stroke and systemic embolism. Um, and the no acts appear to have a superior safety profile. Pics. A band appears to have a lower risk of bleeding. Importantly, for intra cerebral hemorrhage, improved efficacy for stroke prevention. There's been a couple of studies. It's unclear whether there's causation or whether, uh, coincidence about a lower risk of adversarial outcomes, meaning progression of renal disease and possibly a lower risk of osteo product fractures. I still think the major determinant is cost. And so if it's breaking someone's budget to be on a no AC, it still makes a lot of sense to be on warfarin. Um, so when is warfarin preferred? Um, prosthetic heart valves, obviously mechanical valves. I think a lot of people choose for foreign for bio prosthetic valves. Uh, there was a recent study in The New England Journal. It was a randomized trial for patients with atrial fibrillation and a bio prosthetic mitral valve, showing that river rock span was non inferior to warfarin. Um, other indications include severe liver and kidney disease. A pixel ban is the no activist at least dependent on renal clearance pregnancy, anti fossil lipids, lipid syndrome, abnormal GI anatomy, such as post gastric bypass surgery. That's not a contraindications. It's just that you should approach it with caution. I think that some people do have trepidation about not understanding someone's G I metabolism. And you don't have the ability to monitor lab tests such as the i N r. For warfarin. Um, a brief forward about left atrial appendage Occlusion devices. Uh, watchman is the commercial device in America. Um, it's approved for people who have, uh, significant risk for streaming, ischemic stroke or systemic embolism. So Chaz basket two or greater, and they have contra indications to chronic oral anti coagulation. So they've had bad outcomes with being on a blood thinner, so it's still not approved for people who need a blood thinner. But I just don't want to be on one can't afford one et cetera, though there are trials headed in that direction. Um, and this is the typical post implant protocol. Um, while the device and the little guys is, uh, they need to be on a blood thinner, plus aspirin for about 6 to 7 weeks there on dual anti platelet therapy until about six months. And then they're all single anti platelet therapy. The next case is an 85 year old gentleman, his permanent atrial fibrillation and stage renal disease. And he was recently placed on hemodialysis, and he comes in with fatigue. This MC lightheaded e k g. Is done, which shows his underlying known atrial fibrillation. He's in what appears to be complete heart block with a slow escape rhythm. Um, so this is a gentleman who needs a pacemaker. Traditionally, a trans Venus single chamber device would be chosen. But there are downsides to this. Um, by putting a wire in a vein in the subclavian vein, etcetera, um, it sets the stage for possibility. Future downturn downstream. Venous occlusion thrombosis. It can be difficult to put in a port, obtain hemodialysis access. Um, the lead crosses the try. Custom valve can lead to worsening. Try custom valve regurgitation. Um, the risk of infection is not trivial, which can progress to endocarditis. The pocket itself can be infected. Someone with the local pocket infection who had skin erosion, and you can see the hardware underneath. Um, and then removal of the device is associated with nontrivial morbidity and mortality. Um, this is a lead that was taken out, and you see the fibrous cuts throughout the length of the lead, which can attach the vein, which can tear during the procedure and cause significant harm. Um, so that sets the stage to lead this pacemakers, which I'm sure many have heard about. Um, Micra is the commercial device in America right now. Um, the benefits of the devices. There's no lead in the vascular space. There's no generator. Pocket presumably does not interfere with the valve and appears to have a lower infectious risk. You can see a chest X ray here, and you can see the device sitting, uh, in the right ventricle over here. The downsides are right now, we just have ventricular devices. Um, there's research underway for atrial B list pacemakers. Um, but a V synchrony is limited, and so this is great for someone who is in permanent atrial fibrillation and doesn't need any synchrony. But someone who's still in Sinus rhythm. It's a little more limited now. There have been improvements over the last year, so where these devices do provide a limited amount of 80 synchrony. There's been some very nice software updates, which can sense atrial contractions and track the and paste eventual based upon that. But, um, the algorithms aren't perfect, and, um, they could be better. Battery life is also less. It's about 5 to 8 years, compared to maybe about 8 to 14 years. And so it requires more frequent changes and the device can't be removed. So when it's time for a new one, you're implanting a second device next to the old one. Um, alongside this, I'll finish up with subcutaneous I C. D. S. And so, for the same reasons that we don't sometimes want to implant a trans Venus pacemaker, we don't want to implant Trans Venus. I see it. So these have been out for a while Now, um, you have a device sitting typically under the left arm in the subcutaneous area, and the whole device resides in the subcutaneous space, so it goes underneath sternum and it goes over the breastbone. Um, the downside of this is that it's a larger device, So because it's external, it requires more power to defibrillate. The heart and the can is significantly bigger and can cause more discomfort again because it's external. There's limited pacing support. There's also a higher risk for inappropriate shocks. Since there can be sub, they can be tissue in between the lead and the heart. Um, I'll try not to bore you with this, and I'll just focus on some particulars. But this is a tracing from the device interrogation. If you look at one of these lower slides, you can see that this person is in Sinus rhythm, and there's a Q R s and the T wave, the cure s and the T wave. And you see this little little s letter. And each time it says s the device senses that there's a Q r s. So there's a QRS QRs. If you go to the top when this patient is in possibly a Sinus tachycardia, it's over reading this. So it's sensing the QRS. But it's also thinking that this T wave is a Q. R s. So even though this patient has a heart rate of, say, 100 125 it thinks the heart rates 250 thinks this person is in ventricular tachycardia delivers an inappropriate shocks. So that's one of the major downsides of this device. Um, what we have just started enrolling patients in is a substantial subcutaneous I CD. So same principle. The device, um, is on the lateral side in the subcutaneous area, but when the wire reaches sternum, it is actually tunneled underneath, so it's sitting on top of the heart. So there's left. There's less, um, interference between the lead and the heart. This is not This is not an open heart surgery. It's tunnel underneath. And so what that means is, can is smaller. It's the same as a typical trans Venus I C. D um, and it allows for limited pacing support as well. And we we just started enrolling in this a few months ago. Um so to summarize, uh, in regards to atrial fibrillation. But those with symptomatic atrial fibrillation or pouring control, a rhythm control approach may be beneficial, especially in people with the recent diagnosis. Um, in those with the associated heart failure. Catheter ablation may also be a superior intervention. Oral anti coagulation jokes are not inferior to warfarin. They may have a better side effect. Profile pacemakers. Leaderless pacemakers are a reasonable option, especially for those who do not require a V synchrony they have poor venous access or their high risk for future infections and subcutaneous ICDs are also a good option for those who do not require pacing and thank you for your time. And I'm also here for questions.