The Omega-3 Index and Heart Remodeling

OmegaMatters: Episode 32

Hosts: Drs. Bill Harris & Kristina Harris Jackson

Guest: Dr. Raymond Kwong

Background and Key Takeaways:

Dr. Raymond Kwong, Director of the Cardiac Magnetic Resonance Imaging or MRI Center at the Brigham and Women’s Hospital. And he’s an associate professor of medicine at Harvard Medical School. Dr. Kwong is most interested in studying the heart and how it remodels itself or heals itself after a heart attack. In this episode, Drs. Harris and Jackson speak with Dr. Kwong about how omega-3s play into the heart remodeling process when someone experiences a heart attack or other heart-related event. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/

 

SHOW TRANSCRIPT

Dr. Kristina Harris Jackson: Welcome to OmegaMatters, where we talk all things omegas. I’m Kristina Jackson. This is my dad, Bill Harris. And today, we’re welcoming Dr. Raymond Kwong, Director of the Cardiac Magnetic Resonance Imaging or MRI Center at the Brigham and Women’s Hospital. He’s also an associate professor of medicine at Harvard Medical School. Dr. Kwong is most interested in studying the heart and how it remodels itself or heals itself after a heart attack and how omega-3s play into that process. So welcome, Dr. Kwong, and thank you so much for talking with us today.

Dr. Raymond Kwong: Thanks so much, Kristina and Bill. It’s so nice to see both of you.

Dr. Kristina Harris Jackson:  Yeah.

Dr. Raymond Kwong: Yeah. So this is an area that I’ve been interested in for many years in the peri-infarct or acute coronary syndrome period, when the patients are going [00:01:00] through a very high risk towards their future outcome. The reason I’m very interested in this is that we’ve had very effective therapies for now, 20 years, in revascularizing the heart, in stabilizing the heart muscle, preventing further, for example, preventing arrhythmias. And I think medical therapy has come along very nicely. And heart attack survivors now enjoy, [00:01:30] overall, much improved event-free survival in the few years after the MI (myocardial infarction).

In terms of the short term, the mortality has dramatically reduced primarily because of better intervention. Nationwide, there is a very high availability for 24-hour cath lab, urgent intervention, primary angioplasty, or [00:02:00] stenting of the acute vessel. So mortality is improved. However, the chance of having heart failure related to a substantial injury, that actually has not changed much at all in the last 30 years. And indeed, with better patient survival, overall, in the short term, patients end up living with heart failure, and the one-year heart failure incidents after a heart attack has not changed. If anything, it’s actually probably going up.

So one of the [00:02:30] issues is that we don’t have a very safe and specific therapy to improve the heart muscle. From salvaging the heart muscle, the initially injured heart muscle, the inflamed heart muscle, we don’t have a really good and safe and effective treatment to suppress inflammation and promote healing of the heart muscle. Now, a few years ago, there was the COLCOT [00:03:00] trial, which I should mention, is to use colchicine, and that actually showed very promising results. But there is still a very limited panel of medications that we have available to remodel the heart, bring the injured heart muscle back to a normal state and  suppress the inflammation, the prolonged inflammation. The initial inflammation is crucial for tissue healing. But a prolonged inflammation or inability [00:03:30] to remodel, to reconstruct the heart muscle, can actually lead to heart failure.

So I think that’s something that I’ve been interested in. And omega-3 fatty acids, the different formulation is certainly one class of medications that seem to be promising in terms of anti-inflammatory effects but also anti-arrhythmic effects and a whole host of other benefits to the heart muscle. So I was interested and got to collaborate [00:04:00] with Bill on several studies. The main one was a randomized controlled trial that we recruited in Boston, from three major teaching hospitals. We recruited 358 patients over a two-year period. And then we’ll followed them up for a few years to look at how the heart changed.

Dr. Bill Harris:               Ray, can I stop you right there?

Dr. Raymond Kwong: Yeah. Sure. Right.

Dr. Bill Harris:               I think the word remodel probably doesn’t make a lot of sense to [00:04:30] layman. What do you mean by the heart remodels?

Dr. Raymond Kwong: Yeah, that’s a great question. Remodel is the way… If you look at the literature, there are several different ways to look at the heart structure, and there are different definitions. So the way is the heart, the left ventricle, the shape, and the function, how it changes over time after an injury or an acute event. It could be a heart [00:05:00] attack, could be a myocarditis, and it’s a general term to look at how the heart restores the structure and its function, how it restores the energy of the heart, so that it can pump blood effectively.

So remodel is, there are positive remodel, there’s also negative remodel. The negative remodel tend to be what we mean by the heart being dilated and impaired in systolic function in the heart. The way it pumps blood is impaired, and that’s so-called adverse remodeling. And there are different definitions [00:05:30] in the literature about how to define like 10% reduction in EF or 15% increase in the size of the left ventricle. There are different definitions.

Dr. Bill Harris:               And this happens how long after you have a heart attack? How long does this take?

Dr. Raymond Kwong: That’s a great question. So it happens in general. The heart has initial damage, but it can continue, the first six months, in the literature that, depending on the different types of injury, myocarditis or infarct, but let’s say [00:06:00] for the argument, for acute infarction, a substantial heart attack can take up to six months to improve, to finalize how the heart will end up settling, in terms of dilatation and function.

Dr. Bill Harris:               How do you measure that?

Dr. Raymond Kwong: Yeah, so that’s a great question. There are many ways of measuring the structure and the function. Historically, the most available tool is by echocardiography, which is an ultrasound [00:06:30] the heart. In the last two decades or so, the improving technology, using cardiac magnetic resonance, which is more precise, which is a three-dimensional technique that make no geometric assumption of the heart, is more accurate. So there has been a lot of studies and interest in using cardiac magnetic resonance, which is a noninvasive, no-radiation technique, to quantify the heart size and function.

It can [00:07:00] also look at the damage of the heart. That’s another unique thing about cardiac MRI, is it can look at the infarct size and look at the fibrosis, which is sort of the little bit of scarring in the area that is outside of the damage, outside of the heart attack. So all these benefit make cardiac MRI very attractive in studying remodeling.

Dr. Bill Harris:  Yeah, yeah. Okay, great. That brings us around to then the study you were starting to talk about, omega-3. It’s called Omega-3 Remodel or vice versa?

Dr. Raymond Kwong: [00:07:30] OMEGA-REMODEL.

Dr. Bill Harris: OMEGA-REMODEL.

Dr. Raymond Kwong: OMEGA-REMODEL is the main, we’ll call it a parent study. And then we studied a little further about the patient’s effects in certain subgroups and certain conditions such as the genotypes. So we study and publish a few other papers from the original dataset.

Dr. Bill Harris:               Yeah-

Dr. Kristina Harris Jackson: Okay. So I’m going to tell the details of what that study was, so people can go find it. So the first paper we’re going to talk [00:08:00] about is, the first author is Bobak Heydari, I don’t know if I’m saying that correctly, published in circulation in 2016, and the title is Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction. So you started to give us rationale, study design, findings, so just give us kind of the overall basics. And then we want to talk about why you think this might be happening, the mechanisms.

Dr. Raymond Kwong: So [00:08:30] it was a very exciting study to us. This is about 10 years ago now. But we felt that we had such a strong need for a therapy to suppress in the acute phase, in healing the heart, improving the heart muscle. So the culprit blood vessel that caused the heart attack has been opened up in 98% of all the patients basically. But during this six-month period, we wanted to know if we could treat [00:09:00] with high dose of omega-3 fatty acids and make the heart stronger, so the patient has a lower likelihood of ending up with heart failure?

So we gave the medications to, divided patients into two randomized group. One group got 4 grams of Lovaza, which is a combination of EPA and DHA, about 50-50, about one-to-one proportion. The other group get the placebo. Both groups get the, [00:09:30] as much as possible, guideline-directed medical therapy, meaning that they get the usual as prescribed at the time of what the cardiology community considered to be the must-have medication. So both groups get exactly all the other medications, beta blocker, ACE inhibitors, as they need it, aspirin at the time, and other medications to prevent them from having further heart attacks.

So what we did was we looked at the [00:10:00] heart structure at the time they started on the drug, which is omega-3 fatty acid, or placebo, at around two weeks, two to four weeks’ time. And then we continued the treatment for about six months, and at the end of the six months, we brought the patient back. We repeat the cardiac magnetic resonance. And also, we collected blood samples and assessed how they did overall. And we found that the group that was treated with omega-3 fatty [00:10:30] acid, I would call them the Omega Group, the Omega Group performed substantially better on the MRI. And the heart was able to pump better. So the heart pump down to a smaller volume is a good thing. So we adjust it. We look at how much it comes down, adjusting to the size of the patient, so-called ESVI, end-systolic volume index, which is the reason [00:11:00] we chose that. That’s a very consistent marker to look at remodeling, how the heart can pump down, adjusting to the patient’s body size.

We also look at the area of the size of the injury, which is the infarct size. We’ll also look at the area that is outside of the injury, which is the fibrosis. Why is it important? Because it’s well known that if the heart did not remodel well, [00:11:30] if we did not treat properly, if there’s a substantial heart attack, the remote area, the area of the heart muscle that is away from the heart attack, will form fibrosis. And that’s a bad thing because the forming of fibrosis in the remote area triggers arrhythmia and heart failure over time. So we look at these three markers. We actually did not anticipate the injured, the infarct size to change much because that was determined by the primary event. Once it’s injured, [00:12:00] it is injured.

We are mostly interested in how the heart can pump down, because the rest of the muscle, if it does not fibrose, is able to pump down, the patient will do better. And suffice to say, it was exciting for us to see. We analyze the results in a double-blinded fashion, meaning the patients and the doctors, both of them do not know what the patients was taking. And when we measured them, we also [00:12:30] did not know what treatment the patient was assigned to. And at six months, the heart function, the ESVI, was substantially better or smaller in the Omega Group, and the fibrosis area was borderline, was significant, improved in the remote myocardium. There was less fibrosis. So the whole picture fit together very well.

Then we also look at the inflammatory markers. [00:13:00] We understand, we wanted to know, why is that the case? What caused these benefits? We look at the inflammatory markers that are very crucial to the survival of patients. Some of them are the not so surprising. The triglycerides level has gone down a lot because omega-3 fatty acid does treat that. But also, it

was exciting to know that some of the more survival-related markers such as ST2, ST2, which is a marker of remodeling and fibrosis, was substantially [00:13:30] driven down in the Omega Group.

So we’re very excited. The absorption of the omega fatty acids in this period by the patients were about two-and-a-half-time increase, which was exciting to us because we were also concerned that, what if the patients who were on the placebo arm just go out and start changing the diet and consume a lot of over-the-counter omega- [00:14:00] 3 fatty acid because they’re interested in the idea? It turned out to be not the case, turned out that the treatment provided substantial increase. And so that was actually the result because of the consistent and several lines of evidence, so a poll pointing to the same thing. It was published in Circulation, and we received a good amount of support to the results.

Dr. Bill Harris:               [00:14:30] So you mentioned you didn’t start the omega-3, still, two to four weeks after the heart attack, right… Why?

Dr. Raymond Kwong: Yeah, that’s a good question. We wanted to start earlier. At the time, this is back in actually more than 13, 14 years ago now. When we started the trial, there were some concern at the time that patients were getting a lot of these very powerful [00:15:00] anti-aspirin, so-called the antiplatelet medications, and they were getting very high dose because putting in a stent is a standard therapy. Some of these stents are drug-eluting stents, and that means that they have to be taking these super aspirins. At the time, they were taking both of them.

And there was a concern that some patients may even need to have a blood thinner for other reasons such as atrial fibrillation, and that combination and combining with omega- [00:15:30] 3 fatty acids, some clinicians were concerned that there is some histologic evidence from animal model that the clotting time of animals who were taking high-dose omega-3 fatty acids were prolonged, and patient may have increased likelihood of bleeds.

So we were strongly discouraged, and the IRB made it very difficult for us to give this amount [00:16:00] of high-dose omega-3 fatty acid. At the time, it was considered to be novel but also a boldly new change in direction in giving such a high dose. It turned out that when we actually analyzed our data years later, there was no excess increased bleeding at all in any of the patients treated with omega-3 fatty acid. So unfortunately, that means our trial started at two to four weeks.

Now, you brought [00:16:30] in a good point. Had we treated earlier within the first few days with high dose, I personally believe that there was a very good chance that would have made even a stronger impact, a stronger remodeling, and maybe even stronger benefits to those who took the high dose, because the first two weeks, a lot of the remodeling already has settled in, already had happened. So that will be for something that [00:17:00] we should address in future trials.

Dr. Bill Harris:               Yeah, yeah.

Dr. Kristina Harris Jackson: Yeah, that’s so interesting. So when they’re on standard of care, then they’re fully, basically, aren’t clotting, adding something, it seems like you don’t even have anywhere to go as far as being able to clot less than when you’re already on these pharmacological drugs. And the omega-3s do have a… It does extend bleeding time without having anything else on [00:17:30] board. So I just think it’s interesting that that keeps coming up. They think it’s going to add on top of the drugs as far as the bleeding goes.

Dr. Raymond Kwong: Yeah, that goes to the same… Based on my experience, clinicians tend to be much more conservative when it comes to a clinical trial. When it comes to treating clinical patients, they’re willing to take on new therapy when there’s an indication on the patients. Especially those who are sick, they were willing to take [00:18:00] on any risk. When it comes to a clinical trial, the patient’s otherwise seemingly doing okay treating, they will be wary of every little thing, every little concern that is in the literature. What if this caused an issue to this patient?

So they tend to be more protective, which I can understand. But I think that, over time, I think that’s less of a concern. For example, [00:18:30] locally, I can say that with the results of OMEGA-REMODEL, and also, in a great extent — the benefit certainly outweighs any increased risk of bleeding. And I personally don’t think there is an increased risk of bleeding at all, given the current evidence of omega-3 usage.

Dr. Bill Harris:               Great.

Dr. Kristina Harris Jackson: [00:19:00] Yeah, that’s just a fantastic study, and especially, when all of the different endpoints that you measure all point to the same direction. In conjunction with having the proof that you had good compliance, you had higher blood levels on that group, it’s just a really tight story. It’s really nice.

And so you said you’ve done a lot of secondary analysis on this study. And the paper that we wanted to look at was just published in 2024, January 2024. It’s entitled [00:19:30] Effect of Six Month’s Treatment with Omega-3 Acid Ethyl Esters on Long-term Outcomes After Acute Myocardial Infarction, The OMEGA-REMODEL Randomized Clinical Trial. This first author is Bernhard, and it is published in the International Journal of Cardiology. So can you set this paper up and tell us why you decided to do this analysis?

Dr. Raymond Kwong: Yeah, that’s a great question, Kristina. So it’s always been our plan to understand the [00:20:00] clinical outcome because understanding remodeling is very useful. But from a mechanistic standpoint, we know what the heart is doing is very believable that that’s a very good marker of future outcome. In fact, in the post-MI period, the single most important marker to determine the patient’s outcome is remodeling. So we already addressed that. We know we conquered that. There is a good mechanism [00:20:30] that the heart is actually feeling better, doing better, and at a mechanistic level, the omega-3 fatty acid is beneficial because of the different lines of evidence. But we still don’t really know. We still want to know what is the actual event that happened to the patient.

Now, OMEGA-REMODEL was a small study. It’s only 358 patients. And these days, as I mentioned, patients overall, [00:21:00] it’s a good thing that the overall risk of a bad outcome after a heart attack, actually, is reduced a lot compared to a few decades ago, in the first year, which is the higher-risk period. Even that high-risk period is driven down to 5- 7% of bad outcome, what happened to patients, even with substantial heart attack. So with that backdrop, that means that to understand the outcome of these patients, of this small [00:21:30] number of patients split into two groups, we have to follow them longer. We have to let time figure out. We have to have further understanding because some patients are not going to develop heart failure until years later.

So we follow them for about eight years. And that’s why it took so long for us to publish this paper. We follow them every year. In fact, most of them we’d follow every six months, and then we still give advice about how they’re doing [00:22:00] and so forth, the many patients who are very appreciative and stay in the study. And we follow, as much as possible, everyone after eight years, and then we have enough numbers of good events but also not very good events. We need to have enough proportion of patients with unfortunately bad events before we can answer the question whether omega-3 fatty acid has an impact.

And we actually observed that. There was a significant [00:22:30] difference, the remodeling, which is in line with the remodeling. Those patients who actually increased their Omega-3 Index level in the blood sample, if they were initially able to change that, they did a lot better clinically down the road, meaning that they had less chance of dying from a heart-related disease, a heart-related cause, [00:23:00] or coming into the hospital with clinical heart failure. So that was significant. But only we observed that, only seen that in those patients who was able to show that they absorb a lot, they were able to change a lot.

Now, they could either have a poor, a very low omega-3 fatty acid index to start with but increase substantially. But they have the increase by 5%. [00:23:30] Now, that has important implication because I think that it’s true that in patients in this part of the world, in North America, they tend to have a relatively low Omega-3 Index to start with. The average was about 3%, which is substantially lower in some other countries such as Japan and Korea. So 3 to 4% is fairly low. But if they can mount it to about by five [00:24:00] points, that’s when those patients tend to perform a lot better down the road. So this is important because this is actually an objective assessment of what they did clinically as opposed to an indirect assessment of what was happening at the heart level.

So I think that we need a larger study because this is, again, it’s a small study. We observed that, overall, the assignment did not change, did [00:24:30] not seem to be a direct factor in driving better outcome, but it’s the patients who had a high Omega-3 Index had a good response. Whether have we studied a lot larger number of patients, maybe we’d have seen a bigger response, had we treated them early, we’d have seen a bigger response, it’s beyond the context of this study. But it will be interesting, [00:25:00] with these sort of background evidence, to study these trials in the future.

Dr. Bill Harris:               So not everybody who got the omega-3s got a big enough increase in their omega-3. What percent? Do you remember what percent of those that were randomized to omega-3 actually had that delta of 5%? Was it half of them or-

Dr. Raymond Kwong: No, not that high. I don’t remember an exact number. But I think it was in the order of about 15, 20%, mount at that degree. And those people tend to [00:25:30] do a lot.

Dr. Bill Harris: Were they more compliant, or do you know?

Dr. Raymond Kwong: I think there is a mixed bag. So some of them was because their level was very low to start with, and they took the omega-3 fatty acid so they can raise it. There’s also an observation that we’re still analyzing that it seems that if anyone can get to 8%, no matter what you start with, whether you’re starting with low or higher omega-3 [00:26:00] fatty acid, if you can get to 8 or 8.5, that tends to be very protective.

Dr. Bill Harris: Oh, okay. No matter where you start. Yeah.

Dr. Raymond Kwong: No matter where you start. So that’s sort of in keeping with some of the epidemiologic data from Japan that show that if you have that degree, that confers a lot higher protection towards cardiovascular disease, in this case, bad outcome from a heart attack.

[00:26:30] So that’s a great segue, looking into another paper, that we look at that. We believe that the genetic factors, the genetic makeup of a patient could be related to how well they can mount that response. Although this is still under investigation, our dataset is small, and certainly, it’s a pilot evidence only that we can conclude on how the vast [00:27:00] variability of genotypes, a genetic makeup the patients can have, but we observed. We picked one, the very promising gene in the metabolism of fatty acid dismutase, which is the enzyme that controls how fatty acids can be metabolized.

And we found that there is one gene, although I’m sure there are lots of other genes, but we just picked this one gene because it was in literature, [00:27:30] and it has been reported to have an association, how we can metabolize the initial substrates into effective omega-3 fatty acids. We found that there are patients with this gene that is known to have a deficiency in endogenous metabolism. Those patients benefited a lot more from taking exogenous omega-3 fatty acid. And they benefited, and they can get up to 8%, 9%. Otherwise, [00:28:00] they need it. We found that that has an association with remodeling. That was published in another paper. But again, that was only pilot data. How we can understand the impacts of genetic variation, of course, will take a much larger clinical sample of patients.

Dr. Bill Harris:               So just to summarize, you say the fatty acid desaturase gene, FADS?

Dr. Raymond Kwong: Yeah, yeah.

 Dr. Bill Harris:               So if you had a mutation, if you had a less [00:28:30] common variant, a less effective enzyme, I guess, those people responded better to the same dose of omega-3 than people who had normal fats.

Dr. Raymond Kwong: Right.

Dr. Bill Harris:               Interesting. And they have lower omega-3 levels to begin with?

Dr. Raymond Kwong: Yeah, some patients have a lower… Some patients with the subtype of that gene. It was actually published in Fujikura et al., in our publication [00:29:00] record, that we found that a subtype of that gene, they tend to have a lower baseline, and by taking exogenous omega-3 fatty acid, then the remodeling was was better. But compared to people who have a higher level and another subtype of that gene, the benefit is less.

But the patients that benefit the most are [00:29:30] the people who have a very low level in that subtype of the rs325 gene, that they tend to also relate it to the inflammatory markers as well. We observed results. We observed consistent benefit, not only in the end-systolic volume index, which is how the heart can contract down, but also in the remote myocardium as well, the fibrosis of the heart muscle. So the results are in line and consistent [00:30:00] with each other.

Dr. Bill Harris:               Wow. This is a very novel study. I don’t think I have seen hardly anybody who has used the change in the Omega-3 Index as the primary indicator of whether someone had benefit or not.

Dr. Raymond Kwong: That’s exactly right. We’re excited too because that also opens up, begs the question, “Oh, should we genotype these people and tailor who would benefit the most?” Now, it will be a tough sell for it because [00:30:30] omega-3 fatty acid index is so safe and so effective, and overall, you may as well. Some people will argue that, “Why don’t you just treat everyone?” And it’s such a safe medication and literally no side effects. But there’s still a cost. One can argue that. Would it be effective, sort of have a personalized approach? You genotype someone, and then you treat with high dose, and select those people who can [00:31:00] benefit the most to treat. That’s the intriguing question.

Dr. Bill Harris:               Right, I mean, it makes more sense. A good number of the people that you gave a high dose to did not get a big change.

Dr. Raymond Kwong: Exactly.

Dr. Bill Harris: But if you’ve given them a higher dose yet, it might have. I mean, basically titrating up to an Omega-3 Index of 8%, regardless of what the dose is, so you can get them, would be a great way to go.

Dr. Raymond Kwong: Yeah, the personalized approach is very intriguing, and we’re interested in [00:31:30] studying further. Omega-3 fatty acid is a very safely tolerated drug. In general, that sort of personal approach is more important in drug or treatment that are unsafe, that has a higher-risk profile procedurally.

Dr. Bill Harris:               Yeah.

Dr. Kristina Harris Jackson: Yeah, that makes sense.

Dr. Raymond Kwong: But in this case, I think it’s still relevant.

Dr. Bill Harris: Yeah. How has it changed your practice?

Dr. Raymond Kwong: So the genotype, first approach, has not translated into [00:32:00] clinical practice yet because of logistic challenges, because we have to genotype them quickly and then make a decision very quickly before you treat. But I would say that I don’t have… Right now, such genotype testing is not readily available. There are some companies that can do that, but the turnaround time will slow me from treating the patients. So I just go ahead and treat patients when I think that the patient can benefit.

Dr. Bill Harris: Yeah. Do you measure the Omega-3 Index [00:32:30] in your patients?

Dr. Raymond Kwong: Right now, my hospital does not run that, does not run that blood test. So it would involve some specialized samples sent to a specialized company like yours. And the logistic issue is a little bit challenging. And also, the cost of the blood test is certainly something that we have to improve. But because I know that the patient can benefit, I just go ahead and treat the patient.

Dr. Bill Harris: Yeah, [00:33:00] yeah. And again, roughly 4 grams?

Dr. Raymond Kwong: 4 grams, yeah. Now, I think FDA allow it to give even higher to 6 grams now. But I have been giving patients 4 grams, because I know that that was something that I was very comfortable with using.

Dr. Kristina Harris Jackson: Yeah. And that 5% change was within the study. It was that six months of dosing. And you followed them for eight [00:33:30] years out. Did you get any other blood sampling from those visits, or were you just like to be able to look at what their blood levels were as they [inaudible 00:33:39] the study?

Dr. Raymond Kwong: Yeah, that would be interesting. It would have been interesting to know, did this patient… Did it stay up? Did it change their dietary behavior? But because of cost issues from NIH, from the study, we were not able [00:34:00] to bring them back for a third blood sample beyond the six months. So we only rely on following them, talking to them over the phone about how they’re doing. We do follow them with validated risk scores about how they behavior, how they’re feeling, and the angina scores, and so forth. But blood test-wise, we only had the two samples, the two to four weeks and the six months.

Dr. Kristina Harris Jackson: Yeah, so-

Dr. Bill Harris:               Did you ask them? In this long follow- [00:34:30] up, do you ask them if they are taking fish oil supplements?

Dr. Raymond Kwong: I have to go back and look at that. I don’t think we did. I think we’re focusing on clinical outcomes only.

Dr. Bill Harris:               Yeah, yeah. And you reported a benefit in total mortality, right?

Dr. Raymond Kwong: Yeah.

Dr. Bill Harris:               In your most recent-

Dr. Raymond Kwong: Cardiovascular mortality. Cardiovascular. Right.

Dr. Bill Harris:               Okay. And then did you look at heart failure per se, developing heart failure?

Dr. Raymond Kwong: Yeah. So all patients [00:35:00] were… We assessed actually not only heart failure. But the outcome, we also included if they have a serious arrhythmias as well. But if you look at the patients who had a bad outcome, they’re dominated by death or heart failure presentation. Some patients, we also counted arrhythmia. So in totality, the total number of events included some with [00:35:30] a bad arrhythmia. We’re not counting the minor extra beats. We’re counting the serious arrhythmia. Some patients ended up with an ICD. If the ICD fire, if the ICD of the patient had serious arrhythmia, we count those as well. But the majority of outcome were heart failure hospitalization. We’re talking about heart failure, presenting to a doctor’s office, and necessitated increase in medications or hospitalization, [00:36:00] coming into the hospital.

Dr. Bill Harris:               Yeah, yeah.

Dr. Kristina Harris Jackson: That’s great.

Dr. Bill Harris:               Great stuff. Great stuff.

Dr. Kristina Harris Jackson: Yeah. I think we’ve covered a lot of what we wanted to, just hearing how you run through these studies and how it actually is affecting your practice. It’s so great to get clinicians on who are also in the research field because we feel like that’s such a big block right now, and they make it [inaudible 00:36:28].

Dr. Raymond Kwong: Yeah. The exciting thing is that, [00:36:30] as you mentioned, Kristina, that this is unique in the fact that it is one of the few medications that we have, one of the few things we have in our ammunition, to suppress inflammation. Another thing is that it is not unique to acute coronary syndrome or heart attacks per se. I believe that [00:37:00] this can apply to other types of injury, a patient with myocarditis, which is very common, affecting even younger patients, or other types of myocardial injury. And the fact that omega-3 fatty acid is distinctly different from other more sort of, in some way, nonspecific in terms of the inflammation, but it [00:37:30] also has component, has substrates that can promote healing, promote reconstruction of tissue-building blocks, which is not this case in some of the more very potent inflammation medications.

Inflammation is crucial for our heart to heal. So inflammation is good. It’s this later prolonged type of inflammation that will generate fibrosis that is not good. So we need to have a drug that can balance both acts [00:38:00] and be able to shut down the harmful prolonged inflammation but promote tissue healing. And I think this distinctly make omega-3 fatty acid stand out compared to other drugs. We have tested steroids, we have tested cyclosporine, none of them worked. Now, COLCOT, colchicine is promising too, but so is omega-3 fatty acid. So I think this is sort of we’re just really scratching the surface in how this medication can benefit [00:38:30] cardiovascular patients. During the acute window, what I noticed was that it takes the acuteness of an acute window, and treating it with high dose during an acute window, that changed the outcome of the patients.

Dr. Bill Harris:               Yeah, that’s a great way to end.

Dr. Kristina Harris Jackson: Yeah, I think that said it all.

Dr. Bill Harris:               [inaudible 00:38:49] soundbite there. I love it.

Dr. Kristina Harris Jackson: Yeah. Thank you so much. This was fascinating. And also just thank you for explaining the heart so well. It’s just fascinating to hear it from such an expert. And [00:39:00] yeah, we’ll be watching you and hoping to see some more papers coming up.

Dr. Raymond Kwong: Thank you so much. Thanks for the time and the opportunity to discuss our research. And it’s a very exciting time.

Dr. Bill Harris:               Thank you. Thanks, Ray.

Dr. Kristina Harris Jackson: Great. Thanks.

Dr. Raymond Kwong: Okay.

Dr. Kristina Harris Jackson: All right.

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