Episode Transcript
[00:00:00] Jill Brook: Hello fellow POTS patients and lovely people who care about POTS patients. I'm Jill Brook, your hyper adrenergic host, and today we are going to talk with the amazing and the brilliant Dr. Artur Federowski, who is in Stockholm, Sweden. He has specialist training in both internal medicine and cardiology, and as a fellow in the European Society of Cardiology.
Associate professor of cardiovascular medicine in the Department of Clinical Sciences at London University in Sweden. Dr. Fedorowski has published more than 100 scientific papers and two books. He is Associate Editor for the Journal, frontiers in Neuroscience, guest editor for Frontiers of Cardiovascular Medicine and Reviewer for approximately 60 medical journals.
And his research lab just does amazing work. We are proud that Standing Up to POTS is currently funding one of Dr. Fedorowski's research projects, and that he serves on our medical advisory board, Dr. Federowski, thank you so much for being here today.
[00:01:12] Dr. Artur Fedorowski: Oh, Jill, thank you so much for your invitation, and I'm very happy to be with you and to share some of our recent findings with you.
If I can break here. Actually now I'm, at Karolinska University Hospital in Sweden. I'm a senior consultant and associate professor in cardiovascular medicine at Karolinska University Hospital and Karolinska Institute in Stockholm, Sweden. I have published more than 170 papers if it does matter, probably doesn't. but sometimes it used to be very important. So anyway, a little update cause your information's probably two years old
[00:01:56] Jill Brook: Well, that's a testament to how quickly you publish that. Just two years old, and we're already that out of date. So for my first question then, could I just ask you to introduce yourself to any POTS patients who don't yet know about you? Anybody who's paying attention to the research knows your name, they have seen your video.
They know that you are doing some of the most interesting and most important work, but to anybody who's new, do you mind introducing yourself to them a little bit?
[00:02:27] Dr. Artur Fedorowski: Oh, thank you for your question. So I started my Dr. Career many years. 1990s in Poland. Then I moved to Sweden in 2001 and started as actually a few years as a general practitioner before I moved to the southern part of Sweden and started working at cardiology department in Malmo University Hospital and at Lund University
2008, I met my first POTS patient. I didn't know it was POTS patient at all. This young lady, she was a nurse. She had problems with orthostatic intolerance, with fainting. She couldn't stand very long, and when we performed her up tilt testing, she demonstrated for us a magnific and steep increase in heart rate up to 150, not feeling very well.
So I had never seen something like that before. And she was diagnosed with psychosomatic psychological problems.
And then after talking with her, I understood that she was completely sane, but she g ot affected by a disease that nobody knew anything about. Then I started my private research and then I ended up with POTS diagnosis that I found on some internet site.
Then I started exploring the issue, and then in some magic way patients started showing up at my practice, probably the word spread. But there is a guy who can diagnose this strange heart rate increase on standing, especially, or predominantly in younger women. So this was the onset of my POTS career at Head Up Tilt lab in at Scon University Hospital and London University in Malmo.
[00:04:28] Jill Brook: So what is it about POTS that is interesting to you.
[00:04:31] Dr. Artur Fedorowski: First, I realize that it affects very young people and especially women, and they feel so desperate and there was no cure for it. First, there was no proper diagnosis, and second, there was no cure for it or nobody knew how to treat it. So this desperation and lack of knowledge. Lack of therapeutic options made me very inspired to find a way to treat them.
And first we started an patients serious to understand the disease, how it looks like in a reality. And after collecting a few cases we understood, but some of them shared not only cardiovascular or heart rate abnormalities, but also a wide range of very characteristic, repeated symptoms, just like deconditioning and chest pain, shortness of breath post-exertional malaise and problems from other organs, such as gastrointestinal issues. So it was like a revelation that this is not only the disease of heart and vessels, but all the whole body. Then we started asking them, how did it all start?
How did it happen that you got it? And then we started asking them whether there were some family cases. And in most of the cases there were none. it just appeared at one point after having some violent infection, trauma, or surgery. Some claim that it all, started after vaccination.
Of different vaccines, not only one, with different vaccines. And then we understood quickly that it must be something about inflammation in the body or autoimmune process that started, triggered by some autoimmune triggers.
[00:06:26] Jill Brook: So I have followed your research on some of this autoimmune stuff, and you looking at not only some of the autoantibodies, but can we talk about one of your most recent papers that was the plasma proteomic profiling in POTS and how it reveals new disease pathways, because when I first saw this, well, first I was very intimidated because the term plasma proteomic profiling was so new to me and I thought, oh my goodness, I'm never going to understand this.
But then I looked it up and I think while I'm sure it's very, very complex to do it. I think the idea is rather simple. Is it correct that in plasma proteomic profiling, you take plasma from a patient population and from a healthy population and you compare what proteins are in the plasma and you have ways of understanding what different prints of proteins look like and what that means. Is that correct?
[00:07:35] Dr. Artur Fedorowski: I think that you cut the essence in a very nice way. So this is called in science, case control study, meaning that you collect cases, POTS, patients on one side and healthy controls on the other side, and you try to match them as good as possible. So you select people in the same age, the same gender, and you create two different groups.
One with the disease, the other one healthy without the disease, and then you collect blood samples or plasma samples from both. And then you analyze the protein composition or protein components in the plasma, this is called untargeted way, but you just let's say throw a fishing net into the protein ocean, and you try to catch as many as possible. And then if you identify, we call them differential proteins, that the levels of these proteins differ between the groups. Then you say, oh yes, there is some signal here. So this protein and the other one are different in POTS compared with controls.
And you use special sophisticated method, mass spectrometry to get the signal from the proteins. So just to make it as understable as possible. So if you have identified this differential proteins, but differ between the groups, then you look which ones are most different or most significant or differentiate the groups in the best way, differ between the groups in the most significant or distinct way. In the first wave, we have identified 393 proteins that were different between the groups. Oh, it's a lot of course, and probably not only for you, but also for us, it doesn't make such a big sense.
So we have to simplify the signals to simplify the message from this protonomic ocean. So what we do is that we perform analysis and we are separating less significant from more significant, and in the end, you will end up having a few of them that are most significant, that differ most between the groups.
In this way, we were able to identify some of them 16 proteins that were significantly different between the groups. And then what you do in the next step is that, oh, these proteins are upregulated, meaning that they're more abandoned in POTS compared with controls, healthy people, or this protein these ones are less abundant or downregulated. They're less of them in the plasma of POTS patients. This is not the end of the project. Of course, now we have some proteins up and down compared to, to healthy people. Now it should make sense to you. How do you do it? You compare them, you, you connect them, you link them, and we call this pathway analysis.
We are just asking her, I said, what they do in your body, and then you connect them like small balls with connecting lines. And we create a diagram, a graph, and then we look which biological process it represents. And then when we did it, we were amazed. We look at the underlying biological processes represented by these 60 significant proteins.
[00:11:09] Jill Brook: Is it okay if I just summarize quick to make sure that everyone understands, because I think what you're about to say is so important and so fascinating that I want to make sure nobody's confused. Is it correct to say, so you took plasma, that's the liquid part of the blood from 65 POTS patients and 65 healthy controls, and then you looked at proteins in that blood. Like you said, you cast a a net just to see what's in there. And you found a bunch of proteins that were very different in the POTS patients compared to the healthy people. Either there were many more of those particular proteins or many fewer of those.
But then you had to do this very complex step where you figure out what it means, where you look at the combination of proteins and you compare it to, I think a, probably a database of information so that you can tell based on the protein fingerprint. What are some underlying mechanisms going on in the bodies of POTS patients that would make those proteins show up like that in that pattern?
[00:12:18] Dr. Artur Fedorowski: Yes, that's exactly what I did. That's absolutely correct. This is exactly what we did first to get a signal from proteins, and then you try to understand what this signal means in the biological way of looking at the body. So what do they do in your body in other words. So what we found was that there were 18 of 19 aggregated proteins.
They were associated in different networks, and as you mentioned, we took this information for a specific database, that contains information about different functions performed by different proteins. So we figured out what they do in your body, or what we found was that 18 af out of 19 upregulated proteins, what they did was that they were involved in. There is some signal, meaning that there is some, we call it hyper coagulatable state, which means that the body has a readiness to start coagulation building or creating thrombi or blood clots.
[00:13:29] Jill Brook: So 18 of the 19 upregulated proteins were associated with having your blood be more likely to make blood clots.
[00:13:39] Dr. Artur Fedorowski: Not exactly. 18 out of 19, we are able to connect into pathways, into network, and there were different signals from the network, and one of the most important signals were this. blood clot susceptibility in the plasma, meaning that they're represented actually platelet activity.
Platelets are responsible for stopping your bleeding. In normal body, they protect you. But when they start being overactivated, they may start creating clots in normal vessels, and in this way they may clot them. So this is one of the signals. There were other signals from this network of 18 up-regulated proteins, such as inflammation.
Then there was some representing cardiac contractility, the power of contraction and hypertrophy, meaning the heart muscle would grow or undergo overgrowth, which is not so good either. And then some represented adrenergic hyperactivity, which would be expected in POTS.
So we would expect inflammation, cardiac conductivity, hypertrophy, other energy activity, but this hypercoagulation and platelet hyperactivity was quite unexpected for us.
[00:15:04] Jill Brook: With this upregulated hypercoagulability, that means that the blood might be thicker in general, is that correct? Or it makes you at more risk for blood clots, or can you talk more about what it means to have more platelet activity and hypercoagulable state?
[00:15:25] Dr. Artur Fedorowski: This is very interesting. If you perform any lab tests on the blood of POTS patients, you will see quite often normal count of platelets. You will see normal coagulation. Or readiness in your blood. So you will not see this very subtle changes in the rough lab tests, meaning that patients looking for abnormalities in the coagulation system in normal lab tests will not find it.
So these changes are very subtle. They may underlie some process that may start at one point triggered by some other important trigger. Let's say that you are building a wall, adding bricks, one upon another. So until you build the wall, you will not see the wall standing there, but you may see the bricks being collected at one place.
So all these proteins are just like bricks, but you put one upon another. Lab tests will show you the hole standing and is it too high or too low? But you'll not see the bricks being prepared for the construction of the wall. So the proteins are like bricks and let's say there are too many bricks, but it has to do something with it and may start using them for building the wall, but maybe a clot in the end.
[00:16:50] Jill Brook: Have you noticed in your patients, or are you aware of blood clotting being a problem for POTS patients More than average.
[00:17:00] Dr. Artur Fedorowski: I'm quite new to the whole concept of micro clots and I have to study it a little bit more to get my opinion on it. But what I have seen in the past were patients complaining of bleeding or let's say bruising traces of bruising in the skin. or having dots in the skin that were related to spontaneous bleeding in the skin. So this is not a general problem, but some of POTS patients have complained of it to me in the past. And I didn't understand this issue very well.
Why should it be like that. But now having all this data in your hand, you may understand that some of these patients may have collected too much bricks. At one point they were prone to be more of the up-regulated site. And this is a continuous line. Some patients are maybe just in the middle of the line on the curve, and some may have susceptibility. Some of them may have very high susceptibility to bleeding or to hypercoagulative state. So meaning that for some it may not be a problem. For some it may be a huge problem. They may have symptoms. They may have complaints of just bleeding or spontaneous bruises in the skin.
[00:18:21] Jill Brook: And I'm guessing this is why you were surprised that this was the strongest signal that you saw in the plasma protein. It was even stronger than the inflammation signal and the adrenergic signal and the heart contractility signal because those things I think you expected, right.
[00:18:42] Dr. Artur Fedorowski: Yes on one hand, it gives you a sort of confidence that your signal is right, that you are not just finding things that do not exist. Cause they're logical, hyperadrenergic state and inflammation. They were more or less logical for us. But this hyper coagulative state was something new, but it fitted to the whole. So that's why it's another piece of a POTS puzzle. This is another point that needs more attention. Probably in the future studies, we should explore it even more.
And I remember one reviewer defining, saying, oh, just because you found some upregulated protein, you don't want to claim that this patients need some anticoagulants or to be treated with anticoagulants, and my answer is this is not our claim. Our claim is that we found something that is divergent, that is different. If you compare POTS patients and healthy controls, and with this findings in your hand, you have to of course verify the findings in the independent sample in another population of POTS patients using similar methodology probably.
And then knowing this, we should just figure out how to approach it and whether we should treat it or not. So this is the next step of course, but absolutely we should not ignore this finding.
[00:20:06] Jill Brook: Well, one of your sources that you cite in your paper is called orthostatic intolerance and Coagulation abnormalities, an Update, and I had never heard of this before, but I was fascinated to see that it said that in patients with orthostatic intolerance, including POTS, that orthostatic hypercoagulability can happen with orthostatic stress.
And I thought, gosh, that's fascinating. Never heard of that before, but it supports what you found. And is that a widely known phenomenon?
[00:20:48] Dr. Artur Fedorowski: There has been not so many studies performed on this issue. And actually the study you quoted, is it our study?
[00:20:55] Jill Brook: No, let's see. It was in Neuroscience Bulletin in February, 2019 and it was source number 20 in your paper.
[00:21:06] Dr. Artur Fedorowski: Okay. The reason I'm asking is that we published a paper a few years ago on orthostatic hypotension, finding that in patients with orthostatic hypotension demonstrating blood pressure, fallen standing, usually found in a little bit, older patients above 65 years of age, then you will have upregulation of Von Willabrand factor, which is also hypercoagulable factor, I mean factor promoting coagulation. And then we compared coagulation factors supine lying down with standing levels in another paper. And then we found upregulation of coagulation factors just not in specific patients, but just in general, meaning that if you add some hypercoagulative state and then on standing, you will have stress induced by tachycardia, by not feeling well.
And on top of that you will have normal physiological or almost physiological hypercoagulation, then you may expect that these three factors may act together, promoting coagulation or blood clot building. So you are right. You are absolutely right. There is an orthostatic effect, orthostatic challenge promoting coagulation or hypercoagulation, and that is disease related probably.
In general, POTS related hypercoagulative state or procoagulant condition. So if they two meet together, then you may expect what may happen. So you may expect that by standing, having tachycardia, having POTS, and this hypercoagulative state. Then you are at high risk of getting blood clots and then probably in your limbs because there the circulation is much more compromised on standing.
So this is probably why some POTS patients complain of having blue toes or something is wrong with the feet when they're standing.
[00:23:10] Jill Brook: Mm-hmm.
[00:23:12] Dr. Artur Fedorowski: So probably there are not so many clots yet there, but the circulation is compromised.
[00:23:18] Jill Brook: Yes, I'm a person with blue extremities and this feels really important to me and I'm going to be a little bit more careful to take a walk every hour or so on long airplane rides. Now, thanks to this.
[00:23:32] Dr. Artur Fedorowski: Jill, this is why Rehydration is so important. You have a lot of, let's say, water fluid in your veins. Then the circulation should go smoother, and in this way, probably you can protect yourself. So just more water is not just a trivial instruction. It may save your life.
[00:23:53] Jill Brook: Yeah. This is so important. Well, so you found, as you said, other signals in your proteins as well. Is there anything more to say about the inflammation signal that you found? Like did that surprise you. Do you think that inflammation is indicating autoimmunity or is there anything else to say about the inflammation proteins that you found?
[00:24:18] Dr. Artur Fedorowski: Oh, this proteins used to be upregulated in any form of inflammation regardless of the initial or primary trigger. But it means that there is inflammation or subclinical, but there is some inflammation going on underlying the POTS as what we call phenotype, the composition of symptoms.
So behind the symptoms, there might be some subtle inflammation that we cannot see, and this inflammation is expressed by, let's say, over-expression upregulation or higher amount of different proteins, inflammatory or inflammation related proteins. What I mean is that there is signal, there's some inflammation.
We cannot refer it to autoimmunity, but we know there is something which is inflamed in your body.
[00:25:08] Jill Brook: Okay. So my next question might sound silly, but I am naive about this. So you found a protein signature associated with heart contractility and hypertrophy, which means I think that the heart is beating harder and part of the heart is getting bigger. And to me that sounds like a healthy thing, but you say no?
[00:25:34] Dr. Artur Fedorowski: If you're a cardiologist, if you hear about cardiac hypertrophy, you get concerned. It doesn't mean that the heart is beating harder or more efficiently. It means that the heart will get stiffer will need more oxygen. So the heart will develop more demands and will get stiffer.
And heart otherwise is a very elastic instrument. It is very flexible, being filled with blood and being elastic and allowing blood the chamber s. So if the chambers get stiffer, this process, which is more or less passive, it will get compromised, which is not good for pumping ability of the heart. So this is a source of concern rather than it source of
[00:26:22] Jill Brook: Okay.
[00:26:23] Dr. Artur Fedorowski: Your question is actually very interesting. Very good actually, but because you're asking what does it mean for POTS patient, if you perform a echocardiography on any POTS patient, you cannot expect seeing cardiac hypertrophy or overgrowth of your heart muscle. You will not expect that.
You will not see it in most cases. 99% of cases you will not see hypertrophy. What it may indicate in this case, there is some subtle subclinical, again, not seen with a naked higher process, but may be promoted in the end after many years of disease, which of course we do not know, but the heart is sending a signal to us because I have to work so hard.
[00:27:10] Jill Brook: Okay. That makes sense. Yeah, so you bring up an interesting point. I cannot wait to see what happens when we have a lot of 80 year old POTS patients because we just don't know right now what POTS looks like at an old age.
[00:27:25] Dr. Artur Fedorowski: They have already been around here. Probably without knowing they had POTS. Maybe some of patients with atrial fibrillation, with heart failure where we do not really know what happened before they got the disease. We have a lot of atrial fibrillation cases, a lot of heart failure cases, hypertension cases in later age without identifiable etiology or causal factors. And maybe some of them had POTS many years without knowing it. And after being adapted to the situation, after having learned how to live with POTS, trying to find the strategies, and then with age, your maximal heart rate decreases, diminishes, which means that you will not get so POTSie when you get 60. You will not develop heart rate of 160 on standing. You will end up having heart rate on of 100, 110. So you will not get this typical POTS symptoms, tachycardia or tachycardia symptoms then you will get other symptoms and then your heart may get damage in the end. So this is of course, something that we do not know because we have to identify POTS patients in the very beginning and then follow them over a little bit longer period of time.
But probably I will not accomplish it during my lifetime Now, Cause by the time my POTS patients get 60 or 70, I may not be that anymore, but we can create a good ground for it so that we will learn in the next generation more about POTS and its consequences.
[00:29:09] Jill Brook: Well, I'm so appreciative for all the work you do because I feel like I've heard you say in some of your presentations things that make me realize you are so thoughtful about the big picture of what the heck is POTS and some of your research makes me think, boy, there's so much going on in POTS. How does POTS have so many different ways to make my circulation bad?
You have the hypovolemia and then you have the neuropathy that makes the blood vessels not constrict very well, so you get the blood pooling, and now maybe there's even some hypercoagulable state, and I know that you have more. Keep going. Finish my thought for me,
[00:29:58] Dr. Artur Fedorowski: Oh, I will be very happy to continue. So one of our most lesson findings was so-called microvascular dysfunction. We have just found in post COVID POTS patients. This is very interesting. Very important. What we have suspected for a very long time, that blood vessels, small blood vessels, or we call them distals or small blood vessels that are in your limbs, in the distant part of your limbs, they do not react as they should.
Meaning that if you squeeze your artery in your arm for a while, you stop circulation in the distal part of arm, in your hand. Then if you put a sensor on your finger artery, then you may see what happens when you just let your blood go again downward, and then the usual behavior of your finger arteries.
But it opens up to let the blood flush. Just through the distal part of your body to clean it, to take away all metabolic stuff that had been produced during occlusion of your artery and this is normal behavior. So your finger would open up very widely to let the blood go through it.
Now, in POTS patients, what we found was that this small finger arteries, they are not very compliant. They don't want to open up, they open up like 20, 50% of what's expected. So instead of being doubled the same diameter, they just open up by 20%. They increase the opening by 20% only, not by 100%.
So they remain constricted and which it means that the blood cannot get to the part that need this fresh blood very much. What you can feel is sort of tingling or we call it parasthesia or some strange sensation in your fingers. You are intolerant against cold or warm.
So you do not tolerate warm or cold very well. These are typical effects of this dysfunctional small arteries, and we call it microvascular dysfunction. Micro mean, small vascular, small arteries dysfunction, but they do not cooperate with the rest of your body, the rest of your circulation. Now having it in your fingers can make you feel a little bit strange, feeling tingling or something is wrong, or think pain, sometimes, changing colors. Your finger. Make change colors in a strange way. Being becoming blue, as you mentioned by yourself. Done. What happens if it happens in your head, in your brain?
[00:32:55] Jill Brook: Well, what.
[00:32:56] Dr. Artur Fedorowski: You, you tell me.
[00:32:58] Jill Brook: I am guessing all of the symptoms we see in POTS, the brain fog, dizziness, not enough blood up there.
[00:33:05] Dr. Artur Fedorowski: Migraine and so on. Yes. What if it happens in your heart,
[00:33:10] Jill Brook: Ah, I don't know what.
[00:33:12] Dr. Artur Fedorowski: chest pain, angina, inexplicable chest pain, which we call angina and deductible will tell you you don't have angina. We performed coronary angiography. Your coronary vessels, they looked okay to me. So what happens if it happens in your gut? Then you have problem with your gastrointestinal tract, with food processing and so on.
So any part of your body can get affected by dysfunctional vessel. and it would create the whole picture of POTS patient having so many ailments, so many symptoms in different parts of your body because vessels are everywhere. If they're compromised, if they function is impact in one place, it may be impact another place.
And the symptoms depend on what they do in this part of your body. If this are supposed to deliver oxygen and other important elements to your brain, then the function of your brain will be impaired. Then probably you will get brain fog and cognitive impairment, and if your brain vessels or vessels in your skull get stressed, then you can have a migraine in the end. So this is how we look at the typical POTS patient nowadays as a whole, as a circulatory problem. And probably there is some underlying inflammation as well going on, and probably the central nervous system and autonomic nervous system are affected as well by the same inflammation.
So you may have inflammation in your nervous system and circulatory effects that we see in dysfunctional vessels. And in the end, your heart gets crazy. And we thought in the very beginning that it might be due to antibodies, stimulating receptors in your heart. Probably yes. It may be one of the explanation.
Another explanation might be that you don't get back to your heart chambers on standing due to volume shift downwards. Then you have patients having tachycardia, having very high elevated heart rate lying down. and then you cannot claim that this is some crazy green syndrome or problem with the venous return.
If you have your cardio lying down in the resting condition, then you cannot claim this is due to gravity problems in the first place. Then I would say there is some primary heart stimulation going on. So you may have tachycardia due to primary heart stimulation, and then you may have circulatory problems.
If you have both, then you know what happens? This is very debilitating condition. You don't feel well lying down. You don't feel well standing up.
[00:35:58] Jill Brook: Is POTS unusually complex? Or do other diseases have this much going on? Because when we talk about all the different things going on in POTS, honestly what goes through my head is that it almost feels like there's an alien somewhere that wants my circulation to be bad. And he has thought of several different ways to do it, and he's doing them all at once just to mess with me.
And it seems like too much of a coincidence. That you could have so many different things going on that all make your circulation bad. Tell me I'm crazy. Is there an explanation? What's going on?
[00:36:41] Dr. Artur Fedorowski: Jill, this is quite funny because I'm thinking quite often about the same. If you were about to design a disease that nobody believes in, that you cannot see with your naked eye, that makes people just miserable. So you would definitely think about POTS in the first place. Because this sort of disease and tested to make a comparison to another disease. Autoimmune disease, just like lupus. Lupus affects many parts of your body. And it may show different faces, but primarily this is the same disease. This is autoimmune process, creating different manifestations in your body.
So we are at the same position now against POTS. We know there is probably one common mechanism manifesting in different ways, but we cannot see the original mechanism yet. We believed in autoantibodies, probably we do not know if they are the product of the disease or the primary factor of the disease.
So this is what we do not really know. And different groups looking at POTS from different view angles. They see different parts. If you get a spotlight in your hand and then you enter the dark room. and there are paintings on the wall. If you put the spotlight in different places on the walls, you will see different fragments of paintings.
And when we say, oh, POTS is a head of a giant monster, and oh, POTS is a very nice woman, naked woman standing close to the tree and another one entering the, oh, no, no, no. Now I POTS is a huge tree.
[00:38:22] Jill Brook: That's an excellent analogy,
[00:38:24] Dr. Artur Fedorowski: who's going to put the light on in the room?
[00:38:27] Jill Brook: Well, nobody's doing it faster than you.
[00:38:30] Dr. Artur Fedorowski: no there are a lot of dedicated colleagues. just like the group of Satish Raj in Calgary. They're doing an excellent job. And Blair Grubb is very much dedicated. We have a very nice team at Karolinska Marco Stalberg and the rest of the team. So they are groups popping up now in different places and probably due to the huge interest in post COVID syndrome.
So we may get on the same wave and take advantage of it and be happy at one point to bring a good solution to this issue.
[00:39:04] Jill Brook: Yes. So I know you don't have very much time left, but you have also recently published a new POTS symptom score. Do you mind telling us about that?
[00:39:17] Dr. Artur Fedorowski: Oh, it is a very interesting story. Cause when we wanted to quantify the symptoms in POTS, then we had to start somewhere. But there was no good symptom scale develop on the market. In the literature, we couldn't find any. There were some autonomic score systems that were not very practical for us. So we sat down and then we started thinking, we need another one. We need a new one. What should we look for? And then we decided to look at the big POTS study, which was founded, by Dysautonomia International. We should be very thankful
[00:39:53] Jill Brook: Yes.
[00:39:54] Dr. Artur Fedorowski: but the study was founded and the study was done.
This is a great study because this was one of the first study giving us a whole picture of POTS and its symptoms. So we just selected symptoms that were most prevalent, meaning that they dominated in the whole clinical picture of an average POTS patients. So we decided to include all the symptoms that were present in at least 75% of all patients.
So this 12 item scale includes 12 most let's say prominent POTS symptoms that exist. And then we copied just visual analog scale one to 10. We put it together and we started using it. What was amazing was that when we look at the average scores or points achieved by our patients that were included in the original project, we realized that all the 12 domains, they were equally represented in score system. So patients used to score between seven and eight on average in all 12 domains. Of this, only five were cardiovascular.
Seven remaining domains were not cardiovascular. It's about insomnia, gastrointestinal problems, and headache. So these are not typical cardiovascular symptoms, but they are present in almost each and every POTS, patients, or almost. And the level of symptom burden is almost the same as for typical cardiovascular symptoms, seven, eight on one to 10 scale, meaning these symptoms are a real problem for the patients. They're putting score 7, 8 or nine.
meaning that they feel that this is a symptom, this is a problem that is about to destroy their life on this level, if you put 7, 8, 9, this is a very high score. And just to put it in a perspective, when we looked at normal people, age on sex, matched normal healthy contrasts, just like in the mass spectrometry study
the 65 patients and 70 controls. So the total score for patients was 78 of 120, which was the maximal score. So if you, if we compare it with healthy people, they would score 14.
[00:42:33] Jill Brook: Wow.
[00:42:33] Dr. Artur Fedorowski: and there was none over 40.
None. Over 40 and average 14.
[00:42:39] Jill Brook: Okay.
[00:42:39] Dr. Artur Fedorowski: And you would have all POTS patients with an average score of 78.
[00:42:45] Jill Brook: Wow.
[00:42:45] Dr. Artur Fedorowski: There is a huge difference in symptoms. You may have two girls, one with POTS, one without POTS, this one without POTS would say, oh, I have symptom one to two in all 12 domains or 12 symptom groups, categories.
And then you will have a girl as old as the other one with POTS. And she would estimate her symptoms to the level of seven, eight in each category. This is a very sick girl actually, even if she doesn't look like that. So we just realized these symptoms are very serious.
It's very serious problem. Severe symptoms in many of them. Of course we don't meet mild cases, all the patients that are referred to us. There's some bias in it because we get severe cases. So this group represents severe POTS patients, of course, and there is of course a lot of patients having symptoms, which on average are situated just in between probably.
[00:43:50] Jill Brook: So that fits with a joke that we like to make on this podcast, which is that POTS is named for its least bothersome symptom. I've never heard anybody say that it was the tachycardia that really was ruining their life. It's all the other stuff. But maybe if we don't put it in the name. We'll forget about it.
[00:44:13] Dr. Artur Fedorowski: It's quite a funny story cause POTS is known for its least bothersome symptom tachycardia. But just to make another comment on it. So when we look at tachycardia and which symptom was most related to tachycardia I don't know if you read the paper, it was quite amazing. It was cognitive impairment, not dizziness on standing, lightheadedness.
Cognitive impairment was correlated with the level of tachycardia on standing. So the more, the higher heart rate level you achieved on standing, the more cognitive impairment. So this is not only about orthostatic intolerance, lightheartedness, it's also about the affection of your higher functions in your brain,
[00:45:02] Jill Brook: Yeah.
[00:45:04] Dr. Artur Fedorowski: functions. So it was quite amazing, not lightheadedness, cognitive impairment was most correlated with heart rate.
[00:45:11] Jill Brook: Well, and I thank you for doing this work because I feel like your symptom score is going to help get POTS taken more seriously and hopefully get more attention and more research funding.
[00:45:23] Dr. Artur Fedorowski: Oh, we are very happy that there are people out there that appreciate the work, what we do. We take it very seriously and this is our mission to put an end to POTS.
[00:45:34] Jill Brook: Well, one last joke. What will it take for us to get you never to retire? Because I'm pretty sure our audience would be willing to pitch in whatever it takes because we so appreciate the work you do. You do so many studies and there's so. Thoughtful, and they're looking at the big picture and they're solving the big problems.
And we didn't even talk about most of your highlights of what you have done. So we just want to say thank you for your time today. Thank you for your ongoing work, and thank you for putting your brainpower and compassion onto team POTS.
[00:46:09] Dr. Artur Fedorowski: Oh, Jill, thank you very much for invitation for your very kind words, for your appreciation. It means very, very much to all of us who are out there and working on this issue. We very, very much appreciate your attention.
[00:46:23] Jill Brook: Well, wonderful. And I do mean it. If you think of anything that the listening community can do to keep you ever from retiring, we're on it. So listeners.
[00:46:33] Dr. Artur Fedorowski: I am not going to retire so easy.
[00:46:36] Jill Brook: Good. Good, good.
[00:46:37] Dr. Artur Fedorowski: This is the only thing. I'm good at it. So what should I do otherwise? Listen to music.
[00:46:42] Jill Brook: Good, good. I'm always worried that maybe you've been wanting to play more golf or something,
[00:46:47] Dr. Artur Fedorowski: I don't play golf.
[00:46:48] Jill Brook: Excellent. Hey listeners, that's all for today. We'll be back next week, but until then, thank you for listening. Remember, you're not alone, and please join us again soon.
[00:47:00] Dr. Artur Fedorowski: Thank you so much.
