Did you know that Postural Orthostatic Tachycardia Syndrome used to be called irritable heart syndrome?
In the first part of this two episode series, Dr Mark Donohoe returns to FX Medicine to discuss Postural Orthostatic Tachycardia Syndrome, or POTS, a condition affecting the autonomic nervous system. POTS occurs when an inadequate amount of blood returns to the heart when the patient moves from lying down to a standing position.
Mark guides us through the definition and history of POTS, providing an in depth discussion of the symptoms that define the syndrome, the challenges for practitioners in alleviating those symptoms, and the connections between POTS and other conditions such as Chronic Fatigue Syndrome and Ehlers-Danlos syndrome.
Covered in this episode
[00:51] Welcoming back Dr Mark Donohoe
[01:48] History of postural orthostatic tachycardia syndrome (POTS)
[06:18] Diagnosing and different subsets of POTS
[19:16] POTS and people with chronic fatigue and Ehlers-Danlos syndrome
[27:10] Diagnosing, referring, and treating POTS
[32:54] Supporting resilience in POTS patients
[36:18] Treating the gut, vagus nerve, and blood pressure
[40:18] Should POTS patients do aerobic exercise?
[45:48] Stimulating the vagal and trigeminal nerves
[49:06] Call to listeners: tell us about your POTS patients and successful treatment
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining us in the studio again today is Dr Mark Donohoe who end his medical degree from Sydney Uni in 1980. Mark worked around the Central Coast honing his medical skills and this is where his interest in integrative medicine sparked because patients just weren't fitting into the boxes of diagnoses and treatment which were drummed into him in medical school. Mark is considered one of the fathers of integrated medicine in Australia and he's been a vanguard for patient health throughout his whole career. And today we'll be discussing POTS, postural orthostatic tachycardia syndrome. Welcome to FX Medicine, Mark, how are you?
Mark: I'm well until my date of graduation was just told to the entire world. Now I can be considered a grandfather. That's irritating.
Andrew: That's irritating. And today we're going to be talking about irritated hearts.
Mark: We are. We are. The postural orthostatic tachycardia syndrome started life back in 1871 when it was named irritable heart syndrome and as anyone will know, like irritable bowel syndrome, that's the way that the medical provision dismisses something to say, "It's just an irritated heart, darling, just like it's just an irritated bowel." No matter how much of a problem it causes, irritable heart syndrome became the kind of overall term for these dysautonomia adrenergic type of problems that went on with the heart where there was not even cardiograms, electrocardiograms at that time, so it was just the only thing you could do is measure the pulse, measure the blood pressure, and even the blood pressure, to my surprise, was rarely measured. The blood pressure was not considered a thing just over a century ago.
Andrew: I wonder if there was some skills back then that might've been lost with the advent of technology with measuring not just the beat, the rate of the pulse, but the feel of the pulse. We know about bounding pulses and faint pulses and thready pulses, but they're not often discussed now, it's a very diagnostic thing. It doesn't feel normal. Get the machine that goes beep.
Andrew: Well, I wonder back then, if there was a real skill.
Mark: I think that skill was there even at the point...I think it was lost around the time of my medical training. So if I graduated in '80, you can probably guess that I was educated in the '70s.
Mark: And that was the rise of the machines, to steal an analogy from somewhere. Everything that you could examine that required skill, thought, delicacy, and division of, you know, clinical judgment became replaceable with something that was a machine. The cardiograph we relied on, the CAT scans were just coming out at that time. There was a thing in the past called pneumoencephalography, which was considered the ants pants of diagnosing what went on in the head. Put a bubble of air into the brain, have the person as sick as a dog for days, and do an x-ray so that you could see where the air went, and that was considered very sophisticated machinery prior to the arrival of the CT scanner.
Andrew: I'm just picking my jaw off the floor here.
Mark: Yes. Yeah, so we saw patients who were rather damaged by that, but putting a decent bubble in the right...
Andrew: This is evidence-based medicine.
Mark: Yeah, it was. Well, the definition of evidence-based is whatever commonly is done in medicine and, you know, we find that to this day that whatever the common practice is, that's the right and good practice even if next year, it's terrible.
Andrew: That’s right. That’s right.
Mark: It’s always right. Medicine is, by definition, right because we define the diseases, we define the diagnostic criteria, and if they change next week, next year, or next month, or next decade, we think of the bad old days is that time yesterday where we did it a different way and that will go on into the future. I think that, you know, what we see in the progression of integrative medicine is we see it coming up in the future, people will forget some of what we did.
Best study ever. One done in 1999, looking back in history about 1960s and the diagnosis of neurological disorders found that 80% of the people who were diagnosed with a psychiatric disorder, in fact, had neurological disease. And the paper went on to say, "Thank God we've moved beyond that time where we were incorrect, now we know with our new technology in 1999, what's really going on and now we don't have that misappropriation of people and putting them into the psychiatric category."
Andrew: But that's not true.
Mark: No, of course it's not true. Psychiatry is brain science. Anybody can actually say that.
Andrew: I remember some research done in my nursing training and it was that I think they were psychiatric students, as in doctors learning psychiatry, and they were admitted...they were basically scheduled. The only sort of symptom that they kept on repeating was, "I hear bells, I hear bells." And they were all admitted or something like that.
Mark: Yeah. You classify people according to that. Then it became famous because these were perfectly normal people, if you can call a medical student perfectly normal, right? You can make an argument.
Andrew: How derogatory.
Mark: But if you put the DSM-5 against most medical students, we'd all fail. We would all fail.
Andrew: Okay, so let's get back to POTS.
Mark: So, yes, we categorise things in our own ways and we usually categorise them to make sure that doctors are okay and everyone else is the problem.
Andrew: Let's get back to postural orthostatic tachycardia syndrome. What is POTS?
Mark: It's a pretty easy thing to diagnose. POTS, first of all, I'll say there are subsets and subsets here. POTS has become well known because it's a name, it's like MTHFR. Whenever you've got an acronym that reminds you of something, POTS is POTS. Postural orthostatic tachycardia syndrome is simple to diagnose. You stand a person up for 10 minutes, you get their pulse rate when they're sitting. and if on standing their pulse rate goes up by over 30 beats per minute, then they technically fulfil postural orthostatic tachycardia syndrome. If they are youngster, 12 to 19 years of age, it's going to go up by 40 because apparently kids get wider variations in heart rate anyways. So we have a definition which looks very straightforward, but POTS is a subset of a broader group of conditions, which we call orthostatic intolerance.
Orthostatic intolerance just means gravity is not your friend. When you stand up, something goes wrong and it goes wrong in the vascular system. Some people get dropping blood pressure, we call that orthostatic hypotension and it's something that we all know, you would have known from your nursing career, you lose blood, you get orthostatic hypertension because you've lost blood. And when you stand up, the blood pressure drops and the pulse rate goes up trying to compensate for it and the person feels like they're going to die because apparently, in the history of evolution, the only time you ever lost enough blood to make that a problem was when something was eating your leg and there was a really good reason to feel that things were going badly.
So people, when things go wrong with that autonomic cardiovascular system, feel dreadful. There is a sense that...they keep on using this term, "I feel like I'm dying." You know, the term we use is impending sense of doom. The impending sense of doom is a question that we actually ask people. They go, "Yes, that's it!” you know, something terrible is happening, and you go, "Oh, it's only a pulse rate going up and your blood pressure going down." But internally, the wiring is that's really bad news for a human. So we have orthostatic intolerance over the top. Underneath, one of those items is postural orthostatic tachycardia syndrome, and weirdly, if your blood pressure drops, you're not in POTS. Even though we're using that term more loosely these days, if your blood pressure drops when you stand, you're not a POTS patient because the preference is orthostatic hypotension and there are better-known treatments for that and there are better-known investigations for that.
If your blood pressure stays stable, then you have POTS. Then the question is, well, what kind of POTS? And there are two big divisions. The first one is called adrenergic POTS. Adrenergic POTS is someone who is responding to adrenaline very, very aggressively. Now, that can be...you know, we do our genetics test now. You know the gene, the COMT, the catechol-O-methyltransferase gene. COMT is a gene which means you fail to clear adrenaline, noradrenaline, and the like from receptors. So the effect of adrenaline can be much, much higher on those people, and therefore, when adrenaline binds to its receptors and isn't cleared, you get a rise in pulse rate and a sense of panic in the person, a sense that the adrenaline is racing through their system.
The other one is called neurogenic and this is...I mean, these are all subject to later edits and revisions, but the neurogenic one is one where something has gone wrong with the autonomic system and you get other blood volume losses and either autonomic or even endocrine, neuroendocrine, but you get either loss of fluid or you get loss of tone in the blood vessels, pooling and you see those ones as, you know, people that stand for a while and their feet go blue as the blood pools down in the bottom. And for those people, their tachycardia is an attempt to maintain blood pressure. And so, they will do that for a while, the pulse rate will go up and up, but if you give them long enough, eventually the blood pressure also drops in those people.
Andrew: What about hands?
Mark: Well the hands…
Andrew: So you a total peripheral vascular dilation or only mainly pooling in their feet?
Mark: Look, the medical literature is all about what happens in the legs because the legs are always the most gravity-dependent area of the body. And so, one answer is, well, it's a loss of the autonomic responses that normally cause the vascular reflexes in the legs, but people do describe it in the hands as well. And, you know, we are often thinking about, well, there are relationships with autoimmune diseases. There's all kinds of relationships here, but the autonomic nervous system is not doing the job that you would expect it to do, and that is constrict the blood vessels, you know, make the veins return blood to the heart. And when you go vertical, the job is to keep blood flowing to the brain. If you don't get it to the brain in sufficient amounts, then the brain are the main symptoms, the kind of nervousness and the irritability…
Mark: …nausea, you get a whole range of symptoms that don't appear to be related to blue legs but are related to the autonomic response of the body trying to keep blood pressure up, trying to keep perfusion adequate. So I think that we can divide it loosely into those areas.
The third one, the neuroendocrine, has become a big thing with our ideas of, you know, the hypothalamic-pituitary-adrenal axis, the HPA axis, because there is such a high crossover between POTS and chronic fatigue syndrome, about 50% in the Venn diagram of CFS people, up to 50% have POTS, and up to 50% of POTS of people have what you would define as chronic fatigue syndrome. Because of that large overlap, there's been a move in medicine to look at chronic fatigue syndrome as not just an immunological disorder, not just a post-viral disorder, but an autonomic response to a viral insult. And that's the fascinating thing. Out of all the POTS patients, half of them are triggered by viral infections.
Why would that be? You know, viral infections make all of us want to go and lie down. It could be a protective response. You get the flu or you get Epstein-Barr or you get something and the body switches you to wanting to go horizontal, not do activity, get over the virus. And some people just don't switch back. So people with the flu tend to have POTS, they tend to have high pulse rate, they tend to have dropping blood pressure. But if you've got the flu for two weeks...
Andrew: But is that POT? Not a syndrome? Like is that just the...
Mark: Yeah. You're probably right. It's only a syndrome when it's been there six months.
Mark: And so, that's the other thing that it has in common with chronic fatigue syndrome is this is not an unusual response of the body for a whole lot of reasons. Even half the medications we give can cause these kinds of problems. You know, we put people on hypotensive medications, we overdo it a bit and the blood pressure drops enough for the heart rate to have to increase. So iatrogenic POTS is a very, very common thing to happen. But if you take the drug away and the person gets better and then you don't have POTS, you don't have the syndrome because you haven't had six months and you know the cause. So it is a tough kind of problem, right? In my own career, there was always the problem with a drop in blood pressure. So we had a hospital unit where one of the things we measured was the people's temperature was about a full degree lower than it was for other people in the hospital.
Mark: Lower. So the lower temperature, fitting in with this idea of could they be going into a hypometabolic state? Is this the reason for the fatigue, that the battery is down at 9 volts instead of 12? The other issue was blood pressure was significantly lower and people couldn't stand long to get their blood pressures. So these were hospital staff that saw, if you like, ordinary people going into hospital for elective surgery, all of that kind of stuff and the blood pressure was lower. The other thing was their sleep breathing patterns were more aligned with what you would consider cot death syndrome. And if it was a tiny baby, long periods of up to a minute, not breathing through the night and then coming back kind of hyperpnea for a while where they caught up breaths and then they went for long periods without breaths.
Andrew: So not a Cheyne-Stokes breathing? Different.
Mark: No, it wasn't anything like that. But what we did was the area under the curve and said, "Look, they've exchanged about 40% less oxygen overnight than a normal person with normal breathing patterns would." And they wake up very tired in the mornings. So what we saw in that hospital setting was we were staring at POTS, but we didn't give it a name at that time. This was back in the '90s and, in fact, the term POTS, postural orthostatic tachycardia syndrome, only ever entered the medical literature in 1994, which was right at the end of our time in the hospital.
So we were staring at something we didn't have a name for at that time. It wasn't just one thing going off, sleep, automatic functions of the body, the temperature of the sleep, the pulse, the blood pressure, all of them seemed out of whack. We knew most of these people were post-viral and so, there was no mechanism in our thinking at that time to say, "Well, how would the immune system possibly cause that?” You can make a case for it acutely, but you can't make a case for a person who had Epstein-Barr five years before still having any carryover of that kind of infection later.
So we had this and we had people complaining of irritable bowel syndrome, of the sense of impending doom, of nausea, vomiting. We had a whole lot of these things, which in retrospect you'd say that's probably the neurogenic type of POTS. There was the occasional one where there was heightened response to any insult. So we were challenging people with, say, food allergens and when they had certain foods, everything went haywire. Pulse rate would go up to 150, 160 beats per minute about 15 minutes after delivering a food and the blood pressure and the pulse rate were, again, all over the place.
Andrew: A vasovagal response, like?
Mark: It might've been. I mean that's the temptation, but I think more recently it's been linked to this thing called mast cell activation syndrome, that there's a bunch of allergic-type phenomena and the mast cells are lining the gut and at some point they become activated and say you have a histamine vasodilatior, you have a kind of an effect, which is a biochemical effect, God knows why it's there. It doesn't seem adaptive to much, except if your method of escaping a predator is to drop to the ground and pretend that you're unconscious or dead and maybe the big cat loses interest in you. But has become interesting because there are people for whom POTS is fixed by a good dose of antihistamines. It doesn't make much sense because their IgE is not raised. But if this mast cell histamine-releasing gastrointestinal response is going on, then they're maybe falling into a complicated group of dysautonomia, dysregulation of the catecholamines, the adrenaline, noradrenaline, dopamine playing out different roles and they seem to get stuck in this area. And the sticking point is you'd think if it's an unstable state, all we have to do is give them a gentle push in the right direction, and all the gentle pushes we give just seem to worsen the problem.
So in the hospital setting, we would try everything we could, we'd try compression stockings, it would work for some and not work for others. I think that the 25 years since then has given us an understanding that immunology, and the brain, and the autonomic nervous system are not separate systems at all. It's a one-regulatory system. Half of the receptors in the body are feeding back to the brain on autopilot and if you disrupt their process anywhere along the way, you can end up in a stable state of ill health, which is what we see as chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and even hypovolaemia.
So what we're looking at is many disorders all coming under one name, half of them triggered by a virus, which would normally be a thing that a person recovers from without incident and the thinking is some people are closer the edge than others, they're hanging on by their toenails, and a virus or a severe stress, a shock, a bereavement, a trauma, almost anything is able to push them over that edge into an area where they don't die, but they don't recover. And our job is to think not of homeostasis in this kind of bowl of safety that if you don't die you fall back into good health, there's a whole lot of little bowls which are stable states of ill health, which is, as I keep on saying, the least worst way that the body can get by. It's not the best way. The best way is recovery. But if you can't find your way back to recovery, keeping things at a low rate, dropping the temperature, dropping the pulse, dropping the blood pressure, managing as best we can is the best that we end up being able to do. And what we as doctors and naturopaths are trying to do, is encourage them to go out and explore and find a way back to that better health where all of the things are stable but it's now good health again.
Andrew: …into the interstitial space? And then what about, you know, compensatory mechanisms of the heart?
Mark: We don't know that there's leakage outside the vascular system so that may be a difference. And one of the reasons I say that is after a big meal, a person has a big meal, splanchnic pooling, that's enough to trigger quite an aggressive response. Not while they're sitting, but they stand up after a meal and things go wrong.
Mark: That doesn't suggest there's leakage from the blood vessels, it just means that if you shunt your blood to one area, you become vulnerable for the lack of vascular response to the periphery. So most of the symptoms truly are not related to their legs. They do describe very heavy legs. It's very difficult for them to walk. But most of the symptoms are neurological and the neurological symptoms, the disabling fatigue is expressed more of, "I can barely think." And so, we have ways of considering neuroinflammation, not really the big issue here, the neuroinflammatory studies have not suggested anything's wrong. So what we have, we think, is a dysregulation that just can find its’ way back home, and so what we end up doing is trying to give a gentle tap, you know, drink more fluids, have more salt. We give gentle advice and trying to get people back. Most people respond a bit to that, but they don't recover.
Now, the natural history of POTS, it's different whether you have chronic fatigue syndrome or not. So the chronic fatigue syndrome and POTS together has a low recovery rate of around about, you know, the same 50% in years 1 and 2, but then around about 5% per year afterwards. POTS without chronic fatigue syndrome has a recovery rate of about 60% in the first 2 years. So it still takes a while, but it's around about another 20% to 25% in every year afterwards. So nearly all POTS people...
Andrew: That's four years, within five years.
Mark: Yeah. Within five years, they're back to normal and you don't have to do much with it. The other interesting correlate with chronic fatigue syndrome is about four or five to one females over males. So there is something about females and their responses rather than males and their responses. And that may fit with males under adrenaline push go to hypertension and cardiovascular disease and high throughput, and females under that same stress drop their blood pressure to be able to survive longer. And so, males, in a sense, are expendable. You can push the blood pressure up and if they die earlier, as long as they've done the hunting, shooting, killing, and mating, then they're fine. Better off without them. So there are sex differences that are very considerable, but the ratio of around about four or five to one is the same as chronic fatigue syndrome. The people with POTS tend to get it younger. Typically, it's in the 20s to early 30s. It's not teenagers that get POTS. It tends to be the 20s to 30s, whereas with chronic fatigue syndrome it's more the 30s to 40s or the youngsters. There's a group of youngsters and there's a group of others. So there are age differences, there are sex differences that make us think that immunology may be involved.
The other differences between the two are POTS people sometimes only have fatigue when they're vertical and chronic fatigue syndrome patients typically have fatigue that they describe even when they're horizontal, the brain and the body still feels exhausted. They still feel exhausted the whole time. So in dealing with the differences, what would we think of? Well, one group here is the collagen disorders, the Ehlers-Danlos syndrome, EDS, which is a collagen variant. It's not a disorder at all. I use the word incorrectly, but an EDS is a variant of collagen, has very flexible blood vessels, very flexible bowel, long loops of bowel.
Mark: You tend to get those kinds of issues arising. And that's a very strong correlation with POTS and very strong correlation with orthostatic hypotension as well. And our thinking there is, this is just the elasticity, you know, of those blood vessels, that the pooling is just because they stretch more than the average person and fluid goes down there. Those people tend to respond pretty well to salt and water increases in their diet. Increase the vascular volume and you're compensating for the kind of more flexible arteries and veins around the body.
But it is, again, a strong correlation, probably almost half of the people with Ehlers-Danlos syndrome, which is becoming a much more significant group of society, end up with POTS. And so, their presentation to a doctor is, "I'm feeling dizzy, I'm feeling nausea every time I stand up, every time I have a big meal." And we all think, "Oh, that's psychological, you know, put it into that category of it's irritable bowel syndrome, darling, and go home and you'll be better." And my now thinking, "Well, that's a mechanism." And these people get missed because the diagnosis is very nonspecific syndromes until something big happens. Until they get a dissected aneurysm, or they get a pneumothorax, or they get something or recurrent dislocations of joints.
Mark: Then we place it and we go, "Oh, aha. That is a collagen variant and your POTS is all due to flexible arteries.” Now, the problem with that is we do what we think should fix it, only half of them get any better. So our concept of increase the vascular volume, give them lots of water, give them lots of salt, give a bit of fludrocortisone if necessary to try and hold all that sodium in and it still doesn't work. And the other question is, why do they only get it after a virus? Why do they go 25 years of their life with this same collagen variant and then suddenly get it after they catch a glandular fever or they get a flu virus or something like that? So they're the mysteries about it. There are still, you know, practical ways we could go and manage it, but trying to divide it up in the surgery, in the consulting room, when you see a person that you suspect, one simple thing to do is they sit down, you take their blood pressure after five minutes, stand them up.
Andrew: Without white coat syndrome.
Mark: Yeah. Hopefully, without that. But you get a resting pulse rate and you get a standing pulse rate. Now, our problem is Medicare doesn't give you 10 minutes to wait for that trial pulse rate to rise. But for way more than half, the pulse rate is rising fairly quickly. The first minute or two, you see it go from, say, 75 or 80 beats a minute to 120 then you've already got your diagnosis. And I would encourage everyone just to do the simple thing of a sitting and standing pulse rate even before you get blood pressure.
Andrew: But what I don't understand is you're saying a stable blood pressure from sitting to standing. I would've...
Mark: That's POTS, right. So in my practice, with CFS patients, the majority of people, when they stand, the systolic blood pressure and the diastolic drop fairly evenly and they'll drop about 20%. So there is a mixture, although we say orthostatic intolerance covers orthostatic hypotension and postural orthostatic tachycardia syndrome, we love divisions. But when you get dropping blood pressure as could be known, you know, if you've got pooling of blood, of course, your blood pressure is going to drop because your blood is down in your feet and there's just not enough to keep pumping.
Mark: So although in the literature there's this division that we love to have, hypotension versus tachycardia, the fact is in life, most of these people drop their blood pressure to some extent and the pulse rate goes up. Now, if it's a huge pulse rate increase, we focus on the pulse rate.
Mark: If it's a huge blood pressure drop, we think about pooling and we think about vascular and, say, vasopressin, and we think about the endocrine system. And yet, in both categories, they're triggered by viruses, they're triggered by stress. Stress has an undue effect on them. They're not really separate categories. There's a vascular system that we have to pay attention to.
Mark: Yes. So takes me right to the...what we do next, we send them to a cardiologist because if you miss something that is a potentially fatal disease, it's always bad news for you as a practitioner. And so, seeing that there is an abnormal vascular response means that in a single sitting, a good cardiologist will say, "This is none of those conditions." You do the cardiograph, you do the stress echo, you do an echocardiogram of the heart, there's no mitral valve reflexes, none of those...
Andrew: There's no MI. We haven't even stated the obvious.
Mark: Yeah. Well, of course, that's an acute tachycardia syndrome.
Andrew: Feeling of impending doom.
Mark: Ventricular tachycardia is 300 beats per minute. I think we could exclude that one quickly because of the death of the person in front of you. But, otherwise, the recurrent ones, you pass through a cardiologist to take the curse off it.
Andrew: Yep, yep.
Mark: I mean, most of us see if the person's 23 years of age and this has been going on for 12 months, it probably is not one of those. But occasionally, you do pick up Wolff-Parkinson-White. Occasionally, you do pick up complete heart blocks, right? You do find things that you don't expect. You stand them up and the pulse rate is 40 and it stays at 40 and they're going hypotensive right before your eyes. So cardiological referral is a worthwhile thing to do, but 19 times out of 20, the cardiologists will return them to your care. And I've worked with Jason Kaplan and others who are really, really good cardiologists, really good and very thorough, and it looks so cardiological that you want to say, "Just treat it." But the effective treatment, if it's not cardiac disease, is not cardiac drugs. That's not the first line of treatment. So the best cardiologists will pass them back and say, "It's none of the conditions that I would normally treat. It is postural orthostatic tachycardia syndrome. Do you want to try the following?"
And I think that that's probably the way to go, is that we see them, get the cardiac assessment, try and keep them out of cardiologist's hands in the sense that you don't want the assessment to find incidentalomas that the cardiologist says, "Oh, well, there's nothing wrong on the first...Let's do angiograms. Let's do CAT scans, let's do whole body...there's got to be something." We almost want the cardiologist to give up when it's not the obvious, say, "Well, it's probably POTS," and then return them for simple, safe, and effective care. And sometimes you get the simple, safe, and effective is increase your fluid intake by about a litre of water, take your salt at about an extra two to four grams a day, people vary on that.
There is one line of thinking that herbs like liquorice do a very good, stable, and safe job. Some of the herbs you have to watch out that if it's not hypotension, you can push the blood pressure up a little bit too high. And so, that's something that we always have to keep that eye on. If I see the people primarily, his blood pressure is low end, their resting blood pressure even sitting is, say, 105 on 160 and when they stand, it drops to 80 on something, then you're not going to make them hypertensive by using liquorice or a herb. But people who are 130 or 140 on 80, you can't really use hypertensive agents. You can't push their blood pressure up. It doesn't help their pulse rate and all it does is just...it give them hypertension and now there's a reason for them to actually suffer disease.
So the cardiologists are a good first step. They will normally hand back the patient saying, "It is POTS, or it is postural orthostatic hypotension, and here's the things that you can try." And I think that that's a good first move. There are others where we may...there is more, especially in Ehlers-Danlos, collagen disorders now and there is an Ehlers-Danlos...our clinic at Sydney University, they're coming up a little bit more. And so, the mascot of Ehlers-Danlos is the zebra. Why? Because in medicine, we're taught, when you hear hoofbeats, think horses, not zebras. They're the zebras.
Andrew: They're the zebras.
Mark: So, yes, common things are common, but uncommon things can still be there in the background. And if you never, ever think of them, you will miss cases. It's not that they're everybody, you've just got to think that those collagen disorders have so many symptomatic presentations, mainly irritable bowel, POTS, orthostatic intolerance. But those are common presentations that we keep putting into psychological disorders. We keep attributing them to if you just stopped worrying, if your stress didn't bother you so much. So keeping our eyes open for that and successfully categorise them means we can do effective treatment that really does make a difference.
What is true is that once you see Ehlers-Danlos, you can't unsee it anymore. So the temptation is to want to say everything is. When we were taught about collagen variants, we were taught that they are very, very rare, that really they're just Marfans, arachnodactyly.
Mark: We all remember that term of spider fingers and they pop their lungs and they're 6'7 tall and they're really easy to pick. And we've always thought that if this is the one-percenters, but it does seem collagen variants are around 30% of the population. Some are mild and trivial, others are important, but give something time. Termites are trivial, but give them time and your house falls down.
Mark: Same with EDS, that you get this kind presentation when people are in their 20s and 30s of what just seems mysterious. But when you think of collagen as 60% of all your proteins, the structural proteins in the body, almost everything can fail when its structural proteins are too lax.
Andrew: So time and, obviously, the base resilience we're talking...you mentioned termites and house destruction, so let's talk about, you know, resilience of the structure of the house. You know, what percentage, if you like, do you attribute or treat with regards to resilience in these patients?
Mark: Well, in my practice, the first thing is what was the year before? I'd say usually the story goes back that it's rare, I saw one yesterday where nothing happened until the day something went wrong. But the year before, things are usually going wrong and they are attributed to, "Oh, you're under stress."
Mark: There is always a good explanation because most people get better from most things most of the time. Eventually, the person's story is typically, "Well, I was working long hours, I was under stress, I was grabbing meals, high carbohydrate meals, big meals at one sitting, no other eating through the day." And we think of hypoglycemia and could it be, you know, our fuel supply issue.
We go through all of those, but eventually, when you measure the blood pressure and you measure the pulse rate and you've got a good measurement that says, "This is a POTS person and their blood pressures is either stable, low, or high," then we have a second way of dealing with that, is simple advice like, "Don't eat big meals, make them smaller meals." High carbohydrate meals are worse for you, partly because of the insulin response and the dropping of the blood sugar, which is not a fuel supply, it's an osmotic problem. You know, it's just as sugars change, brains swell and shrink and the autonomic response gets lost very easily. And so, we give simple advice like that. When you have these symptoms, lie down, find out if they are eased up. I'm forever trying to separate is it a persistent virus from is it a virus that triggered an underlying problem?
Mark: And I see this as there was always an underlying problem. The virus is the event that we focus on, and that may be why many of our antiviral treatments, you know, we go hell-for-leather after the bug because we are doctors and we believe in the bug theory of everything. We go hell-for-leather after those and the person doesn't recover and we've got good evidence that we've done all we can for the bug. So going back to lifestyle, what do you eat? How do you rest? You know, getting up, sitting on the side of the bed before standing. People tip over. Not for no reason, but because it's hot weather, big meal, or they've got up too quickly and started to make a move to somewhere.
So lifestyle modification can reduce symptoms, but we don't think it changes the vascular and the other responses at that point. But if you're less symptomatic and you're not fainting, it's always a good start. There are specific treatments and the specific treatment, one is compression stockings. If you see the pooling in the feet and they go blue and the person's symptomatic at that time and the blood pressure was dropping and the pulse rate is rising, then simple compression stockings. And Peter Rowe from America who's developed this system of treatment, which is nothing more than very sophisticated lightweight compression stockings, and people put those on, keep the compression in the periphery, and they’re well, they are actually back to normal. They are pain in the bum to put on because you don't have them at night but you put them on and then once you've got to that level of function, that gives us plenty of time to then think about what do we do more deeply.
There’s still the issue about why they fell into that category and what we can do at the cardiovascular or the neurological or the autonomic level. But if you are going for autonomic modification, the gut is the place to go. The gut and the vagus nerve between them control an enormous amount of what goes on. And the story, typically, for a POTS person is things went wrong in the gut and the gut problems were manageable enough, but the gut problems led to blood pressure changes, dysautonomia, and what we're trying to do there is do something for the gut, even if it's on the side and the person can make no sense of it, do this stuff. Even if it's just this plain old stewed apple probiotics and Saccharomyces boulardii, which people will never have heard of before having listened to this podcast. Even if that's the only thing, you get good stability of the autonomic nervous system once the gut stopped signalling inflammatory responses.
Can we go further? Yeah. There's a drug that you would know, pyridostigmine, it's a thing that we use for myasthenia gravis, but it has an autonomic effect, a vagal autonomic effect, which can be very, very positive. At low doses of pyridostigmine, it's a drug that may be reversing some of the processes of the miscommunications of the autonomic nervous system. Certainly, not a first-line drug, but it sits there in the background saying, "Yes, the vagus nerve, the gastrointestinal tract, probably involved. And if it's abnormal signalling, you can break that signalling with the pyridostigmine.
Andrew: What about beta-blockers in certain forms?
Mark: Yeah. Well, it's the blood pressure is not low to begin with, right, you have the problem that we are trying to make a judgment, is the pulse high because the blood pressure is low, and if what we do is do something that lowers the pulse rate but also may lower the blood pressure, then all you do is put people in a more disabled form so now their compensatory mechanism's being sabotaged. And the same goes with a drug which is more commonly used than the beta-blockers now called ivabradine. Ivabradine sits and modifies the sinus rate without affecting other areas of the body. And so, you can specifically slow down the heart without having other autonomic effects around the place. And that works in about 30% to 40% of POTS patients.
So just doing nothing other than a drug which hits in there, stops the sinus rhythm going out of control is a good initial treatment. It's not commonly used because it's a lot more expensive than beta-blockers and it's indicated for other conditions, but the cardiologists are using it very successfully now. That still only gets you 30% or 40% of the way there for symptom control, so beta-blockers are used.
There's another one. If blood pressure is low, one that we use with a fair degree of caution, which is called midodrine. A midodrine is an alpha-1 adrenergic agonist. It's one that increases the blood pressure, used routinely in hospitals for people who have a measurably low blood pressure to try and keep them alive. And so, there's a big danger with that one that if you use it on a person who's normotensive or high blood pressure, you are doing harm. So there are tools around there, pyridostigmine, midodrine, ivabradine, beta-blockers and the one that is probably the most commonly used, especially when we think there's a volume issue, where theres's pooling is fludrocortisone.
Mark: It’s a mineralocorticoid, but unfortunately, no mineralocorticoid is perfect. There's a bit of glucocorticoid or cortisone-like activity in there and there is a thinking, "Well, maybe that's the upside of it,” that there's a little bit of cortisone and a fair amount of something to retain the sodium and to keep it in the system. And I would say that's more commonly used than any other medication in trying to treat the hypotensive tachycardia syndrome where the blood pressure drops and the pulse rate goes up and you can keep the fluid in there.
Mark: Very controversial.
Andrew: Oh, okay. I thought it would have been indicated.
Mark: No. You probably have heard the controversy in this area for exercise, graded exercise programs in chronic fatigue syndrome.
Andrew: Yeah, yeah.
Mark: And where the controversy arises that if you misclassify people and you say, "Let's do exercise," the idea of the exercise is to get the heart back that's been deconditioned. Really good idea except that if the exercise pushes the pulse rate up a bit higher, which aerobic exercise tends to do, you can get a rapid escalation of that pulse rate. And so, what people do with exercise is they get really good heart monitors and the exercise is limited to a pulse rate going no higher than 110 beats per minute. As soon as it gets to that 120, 130 range, it tends to escalate out of control and give an acute exacerbation.
Andrew: Tachycardic, oh.
Mark: And the tachycardia then is not working for the person, their blood pressure drops and it's precipitous and sometimes there are pretty catastrophic outcomes. The second thing about exercise is there's normally a post-exercise fatigue and an in-exercise frustration, meaning the person feels they want to do more, but they're being told not to. And so, they'll exceed it anyway just to see if they can and pay for it for two to three days afterwards. So the reason that...it's not that aerobic exercise is not indicated, reconditioning a heart, allowing it to be stressed a little and then back off. We have good knowledge that whether it's the NRF-2 gene or anything else that the body needs, it's little pushes to be able to find its edges and not to get kind of caught in a corner where it cannot escape. But you have to be so careful about it, and that's a place where a good investment is a heart monitor. The wrist monitors and the watches and the like sometimes have a bit of a lag, so you're thinking that you're running at about 110 but by then it's up to 125 or so. So people invest in this...
Andrew: The chest.
Mark: They do the chest ones and it's giving them second by second readouts, which they can look at on the little monitor. And if they keep below 110 beats per minute, which means, obviously, since your pulse rate rises when you stand, you've got to stand and let it settle again before you even try exercise. You cannot go from sitting to exercise because the pulse rate's already rising beyond that.
So that's where the controversies lie. It isn't an easy disorder, right? It looks easy. You think, "Ah, pulse rate up, we know how to slow down the pulse rate. Ah, blood pressure low, we know how to bring up the blood pressure." We know all the individual things, but a story that haunts me to this day happened late last year where a young girl had dropping blood pressure, rapidly dropping blood pressure, rapid rise in pulse rate. She had all of the symptoms of chronic fatigue syndrome and was extremely disabled, almost bed-bound, and I sent her to the cardiologist, we had a good treatment regimen. She was on midodrine, she was on ivabradine, she was on a bit of fludrocortisone, and the mother sent all of the pulse rate, blood pressure, all of the ratings. She was cured, right?
So I looked at it, perfect blood pressure, perfect pulse, perfect everything. They came in, they cancelled once, they cancelled the second time, and on the third time that they came in, they said, "Oh, look, the reason that we didn't come in is she's been sicker than she has ever been before on these medications." Every measurable parameter was fine.
Mark: We thought that we cured her, but the fatigue syndrome was significantly worse. She was spending more time in bed and it made me think, "Why does the body get into this state?" It may be adaptive and when we as doctors say, "I know how to override that," we're well-meaning. We say, "I know how to get your pulse rate down. I know how to get your blood pressure up." But if the body's kind of...
Andrew: Telling you something.
Mark: ...selected this as the least worst place to be, then when we override it, we have to be humble about that and say, "Let us see what you are feeling rather than what the numbers look like." The numbers looked great. She was sicker than she had ever been. Now, all it took in her case was to take out the midodrine and there was a significant improvement after that, but we didn't know that at the time.
So the thing about POTS is, if you can find an underlying cause like Ehlers-Danlos, if you can find a virus that is a treatable virus, it is probably worth doing everything you can for that underlying disorder rather than go for the pulse and the blood pressure. When you go for the pulse and the blood pressure, you want to make sure that the lifestyle is right, that the meals are right, that the carbohydrate loading is not there, that the fluids are up, that the salt is in place, and if the person doesn't correct with those, then careful use of some of the drug therapies or the herbs like liquorice, and I'm sure there are other herbs that would have a similar pressor response without raising the pulse rate, then you carefully do those.
You don't do what I did, which is run in with the whole bloody lot for a person who's already pretty vulnerable and say you can cope with the adverse or side effects of all of these drugs together. So small gains over a reasonable period of time. The goal of the doctor or the naturopath should probably be over the next six months, we will encourage your body to find its autonomic set point in a far better and more stable state than it is. Not next week on ivabradine and fludrocortisone, magic will happen because that magic almost never happens. We overdo it.
Mark: That is really appealing to me. I mean, partly because one of the things we think with pyridostigmine is that it is affecting vagal tone, that we are a kind of increasing vagal tone and vagal communications between the brain and the gut. But I've listened to this stuff about how we get vagal nerve stimulation, it's becoming more of a reality, it seemed like voodoo to me at one point. How do you get this nerve that winds its way around here, how do you communicate with it to do something?
Now, we have another thing, which is trigeminal nerve communicates with the vagus nerve, and the vagal tone is massively altered by trigeminal things. And so, looking to the trigeminal nerve for where the stimulus enters to go back to the upper part of the spinal cord to modify the vagus nerve now has got a mechanism. So now I can think about it a little more brightly and think, "Oh, come on, how can just fiddling with the ear do something like that?" And I forget, bodies are bodies, you know, they take inputs from everywhere. We've got baroreceptors all around the place. We have got vagal inputs from all the sensory nerves. Of course, there's some way of modifying the vagus nerve. And that's a really interesting area of science now, isn't it?
Andrew: I love the way that systems of medicine, like, for instance, TCM, is lampooned by orthodox medicine. Oh wait, there is that physiology bit, sorry, the anatomy bit. Whoops.
Mark: There is. There's also a thing called an autonomic nervous system, which in the medical mindset, it's like voodoo, everything self-regulates except when it doesn't, and then what do we do? We'd have a very literal response to that of “what will I do to this person to make it regulate?” Whereas, the brain and the baroreceptors and the pain receptors, all of these receptors are feeding into a thing that we have not got a clue about. And having a bit of humility at that point to say, "Let us now go back and do the basics. Do the basics of diet, lifestyle. How do you do your exercise? Where's your fluid intake?" That has a massive effect, but it takes time. Drugs have a lesser effect. It happens quickly. We doctors love that, you know, I have grateful patient who says, "Yeah, you fixed by tachycardia." I can do that with a beta-blocker, but they will get sicker on the other side.
So I think re-learning that, that's the art of medicine. You go back that 100 years that you were talking about, the pulses did mean something. The way that the pulse was bounding, the speed of it, what happened when they stood up, doctors took the time to do it because we were not limited to a 10-minute consultation. We even did home visits and knowing that gave a whole different set of tools to a doctor in the past, experience grew, and they would provide advice which got people through it. Now what we do is we refer to cardiologists, use drugs and then are irritated when people don't get better. And I think going back and changing expectations, say if the body's found its way into this dead end, let's work our way out of it. Let's do the basics first. However boring that may seem, it has a better long-term outcome than if we just race in and use drug therapy.
Andrew: There's a lot more to learn on this. I'd put a call out for our listeners here, if you've treated, you know, a few, at least, patients with POTS and you're finding that you have repeatedly successful treatments, I'm interested here in what herbs you'd be using but also physical therapies and diet lifestyle measures as well. Let us know, we'd love to hear from you and we'd love to sort of get this conversation going. I'm going to put some links up with some research that's been done on POTS and also describing the syndrome, talking about the drug therapy mostly. So we'll put that up on the FX Medicine website for you to access as well. But, Mark, thank you once again for taking us through a little bit of a confounding syndrome. I think the interesting thing is how we look...as you say, if you hear hooves, think horses, not zebras, what the doctors in Africa think of?
Mark: Zebras. That is where you are. That's true.
Andrew: So maybe we should all take a trip to Africa and think possibly that it could be a zebra every now and again. Thanks so much for taking us through POTS.
Mark: It's been my pleasure once again.
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.