Brian Lacy, MD, and Lucy Harris, MD, on Postural Orthostatic Tachycardia Syndrome

Drs Lacy and Harris discuss how to recognize, diagnose, and treat postural orthostatic tachycardia syndrome in gastroenterology patients.

Brian Lacy, MD, is a professor of medicine at the Mayo Clinic in Jacksonville, Florida.
Lucinda Harris, MD, is a professor of medicine at the Mayo Clinic in Scottsdale, Arizona.

TRANSCRIPT

Brian Lacy, MD:
Welcome to this Gastroenterology Learning Network podcast. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida. I am absolutely delighted to be speaking today to Dr. Lucy Harris, professor of medicine at Mayo Clinic in Scottsdale, Arizona. Our topic today is one that frequently comes up when evaluating patients with chronic symptoms of nausea, bloating, or abdominal pain. Could POTS or postural orthostatic tachycardia syndrome be the cause of these GI symptoms? Dr. Harris welcome. Postural orthostatic tachycardia syndrome, which we'll refer to as POTS today for this discussion. How common is this?

Lucy Harris, MD:
Well, first of all, thank you again, Brian, for inviting me today to talk to you about this important topic. We actually don't know the true prevalence of this disorder, but it's thought to be about 0.1% to 1% of the U.S. population. And it's actually the most common present of orthostatic hypotension, secondary to autonomic dysfunction. And I think it's really important to understand these symptoms because a lot of us as GI docs are seeing this disorder, but it's also important to know that the cardiologists and neurologists are actually the primary people that see these patients.

Dr Lacy: 
Great. And maybe emphasizing later when you discuss treatment and a team approach too. So Lucy, thinking about this disorder, more common than I think a lot of people believe, are there identifiable risk factors for developing this disorder? And can kind of as a corollary to that, are there special populations who may be at increased risk to develop POTS?

Dr Harris: 
Yes, that's a great question. And you know me for a long time and my interest is in irritable bowel syndrome. It has a similar risk factors to irritable bowel syndrome. The female male ratio is about 4.5 to one. It affects primarily 15 year olds to 50 year olds. And there's often a family history of the disorder. And in terms of asking about special populations, again, there are some crossovers between this and irritable bowel syndrome. Populations that get this disorder are populations with chronic fatigue and chronic migraines, which you and I see a lot of. Then there's also populations that have mast cell activation, Sjogren's disease, post-concussion syndromes. It's also supposed to be associated with autism spectrum disorder. It can even be seen in celiac patients, patients with anxiety, depression, and fibromyalgia. And then there's also the Ehlers-Danlos or joint hypermobility patients.

Dr Lacy:
Wonderful, great teaching points. I think a nice reminder for us to keep our blinders off as we evaluate these patients. Lucy, following up on that, and we could probably spend an hour discussing this one topic alone, but there's certainly a lot of interest in the possible association of POTS with Ehlers-Danlos syndrome. And what's your perspective? What about the association too of POTS with possible mast cell disorders?

Dr Harris:
So both of them, I see very commonly when I see POTS patients. About 18% of patients with POTS actually also have Ehlers-Danlos syndrome. And I also see a great proportion of these patients with mast cell activation. And when we talk a little bit more about the pathophysiology of this disorder, they actually say that mast cell activation is seen a little bit more in hyperadrenergic POTS.

Dr Lacy:
Lucy, let's say you evaluate somebody in clinic and they ask you the question of, what mean to me? How long will I have it? What's really the natural history of POTS? Does it resolve in some patients? Does it go away or is this a chronic disorder for most patients?

Dr Harris:
That's an excellent question, Brian. And I actually think that question definitely needs more study. It can be chronic. There is data to suggest that with lifestyle changes about one third of patients in the adult population, no longer meet criteria for the disorder after a year. But another study in adolescents that followed them for five years showed that maybe about 20% resolve their symptoms. About half of them had persistence of their symptoms, but with improvement. Another 20% only had intermittent symptoms. But there's still a sizable portion of these patients about 14% to 15% that have worsening symptoms and very persistent, severe disease.

Dr Lacy:
Lucy, thank you. So we've kind of assumed that our listeners here today who are obviously very smart and interested in this topic, kind of know a lot about POTS and to some degree, the definition is in the title, right? Postural orthostatic tachycardia syndrome. But how do you, in clinical practice, how do you define POTS?

Dr Harris:
That's a question on sort of two different levels. I mean, one of the reasons that I got interested in this is that I started to notice a significant proportion of my irritable bowel syndrome patients were reporting very similar symptoms of things like anxiety disorder or increased palpitations, sort of pre-syncope type symptoms. But the people that meet the diagnostic criteria, they actually go for autonomic reflex studies. And basically it's a study where they are either tested, going from the lying down to standing position, or they use a tilt table. And basically they define it as a increase in the heart rate of greater than 30 beats per minute within 10 minutes of upright position in adults. And in adolescence or children, you have to have a greater than 40 beat per minute increase.

There's also an absence of orthostatic hypotension. That means no sustained drop in blood pressure of greater than, or equal to 20 over 10 within minute of upright position. And they have to the symptoms for greater than, or equal to six months. And you have to rule out other causes of orthostatic hypotension or these symptoms, such as dehydration, other medical conditions. They have to follow very strict guidelines in terms of medications that they need to be off of things like anticholinergics antihistamines, SSRIs, and you also have to look at their diet and make sure that's not playing a role in meeting the criteria.

Dr Lacy:
Great teaching points, just to recapitulate a little bit. Think about those medications, make sure it's not just symptoms. There is objective testing and probably involve a cardiologist, as you mentioned earlier. Lucy, you mentioned a little bit earlier, the hyperadrenergic form. That's a great segue. Could you briefly describe the pathophysiology underlying POTS?

Dr Harris:
It doesn't sometimes pan out in terms of clinical pictures across the board, but generally neurologists and cardiologists usually define two different populations. One's the hyperadrenergic POTS and the other is the neuropathic POTS. And in the neuropathic POTS, they think that the patients have a partial autonomic denervation that's characterized by orthostatic venous pooling in the lower limbs.

And for the hyperadrenergic POTS that has maybe centrally driven sympathetic activation. And those patients often will have what we call supine vasoconstriction and they'll show clinical symptoms of pale and cold skin, they'll have tachycardia. They also, on autonomic testing, they actually do this test checking catecholamines and they'll have higher plasma norepinephrine levels when they do this testing. So that's a little bit about it. I don't think we understand all of the pathophysiology. I think that's still being worked out. I think, like irritable bowel syndrome, we're going to find that there are probably many different causes of this disorder.

Dr Lacy: Wonderful. So now we're clear on kind of the epidemiology and risk factors and the natural history and how we define it and the pathophysiology. So what are some of the most common symptoms of POTS, both gastrointestinal and non gastrointestinal?

Dr Harris:
A lot of these patients will start telling you that they have weakness or palpitations, or they may actually have an increased incidence of fainting spells or pre-syncope. They'll complain to you of brain fog and even dyspnea, which we kind of associate with other things, can be symptoms of POTS. They'll also mention paresthesias, lightheadedness, dry eyes. And the other key thing is urinary symptoms. If you are talking to patients and they start telling you, well, I have difficulty starting my urination or a weak flow. That may be the sort of a non GI symptom.

And then in terms of GI symptoms, they have a slew of symptoms. Most commonly sort of nausea and vomiting, which you could maybe also associate with the orthostatic sensitivity. They'll also complain of dysphagia. They'll have either constipation probably a little bit more than diarrhea, and maybe even dyspepsia.

Dr Lacy:
Lucy, when I see these patients in clinic and probably similar to you, just to hone in on that a little bit more, a lot of them ask kind of what's the with POTS and the GI symptoms you just discussed? Does having POTS guarantee GI symptoms? If I have mild POTS, do I only have mild GI symptoms? If I have severe POTS, do I have more severe GI symptoms? Is there any relationship there?

Dr Harris:
In my experience, patients who have more severe nausea and vomiting probably have more severe symptoms and also symptoms of early satiety where they have pain with eating. I see that particularly in the Ehlers-Danlos population. They seem to very traditionally get sort of epigastric pain. I see that in, and not everyone, but a large percentage of them. I think that the treatment and we can talk more about this, can dissipate some of these symptoms. I think constipation is another big symptom.

Dr Lacy:
Lucy, you've alluded to this a little bit twice already, but in terms of making the best diagnosis, is this something we should be doing alone in GI clinic? Should we always pull in a cardiologist? Should we always pull in a neurologist? Or is it more patient independent?

Dr Harris:
I think with those with milder symptoms that you may not reach for the neurologist or the cardiologist so much. I think though, if you're truly considering this diagnosis, you need to really reach out to a cardiologist or neurologist that understands this syndrome. Because too often, the testing is not accurately done if the cardiologist or neurologist is not well versed in this disorder and the testing. Because in addition to the tilt table, changes that I alluded to, academic centers they'll do more kind of pseudomotor testing. Things like sweat and breathing. And so I think it can be more complex than we appreciate, as gastroenterologists anyway.

Dr Lacy:
Agreed. So let's think about a patient who we know has documented POTS and there are there in GI clinic with you that day and whether it's the neuropathic type or the hyperadrenergic type, is there a validated algorithm for specific testing of the GI tract? Does everybody require esophageal manometry and a gastric emptying scan and a colonoscopy, or is it really very variable?

Lucy Harris:
Well, the way I generally do it, is that I of ask them what their predominant symptoms are. And that's how I decide about testing. There have not been well designed trials to look at what testing should be done from a GI perspective anyway. So if they complain of difficulty with swallowing, then I'll do a barium esophagogram and perhaps an esophageal manometry.

If they complain more of nausea and vomiting and early satiety, then I might do a gastric emptying study, an upper endoscopy. There is by the way, an association with celiac disease. So about 3% of celiac patients actually also have POTS. So I also want to roll that out. And about 8% of patients with inflammatory bowel disease get POTS symptoms. So depending upon the symptoms you may want to do more or less in terms of endoscopy. And definitely, I would say if the patient complains of constipation, we've actually studied this, and unfortunately we haven't published it. We've presented a few abstracts, but we have found that there's a higher degree of pelvic floor dysfunction in these patients with constipation. So I like to do the anal manometry and possibly defecography in these patients.

Dr Lacy:
Wonderful, great teaching points. Especially if about the higher prevalence in IBD patients. So let's shift gears a little bit now and think about treatment options for the GI patient with POTS. And one belief is that if all of the cardiovascular manifestations of POTS are addressed, all GI symptoms will resolve. Is that true?

Dr Harris:
I wish it were so, but particularly challenging can be the symptoms of constipation and nausea and vomiting. Generally, I think it is important to push fluids and push salt. That is really the basis of the lifestyle things that are important in patients with postal orthostatic tachycardic syndrome. And also it's again, a very similar to irritable bowel syndrome. I think you also have to look at things like sleep quality. And also exercise because that's very important with pathophysiology of postural orthostatic tachycardic syndrome. So even as gastroenterologists, I think you have to push those lifestyle changes and then you need to concentrate on the nausea and vomiting and constipation. I think those are kind of those symptoms that I find the most challenging to treat in this population of patients.

Dr Lacy:
See, let's think about that patient who you evaluate, who truly is POTS. And they say, I'd like to avoid medications. You've already mentioned better sleep, exercise, pushing fluids, higher salt content. Are there other dietary modifications you could recommend or maybe even herbal products?

Dr Harris:
We do kind of anecdotally find that a lot of our postal orthostatic tachycardic patients do better with a gluten-free diet. So I think there may be something to that kind of diet. I think one of the challenges that we face in motility in general is getting a good test that actually assesses small bowel motility. And there's some suggestion that in this disorder, there may be autonomic dysfunction that affects the small bowel.

And so I think when we put our patients on a low FODMAP diet, the fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet, that sometimes this helps with some of the symptoms of bloating. And sometimes with a nausea and vomiting, I may use a gastroparesis diet that's low fat and low fiber to help with those symptoms. I haven't really found that much in the way of herbal products. I might use some of the things that I would use with patients who had gastroparesis things like ginger teas, fennel, ginger chews, Iberogast. Those are probably some of the natural things. And then the things that you might use for constipation, like kiwis and prunes, although those are higher in fructose. So those are the kinds of things that I'm using in that regard.

Dr Lacy:
Yeah, no. Great recommendations. It's always nice for people to have options. So let's think about pharmacologic interventions for POTS. What are our options?

Dr Harris:
Well, I think that part of things is often handled more by the neurologist or cardiologist, but they do use drugs like midodrine and pyridostigmine. Pyridostigmine does stimulate the acetylcholine receptors. So sometimes if I feel patient is having issues with motility, I might also use that medication. The neurologist is using other medications, such as beta blockers to perhaps work on blood pressure and pulse rate.

From a GI standpoint, I'm pretty much using the same armamentarium that I'm using for gastroparesis patients and constipation patients in terms of all the medications that are available in that regard. And I do think one of the challenges that we have with patients with postural orthostatic tachycardic syndrome are that the lot of the medications for nausea and vomiting can potentially be constipating. So you're kind of always trying to get that balance between treating the nausea and treating the constipation.

Dr Lacy:
Lucy, those are great tips and it kind of comes back to how you almost started this discussion. Identify the predominant symptom and really kind of focus on that. So Lucy, this has really just been a wonderful conversation. I learned an awful lot. I know our listeners did as well. Any last thoughts for our listeners?

Dr Harris:
I think just be aware of this, not everybody that presents with or billed as irritable bowel syndrome actually has irritable bowel syndrome. They may actually have postal orthostatic tachycardic syndrome. This, too, may also cross over into our patients that we think have gastroparesis. Although, one interesting thing I'd like to mention before we stop, is that when they actually do testing on these patients, they actually have on average, faster gastric emptying rather than slower gastric emptying.

Dr Lacy:
Good teaching point there. Because if you give them something like a prokinetic and accelerate their gastric emptying, maybe it'll get worse.

Dr Harris:
Mm-hmm (affirmative).

Dr Lacy:
All right, once again, Lucy, thank you so much for taking time out of your very busy day. This has been a great conversation. I know you've helped a lot of our listeners. Thank you so much. I'm looking for forward to having you join us on another podcast in the future.

Dr Harris:
My pleasure. Thank you.