Understanding Blood Volume & Hemodynamics in POTS

Aug 24, 2023

Understanding Blood Volume & Hemodynamics in POTS

In this webinar, Dr. Raj explains how to understand blood volume and hemodynamics in POTS.

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Content

8.731 -> [Music]

9.04 -> good evening this is lauren stiles i am president and co-founder of dysautonomia international and

15.76 -> i'm really excited this evening to have all of you joining us we're joined by special guest

22.96 -> dr satish raj who's a professor of cardiac sciences at the university of calgary and a

29.12 -> direct the director of their um cardiac arrhythmia unit if i got that wrong sorry and he's also

37.68 -> a long-standing very active member of dysautonomia international's medical advisory board

43.28 -> and he's the guru of potts blood volume so we're going to get a great lecture tonight

49.12 -> just a little housekeeping notes there is a feature on zoom where you can type

54.64 -> some questions into the q a i think it's scroll down towards the bottom of your um

61.84 -> zoom panel and so we'll try to get to as many questions as we can at the end but generally

67.04 -> speaking there's usually way more questions that we could possibly get to in one evening

71.68 -> so please try to keep your questions um general something that would apply to a lot of patients

77.2 -> um dr raj can't give individualized medical advice over zoom and we're going to record this so if

84.8 -> there's anyone who couldn't catch the whole uh uh session then they'll be able to catch a recorded

92.08 -> copy later so with that um i'll uh oh i do have to thank our sponsors too one sec there we go

98.96 -> i wanted to thank just autonomy international sponsors all of whom have great products that

103.84 -> can help you increase your blood volume uh liquid iv vitasium and normalite are all

109.84 -> good salty hydration products and their generous sponsors of just autonomy international throughout

114.8 -> the year and they help us put these webinars on for free so um i get done with my slides and dr

121.44 -> raj you can start to share your screen now great thank you lauren uh let me pull this up quickly

133.28 -> so um thank you again for for joining uh in in what is evening for most of you i'm going to

140.96 -> touch on different things and happy to try and answer questions if there

144.8 -> are sort of more detailed aspects and i've taken a fairly expansive view of what blood volume

154.16 -> can do but also what uh approaches we have to to improve or alter it so i'm not going

160.88 -> to belabor the point i suspect that if you're all here you already have a good

165.52 -> basic handle on pots um this is a slide i've used before just showing a tilt table

173.52 -> response and a control subject on the right and a pots patient on the left you can see

178.4 -> that there are the heart rate channel on top of blood pressure channel continuous blood pressure

182.48 -> channel in the middle and a tilt angle when you can see with the table's up and the tables down

187.92 -> and the key thing here is that pots isn't primarily a disorder of

192.64 -> low blood pressure certainly the blood pressure trace may look a little different from the control

197.76 -> subjects that may be important but the real money here is in the top channel the heart rate channel

203.44 -> when some when the control subject stands up the heart rate goes up right so the key thing

207.6 -> here is the heart rate increasing isn't in and of itself abnormal but you can see the potts patient

213.52 -> does it a lot better than the control subject this patient um didn't make it through a full 30 minute

219.84 -> tilt which was a protocol we were looking at because she basically had enough and when she told

225.68 -> us to put the table down her heart rate was almost 180 beats a minute now the truth is that most of

230.24 -> our patients don't get their heart rates that high but but it obviously is excessive and can be

236.16 -> incredibly excessive as in this case and importantly um this is associated with a

241.68 -> bunch of troubling symptoms to patients and they can be broken down in different ways if you had

246.88 -> a neurologist giving this talk they may break it down differently but as a cardiologist by training

251.84 -> i've broken them down to symptoms on the left that could plausibly be attributed to the heart

259.04 -> racing heart palpitation chest discomfort shortness of breath lightheadedness and symptoms

265.36 -> on the right that i have a lot more trouble directly blaming on the heart or cardiac function

271.36 -> per se brain fog or mental clouding is incredibly common headaches very common nausea very common

279.76 -> a tremendousness or shakiness are very common and again most of these symptoms in black here on both

285.2 -> sides tend to be worse with upright position but there are some symptoms that aren't positional so

292.24 -> sleep complaints very common fatigue very common exercise intolerance very common and i'm not sure

297.6 -> the blood volume is is the bl and end all for all of this but it certainly i think can help

303.04 -> with some of the cardiovascular symptoms and in some cases some of the other symptoms as well

309.2 -> in summary um you know the the symptom burden is is fairly high in pots patients

316.16 -> this is from the same study where we had the tilt data from a couple of slides ago

321.04 -> and what we see here during this 30 minute tilt is the control subjects in black for

325.6 -> the most part are asymptomatic um occasionally someone will become slightly symptomatic and then

332.4 -> they'd faint and then they sort of drop out and so you see

336.32 -> numbers going up marginally and then flipping back down the pots patients on the other hand in red

343.68 -> quite symptomatic from right in the beginning of the tilt and and it really stayed that

347.52 -> way all the way through interestingly a higher proportion of the plots patients

353.04 -> made it through the full 30 minute tilt in the control subjects

357.28 -> right so think about that the pots patients felt like they're going to faint throughout the tilt

362 -> but actually more of the control subjects actually painted so it just drives home the point that pots

368.8 -> it's not the pots patients can't faint they can a minority do but it's pots isn't primarily a

374.64 -> fainting disorder it's a feeling faint disorder among other things so that brings us to blood

380.56 -> volume and my interest in this dates back to you know right at the beginning of my time working at

386.64 -> vanderbilt university under david robertson and we were interested in blood volume blood volume

392.8 -> shifts in patients with pots and in that first study we actually did a direct measurement of

399.12 -> blood volume this is something that's available typically through nuclear medicine labs clinically

404.8 -> when they're available in the states you can't get this from a simple lab test

410 -> and what we found is that we had a tool that measured the volume and then you know we

416.16 -> recognized that bigger people have more blood so i don't know how many of you remember andre

421.92 -> the giant but you know if if you know andre the giant you compare it onto the giant's blood to

427.52 -> uh to lauren his blood volume would be expected to be much higher because there's so much more of him

434.08 -> um so the technique we used actually accounted for this they used old formulas to estimate

441.68 -> or predict what the blood volume should be based on someone's height and weight

447.52 -> and sex because the curves are slightly different from men and women and based on

453.84 -> that we found with the control population on the left you see here there is a spread i mean not

459.92 -> everyone's the same but on average the formulas were pretty good there was really no plasma

466.16 -> volume deviation it was almost bang on whereas the pots patients on average had about a 12

472.8 -> deficit in blood volume so they're they're down you know realistically we're talking about a can

478.16 -> of coke right it's not we're not talking about leaders and leaders down but their blood volume

483.2 -> was a little bit contracted and we thought that might be part of the problem so we actually looked

489.92 -> at some of the hormones that regulate blood volume and two of the hormones here are renin activity

496.24 -> on the left and plasma aldosterone on the right so these are aldosterone's a hormone

502.24 -> that works on the kidney to retain sodium and renin actually helps as you'll see in a moment

508.4 -> indirectly to drive aldosterone levels now if the blood volume is low and these

516.32 -> components or this mechanism is not

519.44 -> part of the problem you'd expect it to be trying to be part of the solution and what

523.68 -> we'd expect is that the levels of the renin activity and the aldosterone things that would

529.68 -> try to work to increase the blood volume would be elevated in the pots patients with the low

535.12 -> blood volume but that's not what we found what we found was that the renin activity was the same or

541.84 -> you know it's inappropriately low and the aldosterone levels were really lower in the plots

545.52 -> patients than the control subjects which led us to conclude that this may be part of the problem in

551.68 -> some of these pots patients that we were studying is that their renin angiotensin aldosterone system

559.44 -> might not have been working properly to fully hold on to the sodium in their kidneys and this

565.44 -> is just a little schematic cartoon of the pathway so there's angiotensinogen that gets converted to

572.96 -> angiotensin one and the pra is the plasma being inactivity that's what i showed you on the prior

577.2 -> slide and that gets converted via the enzyme ace or angiotensin converting enzyme to angiotensin ii

585.6 -> and then that works activates the angiotensin receptor and when it does in the adrenal gland

593.6 -> can produce aldosterone and and ultimately this promotes sodium retention and increases blood

599.12 -> volume so this is how things are supposed to work and based on sort of where we were in 2005 after

605.04 -> that first study we found that the renal activity was on the low side the aldosterone was on the low

611.04 -> side the blood volume was on the low side and i submitted this to circulation the reviewer came

616.08 -> back and said well yeah that's great you showed the aldosterone is low and the arena is low but

620.96 -> you ignored all the stuff in the middle with these angiotensins and the reviewer is right we sort of

627.52 -> assumed that it this is low on the left and it's low on the right it'll be low in the middle

633.12 -> and the reviewer took pity on me and were able to get the paper published

638.08 -> but it turns out it may be more complicated so over the next few years julian stewart who

643.36 -> i'm sure many of you are familiar with from new york medical college published

648.72 -> some work suggesting that he found in one of the subgroups of potts patients that he was studying

654.64 -> that they actually had a high angiotensin ii level and then he did some very nice work using

659.68 -> a skin model a micro dialysis skin model where he thought there was decreased ace2 activity

666.16 -> and and i will say until about you know 18 months ago there are very few people i talked to that had

671.92 -> ever heard of ace2 that's changed because of cobit but this is where that fit in so ace2 infections

681.68 -> aside its main historical role is has been as a enzyme degrades angiotensin ii into angiotensin

689.76 -> one to seven it does a few other things but that was its main role and so we now had that h2

696.64 -> levels were elevated and perhaps ace2 levels were decreased in potts patients and in fact we later

702.72 -> showed as well that and shoe levels were elevated in a paper that we published a little later on as

709.6 -> i mentioned ace2 has gained prominence in the last year because it turns out the sars cove ii

717.2 -> virus the virus that causes covet 19 actually in the body binds to the cells via the ac2

723.52 -> receptor and then gets in the cell that way and so people have paid a lot more attention to it for

728 -> that reason this mechanism is entirely different than any covert related mechanism we think

735.68 -> and so we found that plots patients had high angiotensin two levels as you see in the top

740.72 -> left the breakdown product angiotensin one to seven was less high and and so if you look at

748.4 -> ace two activity basically the conversion from one to the other it seemed to be low in pots so using

755.12 -> blood tests we showed similar findings to what julian showed in his skin work in potts

762.48 -> patients and then we also wondered about whether that receptor that triggers the production of

770.48 -> aldosterone was not working properly or blunted in pot so the net result is lower aldosterone levels

779.2 -> and so that's sort of a lot of stuff summarized here

783.68 -> the key things that i think we're very confident about is that a lot of pots patients not all but a

788.72 -> lot had low blood volume there was low plasma renal activity low aldosterone so hormones

795.52 -> multiple hormones in that that pathway the arena angiotensin aldosterone pathway were affected

801.92 -> but angiotensin ii was high suggesting that there may be a problem in its degradation or metabolism

808.72 -> but there ultimately was a paradox because if they're high energy into angiotensin ii levels it

813.28 -> wasn't clear why they were low aldosterone levels and there may be a separate receptor problem um

821.12 -> realistically you know the net result of that is that there may be this would all

825.68 -> suggest that there may be a problem holding on to sodium in the kidneys of some of these patients

832.88 -> so that first set was just to point out that there's some data suggesting there may be

838.32 -> problems there so then the question is well how do we go about trying to increase blood volume or the

843.76 -> effective blood volume and there are different approaches that can be taken i'm going to focus

849.04 -> largely on non-pharmacological approaches and then touch just briefly on a couple of drug approaches

855.52 -> used loosely so first dietary salt i suspect that many of you out there

861.84 -> that that have pots have been told to increase your dietary salt intake

868.32 -> and you know we sort of joke with patients that they should just get a salt lick uh you know and

874.64 -> put in their living room and lick it every time they go by that really we we are pushing salt in

878.96 -> a very big way but of course you know this is countered by the fact that the american heart

885.04 -> association in the u.s and the heart and stroke foundation in canada and i suspect the british

889.52 -> heart foundation you know have for years made the point that as a society we need to lower our

896.56 -> sodium intake and that's because they're dealing with the population health problem of hypertension

902.56 -> and long-term risk of stroke however for our patients that hasn't been the advice we have

909.92 -> seen low blood volume and we've been trying to augment the blood volume augment the salt intake

915.52 -> in the hopes of increasing the blood volume but i guess the question is does that really happen

922.64 -> so years ago we were i was shocked when we were sort of designing a grant building on

927.04 -> our aldosterone angiotensin work that i shared with you that despite the fact that we've been

934.16 -> recommending high salt intake there's actually there have been very little data published

940.96 -> suggesting the sodium did what we thought it would do so the rationale for increasing dietary sodium

946.88 -> is that it would expand the blood volume you'd hold on to the salt the fluid in the kidneys

952.4 -> would follow the sodium and so you'd hold on to the fluid and expand your blood volume that way

957.68 -> that could then hopefully decrease the need for increased sympathetic tone the crude

964.96 -> measure that we use is measuring the plasma nor adrenaline or norepinephrine levels in the blood

972.32 -> that we think is somewhat is the driver in many patients for the high heart rates that we notice

977.04 -> especially on standing in pots patients and so by blunting this that we could lower the amount the

983.28 -> heart rate jumps up and and ultimately the goal of all this is to see if we can improve symptoms

988.64 -> right i as a human physiologist i'm very interested in the physiologic parameters i know

993.6 -> some of you are interested in that but only the interest really is primarily

998.08 -> to see if that's causing problems that we can then fix

1002.8 -> and so this is a brief cartoon of the study design this data has been many years in

1008.88 -> the making i was actually presented first in 2014 at the heart rhythm society meeting and

1014.56 -> bits of it later at autonomic meetings this is actually going to be published

1018.64 -> next week in the journal of american college of cardiology so the actual paper will be out

1025.28 -> almost momentarily but basically this is a study that

1029.84 -> took a fair bit of effort on the part of the patients that participated so we had pots patients

1034.88 -> and control subjects who agreed to come into our research unit of vanderbilt for two one-week stays

1042.96 -> during one of the stays they were fed a very low sodium diet as low as we could make it and on the

1050 -> other week the other phase they were fed a very high sodium diet and we randomized the order of

1055.92 -> that and we actually tried to bring patients in at roughly the same phase of the menstrual cycle

1062.24 -> so it was at least a month apart some cases a few months apart because we know that there is

1067.6 -> cyclical variability in some of these hormones that we know are very important

1072.08 -> and we looked at the things that we were talking about we looked at plasma volume we looked at

1076.08 -> norepinephrine levels we looked at the effects of heart rate uh blood pressure lying and standing

1082.72 -> the metrics that we use to assess um how severe the pots is if you will

1090.32 -> and this is what we found so the data in the next few slides looks similarly in that

1097.68 -> the the pots patient data are in red the control subject data are in blue

1104.96 -> the hashed portions are on the high salt diet and solid portions in the low salt diet

1110.8 -> you can see that as before the pots patients we saw had a deficit of 12 or 13 percent uh in their

1117.2 -> blood volume on the low sodium diet we put them on a high sodium diet it didn't eliminate the

1122.32 -> deficit but it decreased it it was down to about four or five percent on average and that was a

1127.76 -> significant increase we also were able to increase the blood volume of the healthy control subject

1135.68 -> from the low salt to the high salt diet the high salt somewhat normalized but not did not

1142.96 -> totally normalize the blood volume in the pots patients in other words the pots patients on

1149.04 -> a high steel diet still actually had a lower blood volume than the healthy control subject

1155.84 -> on a low salt diet now blood volume isn't uh one thing it's actually two things largely there's the

1163.36 -> red cell component and there's the liquid part um and the salt actually works on the liquid part and

1169.52 -> that's what we expected and that's what we saw here which was that the high salt diet almost

1174.96 -> entirely corrected the plasma volume deficit that we saw and increased that in the control

1179.92 -> subject but if you look at the red cell volume on the right panel it made no difference and that's

1187.36 -> it makes sense right it's not obvious to us at least acutely in the short term that red cell mass

1194.64 -> the the blood cell production should increase with sodium but the liquid part of blood did

1203.68 -> as i mentioned we looked at standing or upright plasma norepinephrine levels and we use this

1210.16 -> as a crude marker of sympathetic nervous system tone and that's because norepinephrine

1215.36 -> is a neurotransmitter in this in the vascular part of the sympathetic nervous system and what

1222.4 -> we found is that it lowered the high salt diet lowered the upright or standing plasma

1229.76 -> norepinephrine level compared to the low salt diet in the pots patients and in the control subjects

1235.28 -> again even on a high salt diet the pots patients still had the ones we studied had higher levels of

1243.28 -> plasma norepinephrines or higher levels of sympathetic tone

1246.96 -> that we're estimating then did the healthy control subjects on the low salt diet

1251.52 -> so didn't normalize things fully it but it moved things in that direction and it is worth noting

1260.48 -> that these pots patients

1264 -> would probably be would qualify as hyperagonergic by many definitions um so i i struggle with the

1271.28 -> term hyperactinergic plots and neuropathic pots as a classification because i think there are

1276.72 -> there's a lot of overlap and limitations but if you look at the pots patients on a low

1280.8 -> salt diet here the upright or standing plasma norepinephrine level average over a thousand

1286.48 -> grams per milliliter generally speaking anything over 600 or 700 is considered elevated and those

1293.76 -> thresholds are often used to define hyperagmergic certainly within a study so these patients that

1301.76 -> we improved were actually hyper adrenergic to begin with and we made them less hyperionergic

1309.44 -> although one could argue they're still hyper adenergic afterwards

1316.56 -> this slide shows some of the heart rate data um when lying down on the left there was a slight

1323.44 -> decrease in heart rate in the plots patients not so much so in the control subjects not a huge

1329.68 -> difference but if you focus on the right panel there's actually two bits of data the left part of

1336 -> the data is actually the upright heart rates and you can see that there was a significant decrease

1345.2 -> from low salt to high salt low salt here are the open squares the high salt or the solid squares

1352.88 -> in the control subjects it didn't quite reach statistical significance but there

1356.16 -> was a decrease as well and because the upright values decreased but the lying down values

1364 -> didn't change much there was a big difference in the orthostatic tachycardia or the delta heart

1368.72 -> rate shown on the far right here so the high salt diet decreased the orthostatic tachycardia

1376.8 -> so tish could you clarify for people what the salt was how much salt was the high

1382.08 -> salt and how much salt was the low salt sure so these were extreme diets so the low salt

1388.64 -> we were aiming for 10 ml equivalents a day which is you know almost absent um we it was so low that

1396.48 -> we couldn't actually measure the document that it was absolutely that low but it was a very very

1401.6 -> you know think of the blandest possible food you can have and that's what we had having said that

1407.76 -> the kitchen did a reasonable job it didn't taste quite as bad as i thought it should

1411.84 -> um the high salt diet was 300 ml equivalents a day which is uh an aggressive salt intake now we

1419.2 -> didn't have people add salt uh you know we didn't use salt tablets or things like that it was that

1424.48 -> we actually had a metabolic kitchen created but it was a very aggressive high salt diet

1432.48 -> and again you know as i mentioned earlier you know the goal of these treatments is to make people

1438.56 -> feel better and unfortunately our data collection and storage on the symptom ratings wasn't as

1445.36 -> good so we're missing a bit of data you see less data points here um than in the prior slides but

1452.64 -> quantitatively there was a decrease it didn't quite reach statistical significance from

1456.96 -> low salt to high salt but you can see that from the data we have there was an

1460.64 -> improvement or a reduction in symptom burden in the pots patients not really

1467.28 -> in the control subjects but again they weren't that symptomatic to begin with so the summary

1472.96 -> of the salt uh dietary salt study was that a high salt diet increased plasma volume in pots patients

1479.12 -> it decreased the plasma standing norepinephrine levels it decreased the orthostatic tachycardia

1488 -> it didn't fix the pots patients right i mean it didn't make the pots patient

1492.88 -> look like you know a healthy subject but it shifted everything in the right direction

1499.52 -> at least in the parameters that we were looking at

1505.36 -> so um there's been a study in the last couple years on oral rehydration solutions so i thought

1511.2 -> it'd be worth mentioning that so some of you may be familiar with this some of you may be familiar

1516.4 -> with this in terms of your your young kids or babies but these are solutions that consist

1524.24 -> of electrolytes primarily salt as well as sugar and you know the world health organization made

1532.8 -> them widely available to treat diseases like cholera really bad diarrhea in many parts of

1540.48 -> the third world and in fact versions of this are available on the u.s market to treat babies with

1547.36 -> diarrhea and the principle of using in addition to the sodium having glucose in the solutions

1553.84 -> that you drink is that there are transporters in the gut that transport sodium with the glucose

1561.2 -> and so the theory is the the absorption of the sodium may be better with the glucose in toe

1568.88 -> and so dr marvin meadow from new york medical college a colleague of dr stewarts

1573.52 -> um published this paper back in 2019 they used a model uh it was an acute study it wasn't a

1581.76 -> a lo i mean not sure that our study of one week here one week there is

1585.36 -> long term but this was a this was a shorter single session at a time study

1593.28 -> they use lower body negative pressure as their model of orthostatic stress instead of standing

1597.6 -> or tilt but you can see here just looking at representative samples that compared to

1604.16 -> the patients that went into the lower body negative pressure box and then had suction applied

1613.12 -> sucking blood into their legs and effectively mimicking the standing stress um compared to when

1621.28 -> they fainted the pressure dropped is what we're showing here both intravenous saline so salt water

1628.72 -> intravenously and the oral rehydration solution provided more support they lasted longer before

1637.28 -> the patients fainted now you can say well but the patient's still fainted and that's true but one

1644.32 -> of the interesting features of these lower body negative pressure blocks are boxes are that you

1649.12 -> can impose enough stress that you can make anyone faint so sometimes the key isn't whether they

1655.36 -> faint or not but it's how long they can hang in there before they faint and so this was considered

1661.2 -> a positive response to the oral rehydration solution and the saline compared to neither

1670.64 -> um that that was just a representative example slide but but overall the the patients with

1675.76 -> pots had reduced orthostatic tolerance or lbnp tolerance compared to controls as you'd expect

1683.2 -> but they concluded from this that oral rehydration oral rehydration solutions may be convenient safe

1688.88 -> and effective therapy for the short term relief for the static intolerance i mean i think this

1693.84 -> study provides sort of foundational data that it may be a reasonable thing to try obviously

1700.24 -> we'd love to see uh that's the first thing the second thing is i believe the study is mainly in

1706.64 -> kids and young adults which is a significant portion of the plot's population but um not

1712 -> testing the spectrum of ages but we'd like to love to see sort of the study over time and

1720.16 -> really assessing symptom burden which is what we want to improve in many of our patients

1728.24 -> so the next bit's going to be on some compression garment work performed by kate born a phd student

1734 -> of mine here in calgary this isn't so much about increasing blood volume as redeploying or shifting

1740.48 -> the blood volume and so this is a proof of concept study using a segmental compression garment it's

1748.96 -> not something that people would wear in the real world are the garment that we used in the lab

1753.68 -> was made of neoprene and velcro honestly it was butt ugly but it allowed us to look

1763.12 -> at compression of just the legs simulating sort of knee-high or calf compression garments um it

1772 -> allowed us to look at the abdomen and upper thigh as well as the combination to see if there were

1777.12 -> real differences with compression overall or if certain segments played more of a role than others

1784.88 -> so our primary goal was to see if compression helped and so the study involved having patients

1792.32 -> undergo a series of 10-minute tilt tests in the lab with these different compression

1797.52 -> configurations and really we were looking at the heart rate and so you can see here

1803.52 -> the heart rates on average before the tilt these are the negative numbers minus four minus three

1809.2 -> minus two and then the positive numbers are you know at 70 degrees head up tilt so simulating

1815.12 -> standing you know many of you have probably had tilt tests and with no compression um in blue

1822 -> you can see the heart rate went up quickly with tilt and then continued to go up

1827.44 -> and the average heart rate at 10 minutes was 110 beats a minute

1832.32 -> with the full compression heart rate still went up on standing remember

1836.08 -> orthostatic tachycardia heart rate increase on standing or upright tilt is not abnormal it did it

1843.44 -> went up but then the increase over time as these patients stayed tilted was significantly blunted

1853.76 -> and decreased you know with the with the compression and this shows some of the

1860.72 -> heart rate changes so the panel a on the left is is the delta heart rate or the orthostatic

1866.8 -> or the change in heart rate and you can see that overall on average it was much higher uh in the no

1873.28 -> compression group and it was blunted in the full compression group although there were some people

1878.72 -> shown here in red which who had very low levels in both cases levels that certainly wouldn't meet uh

1886.08 -> or with us that you know the traditional 30 beat increase of pots patients um you know even without

1892.8 -> compression they didn't benefit that much and we have some data showing that more clearly

1899.76 -> on the right we see that again the compression didn't do much to heart rate when people

1905.04 -> were lying down but it really blunted or prevented some of that increase on standing

1913.6 -> and we wanted to understand why so this slide shows two things one is in addition to the no

1920.8 -> compression versus full compression we actually have the the dose response if you will we have

1926.96 -> no compression in blue the calf only leg only compression in red the abdomen and upper thigh

1933.68 -> compression in green and then the full is both the leg and the abdomen upper thigh

1939.04 -> and you can see that the increase in heart rate the orthostatic tachycardia

1944.24 -> decreased in a dose-dependent fashion the more compression you did so full

1949.68 -> compression was the best the abdomen thought and thigh was second best the leg compression

1956.72 -> helped a little but really not a lot compared to no compression

1964.16 -> part of the effect we always say that you know pots is the excessive increase in heart

1969.44 -> rate the excessive tachycardia in the absence of orthostatic hypotension and that's true because

1974.16 -> significant orthostatic hypotension requires a drop of 20 millimeters of mercury

1978.88 -> um but there is uh you know in our patients there was a a subtler a smaller drop in pressure

1986.16 -> this is in systolic pressure of about 10 millimeters of mercury um with no compression the

1991.28 -> light compression really did nothing for that but when we got to the abdomen compression we started

1996.56 -> decreasing that and and with the leg and abdomen together it was decreased a little bit more

2001.36 -> and that may be part of what's driving the heart rate there's not severe orthostatic hypotension

2007.2 -> but there may have been mild orthostatic hypotension that we were able to blunt

2013.04 -> when patients get tilted up fluid shifts from their chest to blow their chest

2017.36 -> less blood comes back to the heart and that can drop their stroke volume and we see that

2020.96 -> in panel c here where the stroke volume dropped a lot with no compression again

2025.84 -> the leg compression did very little but the abdomen

2030.32 -> and the full compression decreased that drop in stroke volume it significantly blunted that drop

2035.68 -> so it didn't increase the stroke volume it just prevented things from getting a whole lot worse

2041.84 -> um these slides show orthostatic index it's a fairly clever way of presenting data that

2048.56 -> robert holtke who's an autonomic specialist in west virginia and

2053.2 -> the last i heard was a jazz musician in new orleans post-retirement

2057.84 -> he created this and basically what it did is it takes uh it says okay well we want

2065.44 -> patients with pot you know a good result of a drug or treatment in someone with pots would

2070.72 -> be to either lower the heart rate or have them standing more or both so he took the inverse of

2076.4 -> the heart rate which is the rr interval because so basically the r interval the the bigger it is the

2081.6 -> lower the heart rate so that's a good thing and the longer you can stay up that's a good thing and

2086.8 -> sort of did the integral of the two and so the area under the curve the orthostatic index is

2091.76 -> sort of the multiplication of the or the integral of the time on tilt that you're able to stay up

2098.88 -> and the r or interval in this case up to 10 minutes and

2103.68 -> what we found it fits with the other things we found using just heart rate measures or just

2108.96 -> stroke volume measures that is that the orthostatic index was lowest for no compression

2114.4 -> was highest for full compression and was somewhere in between with the abdominal only compression

2120.8 -> second best and leg only compression barely better than no compression right so these findings all

2129.2 -> consistently are telling the same story and importantly

2136.72 -> symptoms tracked along right so the patients with full these were the same patients that did all

2142.48 -> for these modalities so the same patients with the full compression reported less

2149.84 -> symptoms when upright using the vanderbilt orthostatic symptom score then with no

2154.24 -> compression and it decreased in a graded fashion with abdominal and thigh compression

2160.8 -> being better than leg compression but not quite as good as everything and if we look at

2167.6 -> the change in heart rate and the voss score there was actually a pretty good correlation

2172.96 -> right so that's not to say that symptoms are all about the tachycardia but this suggests that

2177.84 -> this approach to improving the tachycardia was also associated with a decrease in these

2182.96 -> acute tilt symptoms i alluded to the fact earlier there are some patients that actually didn't meet

2190.72 -> pots criteria even with no compression when we sort of broke that out and looked at

2199.36 -> response based on the baseline increase in heart rate um what we found is that the worse

2205.68 -> the patients were at baseline the more benefit they got so the people with a lot really high

2212.88 -> levels of orthostatic tachycardia seem to still have the highest levels afterwards but had the

2218.64 -> greatest benefit as well and that's what's shown here in panel b so the worse you were to begin

2223.36 -> with the more more benefit there was to be had with an aggressive compression garment strategy

2231.04 -> so this is a proof-of-concept study we want to be quite clear about that i i personally

2236.48 -> believe the compression garments do work um but the study to see if they work in the real world

2243.36 -> is one that uh that's kate's next study that's the study that's just started um to see if this uh

2250.56 -> will give us the same results in in people's homes and in day-to-day their day-to-day lives and then

2255.92 -> regular practice but but this shows the concept of compression anyway can be very helpful to patients

2262.08 -> with pots a few words about exercise training i'm not going to belabor the point but it does

2269.68 -> it does uh play to this blood volume issue many of you probably heard about the pros and cons of

2278.96 -> exercise in pots it's it's a very difficult thing to start doing there's a huge exercise intolerance

2285.84 -> component that's intrinsic um to the disorder um but but there are patients that historically have

2294.48 -> seemed to do better with exercise and that's been borne out now in at least three studies

2300.8 -> from different centers that that we've seen so this slide is from uh the dallas study was

2307.12 -> published over a decade ago now where they took patients and and did really heroic um assessments

2316.24 -> of physiology as well as simple things like quality of life before and after a three-month

2321.68 -> program that sometimes took longer to do um but one of the things that they measured was blood

2327.92 -> volume and they used they looked at the total blood volume which we showed in plasma volume and

2334.08 -> um what we see in both cases of total blood volume and plasma volume is that there was an increase

2341.76 -> with exercise again similar to what we found didn't

2345.04 -> normalize the patients it didn't get the patient's blood volume to the level of the control subject

2351.28 -> but it did move things in that direction and that's actually something outside of pots has

2357.52 -> been well recognized that exercise both an acute bout although that's a transient effect and

2364.64 -> regular exercise does increase blood volume and part of that mechanism relates back to one of

2369.76 -> those things that we were looking at in the first couple of slides looking at the renin

2376.56 -> to aldosterone conversion so if you look at the aldosterone to renin ratio the amount of

2381.2 -> aldosterone produced for a given amount of renal activity

2384.8 -> that's actually been shown to go up with exercise and in fact that was shown by chifu

2389.68 -> in another paper related to the study so exercise can actually increase blood volume as well

2398.4 -> so this lists some of the benefits of exercise training i won't go into them all obviously

2404.48 -> if what patients want is improved quality of life

2406.8 -> but one of the mechanisms here is an increase in blood volume

2412.24 -> we can talk about you know my approach my advice for patients uh when doing it uh the important

2419.12 -> things to recognize are it's not easy and it's not fast right this is a it takes a

2424.32 -> big commitment and a long-term commitment um many patients i have have benefited from this

2430.24 -> but it doesn't occur quickly so for the last bit i just want a few words on some medications for pots

2438.56 -> they're different uh we obviously recommend salt and water we've talked a little bit about that

2442.88 -> i'm not going to say too much about pluto cortisone or octreotide if there are questions

2446 -> i'm happy to answer that i just want to say a couple of words about intravenous saline and which

2451.12 -> i'm fairly confident you've all heard about and ddavp which some of you may not have heard about

2460.32 -> so there's been data now for almost 25 years that um acutely intravenous saline

2469.68 -> can decrease orthostatic tachycardia a lot and this is a study published by uh just jacob when

2476 -> he was a fellow at vanderbilt a long time ago he's now head of medicine in tel aviv

2483.04 -> in one of their departments but with placebo you can see that there's excessive orthostatic

2491.84 -> tachycardia the heart rate increase shown on the left is above 30 beats a minute

2497.84 -> if you look on the right after they give a baseline it's that high but after sailing it drops

2505.44 -> in half it's probably a 15 or 16 millimeters of mercury or 50 or 60 beats per minute

2510.4 -> so in essence it's normalized the heart rate increase on standing it's normalized

2516.8 -> orthostatic tachycardia acutely so this is a liter saline over an hour so there's no doubt

2522.88 -> that this can be useful if someone is in acute distress right as a as a one-off therapy um

2530.4 -> plots as we've shown pots patients many of them not all are hypobulimic have a contracted blood

2537.12 -> volume state and saline acutely can fix that it's not a long-term fix but acutely fixes that

2545.2 -> and that's reflected in different guidelines this is from the heart rhythm society

2549.6 -> position statement on pots from 2015 i believe where it was felt to be reasonable to treat pots

2557.44 -> for short term clinical decompensations with an acute infusion of up to two liters of saline my

2562.48 -> advice is often if you end up uh so bad that you end up in the emergency room and they're trying

2568.24 -> to figure out if if the doctor's trying to figure out you need to be admitted or not before making

2572.56 -> that decision my advice is usually to try to get them to give you a couple liters of saline because

2578.4 -> in many cases i think in most cases you might feel well enough not to have to be admitted to hospital

2584.96 -> what's more controversial is the regular infusion so acutely a one-off bit of saline is good well if

2591.76 -> that's good can we the problem is it doesn't last the promise can we then can we do it repeatedly to

2598.48 -> get that ongoing benefit and that actually is not recommended class three is you know don't

2604.32 -> routinely do it and the concern is is potential harm and specifically it's over the intravenous

2611.28 -> access so when uh getting a single dose of saline one would put a peripheral intravenous catheter in

2618.08 -> the arm in the emergency room or infusion clinic the problem is every time you do that you clot off

2623.36 -> that little bit of vein and it becomes harder and harder to do and people getting saline long-term

2630.48 -> can go down the path of going from peripheral intravenous catheter to a picc line to

2636.56 -> a port-a-cath or a central line and they have their own concerns and complications there

2642.24 -> isn't a lot of data on this there's a couple of studies that have been published on this

2647.28 -> jeff moak is a pediatric cardiologist at national children's in washington and

2653.12 -> they published a series and and these were presumably kids who were very symptomatic

2658.32 -> that they did give sailing to for varying amounts of time but chronically

2665.76 -> and the vast majority of his kids had picc lines not not ports so picc lines are arguably kinder

2673.44 -> gentler long-term catheters but usually you you have sort of six weeks to two months not

2679.36 -> not usually longer than that out of them and what they found uh that was concerning is the

2685.04 -> rate of complications weren't trivial and actually seemed higher in the groups in his patients and in

2692.64 -> the patients with autonomic problems pots things like that compared to all comers in the hospital

2700.08 -> and the reasons for that weren't clear but that's one of one of the two bits of papers

2704.32 -> two papers available the other is a series that was published by blair grubbs group in toledo

2713.12 -> and the experience was a bit more positive i had about 50 plus patients this is a retrospective

2719.92 -> look they weren't doing it just for the study um and what he found is that there

2727.52 -> wasn't actually a very high rate of complications but the interesting thing in in the grub study

2734.16 -> was that um almost half the patients were off the saline in under three months

2739.68 -> so it really was a short-term bridge for a lot of people and the overwhelming majority

2748.8 -> never required anything beyond peripheral intravenous lines as i said that's actually

2753.84 -> in the short term you can get away with that until your veins um collapse and you can't

2759.04 -> get intravenous catheters anymore and that's when people sort of slide over to picks and ports but

2763.92 -> compared to the experience uh in the milk study most of the patients in the grub study

2771.44 -> had peripheral catheters and were on in a good number we're on for a very short period of time

2777.68 -> so i i still hesitate to recommend it if we have to put catheters in if you're going to do it i

2784.08 -> think you have to proceed with caution and focus on short duration of therapies and trying to avoid

2790.08 -> central central lines for the saline finally um ddavp is a short acronym for desmopressin acetate

2802.56 -> it's a modified version of arginine vasopressin which is is the natural anti-diuretic hormone

2809.04 -> so it causes free water retention it causes your kidneys to hold on to water

2813.84 -> and in fact it's on the market i believe to treat uh enuresis and kids so basically

2818.96 -> little boys that wet their bed so we thought you know if used in little kids it can't be that bad

2828.16 -> uh it may help expand plasma volume in pots patients and so we studied that acutely

2833.04 -> in one of our short-term four-hour trials at vanderbilt and taking ddavp 0.2 milligrams

2841.68 -> with 16 ounces or half a liter of water helped as you can see here it lowered the standing

2849.2 -> heart rate lowered the orthostatic tachycardia and improved symptoms the one concern is that

2857.44 -> by retaining free water you can actually dilute your sodium and your blood down and you can cause

2864.32 -> dangerously low levels of sodium so there are different approaches to using it i typically

2870.32 -> have my patients use it as a special event drug so uh you know one frustration the patients have

2875.68 -> shared with me is that they don't it the pots is unpredictable um they have trouble making plans to

2882.16 -> go out with friends on a thursday night to a movie well now we all have trouble with that because of

2886.72 -> covid but before kobit had trouble making those plans because they didn't know how they'd feel

2892.88 -> in those cases if you were to take the desmopress in thursday afternoon with water

2898.64 -> we have data now that that'll buy you several hours where your blood volume will be plumped up

2904.24 -> a bit and and you can feel better and anecdotally that has certainly worked um blair grub in toledo

2910.08 -> has taken a different approach to it where he's actually used it as a daily treatment

2915.76 -> at bedtime patients will take 0.2 milligrams at bedtime and he actually has them have their the

2921.6 -> patients have their sodium checked weekly in the lab and have that phoned into the office

2927.44 -> and what he told me was that for the most part he didn't have major problems there's only one person

2934 -> that actually had fairly significant hyponatremia or low sodium and that's someone that felt so good

2939.84 -> with the one tablet that she thought for would be better and so this caveat you have to be careful

2947.2 -> that you know just because a little is good more can be dangerous with some of these drugs

2954.4 -> so um i'm going to stop there um mainly because i have no more slides but also

2959.12 -> because lauren would have cut me off anyway and i'm happy to answer questions

2964.96 -> me i would never cut you off what um so there's a lot of really really good questions and um some of

2972.4 -> them um echo things you already said but i think they're worth repeating if a bunch of people are

2977.68 -> asking about them so um somebody asked a question the very beginning about the desmopressin you just

2985.12 -> mentioned at the end and they asked them what is the type of dosing that is safe to use without

2991.52 -> risking hyponatremia so everyone is everyone's different and so i'm not sure there's ever no risk

2998.72 -> but the dose we've used is 0.2 milligrams daily and we used pills in our study that it also comes

3005.92 -> as an intranasal preparation if you prefer that to pills for the most part that dose has been safe

3012.64 -> having said that if you're going to take it i still recommend getting your potassium or

3017.44 -> not your plasm your sodium checked um probably a little more frequently in the beginning and then

3022.64 -> you know perhaps can be spaced out a little more but but have that checked over time

3027.84 -> hyponatremia is one of those things that can be asymptomatic until it gets very severe

3033.04 -> right but it's very easily checked and and you can sort of you know turn the boat around very quickly

3039.76 -> if you catch it early yeah um is if uh someone was tracking urine sodium levels to see if they're

3048.08 -> getting enough salt um is there an ideal that you aim for and is there an upper limit to what you

3054.32 -> would want to see like too much yeah so we uh in in the in our study in theory they should have had

3062.24 -> a level of 300 because the mill equivalence you take in should be what you put out i think it was

3067.6 -> actually closer to 260 or so so we didn't quite reach our target um the only study in terms of

3075.28 -> so i don't routinely use 24-hour urine sodiums um although it can be used to track how much

3080.16 -> sodium you're getting in if your diet's stable there's one study and i think it was is in a

3084.8 -> pediatric population but one study out of china china i believe where 160 ml equivalents was the

3093.6 -> magic number where if patients were below that they seemed to symptomatically benefit uh

3100.32 -> from augmenting their sodium and patients above that they did not find that same benefit

3106.8 -> like i said i don't typically do the 24-hour urines unless there's a major disagreement between

3114.4 -> my impression of how much salt the patient's taking in and how much salt the patient thinks

3118.32 -> they're taking in and it's a way of objectively determining that okay um can you comment on

3126.56 -> um what is preload failure and how does this relate to blood volume in pots and you probably

3133.68 -> know that it's i'm gonna guess this patient sees david systrom or their relative does because dr

3140.48 -> systrom is pretty much the only one that uses that term but it has a medical meaning so yeah

3146.8 -> so i'm not sure i've used the term preload failure but but this is it's all different ways i think of

3153.2 -> addressing the same thing that we're talking about that when we talk we're talking when he's talking

3157.36 -> about preload what he's talking about is cardiac preload how much um blood or it's actually filling

3164.88 -> pressure is coming back to the heart right the heart wilder wheeling an autonomic physiologist

3170.4 -> from amsterdam once published a paper saying the heart can't pump blood that it doesn't see

3175.2 -> right so the blood needs to come back to the heart for the heart to pump it out and in fact

3179.76 -> what we're doing here is trying to address preload failure so the blood not getting back to the heart

3185.28 -> in fact different things i talked about today do that in different ways so the

3189.68 -> increase in salt is to increase the overall blood volume to get more blood coming back to the heart

3195.92 -> and we all recognize the problems and pots patients are more acute when they're upright

3201.36 -> than when they're not and that could be because their blood volume is just so

3207.04 -> critically low that they fall below a threshold or it could be that they may also um shift more

3212.64 -> blood they may pull more blood in their belly for example it's not getting back to the heart

3216.48 -> and that may be where the compression comes in so these strategies we talked about today would

3222.88 -> be strategies that would help with the preload failure term that that david systrom talks about

3229.68 -> um so you did mention this in when you were talking about the the vanderbilt study and that

3237.12 -> the salt study but can you just discuss and just emphasize a little bit

3242.32 -> um should people with hyper adrenergic pots increase their salt and the question specifically

3249.28 -> says if it raises their blood pressure so i you know i would be the short answer is i would

3257.92 -> give it a try um because one of the things with hyper adenorgic patient probably plots patients

3265.84 -> in general but certainly hyperion patients is that um the blood pressure can be all over the place

3272 -> right and and i think you know if you're more reactive your sympathetic tone jumps up your

3277.04 -> your your heart rate and your pressure can go up transiently and you don't want to overreact

3281.12 -> to that the theory behind the expanding the blood volume approach is that if your blood volume is

3288.16 -> very contracted one of the bodies attempts at compensation the compensatory response is to

3293.68 -> increase sympathetic tone that may then increase the heart rate and that times the blood pressure

3299.2 -> excessively and by reversing that process by expanding the blood volume you decrease

3305.2 -> the need for the body to increase sympathetic tone and that may actually paradoxically lower

3309.76 -> the heart rate and blood pressure now blood pressure is really really complicated i mean

3313.68 -> people have been studying this for close to 100 years and there are different mechanisms at play

3318.88 -> so in your specific case if you're taking a high salt diet and over time not a reading or two but

3324.96 -> over weeks to a month your blood pressure has gone up and is staying up and is quite high

3330.64 -> then we mean you may need to back off on that a bit but as a strategy it's not necessarily wrong

3337.36 -> and the other thing to remember is that blood pressure high blood pressure as a problem is a

3341.92 -> chronic problem if not so much the blood pressure that you have today is going to cause you problems

3346.48 -> today or tomorrow but if your high blood pressure stays high this month next month next year the

3352.88 -> year after that you know over time that causes vascular damage and that's what you want to avoid

3358.56 -> so it's not that you need to rush into fixing it tomorrow but you don't want to ignore it either

3365.76 -> can you explain um the concept of pulse pressure and talk about what narrow pulse

3372.48 -> pressure means in the context of hypovolemia so um when you have your blood pressure

3380.48 -> measured it's usually reported as two numbers right something like 100 over 60.

3387.92 -> and the 100 is the systolic blood pressure the 60 is the diastolic or the bottom part of the blood

3394 -> pressure and the pulse pressure is the difference right literally is just the systolic pressure

3399.04 -> minus the diastolic pressure it's the amount that the pulse moved from bottom to top each time

3406.4 -> um when you are hypovolemic you have less blood to move that pressure around each time right so often

3415.76 -> um people that are that have a low volume that are volume contracted um will have a lower pulse

3421.76 -> pressure i'm not sure it's it's it's certainly not the be on end all measurement but often the

3426 -> pressure will be low as as that volume gets lower we definitely hear a lot of patients talking about

3434.4 -> uh when they have a narrower pulse pressure that they're feeling more symptomatic they're feeling

3439.04 -> kind of crappy and i think that correlates the other measure that we look at that we presented

3445.04 -> in the compression study is stroke volume right so stroke volume is these are all sort of fancy

3451.52 -> sounding terms but all stroke volume is every time the heart beats it's how much blood is leaving

3458 -> right how much blood leaves the heart every time and if you think about it that's what makes up

3461.68 -> your pulse pressure right it's if you you have a baseline you know level of tone that you die self

3466.8 -> pressure and then you get this whoosh of blood coming through and depending on how much wash

3471.92 -> you have you know your pressure goes up more or less and that's the pulse pressure

3476.96 -> um so here's a good question um some doctors um have used albumin infusions to

3486.08 -> try to expand blood volume can you share your thoughts on that and sort of what most of the

3492 -> dysautonomia experts think about that so i i know um some doctors don't i

3497.44 -> think there may even be a study going on a small study going on now about this um

3503.92 -> to date there's really no published data on it right so the challenges with albumin

3508.32 -> um you tell people that albumin is first maybe albumin is a human blood product right it's a

3515.04 -> protein that we have in our blood right so the challenges of the albumin are that you're i mean

3521.92 -> literally you're you're taking someone else's human blood product and and uh and infusing it um

3528.24 -> in you're trying to do the same thing you're doing with intravenous saline which is to expand the

3532.8 -> blood volume in theory um you know the salt the salt and the salt water will dissipate right so

3541.04 -> it's in the bloodstream and then the body does things and takes it out of circulation protein

3547.84 -> in the fluid in theory should linger longer should last a little longer is the theory behind it

3555.52 -> i think most you know i certainly would prefer not i mean if you need if i'm going to die without

3563.28 -> someone else's blood products i will take it right i mean absolutely but if there are other choices

3569.76 -> there's there's various risks to receiving blood products so unless you really need

3574.56 -> it there's no other choice i think we have to look strongly at other options

3579.84 -> like i said right now there's no data that it's it's better than other approaches that may change

3584.16 -> right there is at least one study i know that supposed to be going on looking at that

3588.88 -> okay can someone have hypovolemia and a small fiber neuropathy are these subtypes distinct i

3598.72 -> know the answer but you can explain it yeah so so um so the answer is is yes you can have you

3606 -> can have lots of things and and the real challenge with subtyping and and for those that have heard

3612.64 -> prior talks that i've given when when the issue of subtyping or what type of plots do i have comes

3618.16 -> up i usually refuse to answer the question and and argue that we're not ready for the subtypes

3624.48 -> and and the reason is precisely this issue right and that is that what we the stage we're at is we

3632.08 -> can look at different features and try and um you know test 10 people 100 people with test a b c d

3639.68 -> and we can say well a is abnormal b is abnormal c is abnormal um and if a was

3648.4 -> you know looking for small fiber neuropathy you say okay you have neuropathic plots and then if

3653.04 -> b is looking at blood volume you see a hypobolemic plots and if c is looking at norepinephrine levels

3658.16 -> you see in hyperenergic plots the problem is that that these groups overlap i mean i'm i'm a big fan

3664.48 -> of venn diagrams so this is great for me but these are all overlapping circles these are overlapping

3668.8 -> venn diagrams it's not distinct right so one can make an argument and this is a theory i don't

3675.2 -> know this right but one can make an argument that if the neuropathy is affecting say nerves

3682.16 -> affecting the kidney that could actually affect some of these hormones and affect hypovolemia

3687.12 -> we know for sure that some patients with hypovolemia as a response in fact that's

3690.96 -> what we showed in our dietary salt study is a response to the hypovolemia can be hyper adenergic

3695.68 -> but not everyone that's hyper adenergic has hypobulemia so we're really not ready to say

3702.56 -> you have this type of plots or that type of pots to the exclusion of others unless you've actually

3706.64 -> done a detailed assessment of all of those things so then the next question is um from a few people

3713.84 -> you know should you try to get blood volume testing should this be done or should you

3718 -> just sort of treat assuming that you have uh that salt fluids will help you so i am uh so

3726.96 -> i mean it's a good question from a practical point of view you know i actually think

3730.64 -> that there's some value in trying to understand the blood volume mechanism

3734.32 -> not everyone has it in our in the last few years at vanderbilt that estimates somewhere around

3739.76 -> 75 to 80 percent of the patients had a low blood volume so it's common enough but not universal um

3748.24 -> i've since moving to calgary i actually have no way right now clinically of assessing blood volume

3753.2 -> so i've learned to function without it um and and we try and treat everyone with it i think where

3760.08 -> it's useful isn't necessarily at the initiation of therapy but if you know if you've initiated

3765.04 -> therapy you you you're you're doing the high salt and water aggressively and things have improved

3772.64 -> been great it's when things haven't fully gotten better and you're debating whether to augment

3777.68 -> with treatments like fluted cortisone which you know has its own potential long-term risks you

3782.64 -> know that's when i think it can be helpful if it's available right it's an extra piece of information

3787.84 -> i mean one of the challenges with potts patients is pots is a syndrome it's not necessarily one

3793.68 -> thing it's a bunch of things and sometimes it's helpful to know more about the individual

3799.04 -> right you know it but i think it's reasonable to start with sort of standard approaches and when

3804.8 -> those don't work that's when you really want to sort of take a closer look mm-hmm um if a patient

3812.32 -> didn't have hypovolemia would you still recommend increasing salt and fluids to treat pot symptoms

3819.84 -> like i said i don't usually assess it up front so um well like if you knew in

3824.8 -> a theoretical way if you knew that would you still think that salt and fluids would be worth a try so

3830.08 -> i think i think the water like taking getting in a fair bit of water is probably not a bad thing for

3835.84 -> a bad way to start regardless um you know i think the salt isn't a bad thing

3842.48 -> to try i think it's less likely to work but it's probably not a bad way to start regardless

3849.28 -> right but i think it's less likely to work if your blood volume is actually already okay

3854.32 -> what level of compression do you recommend in um compression stocking kind of garments

3860.8 -> so i guess more important than level is is wear um so i'm i'm a big fan uh i mean i think you

3868.96 -> have to if you're gonna do it you have to get to abdomen and pelvis compression um

3874.96 -> and to the point where the knee-high stockings i think are a waste of time unless you're trying

3880.88 -> to prevent blood clots like if you're if you're worried about blood clots when you're traveling

3884.64 -> go ahead but for fluid ships i wouldn't i wouldn't even bother um i i used to routinely prescribe 30

3893.36 -> to 40 millimeter mercury garments um they're hot tight itchy and ugly they're a pain in the ass

3899.04 -> both metaphorically and literally i mean they're tight they're difficult to get on they take a high

3904.24 -> level commitment i have patients that use them because i i don't have anyone that loves them but

3910.24 -> i have patients that use them because they allow them to function what i've i've taken to the last

3916.32 -> few years is using a kinder gentler alternative so i'll often now start with athletic wear i'll

3922.08 -> often tell people to go to a sporting goods store and purchase triathlon tights or high-end runner

3926.96 -> stockings which are about half as tight they tend to be the high end performance that tends to be

3932.16 -> in the 15 to 18 millimeter mercury compression so not as tight perhaps not as much compression

3938.88 -> the flip side is um they look nicer um they're more comfortable and you're perhaps

3945.68 -> people more likely to wear them and if they use that and that's enough then that's great if they

3950.48 -> use that and they think they may it help but need more then that's when i'd go on to the medical

3955.28 -> grade compression the other thing that there's absolutely no data for so take this for what

3960.96 -> it's worth we do want to study this going forward um is that in the summers certainly when i was

3968 -> in nashville but even in alberta summers patients will tell me they just can't wear the full-length

3973.28 -> stockings because if they overheat and obviously lots of pots patients don't tolerate the heat

3979.44 -> and so i my backup suggestions are spanx or body shaping garments now i say spanx because i'm not

3987.12 -> smart enough to know all the brands spanx doesn't give me a dime unfortunately so you know if you

3993.12 -> want to use a competitor please feel free to go ahead right but the idea is that i just want you

3998.56 -> know a garment that's going to provide squish to the abdomen and pelvis so basically if you get

4003.6 -> rib cage to upper thigh that's the focused area and that leaves especially when it's summer it

4009.36 -> leaves more skin area that's uncovered that we're able to sweat and you don't overheat quite as much

4016.64 -> um can birth control medications help increase blood pressure

4022.72 -> can they increase blood pressure uh maybe maybe more broadly can they improve pot symptoms

4030.8 -> yeah so i so i'll answer the question two ways you know yeah so i don't know if it's still

4036.48 -> used as much now but um yes yasmine ocella were three birth control agents that actually did the

4042.64 -> opposite you know there's not good data on it but um i'm pretty convinced that they actually make

4048.64 -> plot symptoms worse and the reason is because the progesterone most birth controls have an estrogen

4054.96 -> age and progesterone agent the progesterone agent in those drugs is a drug called drosparenone

4060.88 -> which is an analog of a drug called spermolactone which is the opposite of aldosterone right so

4068.32 -> it actually works on the aldosterone receptor to block the sodium retention in the kidney right so

4076.48 -> if patients are on that the first thing i'll try and get them to do is switch to

4079.52 -> a different birth control agent that doesn't have the the despairing agent

4085.84 -> more broadly can birth control and help plot symptoms certainly a lot of pots patients will

4092.8 -> say that their symptoms get worse around the time of their period and in fact there's some data

4098.48 -> where we just have patients and healthy subjects rate their lightheadedness at different phases of

4104.24 -> the menstrual cycle and the pattern was identical between pots patients and healthy subjects in that

4109.44 -> it it peaks around menstruation and and just before and mid cycle it tends to be better it was

4117.2 -> amplifying the pots patients so the pots patients at every point in the cycle were more light-headed

4121.92 -> than the healthy subjects as you might expect but that pattern was there and so some patients find

4127.6 -> the birth control agents that decrease the frequency of their periods so there's some

4132.56 -> agents where you have breakthrough periods every four months instead of every month um it doesn't

4139.2 -> necessarily make their symptoms better when they have their period but they have less of them

4144 -> so um i'll take one last question and this one's a doozy for sure it's it's the basically

4150.08 -> what you spent your career trying to figure out so we'll give you like two minutes to answer it

4155.52 -> uh what is the root cause of the low red blood cells and low plasma in pots what what do you

4162.24 -> think and i know this is a sort of theoretical question because if you knew the answer we

4166.96 -> wouldn't have low blood volume in pots anymore but what do you think the the essence of this is

4173.2 -> i have trouble putting our finger on it but but the the plasma one i mean the there's various bits

4179.12 -> of data it's just been hard to pin down that there that there may be uh something that's not quite

4184.8 -> right in the renin angiotensin aldosterone system right and and we've wondered whether there's you

4190.64 -> know there's issues with angiotensin one receptor responsiveness right so you're not producing the

4196.16 -> aldosterone properly um there's a little bit of data from you know a study a colleague

4204 -> did at vanderbilt where they gave angiotensin two infusions and the pots patients actually had less

4210.08 -> of a blood pressure response to it suggesting there may be something there um and i i know

4217.28 -> lauren's very interested in some of the auto antibody work and and one of the things that

4221.92 -> david kem uh has looked at and and we published is that you know in addition to the alpha

4229.2 -> and beta receptors there's a you know he found some plots patients actually had

4235.52 -> antibodies to the angiotensin one receptor and it's possible again these are all different groups

4241.04 -> and different bits of data so it's not all in the same people but it's certainly possible that

4245.36 -> maybe part of the reason for that is is something affecting the receptors but it could be exogenous

4250.56 -> like an antibody as opposed to something they were born with as for the red cell volume that's

4255.76 -> a more interesting question because you're right the red cell volume tends to be down as well

4260.64 -> um the explanation for that might be something a concept that's been referred to as a the kidney

4265.92 -> is a crit meter right so the kidney actually is uni is an organ that uniquely has a role in both

4273.28 -> red cell production through the hormone epo as well as plasma volume regulation

4279.52 -> in terms of the salt retention stuff that we've focused on with aldosterone for example and um

4287.44 -> it's a bit hand wavy but it may be that it regulates the epo levels so if your plasma

4294 -> volume is low if if your plasma volume is low and your red cell level doesn't change then your blood

4299.36 -> gets thicker and thicker it becomes like a thick milkshake and that when that happens you actually

4304.56 -> have an increased risk of stroke right and other vascular problems but stroke is the the most

4309.68 -> serious one and so the theory is that when the plasma volume is low then the kidney over time

4317.28 -> will decrease the epo levels to lower the red cell volume to match to try and maintain the hematocrit

4323.2 -> and hematocrit's what a simple blood test that you do but it's just the concentration so both are

4328.08 -> low the concentration could be the same i don't know if that's too simple or too complicated no

4333.76 -> that's good but um my instinctive response to that when we i haven't discussed this with you before

4339.68 -> but others then why don't we give people chronic saline infusions to increase their red blood cells

4347.44 -> you know i guess the question is there are some people that have had chronic saline i guess

4354.96 -> mean that's actually an interesting question but that might there may be data

4361.52 -> so there's a lot a lot of questions there's over

4363.92 -> 100 questions on here i'm really sorry to everybody we can't get to

4367.12 -> every single question but i hope this has been helpful this [Music] evening

Source: https://www.youtube.com/watch?v=tjdnCXKdslU