POTS Read online

  The key difference in the case of the POTS patient, therefore, is that something causes an ‘extra’ increase in heart rate above and beyond that which should occur anyway. Later in this chapter, we shall consider the two principal theories put forward for why this is the case.

  However, it is important to note, as any patient with POTS will know, that the condition involves more than just a quick heart beat. Rather, there is a range of symptoms which can make daily life debilitating and, in some cases, nigh-on-impossible. As Low and Sandroni write:

  “The following orthostatic symptoms occurred in >75% of subjects: light-headedness/dizziness, lower extremity or diffuse weakness, disequilibrium, tachycardia, shakiness…other autonomic symptoms were dry eyes or mouth, gastrointestinal complaints of bloating, early satiety, nausea, pain and alternation of diarrhoea and constipation. Fatigue is a significant complaint in about half of patients.”[6]

  The wide range of symptoms that the POTS patient feels should be an indication that the condition is more than just a heart problem, as it is sometimes mistakenly viewed. Rather, this is a condition which affects many functions of the body. It is also arguably regrettable that, for a condition in which patients feel unwell nearly all of the time that their condition should be termed ‘POTS’, something which implies that the problems only occur upon the action of standing up. This could not be further from the truth and this is only one reason why, as we shall see, the term ‘POTS’ is inadequate in describing the condition’s root cause: rather, the term is merely a descriptor of certain quantifiable aspects of the condition.

  This brings us to the significance of terming POTS a ‘syndrome’. For, calling a condition a ‘syndrome’ implies that the root cause of that condition is currently unknown, even if its symptoms can be quantified and analysed. This further implies that once the root cause has been identified, the condition can be renamed more accurately. At the moment, however, the importance of the word ‘syndrome’ has often been lost. Amongst many of the heart-wrenching videos of POTS patients online, you often find the idea put forward that they have a ‘heart condition that affects my ability to stand up’. When this happens, the significance of the word ‘syndrome’ is lost, and the word is really significant. It would be more accurate to say: ‘I have a condition, the cause and cure for which is currently unknown, but some of its most pronounced symptoms include a high heart rate upon standing.’ It is important that the acronym ‘POTS’ is not used as a definition of the illness itself but rather as a diagnostic tool for a collection of a certain set of symptoms the cause of which is as yet unknown.

  Current Modes of Treatment

  This book is not intended to be an overview of current treatment protocols nor would it be appropriate for me to focus on them as I do not have any medical training. I mention these treatments only briefly here, primarily as doing so sets the scene for further discussion later of other aspects of the condition.

  Current treatments focus on alleviating the patient’s symptoms, primarily through attempts to increase the patient’s blood volume, so as to stabilise blood pressure, but also on lowering the patient’s heart rate through the use of beta-blockers (typically propranolol in small doses). Other commonly used drugs are midodrine, which in other contexts is normally given to elderly patients to increase blood pressure, and also Flurinef, which is a synthetic replacement of the hormone aldosterone, about which we will have more to say later and which, for various reasons, effectively raises blood volume. Patients are also advised to add plenty of salt to their food and drink extra water so as to increase blood volume further. In addition, many patients begin a cardiovascular reconditioning program with, once more, the aim of increasing blood volume (as a result of improved cardiac performance). The rationale behind all of these measures, given what we currently know, is clearly well-founded - low blood volume is a significant problem for POTS patients. These approaches often do lead to a return of (relative) functionality in a considerable number of patients, but rarely to the remission of the illness.

  What ‘Triggers’ POTS?

  In turning now to the reasons POTS comes about, the key point is that there is usually a ‘triggering event’. You do not ‘catch’ POTS in the same way you might catch an infectious disease. Rather, it seems to be triggered by something which happens to you, and you can develop the condition whether you were previously healthy or not. There is widespread agreement among researchers that the following events nearly always precede POTS and as such seem to ‘trigger’ it:

  - a virus, such as mononucleosis or another illness, such as Lyme disease[7]

  - a surgery, serious physical injury or pregnancy

  - a traumatic event, whether emotional, physical or psychological

  The link between all of these seemingly disparate kinds of traumatic events and the onset of POTS is, on the face of it, rather puzzling. How can so many different things lead potentially to the same condition? However, as we shall see in chapter two, there is a link and it is central to the nature of the condition. Indeed, the idea of POTS being preceded by a triggering traumatic event is central to the whole hypothesis I will be putting forward.

  Underlying Biological Mechanisms of POTS: Two Schools of Thought

  We now turn to the biological mechanisms seen in POTS and, in particular, to considering two of the main hypotheses that have been put forward as to the condition’s biological cause, i.e. investigations into what has actually gone wrong at a physiological level in the patient’s body. Consideration of these mechanisms is essential to the new hypothesis I am putting forward as one of them can, I believe, be explained by that hypothesis. The two theories I wish to discuss are the following:

  ‘The ‘Deconditioning’ theory

  The ‘NET [Norepinephrine Reuptake Transporter] protein deficiency’ theory

  Both theories, as we shall see, have considerable evidence in support of their claims. But only one of them can be right, in terms of the root cause of the condition (or in terms of pointing towards the root cause), for the two theories could not be further apart from each other.

  As I mentioned at the start of this chapter, I am aware there are a number of other theories often put forward regarding the biological origins of POTS. I focus on only these two here as both deconditioning and NET protein deficiency relate most obviously, as we shall see, to the elevated heart rate seen in POTS upon standing. Other theories regarding the biological origins of POTS will be considered in chapter three. There is, however, another benefit to focussing just on these two theories as to do so cuts through much of the haze that obfuscates the condition - there are dozens of ‘causes’ you can find mentioned online but this haze can be lifted by focussing on those possible causes which we definitely know affect POTS patients. Indeed, we know from research that NET protein deficiency affects all POTS patients and we know that cardiac deconditioning also affects all POTS patients. (as we shall see from studies we shall consider shortly). On the other hand, sometimes you find, for example, “chiari malformation” (structural defects in the lower parts of the skull) mentioned as causing POTS but this most likely only affects a very small number of patients. Therefore, in sticking with cardiovascular deconditioning and NET protein deficiency, I am focussing on the most applicable evidence. Indeed, if the root cause of POTS is to be identified then it must be something which all POTS patients share, not just a few of them.

  Let us now consider each of these theories in more detail.

  The ‘Deconditioning’ Theory

  In essence, the deconditioning theory posits that the POTS patient has a very low level of cardiovascular fitness. The basic thought behind the physical deconditioning theory goes something like this. For some reason beyond their control, the patient has a period of prolonged bed rest. After this period of enforced inactivity, the body’s cardiovascular system becomes compromised. Levine, who is the principal researcher into deconditioning in POTS patients, argues that there is ‘…the presence of cardiac atroph
y……along with reduced blood volume…as key components of the pathogenesis of this syndrome’.[8] In other words, the argument goes that the heart has become smaller, weaker and, as a result, less effective at maintaining a strong blood volume, and that these factors are the primary reasons behind POTS. Levine notes that a smaller heart and reduced blood volume are physiological changes that are also usually ‘observed after long-term bed rest’,[9] as might be seen, for example, following illness, injury or pregnancy. In sum, some kind of event leads ‘to a period of prolonged bed rest…often leading to profound deconditioning’ and ‘…deconditioning has a profound effect on heart morphology and function as well as blood and plasma volume.’[10] Indeed, Levine makes the case for renaming POTS ‘Grinch Syndrome’ after the folk-tale character who (from a metaphorical and emotional point of view) had a small heart.[11] Levine has developed an intensive cardiovascular rehabilitation programme for those with POTS. As utilised in one of Levine’s trials, it is described as follows:

  “Patients started a ‘‘personalized’’ exercise training program for 3 months after baseline testing… Three heart rate zones (e.g., recovery, base pace, and maximal steady-state) were identified based upon the maximal steady-state heart rate and resting heart rate. During the initial month of endurance training, patients engaged in base pace training with a calculated target heart rate of 75% intensity of their personal maximum intensity level. Sessions were prescribed 2-4 times per week initially for 30-45 min per session using a recumbent bike, rowing, or swimming. The exercise protocol for this study was specifically tailored to POTS patients by requiring exercise to be performed in a semi-recumbent position for the initial 4-6 weeks of training. The protocol gradually introduced a more upright posture over the course of the 3-month time frame, allowing upright walking activity in the beginning of the third training month.”[12]

  The results after following this three month protocol were encouraging: both blood volume and heart size increased,[13] and, more importantly, from the data one can see that the average heart rate ‘supine to standing differential’ decreased considerably in patients (by around 9 beats on average).[14] For example, let’s say one participant’s heart rate increased by around 34 beats from supine to standing before the exercise protocol. After the protocol, that person’s heart rate might only have increased by around 25 beats, taking them outside the diagnostic criterion for POTS of + 30 beats. For one of the trials Levine conducted this improvement in cardiovascular fitness meant that ‘…ten out of 17 participants no longer met criteria for POTS post-training,’[15] leading to the suggestion that these patients were now ‘cured’ of POTS, but it was also noted that the underlying cardiovascular ‘…pathophysiology improved, but did not completely normalize’ and that ‘…what levels of physical activity must be maintained in patients with POTS to achieve and maintain normal functional capacity is uncertain; however we speculate that a lifetime adherence to an active life-style will be necessary’.[16] In other words, even if the deconditioning theory is correct, three months might not be enough for a complete cure: you may have to keep up the intensive exercise for the rest of your life.

  In sum, the deconditioning theory suggests that the patient is profoundly unfit following a period of bed rest and needs to be mindful of recovering fitness and maintaining it for the rest of his life.

  Let us now turn to the next theory, that of ‘NET protein deficiency’. As will be immediately grasped, this theory is the ‘polar opposite’ from the ‘deconditioning theory’ to the point that only one of them can really point to the biological cause. They are both talking about very different things.

  NET protein deficiency

  One uniting feature to have been discovered in nearly every POTS patient is the fact that their blood stream contains more of the hormone ‘adrenalin’ than is normal. Adrenalin is the ‘fight or flight’ hormone and it is also known as ‘norepinephrine’. I add that the POTS patient has more norepinephrine in the blood stream than the person without POTS whether in supine or standing positions, although there is more in the latter. As Raj points out: ‘The supine norepinephrine is often high normal in patients with POTS, while the upright norepinephrine is usually elevated (>600 pg/ml), a reflection of the exaggerated neural sympathetic tone that is present in these patients while upright.’[17] Indeed, some POTS patients will, as Raj elaborates, have ‘extremely high’ levels of adrenalin in their blood stream, over 1000 pg/mL in some cases, whereas the normal upper limit in those without POTS is just 475 pg/mL. It is for these reasons that POTS has been termed a ‘hyperadrenergic’ condition, i.e. the level of adrenalin in the blood stream is deemed to be far too much, or ‘hyper’.

  Why should it be that the POTS patient has more adrenalin floating around in their blood than the healthy person? Why is it that they can become, in other words, ‘hyper-adrenergic’? And why does this happen especially when the patient is upright? The answer is crucial and is to be found in considering the role of a special protein, called the NET protein, and how it does not function properly in the person with POTS.

  The NET protein functioning well

  Before we can see how NET protein deficiency leads to a hyperadrenergic state, we need first to understand how the NET protein functions in the healthy person without POTS. I add that this section is rather complex and may only make sense once it has all been read through. Please read it slowly: it is crucial to the main ideas I am putting forward.

  The NET protein stands for the ‘Norepinephrine Reuptake Transporter Protein’. Remember at this point that norepinephrine and adrenalin are the same substance and that, in that sense, the NET protein could easily also be called the ‘Adrenalin Reuptake Transporter Protein’. From this name, we can tell that the function of the protein has something to do with ‘reuptaking’ adrenalin. But what does this actually mean? And why would this protein need to ‘reuptake’ adrenalin anyway?

  We all know the feeling of adrenalin being released in response to stressful situations but what many of us are unaware of is the fact that adrenalin is a crucial hormone for overall health which is in fact being used by the body all of the time. For our purposes, it is important to note that the body makes use of adrenalin whenever we stand up. In particular, it makes use of the inherent ability of adrenalin to constrict (or tighten) blood vessels (this process of blood vessel constriction is called ‘vasoconstriction’). This is in contrast to the ‘opening’ of blood vessels that occurs when the body is in a relaxed, supine position (this process is called ‘vasodilation’). Why does the body constrict the blood vessels upon standing? The answer is that it does so because it leads to a more efficient process in which the overall area that the heart’s pumping must fill is reduced. In other words, the ‘tightening’ of the blood vessels upon standing leads to a lower overall ‘area’ of blood in the body which the heart can more easily cope with in pumping blood throughout that overall area. As just mentioned, adrenalin is the substance that is capable of this blood vessel tightening, but it can’t do this on its own. Rather, it needs help.

  This is where the NET protein comes in. Unpicking the acronym will help show us why. ‘Norepinephrine’ refers to adrenalin, ‘reuptake’ refers to its ability to ‘recycle’ this adrenalin and ‘transporter’, to transport the hormone to and from storage in nearby cells.[18] In other words, the NET protein aims to ‘capture’ adrenaline that is nearby in the blood stream, store it in nearby cells, and then ‘draw down’ that stored adrenalin when the body requires it. And, as we have just seen, the body requires adrenalin for the process of vasoconstriction whenever we stand up. This is where the function of NET comes in: it aims to recycle adrenalin easily and efficiently so that blood vessel constriction can happen whenever required.

  To put all of the above into simpler English: there are countless NET proteins in your body whose job it is to recycle adrenalin so that your blood vessels can constrict easily and efficiently upon standing. Ideally, when you stand up, this process is smooth, ea
sy and efficient.

  In the POTS patient, however, it is a different story.

  When NET Ceases to Do Its Job: the Role of NET Deficiency in POTS

  We know something has gone wrong with the NET protein in POTS patients as a result of groundbreaking advancements thanks, especially, to an Australian study, led by E. Lambert. Lambert et al., proved in 2008 that in POTS patients the NET protein has ceased to work properly. As Lambert puts it: ‘Western blot analysis of NET protein extracted from forearm vein biopsies in patients with POTS…demonstrated a decrease in the expression of NET protein…’[19] The NET protein, in the POTS patient, therefore has become ‘deficient’. How deficient? The basic difference between NET function in the normal person and in the POTS patient is as follows: in the healthy person NET recycles 80%-90% of available adrenalin whereas in the POTS patient only between 40-60% of the available adrenalin is recycled.[20]

  What is the effect of this NET deficiency on the patient? In short, it is responsible, as a knock-on effect, for the elevated heart rate upon standing. In essence, the effect of this NET deficiency on the patient is twofold:

  i) the adrenalin that is not stored in nearby cells by NET instead remains in the bloodstream causing extra shakiness, light-headedness, a feeling of being ‘on edge’ and, of course, increased heart rate (as contact between adrenalin and the heart causes the latter to beat faster). This is the direct link between NET deficiency and the hyperadrenergic state of the POTS patient, i.e. the main reason why there is so much adrenalin in the blood stream of POTS patients.

  ii) as the NET protein is deficient it is also unable to do its job of constricting the blood vessels properly upon standing. Rather it is only somewhat successful in this task and the blood vessels no longer constrict fully upon standing up. Instead, they remain partially open. The result of this is that the heart has to beat even faster in order to circulate the blood around the whole body: the wider the blood vessels upon standing, the greater the total ‘space’ in which blood must be pumped around the body, and the faster the heart must beat.