Timothy C. Hain, MD. Page last modified: September 5, 2018
An excessive pulse response to the upright position is termed "POTs" or positional orthostatic tachycardia syndrome. POTs can be associated with considerable disability (Benrud-Larson et al, 2002). Note that pulse can increase due to anxiety and deconditioning as well as autonomic disorders and considerable caution must be used in making this diagnosis. http://cogprints.org/4802/2/raj.pdf is an external web page written for health-care providers concerning this condition.
POTs is defined by a fast pulse on standing, and is not the same as orthostatic hypotension (low blood pressure on standing), or syncope (passing out in any position).
It also should be distinguished from other positional dizziness syndromes:
According to Wu et al (2008), symptoms of dizziness provoked by standing ranges from 4.4% (young) to 5.8% (>=70). This includes both orthostatic hypotension and POTs as well as perhaps other conditions.
Low (1995) states that POTs presents in patients between 15 to 50 years, and that patients with migraine and sleep disorders may be over-represented. Low reported a female-male ratio of 4:1, but he only described 55 patients. Raj (2006) states that POTs primarily affects women of child-bearing age.
The % above are from Thieben et al (2007). They don't add up to 100% as more than one etiology is evidently possible.
There are 4 variants of POTs. According to Raj (2006), of these there are 2 major subtypes -- neuropathic POTs where there is reduced autonomic function in the legs (#2 above), and "central hyperadrenergic POTs" where there is too much sympathetic outflow (#3 above). Others consider a third mechanism most important -- reduced cardiac output (Fu et al, 2010; Fu et al, 2015) -- # 1 above.
To make sense of all this, one must think about feedback control. On standing, about 500 cc of blood descends from the thorax to lower regions, which transiently reduces blood return to the heart. This lowers blood pressure. Via baroreceptor activation and perhaps also cognitive input, this triggers a compensatory sympathetic activation that increases heart rate as well as a systematic vasoconstriction that provides a counter-pressure to gravity. Thus normally, standing results in a 10-20 bpm increase in heart rate, a negligible change in systolic blood pressure, and a roughly 5 mmHg increase in diastolic blood pressure(Raj, 2006).
If we consider next failure points, in POTs the heart rate increases --to do this there must be sympathetic activation of the heart as well as a working heart electrical system (i.e. persons with pacemakers can't get POTs).
- A weak heart might not create enough pressure for a given increase in rate, that might need to be compensated for by an even greater pulse. Conditions such as heart failure, deconditioning, and pregnancy are examples where the heart may not be up to the task of providing an adequate output. Recent authors have emphasized the idea that cardiac output may be suboptimal in POTs (Fu et al, 2010; Fu et al, 2015). This variant might be treated through exercise.
- If sympathetic activation did not result in vasoconstriction, then again the heart would have to work harder, resulting in tachycardia. This is the autonomic neuropathy mechanism. Exercise would not directly treat this mechanism, but might help in an indirect way through compensating for reduced vasoconstriction with a better functioning heart.
- If there were an error in the amount of sympathetic activation, too much for a given change in blood pressure, this might cause tachycardia and increased blood pressure as well. In other words, orthostatic hypertension. This doesn't happen very often ! Raj suggested only about 10% (2006). This variant might reasonably be treated with an adrenergic blocker such as a beta-blocker, clonidine or methyldopa.
How many patients are in each category ?
According to Low, a neurologist who is an expert on autonomic neuropathies, about half of all patients with POTs have an autonomic neuropathy (1995). This means that the small autonomic nerves that regulate "automatic" parts of our body, are damaged. Examples of this include diabetes, as well as many vague situations such as in "neurocardiogenic syncope", mitral valve prolapse, presumed brainstem dysfunction, and others. One would conjecture here that the carotid baroreceptors get information about blood pressure falling on standing, and that the intended response involving vasoconstriction fails as it is mediated through the small autonomic fibers, invoking another central feedback loop to increase cardiac output through a higher pulse rate.
Thieben et al(2007), also from the Mayo clinic as was Low above, reported on 152 patients with POTS that were seen at the Mayo. They stated that half a "neuropathic" pattern of POTS, which they defined as failing either the sweat test or adrenergiv testing. They found about 13.8% who had antibodies to gACHR (see below), suggesting an autoimmune origin in at least 1 in 7 patients. Hyperadrenergic status was documented in 29% (defined as standing norepinephrine level > 2600), and 28.9% were hypovolemic (24 hour urinary sodium < 100)
Presumably roughly the other half of patients with POTs have decreased cardiac output, and a tiny number of them have the other listed mechanisms. Of these, migraine appears to have a frequent association with syncope (Thijs et al, 2006), and may be an example of a central mechanism. One might hypothesize, for example, that in these patients there is an exaggerated central response to baroreceptor input, resembling the hypersensitivity migraine patients often have to other senses, such as sound and light. POTs per se has rarely been reported in migraine (e.g. Yun et al, 2013), and but it is thought to be linked to other vasomotor disorders that mainly occur in females such as Raynauds (Hart et al, 2011). It is conjectured that these disorders are triggered by hormones.
Vestibular disorders may interact with blood pressure and heart rate control (Yates and Miller, 1996). The vestibular system is one source of information about uprightness (the otoliths), there are some effects of vestibular stimulation on the heart (Radtke, 1992), and there are some patients who have a combination of autonomic and vestibular symptoms. Nevertheless, the otoliths are not changed between sitting/standing, so this cannot be an important source of POTs.
Ehlers-Danlos syndrome (hypermobility type) is also associated with POTs.
One might conjecture that other sensory inputs that signal the upright posture such as pressure on the soles of the foot might also affect POTS and blood pressure control. To our knowledge, this has not been studied.
The diagnosis of POTs is made by these three observations (Low et al, 1995)
- Finding a heart rate increase of >= 30 bpm within 5 minutes of standing or tilt up.
- Heart rate >= 120 bpm within 5 min of standing or tilt up
- Orthostatic symptoms consistently develop
According to Low et al, "mild" POTs might be a patient with a HR increment of 30 bpm, but a standing HR below 120. According to Raj, the POTs syndrome should be present for at least 6 months, should also exclude situations where medications are present that might cause tachycardia or chronic debilitating conditions. Additionally, Raj states that the tachycardia should be sustained beyond the first minute of standing, as transient tachycardia might be normal (Raj, 2006). We find this a little hard to follow as we think if the patient is symptomatic while tachycardic, then the tachycardia is probably significant.
Syndromes with orthostatic dizziness or lightheadedness, usually not associated with altered heart rate include:
Orthostatic hypotension (i.e. blood pressure drop on standing) is variably associated with rapid heart rate. When the nervous system control of blood pressure is functioning, then the pulse should rise when blood pressure goes down -- in other words, it is a good thing to have a rapid pulse rate in this situation. On the other hand, orthostatic hypotension where the pressure receptors have failed, may not have any pulse rise. Low calls this "neurogenic orthostatic hypotension". Thus it is easy to differentiate the two. On the other hand, neurogenic OH is just one of many possible mechanisms of orthostatic hypotension.
Low et al (1995) states that POTs is sometimes also named "sympathotonic orthostatic hypotension", idiopathic hypovolemia, chronic fatigue syndrome, and the mitral valve prolapse syndrome. He also mentions it as being misdiagnosed as "neurocirculatory myasthenia", Da Costa syndrome, the effort syndrome, soldiers heart, and panic disorder. However, according to Low, these names are usually inaccurate, and the better term for the syndrome is POTs.
|Tilt table used at Chicago Dizziness and Hearing|
An alternative and more quantitative method of determining if there is POTs is the tilt table test. This procedure uses equipment to record blood pressure and pulse after a 70 degree tilt using a motorized table. Many insurance companies require a diagnosis of "syncope" to cover tilt table tests, and because syncope is rare in POTs, tilt table tests are never obtained. Fortunately, just standing, or the "stand test", is more specific for POTs than the tilt table test (79% vs. 23%).
Patients with POTs often also have abnormalities of sweating (QSART), large variability in the HR to deep breathing, an increased response to Valsalva, and the already mentioned increase in pulse on tilt table (Low, 1995).
According to Raj, the legs often turn a red-blue color on standing (2006). We have not observed this as yet.
The laboratory testing for POTs is almost identical to the testing for orthostatic hypotension.We will not repeat this here.
Recently there has been a report that antibodies against gAchR-alpha3 are positive in 29% of patients with POTs.(Watari et al 2018) . Others have also found autoantibodies to AchR. (Blitshteyn, 2015; Nakane et al, 2018)
Note that neither drug nor non-drug treatment can do as good a job as a well working body. All of the strategies outlined in the next section are intended to alleviate symptoms, but they are unlikely to cure POTs.
Non-Drug Treatment for POTs.
Generally it is best to start with non-pharmacological treatment, and proceed to drug treatment only when this fails. Note that measures such as volume expansion with increased salt and fluid, moderate exercise and tilt training are relatively safe but their effectiveness has not been demonstrated by controlled trials (Kapoor, 2003). Nevertheless, we think it is reasonable to give these things a try. These treatment strategies are nearly identical to those for orthostatic hypotension. They are not relevant for the rare sympathetic excess variant of POTs, but are reasonable for the reduced autonomic function and the cardiogenic varieties of POTs.
- Use an automatic pulse monitor. Check pulse daily, preferably standing and lying flat, and record it.
- If possible, eliminate medications that affect the pulse (usually blood-pressure or heart medications). Check with your doctor first, however, to be sure that this is safe. Sometimes it is helpful to take the medications in the evening, as well as to use longer acting ones rather than ones that act quickly.
- Take in extra amounts of salt - about 10 gm/day total. The intention here is to increase blood volume. This typically is done by taking a 1 gram salt tablet with each meal. Another way to get extra salt is to use salt containing beverages (e.g. "gatorade"). If you start to have trouble breathing or get excessive swelling at the ankles, you may have to use less than 10 gm. Similarly, be careful not to overdo it and end up with hypertension.
- Support stockings can help reduce the blood volume changes associated with standing. These should come up to the waist.
- Sleep with head of bed elevated about 15-20 degrees (4-6 inches). This maneuver increases blood volume and, after a few days, is sometimes helpful. Try to be up during the day, not lying in bed. Reconditioning may be helpful for persons who have been on bed rest for long periods of time.
- Eat frequent small meals. Avoid sudden standing after eating. These are intended to reduce fluctuations in blood flow.
- Get up gradually in the morning. Take 5 minutes to get up and use support. This is intended to prevent falls. Perform isometric exercises before moving about. This is intended to increase muscle tone.
- Water ingestion - -drinking extra water can help. For example, rapidly drinking 16 oz of water over 5 minutes can prevent a fainting spell (Lu et al, 2003). This should not be done very often as it could lead to water intoxication. It is puzzling why this might help.
- Physical Training. The literature suggests that conditioning is very effective for some types of POTs. See this page for more detail.
DRUG TREATMENT for POTs
Certain medications may be helpful in POTS. The most useful drug is Florinef (fludrocortisone). As a general comment, drugs to modify blood pressure or pulse can be dangerous. Be sure that you monitor your blood pressure every day if you are taking the more powerful agents (e.g. Florinef).
- Taking blood pressure medications in the evening rather than in the morning may be helpful as blood pressure often goes down while upright (during the day), and gets too high while in bed.
- Medications to increase blood volume: This would seem generally rational although these are very powerful drugs which must be used with caution.
Fludrocortisone (Florinef) forces more salt into the bloodstream, 0.1 mg is the daily starting dose. Blood pressure raises gradually over several days with maximum effect at 1-2 weeks. Alter doses at weekly or biweekly intervals. Hypokalemia (low potassium) occurs in 50%, and hypomagnesemia in 5%. These may need to be corrected with supplements. Florinef should not be used in persons with CHF (congestive heart failure). Florinef does not work in the orthostatic intolerance syndrome of chronic fatigue syndrome (Rowe et al, 2001). Headache is a common side effect.
Desmopressin (DDAVP) typically used as a nasal spray, also expands blood volume. It can result in hyponatremia, headache and swelling. This is rarely used.
Erythropoietin increases the number of blood cells. This is rarely used unless there is also anemia and other measures have failed. Doses of 25 to 75 U/kg TIW are used, by injection.
- Medications to decrease sympathetic tone, while it makes the "numbers better", given the feedback control concept of POTs outlined above, these drugs are mainly rational in the sympathetic excess variant of POTs), or in persons with anxiety where these sedating drugs are being used instead of anti-anxiety medications. They might also be useful in the form of POTs that accompanies migraine, which may be a sympathetic excess variant of POTs.
- Inderal and other beta-blockers (small doses are used for positional-orthostatic-tachycardia syndrome (POTs), start inderal at 10 mg/d, increase to 30-60 mg/d over 2-3 weeks. Baser (1996) suggests that these agents are useful to block beta mediated vasodilatation. Other useful agents are Nadolol (10 mg qd), Pindolol (2.5-5 mg 2-3 times/day) and atenolol (25). Logically agents should be favored that do not cross the blood-brain barrier to any great extent. Several controlled trials did not show beta-blockers to be effective in preventing syncope (Kapoor, 2003) but this is not the same as saying that they have no utility in POTs.
- Clonidine (0.05 to 0.2 mg BID). This is an alpha-2 receptor blocker, which reduces sympathetic tone.
- Methyldopa (125-250 mg TID). Causes lowered blood pressure, headache, constipation, drowsiness.
- Ivabradine AKA Corlanor (5 mg bid) is a recently approved heart medication (2015) that reduces heart rate without changing heart contractility. It is new but several reports suggest it is generally effective in POTs. One would think that it would only be rational in the sympathetic exess form of POTS. Corlanor has many drug interactions, and it is very expensive. It is not approved for use in children. It has been reported to be effecive in about 60-80% (McDonald et al, 2011; Ruzieh et al, 2017; Gee et al, 2018).
- Phenobarbital may improve POTs. This can be provided with ordinary phenobarbital or as donnatal. This is a mysterious mechanism drug. As it is a sedative, it might be useful in the rare sympathetic excess variant of POTs.
- Pyridostigmine (a cholinergic agonist) can reduce heart rate. This treatment would seem only rational in the sympathetic excess variant of POTs, as otherwise one could be reducing cardiac output. Clonidine would seem more logical here.
- As mentioned above, in persons with antibodies to AChR, immune modulation might be effective, but little has been written ab out this.
OTHER TREATMENTS FOR POTS:
Atrial pacing can be considered as a last resort -- here one might combine a beta blocker (to block down the normal heart) with a pacemaker. This is rarely done in the usual POTs patient.
In patients with antibodies to anti-gAchR, treatment to reduce immune responses would seem logical. Very little has been written on this, other than use of plasmapheresis (Clark et al, 2013). This seems to us to be a treatment that might cause more harm than good. This situation seems similar to that of Myasthenia gravis, also associated with an antibody to Ach, and treated with plasmapheresis, steroids, and sometimes thymectomy.