A 28-year-old female applies for life insurance. She states that she had been diagnosed with chronic fatigue syndrome and POTS at the age of 19 years. She has no history of syncope, only presyncope. She has never been involved in an accidental trauma. She currently works with a personal trainer, takes propranolol daily and is mindful to increase her salt and fluid intake. Although she is no longer able to participate in long distance runs and races, she is able to work from home at a desk job and care for her family, which includes a husband and a three-year-old child.
What is a POTS, and what are the mortality implications?
Postural tachycardia syndrome (PoTS or POTS), also known as Postural orthostatic tachycardia syndrome, is a heterogenous clinical syndrome characterized by sustained and excessive sinus tachycardia upon standing without orthostatic hypotension with chronic symptoms (≥6 months) of orthostatic intolerance which are relieved by recumbence.
POTS is a chronic disorder. Many individuals can experience similar symptoms during periods of dehydration or acute illnesses, and those cases are excluded from this definition.
The prevalence is estimated to be 0.1% – 1% of the US population, and the syndrome has gained significant clinical interest during the past 20 years.
POTS may occur in children as young as six years old and rarely in older adults, but generally ages 13-50 are the most frequently affected with a very strong female predominance (4-5:1).
Family history of orthostatic intolerance is found in approximately 13% of patients.
Polymorphisms in genes coding for nitric oxide synthase and the beta-2 adrenoreceptor have been found in a few patients, and in one family, a genetic mutation in the gene encoding the norepinephrine transporter has been identified. While these findings are not present in most POTS patients, this supports a component of neurosympathetic etiology in at least some patients.
POTS is a clinically defined syndrome with a set of symptoms that are the manifestation of diverse underlying processes. While some authors break POTS into subtype labels, there are no standard definitions. As such, a more realistic way of conceptualizing this disorder is evaluating separate components with varying degrees of overlap.
A large portion of POTS patients show evidence of partial sympathetic neuropathy due usually either to a distal small fiber neuropathy and/or cardiac sympathetic denervation.
In addition, a similarly large portion of patients show evidence of a hyperadrenergic state, determined by using measurements of norepinephrine and susceptibility to isoproterenol. Hypovolemia is a very common finding as well, often accompanied by cardiac atrophy.
Acute restoration of intravenous volume tends to attenuate symptoms in many. In some, mast cell activation is noted by the presence of episodic flushing and elevated measurements of methylhistamine in the urine shortly following flushing episodes.
There appears to be an autoimmune component, as evidenced by various cytokine and antibody levels, onset immediately post viral illness and the presence of comorbid autoimmune disease at a higher rate than in the population.
Finally, while frequently present, it remains unclear whether deconditioning represents a primary cause of POTS or a secondary result of the chronic illness. Using the knowledge of the above findings, treatment is tailored to symptomatology.
Diagnostic criteria for POTS
- Heart rate increase ≥30 bpm within 10 minutes of upright posture in adults. Heart rate increase of ≥40 bpm within 10 minutes is required in adolescents age 12–19 years.
- Absence of orthostatic hypotension defined as a sustained drop in blood pressure ≥20/10mmHg within three minutes of upright posture.
- Symptoms of orthostatic intolerance for greater than or equal to six months.
- Absence of overt causes for sinus tachycardia such as acute physiological stimuli, dietary influences, other medical conditions and medications.
Figure 1 - Heart Rhythm Society Recommendations for Evaluating POTS
|Initial Evaluation||Additional Evaluation if clinically indicated|
|Medical history||Blood work to rule out dehydration, anemia, thyroid disease|
|Family medical history||Cardiovascular testing (ECHO, Holter, exercise stress test) to rule out suspected cardiac condition or structural abnormalities|
|Physical examination||Head up tilt table testing (HUTT) for patients with normal orthostatic vital signs but high clicinical suspicion or for those with seizures|
|Orthostatic vital signs||Autonomic function tests for patients with symptoms of autonomic neuropathyor for those who do not markedly improve with treatment|
Source: Seldon et. al.
Clinical features and diagnosis
Presentation often occurs in teenagers within a few years of their growth spurt and frequently following an identifiable trigger such as an acute illness or injury. The clinical presentation is essentially a prolonged exaggerated heart rate increase in response to an upright postural change, orthostasis, with concomitant symptoms. These symptoms include dizziness, lightheadedness, headache, weakness, blurry vision, palpitations, nausea, fatigue and occasionally syncope.
By definition, the symptoms must resolve with lying down. They can occur insidiously or abruptly after an acute event. These patients may present to emergency rooms, primary care physicians, cardiologists or neurologists.
The minimal requirements needed when evaluating POTS are a medical history, a family history, a physical exam including orthostatic vital signs and a resting EKG.
Clues in the medical history which may support POTS include personal or family history of similar symptoms, evidence of joint hypermobility or autoimmunity. Joint hypermobility and Ehlers Danlos Syndrome are strongly associated with POTS.
A thorough history, physical exam and EKG help rule out some of the differential diagnoses such as vasovagal syncope, an accessory bypass tract or cardiac conduction abnormalities.
Head up tilt table testing (HUTT) is a test commonly described in the literature, where HR and BP are measured continuously while the patient is supine on a tilt table which is moved to various degrees of incline. This eliminates the muscle pump activity normally present in individuals while standing upright, while passively moving the patient into an upright position.
The measurements are thought to evaluate a patient’s ability to accommodate to the normal hemodynamic shift while transferring from a supine to an upright position. A few limitations to the HUTT include:
- the physiologic responses activated during HUTT are different than during active standing
- often there is a greatly increased tachycardia generated during HUTT as compared to normal upright orthostatic testing
- controlled studies have not been performed in younger individuals.
Because of these issues, HUTT must be interpreted as part of the entire clinical picture.
Obviously, syncope (rarely) and presyncope (more commonly) are quite debilitating in regards to everyday, independent activities and functioning. Other comorbidities commonly present include: hypermobility syndromes, gastrointestinal abnormalities, chronic fatigue syndrome, fibromyalgia, sleep abnormalities, chronic pain and Raynaud-like symptoms, while less frequently headaches and urinary issues are troublesome. Each patient is evaluated and treated specifically to their particular symptom complex.
There is no cure for POTS, but there are many non-pharmacologic and pharmacologic approaches toward relieving the POTS symptoms and improving the quality of life.
Non-pharmacologic approaches are the foundation of management. If they are insufficient, “off label” pharmacologic methods may be tried. The FDA has not approved any medications for pharmacologic treatment.
The treatments are tailored to symptoms in each individual patient. While there is no cure for POTS, generally the symptoms can be controlled and hopefully, the patient returns to his or her previous level of activities.
Figure 2 - Treatment Options for POTS
|Exercise training (reconditioning)||Counteracts cardiac atrophy|
|Increased salt-fluid intake||Counteracts hypovolemia|
|Sleeping in head-up position||Increases stroke volume|
|Compression garments||Counteracts venous pooling in lower body|
|Physical countermeasures||Encourages muscle pumping which improves venous returns|
|Blood volume expansion||Salt supplementation, fludrocortisone, desmopressin (DDAVP), IV saline, erythropoietin|
|Reduction of heart rate test||Propranolol, ivabradine, pyridostigmine|
|Peripheral vasoconstriction||Midodrine, octreotide, methylphenidate, droxidopa|
Unless one is in harm’s way (e.g., standing on the edge of a cliff), POTS is not lethal, and the mortality rate is thought to be standard. It is a chronic condition with waxing and waning, generally with eventual improvement. The morbidity, however, can be significant in some patients with great interference in normal daily activities and quality of life.
Returning to the Case
This lady has a history of chronic fatigue and POTS. She is well controlled with non-pharmacologic and minimal pharmacologic treatment, with good function. She delivered a child and cares for her family while holding down a job. She was assessed at near normal mortality.
Arnold, Amy C., Jessica Ng, and Satish R. Raj. “Postural tachycardia syndrome–Diagnosis, physiology, and prognosis.” Autonomic Neuroscience: Basic and Clinical (2018).
Fu, Qi, and Benjamin D. Levine. “Exercise and non-pharmacological treatment of POTS.” Autonomic Neuroscience: Basic and Clinical 215 (2018): 20-27.
Miller, Amanda J., and Satish R. Raj. “Pharmacotherapy for postural tachycardia syndrome.” Autonomic Neuroscience: Basic and Clinical (2018).
Ojha, Ajitesh, Thomas C. Chelimsky, and Gisela Chelimsky. “Comorbidities in pediatric patients with postural orthostatic tachycardia syndrome.” The Journal of pediatrics 158.1 (2011): 20-23.
Sheldon, Robert S., et al. “2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope.” Heart Rhythm 12.6 (2015): e41-e63.
www.uptodate.com last accessed 2/4/2019