The Postural Tachycardia Syndrome

A Concise Guide to Diagnosis and Management

Blair P. Grubb, M.D.; Yousuf Kanjwal, M.D.; Daniel J. Kosinski, M.D.

Disclosures

J Cardiovasc Electrophysiol. 2006;17(1):108-112. 

In This Article

Classification

As was alluded to before, POTS is a group of different disorders associated with similar clinical manifestations. POTS is classified as being either primary or secondary. The primary forms are idiopathic and not associated with other diseases. The secondary forms occur in association with a known disease or disorder. Proper recognition of subtypes is essential in management[4] (Fig. 1).

Subtypes of postural tachycardia syndrome. POTS = postural tachycardia syndrome; JHS = joint hypermobility syndrome.

The most common primary form of POTS is called the "partial dysautonomic" (PD) form.[1,2,3] These patients seem to suffer from a mild type of peripheral autonomic neuropathy characterized by an inability of the peripheral vasculature to constrict in the face of orthostatic stress. This causes a much greater than normal degree of blood pooling in the dependent areas of the body when upright, which in turn causes a compensatory increase in heart rate and contractility that attempt to maintain cerebral perfusion at constant levels. While this increase in heart rate and contractility may initially be fully compensatory, the degree of peripheral venous pooling may continue to increase over time and exceed this compensatory effect. These individuals then become increasingly dependent on their skeletal muscle pump to maintain adequate blood pressure until increased venous pooling exceeds its compensatory effects as well. There is a 5:1 female-to-male ratio. Many patients will report the abrupt onset of symptoms after a febrile illness (presumed viral), as well as after pregnancy, immunizations, sepsis, surgery, or trauma. It is currently felt that this form of POTS has an immune-mediated pathogenesis. Studies have demonstrated serum autoantibodies to alpha3 acetylcholine receptors of the peripheral autonomic ganglia in patients with postviral autonomic neuropathy.

A second type of partial dysautonomic POTS (which we term "developmental") seems to afflict adolescents.[5] Onset is usually around 14 years, often following a period of very rapid growth. Symptoms progressively worsen and frequently reach their peak around age 16. Symptoms of orthostatic intolerance (and often severe headaches) may be of such intensity that the patient may be functionally disabled. Symptoms will then slowly start to fade over the ensuing years such that by young adulthood (19–24 years old) roughly 80% are asymptomatic. The etiology is unclear but appears to reflect a transient period of autonomic imbalance that occurs in rapidly growing adolescents.

The second (and less common) form of primary POTS is referred to as the "hyperadrenergic" form. These patients tend to report a gradual and progressive onset of symptoms as opposed to an abrupt onset. Hyperadrenergic POTS patients report significant tremor, anxiety, and cold sweaty extremities when upright. Many will report a significant increase in urinary output after being upright for even a short period of time, and over half suffer from true migraine headaches. The hallmark of this form of POTS is that in addition to orthostatic tachycardia they will often display orthostatic hypertension, as well as exaggerated response to isoproterenol infusions. As opposed to the PD POTS patients, the hyperadrenergic patients have significantly elevated serum catecholamine levels with serum norepinephrine levels >600 ng/mL. There is often a family history of this disorder. Currently, hyperadrenergic POTS is felt to be a genetic disorder, in which a single point mutation produces a dysfunction of the re uptake transporter protein that clears norepinephrine from the intrasynaptic cleft. This in turn leads to excessive degree of norepinephrine serum spillover in response to a variety of sympathetic stimuli thereby producing a "hyperadrenergic" state that appears similar to a pheochromocytoma.

The term secondary POTS is used to describe various conditions that produce peripheral autonomic deinnervation but with sparing of cardiac innervation. The most common form of secondary POTS is chronic diabetes mellitus; however, it also occurs in conjunction with amyloidosis, sarcoidosis, alcoholism, Lupus, Sjogren's Syndrome, heavy metal intoxication, and following chemotherapy (especially from the vinca alkaloids).

A recently recognized and important cause of secondary POTS is due to the connective tissue disorder known as the joint hypermobility syndrome (JHS). An inherited condition, it is characterized by joint hypermobility, connective tissue fragility, and soft "velvety" skin with variable amounts of hyperextensibility. The condition is also associated with easy bruising, premature varicose veins, diffuse muscle and joint pain, and orthostatic acrocyanosis. Orthostatic intolerance develops in these patients due to the presence of abnormally elastic connective tissue in the vasculature, which results in an increase in vessel distensibility in response to the augmented hydrostatic pressure that occurs during orthostatic stress. This leads to excessive peripheral venous pooling with a resultant compensatory tachycardia. Recent studies have suggested that up to 70% of patients with hypermobility syndrome may suffer from some form of orthostatic intolerance. Adolescents with the developmental form of POTS frequently have been noted to have features of JHS. Studies are currently under way to better elucidate this potential relationship.

POTS may also be the presenting form of more severe autonomic nervous system disorders such as pure autonomic failure or multiple system atrophy. POTS may also present as a paraneoplastic syndrome seen in association with adenocarcinomas of the lung, breast, ovary, and pancreas. Current investigations have shown that these tumors produce autoantibodies against acetylcholine receptors in the autonomic ganglia similar to those seen in the postviral syndromes.

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