This article describes the pathophysiology, clinical presentation, differential diagnosis, diagnosis, and management of postural orthostatic tachycardia syndrome (POTS), a potentially debilitating autonomic disorder that can have many causes and presentations.
POTS can be mistaken for panic disorder, inappropriate sinus tachycardia, and chronic fatigue syndrome.
Clinician suspicion for the syndrome is key to prompt patient diagnosis and treatment.
POTS affects up to 3 million patients in the United States, but the prevalence may actually be higher because of a lack of clinician awareness of the syndrome
The previous incidence is impossible to quantify, but similar clinical syndromes have been recognized under different names for more than 150 years
Patients may be misdiagnosed for a variety of reasons, including
- variability in causes and presentation of POTS,
- lack of clinician awareness of the condition,
- misconceptions about its prevalence, and
- inconsistency in the nomenclature.
Patients with POTS have been misdiagnosed with panic disorder, inappropriate sinus tachycardia, chronic fatigue syndrome, and a variety of other maladies before receiving the correct diagnosis.
A form of dysautonomia, POTS is the result of abnormal sympathetic and parasympathetic activity. However, defining the specific pathophysiology of POTS is difficult because the overall cause remains unclear. In most of the literature, POTS has been classified into subtypes, but these subtypes are not distinct with separate causes; instead they represent the continuum of interrelated autonomic dysfunction typical in most patients.19,20 Although these subtypes are not a comprehensive illustration of the pathophysiology, they are helpful in understanding the clinical manifestations and approach to treatment of POTS.
Most patients with POTS have some degree of hypovolemia.21,22 Studies have found that these patients have a 13% plasma volume deficit as compared with patient controls, a 22.7% deficit from their expected red blood cell (RBC) volume, and an abnormal physiologic response to decreased plasma volume
About 50% of POTS patients have a partial sympathetic denervation, typically in the lower limbs.5,10,21 In normal patients, standing causes a fluid shift; the body compensates with smooth muscle contraction to increase venous return to the heart.24 In patients with neuropathic POTS, the physiologic mechanism to combat gravity is impaired due to this sympathetic denervation. The result is venous pooling, decreased venous return to the heart, and tachycardia upon standing.
This subtype is characterized by a significant increase in orthostatic plasma norepinephrine levels. Elevated orthostatic norepinephrine and sympathetic outflow is theorized to be a compensatory mechanism in patients with hypovolemia and peripheral denervation
This is phenotypically manifested as tachycardia, palpitations, anxiety, and tremulousness
Autoimmunity appears to have a role in the pathogenesis of POTS
Newer research has demonstrated evidence of autoantibodies against cardiac membrane proteins, and adrenergic receptor autoantibodies to alpha and beta receptors in patients with POTS
Mast cell activation and POTS
A subset of patients with POTS have symptoms of mast cell activation and increased histamine release
Patients with POTS present with orthostatic tachycardia and myriad associated symptoms.
Diagnostic criteria for POTS are:
- an increase in heart rate of 30 beats/minute or greater (40 beats/minute or greater in children) within 10 minutes of transitioning from supine to standing.
- an absolute heart rate of 120 beats/minute or greater in the absence of orthostatic hypotension.
- symptoms of orthostatic intolerance for 6 or more months
- symptoms are exacerbated by standing and improved with recumbence.
- no other overt causes of tachycardia, such as hyperthyroidism, acute dehydration, or anemia
Lightheadedness and dizziness (presyncopal and vertiginous symptoms) are the most common presenting symptoms of POTS, but patients typically will have multiple complaints
Other common presenting symptoms may include weakness, fatigue, palpitations, tremulousness, anxiety, difficulty concentrating, mental clouding, blurred vision, dyspnea, chest pain, anhidrosis, hyperhidrosis, nausea, vomiting, bloating, abdominal pain, constipation, diarrhea, sleep disturbances, muscle aches, and headache
Eighty percent to 85% of the patients diagnosed with POTS are women ages 13 to 50 years
The differential diagnosis for a patient presenting with symptoms of POTS is broad. A thorough history and physical examination are essential to rule out other more common disorders or causes of orthostatic intolerance.
Tilt testing is the most valuable and easy-to-obtain initial study for patients who may have POTS. The procedure is performed using a specific tilt table apparatus
The patient’s BP and heart rate are measured while the patient is supine for 10 minutes. The patient is then placed at a 70- to 90-degree tilt, depending on the protocol, and BP and pulse are monitored continuously
Patients with POTS will have a heart rate increase of 30 beats/minute or greater (40 or greater in children) with an absolute heart rate of 120 beats/minute or greater in the absence of orthostatic hypotension.
a group of tests used to measure autonomic function and quantified in a composite autonomic severity score (CASS).
These tests include deep breathing, Valsalva maneuver, and the quantitative sudomotor axon test (QSART), and evaluate the cardiovagal, adrenergic, and sudomotor autonomic domains.
See full article for explanatio for the above.
All patients should have an ECG to establish that their tachycardia is sinus and to evaluate for conduction disturbances
Because most patients with POTS have some functional hypovolemia, blood volume assessments are useful
In patients with suspected hyperadrenergic POTS, plasma norepinephrine levels should be drawn while the patient is supine and again with the patient standing.20-22 The patient should be in each position for at least 10 minutes before the sample is drawn.
Patients with hyperadrenergic POTS often will have a normal norepinephrine level when supine and an elevated level, typically greater than 600 pg/mL, when standing.
Most patients will have a combination of subtype characteristics, so treatment must be individualized to the cause and the patient’s symptoms.
Exercise training is recommended for most patients with POTS and has shown efficacy in some studies.43,44 Encourage patients to start a graded exercise program over a period of months.
Oral fluid replacement is recommended for most patients. Between 2 L and 2.5 L of hydrating fluids per day is ideal
Salt supplementation, in the form of dietary modification or salt tablets, has also been successful in these patients; 8 to 10 g/day appears to be optimal
No medications are approved by the FDA for the treatment of POTS; all medication use is off-label.
Beta-blockers have been proven to reduce heart rate and alleviate symptoms in some patients.
Midodrine, an alpha-1 agonist, augments peripheral vasoconstriction and has shown some efficacy in suppressing orthostatic tachycardia.
Ivabradine is a selective sinoatrial node blocker with proven efficacy in treating patients with significant tachycardia and improving fatigue in limited trials.
Patients with mast cell activation have been treated successfully with histamine1 and histamine2 blockers, mast cell stabilizers such as cromolyn sodium, and high-dose aspirin
POTS is a dysautonomia with many causes and presentations, making it difficult to diagnose.
Clinician awareness is the key to more expedient diagnosis and more effective treatment.
Tilt testing is the most valuable tool that is widely available for the diagnosis
The most remarkable physical examination finding in patients with POTS is orthostatic tachycardia.
About 50% of patients develop dependent acrocyanosis in their legs and feet.. With prolonged standing, this appears as a reddish-blue discoloration that is cold to the touch
POTS has no cure and the goals of therapy are to manage the symptoms and restore function .
In most cases, a combination of interventions must be used.
Patients should also recognize and avoid their triggers, such as heat, dehydration, and alcohol.