Workup and Management of Postural Orthostatic Tachycardia Syndrome

Educational Objectives

The goal of this program is to improve management of postural orthostatic tachycardia syndrome (POTS). After hearing and assimilating this program, the clinicians will be better able to:

1. Relate signs and symptoms to subtypes of POTS.
2. Choose medications appropriate for each subtype of POTS.

Summary

Overview of postural orthostatic tachycardia syndrome (POTS): POTS mainly affects young women and may be mistaken for anxiety; may be linked to long COVID; symptoms of POTS vary widely which leads to diverse clinical presentations; arises from multiple mechanisms and patients may experience multiple ongoing pathophysiologic processes

Symptom characteristics: palpitations or tachycardia can be acute (<1 mo), subacute (1-3 mo), or insidious (>3 mo); the frequency and duration of symptoms should be determined; evaluate the effect of symptoms on quality of life, eg, activities that can no longer be engaged in; symptoms can be categorized as postural or non-postural, and cardiac or non-cardiac; commonly reported symptoms include lightheadedness (nearly universal), tachycardia (≈97%), pre-syncope (≈94%), shortness of breath (≈88%), palpitations (≈87%), and chest discomfort differing from typical angina; non-cardiac symptoms include mental clouding, tremulousness, blurred or tunnel vision, nausea, "coat hanger headache" affecting the occiput and bilateral trapezius muscles, sleep disturbances, malaise, and abdominal symptoms (eg, pain, diarrhea, constipation) which may persist for several hours

Triggers: include prior infections; ≈22% of patients with COVID develop symptoms of POTS; other triggers include vaccinations (eg, human papilloma virus), major surgery, trauma, pregnancy, childbirth, and prolonged inactivity; exacerbating factors include heat, fever, dehydration, morning hours, non-dipper status (lack of expected blood pressure [BP] drop during sleep), strong emotions, alcohol consumption, and low levels of progesterone and estrogen at the start of the menstrual cycle

Detailed autonomic review of systems: important for determining the specific subtype of POTS; an information sheet may be given to patients to complete before appointments to narrow down potential etiologies

Symptoms: musculoskeletal — muscle fatigue, weakness, and pain; gastrointestinal (GI) symptoms include nausea, bloating, dysmotility, gastroparesis, diarrhea, constipation, and abdominal pain; neurological — headaches (particularly migraines), cognitive impairment, brain fog, photophobia, phonophobia, blurry vision, neuropathic pain, and sleep disorders; respiratory — shortness of breath, hyperventilation, and worsening asthma; urogenital — bladder dysfunction, polyuria, nocturia, urgency, and frequency; urogenital symptoms suggest a more serious condition and not simple POTS; skin — rash, erythema, petechiae, telangiectasia, diaphoresis, flushing, pallor, dry eyes and mouth, and sudomotor dysregulation (sweat gland dysfunction); psychiatric components — may involve anxiety characterized by impending doom and feeling of loss of control, depression, panic attacks, rarely suicidal ideation, somatic hypervigilance, and a catastrophizing personality

Review of systems (ROS) and medications: diet (specifically salt and water intake) and meal sizes should be documented; meals should be evenly proportioned to avoid diverting cardiac output (CO) to digestion after a large meal, which can worsen tachycardia upon standing; assess exercise tolerance and how tolerance changed with onset of symptoms; medications that may worsen POTS symptoms include diuretics, vasodilators, antipsychotics, anticholinergics, attention deficit hyperactivity disorder medications, and oral contraceptives that contain mineralocorticoid blockers

Diagnosing POTS: patients have their heart rate (HR) and BP monitored while supine for 10 min; continue monitoring as patients stand at 1, 3, 5, and 10 min; a HR increase of 30 beats per min (bpm) upon standing suggests POTS for patients ≥20 yr of age, and ≥40 bpm suggests POTS for patients 12 to 19 yr of age; HR must be sustained for >30 sec and documented on 2 separate measurements; ensure there is no orthostatic hypotension, indicated by a decrease in systolic pressure by 20 mm Hg or diastolic pressure by 10 mm Hg after 3 min of standing; chronicity is debated; the threshold for diagnosis is symptoms which persist for ≥6 mo in the United States (3 mo in Canada)

Other causes: other causes of tachycardia must be ruled out, eg, dehydration, infection, anemia, hyperthyroidism, pheochromocytoma, medications, sustained bedrest, underlying anxiety or panic disorders; "POTS feet" is characterized by acrocyanosis or darker discoloration upon standing; basic tests include complete blood count for anemia, basic metabolic panel for electrolyte imbalances and renal function, and thyroid function tests for hypothyroidism; electrocardiography (ECG) helps rule out other arrhythmias; an ambulatory monitor (ZioPatch) may be used to detect occult arrhythmias or tachyarrhythmias, and to aid in diagnosis of inappropriate sinus tachycardia, characterized by a resting HR >100 bpm and a 24-hr HR >90 bpm

Subtypes: 5 currently recognized subtypes, ie, hypovolemic, neuropathic, hyperadrenergic, mast cell activation, and autoimmune; healthy persons show neither orthostatic tachycardia nor associated symptoms; patients with POTS experience orthostatic tachycardia and symptoms; some individuals have conditions mimicking POTS (termed "POTS+"), or identifiable alternative causes of tachycardia

Hypovolemic POTS: seen in 70% of patients with POTS; results from blood pooling upon assuming an upright posture; blood pools in splanchnic vessels and legs, leading to diminished venous return and decreased CO; impaired renin-angiotensin-aldosterone regulation occurs over time, which leads to decreased sodium retention and hypovolemia

Neuropathic POTS: seen in 50% of patients with POTS; involves sympathetic denervation in the lower limbs, causing inadequate vasoconstriction and decreased venous return; compensatory sympathetic activation leads to tachycardia; patients tend to have lower supine and standing heart rates and tend to experience less anxiety and depression

Hyperadrenergic POTS: seen in 50% of patients with POTS; characterized by palpitations, anxiety, tremors, and hyperhidrosis; can be acquired or congenital; norepinephrine levels are elevated to ≥600 pg/mL when standing (compared with 200 to 250 pg/mL in patients without POTS); patients have a slight increase in BP upon standing; rarely results from a genetic mutation

Mast cell activation POTS: seen in 9% of patients with POTS; presents with allergic symptoms; diagnosis involves measuring urine methylhistamine or tryptase levels

Autoimmune POTS: seen in 16% of patients with POTS; typically follows a viral illness and is associated with various autoimmune conditions; diagnosis involves referral for antibody testing; routine screening is not recommended because of its rarity

Coexisting conditions with POTS: ≈21% of patients with chronic fatigue syndrome meet POTS criteria, and ≈75% of patients with POTS complain of fatigue; ≈25% of patients with type III Ehlers-Danlos syndrome (EDS), marked by joint hypermobility and autonomic dysregulation, have POTS symptoms; patients with anxiety and hypervigilance may fulfill POTS criteria; ≈30% of patients with celiac disease and irritable bowel syndrome, 20% with fibromyalgia, and 40% with migraine headaches have POTS symptoms; concussions have been implicated in the literature, but the precise mechanisms remain unclear

Differential diagnoses for POTS: hypothyroidism, infection, and pheochromocytoma should be ruled out; conditions other than POTS are suggested by acute or subacute onset, widespread autonomic involvement, functional decline, rare findings, family history (eg, familial orthostatic intolerance), gross neurological deficits, or endocrinopathies; syncope symptoms may warrant a tilt table test; murmurs or suspected structural heart diseases may warrant echocardiography; for suspected dysautonomia affecting other organs, special antibody testing may be indicated; exercise intolerance and deconditioning can be assessed through cardiopulmonary exercise stress testing

Diagnostic algorithm: the Heart Rhythm Society's guidelines on POTS recommend assessing orthostatic HR and BP; if there is no orthostatic tachycardia, assess for resting tachycardia; diagnosis is inappropriate with sinus tachycardia if resting tachycardia is present; assess for orthostatic intolerance if there is no resting tachycardia; if there is orthostatic intolerance, consider systemic disease; if there is no orthostatic intolerance, the patient is healthy; assess for orthostatic intolerance in patients with orthostatic tachycardia; a negative finding typically indicates that the condition is not pathological; a secondary cause should be identified in cases of a positive result; if there is no secondary cause, determine if the patient has systemic disease; if no, the diagnosis of isolated POTS can be made; the diagnosis is POTS+ in cases of systemic disease

Treatment algorithm for POTS: prioritize non-pharmacologic therapies; large meals, heat exposure, and alcohol should be avoided; patients should take in 3 to 4 L of water and 10 to 12 g of sodium daily; salt tablets may be required to meet intake recommendations; consider elevating the head of the bed 10%; whole body binders can reduce venous pooling; compression stockings alone are not effective; crossing legs while standing can decrease venous pooling; squatting may alleviate symptoms; drinking water before getting out of bed is recommended for morning symptoms; exercise is a class 2A recommendation and should be done in a supine or seated position; intravenous saline may be used in emergencies, but chronic use is discouraged because of the risk for infection and venous thrombosis

Pharmacological interventions for POTS: none of the mentioned medications are Food and Drug Administration (FDA)-approved for POTS; propranolol is a first-line medication if tachycardia is the primary symptom; ivabradine is second-line for tachycardia; ivabradine reduces firing from the sinus node, which may alleviate tachycardia; for low supine BP, midodrine is a prodrug, with the active form causing vasoconstriction and increasing venous return; pyridostigmine is an anticholinergic esterase inhibitor that increases vagal tone; for hypovolemia refractory to fluid and sodium intake, consider fludrocortisone; however, it may worsen diabetes mellitus; consider methyldopa or clonidine for hyperadrenergic-type POTS

Readings

Cheshire Jr WP. Autonomic history, examination, and laboratory evaluation. CONTINUUM: Lifelong Learning Neurol. 2020;26:25-43. View Article; Frye WS. Nonpharmacological treatment of postural orthostatic tachycardia syndrome: Commentary and implications for psychologists. Clin Pract Pediatr Psychol. 2023; 2:31-35. View Article; Hulsey B. Recognizing postural orthostatic tachycardia syndrome in primary care. JAAPA. 2022 May 6:10-97. View Article; Jacob G, Diedrich L, Sato K, et al. Vagal and sympathetic function in neuropathic postural tachycardia syndrome. Hypertension. 2019;73:1087-1096. View Article; Kim DH, Park JY, Kim SY, et al. Awareness of postural orthostatic tachycardia syndrome is required in adolescent syncope. Medicine. 2022 Nov;101(45):e31513. View Article; Kimpinski K, Figueroa JJ, Singer W, et al. A prospective, 1-year follow-up study of postural tachycardia syndrome. InMayo Clin Proc. 2012;87:46-752. Elsevier. View Article; Knoop I, Gu S, Fareghzadeh S, et al. Exploring the complexities of illness identity and symptom management in seeking a diagnostic label of postural orthostatic tachycardia syndrome (POTS): An inductive approach. Br J Health Psych. 2023. View Article; McDonald C, Frith J, Newton JL. Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. Europace. 2011;13:427-430. View Article; Raj SR, Fedorowski A, Sheldon RS. Diagnosis and management of postural orthostatic tachycardia syndrome. CMAJ. 2022;194(10):E378-E385. doi:10.1503/cmaj.211373. View Article; Weinstock LB, Brook JB, Myers TL, Goodman B. Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment. BMJ Case Rep. 2018;2018:bcr2017221405. Published 2018 Jan 11. doi:10.1136/bcr-2017-221405. View Article.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Le's lecture includes information related to the investigational or off-label discussion of a therapy, product, or device.

Acknowledgements

Dr. Le was recorded at the 55th Annual Primary Care Review, held February 12-16, 2024, in Portland, OR, and presented by Oregon Health and Science University. For more information about the upcoming CME activities from this presenter, please visit https://www. ohsu.edu/school-of-medicine/cpd. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

FP722301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.