Disclosures. Adult Postural Orthostatic Tachycardia Syndrome (POTS) Topics. Objectives. Definition/Terminology. Epidemiology 2/2/2017

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1 Disclosures Adult Postural Orthostatic Tachycardia Syndrome (POTS) Nothing to disclose (no financial or pharmaceutical affiliations) All discussed pharmacologic treatments are off-label Juan J. Figueroa, MD Assistant Professor, Neurology Froedtert & Medical College of Wisconsin Objectives To tackle the heterogeneity and complexity of POTS by Delineating the core mechanisms of the chief complaint: orthostatic intolerance Considering other symptoms as manifestations comorbidities (e.g. GI symptoms) Describing the necessary multidisciplinary team (e.g. neurology, GI dysmotility clinic, geneticist, etc.). Topics Terminology/Definition Epidemiology Pathophysiology/Etiology Clinical Features/H&P Diagnosis/Testing Treatment/Management Prognosis Definition/Terminology POTS: postural tachycardia without OH 1982: Postural Tachycardia Syndrome 1993: Postural Orthostatic Tachycardia Syndrome Nosology of POTS is confusing due to several terms in the past Debilitating disorder Epidemiology Most common syndrome on young people in autonomic dysfunction clinics Estimates Prevalence: > 170 per 100,000 (underdiagnosis) Over 500,000 Americans, primarily young woman (1999) Age: years F/M ratio: 5:1 Robertson D. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci Feb; 317(2):

2 Postural Orthostatic Tachycardia Syndrome Symptoms occur in association with an inappropriate rise in heart rate in the absence of a fall in blood pressure with the assumption of standing The pathophysiology of POTS is complicated and poorly understood Complexity Heterogeneous nature of POTS Challenging for researchers to design an appropriate cell or animal model Mechanisms underlying POTS are still being elucidated Etiology Hypovolemia in POTS Distal denervation Post-viral Hypovolemia (fluid expansion) Excessive venous pooling with redistributive hypovolemia Changes in venous function (military anti-shock trousers) Decreased venous return Decreased stroke volume on assuming upright posture Excessive venous pooling Cardiovascular deconditioning Reduced maximum oxygen uptake during exercise Small left ventricular size Increased sympathetic activity Hyperadrenergic Genetic abnormalities 12% positive FH Associated disorders Ehlers-Danlos syndrome (EDS) Low blood volume (red cell volume and plasma volume) has been demonstrated in multiple studies in POTS patients (Jacob et al., 1997; Raj et al., 2005a; Stewart et al., 2006a; Fu et al., 2010). Some studies have reported reduced blood volume including red cell and plasma volume in POTS (Raj et al., 2005; Stewart et al.,2006). Bar graphs show effects of medical interventions on changes in orthostatic hemodynamics in IOT patients. ΔSBP, ΔDBP, and ΔHR are compared for measurements taken with the patients supine and after 3 minutes of standing before and then 1 and 2 hours after the administration of placebo, midodrine, or clonidine, or 1 hour after normal saline infusion. Figure 3. Blood volumes. Giris Jacob et al. Circulation. 1997;96: Satish R. Raj et al. Circulation. 2005;111: Copyright American Heart Association, Inc. All rights reserved. Copyright American Heart Association, Inc. All rights reserved. 2

3 Venous pooling in POTS Cardiac Origins of the POTS (n=27) Stewart JM, Montgomery LD. Regional blood volume and peripheral blood flow in postural tachycardia syndrome. Am J Physiol Heart Circ Physiol Sep;287(3):H group. p 0.01 versus healthy controls. CO cardiac output; DBP diastolic blood pressure; HR heart rate; SBP systolic blood pressure; SV stroke volume; TPR total peripheral resistance; other abbreviations as in Table 1. Fu Q et al. J Am Coll Cardiol Jun 22;55(25): Cardiac Origins of the POTS (n=27) Clinical Features HR increase from recumbent to standing position > 30 bpm > 40 bpm if younger than 19 years Provocative actions trigger a cascade of symptoms The marked tachycardia during orthostasis was attributable to a small heart coupled with reduced blood volume. Exercise training improved or even cured this syndrome in most patients Fu Q et al. J Am Coll Cardiol Jun 22;55(25): Orthostatic Symptoms Brain hypoperfusion Dizziness, lightheadedness, weakness, blurred vision, fatigue upon standing Cerebral hypoperfusion despite normal systemic blood pressure? (no evidence) Sympathetic activation Palpitations, tremulousness, anxiety Clinical Features Onset Abrupt Insidious Severity Mild Profoundly incapacitated Course Self-limited Relapsing-remitting over several years 3

4 Dependent Acrocyanosis in POTS Raj SR et al., Indian Pacing Electrophysiol. J. 2006;6:84-99 Diagnosis Heart Rate and Blood Pressure with Upright Tilt in POTS Exaggerated increase in heart rate on tilt table testing or standing Sustained 30 bpm within the first 10 minutes of tilt Raj SR et al., Indian Pacing Electrophysiol. J. 2006;6:84-99 Differential Diagnosis Autonomic neuropathies? Bed rest deconditioning Dehydration Panic, anxiety, somatization disorder, chronic fatigue Management POTS has multiple symptoms and causes A multidisciplinary management approach including a graded exercise program is recommended (Fu et al., 2011; Sheldon et al., 2015) Maintenance of intravascular volume by increasing salt and fluid intake is generally recommended (Sheldon et al., 2015) Improve intravascular volume, blunt tachycardia, improve venous return or reduce central sympathetic outflow, however most therapies used to date are without a large body of evidence, (Sheldon et al., 2015) The development of target therapies has been hindered by a lack of a unifying mechanism 4

5 Treatment of POTS Optimize circulation Tanking up (hypovolemia) Squeezing up (venous pooling) Exercise (deconditioning) Adapt to limitations Treatment (Hypovolemia) Non-pharmacologic Fluids: > 64 oz/day Increase dietary salt intake (fluid retainer) Salt tabs, 3-6 tabs a day (fluid retainer) Drink 2 large electrolyte fluids with 1 teaspoon added salt/day Pharmacologic Fludrocortisone ( mg/d) (salt retainer) Treatment (Venous pooling) Physical compression: Compression stockings, mmhg, knee high (when up and about, off when laying down) Physical countermaneuvers Pharmacologic compression Midodrine mg 3 x day (Gordon et al., 2000) Pyridostigmine 30 mg/day (Raj et al., 2005; Kanjwal et al., 2011) Droxidopa 100 mg 3 x day (Ruzieh et al., 2016) Treatment (Hyperadrenergic State) Troubled adrenergic symptoms (palpitations) Propranolol mg 3 x day Sinus node ablation is not effective Exercise in POTS Short-term (i.e., 3 months) exercise training increases cardiac size and mass, blood volume, and VO 2 peak in POTS patients. The tachycardia in POTS is due to a reduced stroke volume. Cardiac remodeling and blood volume expansion associated with exercise training increase physical fitness and improve exercise performance in these patients Treatment (Deconditioning) Aquatherapy prescription: gradual gentle water jogging and/or swimming Exercise:isthe most important treatment (as important as any medication). Regular exercise is the only treatment that has long term benefit. Cardiovascular exercise may include water jogging, rowing, reclining bike, etc. We recommend to start gently with a water jogging program or swimming, for example before transitioning to land in a reclining or sitting position (rowing, reclining bike, etc). Start at minutes 2 times per week, and gradually build up over 6 months until you are at 45 minutes 4 times per week. You may need a physical therapy appointment or exercise trainer to help you. Avoid reaching the point of shortness of breath, profuse sweating or exhaustion during an exercise session. If exercise session results in extreme fatigue for the next couple of days, reduce duration of session and intensity of training. Rest at least one day between sessions early in the process. Drink fluids prior and after exercising. Goal is to get your heart rate to 75%: Below is a chart heart rate in beats per minute for each intensity zone 50% 55% 65% 75% 85% 95% 20 yr yr yr yr yr yr yr yr yr yr Fu Q, Levine BD. Auton Neurosci Mar;188:86-9 5

6 Life Adjustments in POTS Avoid overdoing it (do not hit a wall ) Listen to you body Pace yourself Scheduled breaks Distribute limited energy If feeling great, hold your horses Incorporate exercise as part of your life Education of support network PROGNOSIS Most patients have a favorable prognosis Kimpinsky et al. A prospective, 1-year follow-up study of postural tachycardia syndrome. Mayo Clin Proc Aug;87(8): Take Home Points Simultaneous physiologic approach to optimize circulation Hypovolemia -> tank your patient up Venous Pooling -> squeeze patient up Deconditioning -> graded exercise through PT Judicious use of energy Multidisciplinary team approach Autonomic Neurology: orthostatic intolerance Comorbidities -> appropriate referrals Migraines: Headache specialist/general neurology Fibromyalgia: PM&R GI symptoms: GI dysmotility Interstitial cystitis: Urogynecology Inappropriate sinus tachycardia: Cardiac Electrophysiology Joint hypermobility -> Adult Genetic Clinic r/o EDS Bibliography Robertson D. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am J Med Sci Feb; 317(2):75-7. Mathias, C. J., Low, D. A., Iodice, V., Owens, A. P., Kirbis, M., & Grahame, R. (2012). "Postural tachycardia syndrome current experience and concepts". Nature Reviews Neurology. 8 (1): 22 3 Low, P. A., Sandroni, P., Joyner, M., & Shen, W. K. (2009). "Postural tachycardia syndrome (POTS)". Journal of Cardiovascular Electrophysiology.20 (3): Schondorf R, Low PA. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia? Neurology. 1993;43(1):132 Streeten DH, Anderson GH Jr, Richardson R, Thomas FD. Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling. J Lab Clin Med. 1988;111(3):326. AUFouad FM, Tadena-Thome L, Bravo EL, Tarazi RC SOAnn Intern Med. Idiopathic hypovolemia. 1986;104(3):298. Stewart JM. Pooling in chronic orthostatic intolerance: arterial vasoconstrictive but not venous compliance defects. Circulation. 2002;105(19):2274. Kimpinsky et al. A prospective, 1-year follow-up study of postural tachycardia syndrome. Mayo Clin Proc Aug;87(8): Gordon VM et al. Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome. Clin Auton Res Feb;10(1): Raj SR et al. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation 2005 May 31;111(21): Kanjwal K et al. Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. Pacing Clin Electrophysiol Jun;34(6): Ruzieh et al. Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome. Am J Ther Aug 25. [Epub ahead of print] Raj SR et al. Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Circulation. 2009;120(9):725. 6