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Disclosures Pots Postural Orthostatic Tachycardia 4/5/2019 AUTONOMIC AND CARDIOGENIC DISORDERS Juan J. Figueroa, MD Assistant Professor, Neurology Froedtert & Medical College of Wisconsin A Practical Guide to Dizziness and Disequilibrium April 5, 2019 DISCLOSURES • Nothing to disclose (no financial or pharmaceutical affiliations) • All discussed pharmacologic treatments are off-label A Practical Guide to Dizziness and Disequilibrium April 5, 2019 POTS POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME 1 4/5/2019 POTS • First case reported in 1982 - Disabling postural tachycardia without postural hypotension • Nosology is confusing due to several terms used in the past - Postural tachycardia syndrome - Hyperadrenergic orthostatic tachycardia - Idiopathic orthostatic tachycardia - Neurocirculatory asthenia - Vasoregulatory asthenia - Hyperdynamic beta-adrenergic state - Irritable heart • Debilitating disorder that is not fully understood A Practical Guide to Dizziness and Disequilibrium April 5, 2019 EPIDEMIOLOGY • Estimates - Prevalence: > 170 per 100,000 - Over 500,000 Americans, primarily young woman (1999) • Women (5:1) • Childbearing age (15-50 years) • Most patients have undergone a cardiac evaluation before neurology referral A Practical Guide to Dizziness and Disequilibrium April 5, 2019 MORBIDITY • Growing source of impairment and disability in working age people • Debilitating with a functional impairment similar to CHF and COPD resulting in poor quality of life • Sources of disability - Dizziness during even simple activities (eating, showering, and low-intensity exercise) reduces standing time and activity level - Severe fatigue and attentional problems may limit ability to work, attend school and to exercise - Comorbidities - Disability correlates with psychological variables - Misdiagnosis with panic attacks A Practical Guide to Dizziness and Disequilibrium April 5, 2019 2 4/5/2019 NORMAL RESPONSE TO STANDING • Reduction in central blood volume - 0.5 to 1 L of blood pools in lower body • Sympathetic activation increases - PVR - Venous return - Heart rate (10-25 bpm) 3 seconds: rapid increased (inhibition of vagal tone - exercise reflex) 10-15 seconds: gradual increase (a baroreceptor reflex) Central command – an excitatory signal from brain center to brainstem A Practical Guide to Dizziness and Disequilibrium April 5, 2019 PATHOPHYSIOLOGY OF POTS • Circulating norepinephrine • Total blood volume • Auto-antibodies • Central blood volume • Red cell volume • Alpha 1 adrenergic receptor • Vascular structure • Beta adrenergic receptor • Venous capacitance • Peripheral vascular innervation • Capillary permeability • Vasodilation • Venous return • Renal sympathetic innervation • Stroke volume • Renin and aldosterone • Left ventricle size • Angiotensin II • Exercise max O2 uptake A Practical Guide to Dizziness and Disequilibrium April 5, 2019 ONSET • Triggers - Concussion - Post-viral - Surgery • Gradual - Increased venous wall elasticity? - Prolonged bedrest A Practical Guide to Dizziness and Disequilibrium April 5, 2019 3 4/5/2019 HYPOVOLEMIA AND VENOUS POOLING • Bullet copy - Bullet copy Insert quote here. Bullet copy Circulation. 1997;96:575-580 Am J Physiol Heart Circ Physiol. 2004, 287:H1319-27 A Practical Guide to Dizziness and Disequilibrium April 5, 2019 CARDIAC ATROPHY • Cardiac MRI performed on a group of patients with POTS - 16% reduction in cardiac mass compared to age-matched controls - 20% reduction in blood and plasma volume • It was hypothesized that the marked tachycardia during orthostasis was compensatory to the smaller stroke volume resulting from a small heart coupled with reduced blood volume. Fu Q et al. J Am Coll Cardiol. 2010;55(25):2858-68 A Practical Guide to Dizziness and Disequilibrium April 5, 2019 KEY MECHANISMS • Cardiovascular mechanisms of POTS - Small heart - Reduced blood volume - Venous pooling A Practical Guide to Dizziness and Disequilibrium April 5, 2019 4 4/5/2019 CLINICAL PRESENTATION OF POTS A Practical Guide to Dizziness and Disequilibrium April 5, 2019 CRITERIA FOR POTS 1. Heart rate increase ≥30 beats per minute from supine to standing within 10 min 2. Symptoms get worse with standing and better with recumbence. 3. Symptoms last ≥6 months 4. Absence of orthostatic hypotension 5. Absence of other overt cause of orthostatic symptoms or sinus tachycardia (e.g. anemia, dehydration, hyperthyroidism, pheochromocytoma or cardioactive drugs such sympathomimetics or anticholinergics) A Practical Guide to Dizziness and Disequilibrium April 5, 2019 COMMON CLINICAL FEATURES • Orthostatic intolerance - Brain hypoperfusion Dizziness, lightheadedness, weakness, blurred vision, fatigue upon standing Near-syncope and syncope - Sympathetic activation Palpitations, tremulousness, anxiety • Chronic symptoms - Fatigue - Brain fog - Heat intolerance - Gastrointestinal symptoms - Chest pain A Practical Guide to Dizziness and Disequilibrium April 5, 2019 5 4/5/2019 PHYSICAL EXAM • Orthostatic vitals • Dependent acrocyanosis • Small-fiber sensory exam • Beighton score Auton Neurosci. 2018 Dec;215:121-125 A Practical Guide to Dizziness and Disequilibrium April 5, 2019 UPRIGHT TILT IN POTS Raj SR et al., Indian Pacing Electrophysiol. J. 2006;6:84-99 A Practical Guide to Dizziness and Disequilibrium April 5, 2019 LABORATORY EVALUATION • Autonomic Evaluation (Tilt table test) • ECG • Anemia or electrolyte abnormalities • Additional testing depends on additional symptoms A Practical Guide to Dizziness and Disequilibrium April 5, 2019 6 4/5/2019 CONDITIONS ASSOCIATED WITH POTS • GI (IBS, eosinophilic esophagitis) • Joint hypermobility/Ehler’s Danlos type III • Fibromyalgia • Chronic fatigue syndrome • Vasovagal syncope • Migraine • Mast cell activation disorder • Interstitial cystitis A Practical Guide to Dizziness and Disequilibrium April 5, 2019 DIFFERENTIAL DIAGNOSIS • Structural cardiac disease • Inappropriate sinus tachycardia • Neurocardiogenic syncope • Pheochromocytoma (paroxysms of hyperadrenergic symptoms) • Other causes of orthostatic symptoms or tachycardia (anemia, acute dehydration, medications, adrenal insufficiency) • GI illness with hypovolemia • Panic and anxiety A Practical Guide to Dizziness and Disequilibrium April 5, 2019 MANAGEMENT OF POTS A Practical Guide to Dizziness and Disequilibrium April 5, 2019 7 4/5/2019 BACKGROUND • No FDA-approved treatments for POTS • No long-term randomized blinded placebo-controlled trials • Optimal management is multidisciplinary • First-line treatment is non-pharmacological A Practical Guide to Dizziness and Disequilibrium April 5, 2019 APPROACH TO TREATMENT • Education • Optimization of circulation - Tanking up (hypovolemia) - Squeezing up (venous pooling) - Exercise (deconditioning) • Adaptation to limitations A Practical Guide to Dizziness and Disequilibrium April 5, 2019 HYPOVOLEMIA • Non-pharmacologic - Fluids: > 64 oz/day Rapid ingestion of 500 cc of tap water - Up to 12 grams NaCl daily Table salt Salt tablets • Pharmacologic - Fludrocortisone (0.05 mg qod - 0.2 mg/d) - Side effects: Edema Hypokalemia Headache A Practical Guide to Dizziness and Disequilibrium April 5, 2019 8 4/5/2019 TREATMENT OF VENOUS POOLING • Non-pharmacologic: - Compression stockings (30-40 mmHg, knee high) - Abdominal binder - Physical countermaneuvers • Pharmacologic - Pyridostigmine 30-60 mg tid - Midodrine 2.5-10 mg tid - Droxidopa 100-600 mg tid https://cvpharmacology.com/autonomic_ganglia A Practical Guide to Dizziness and Disequilibrium April 5, 2019 DECONDITIONING • Cardiovascular Exercise in POTS - Rowing, semi-recumbent bicycle, swimming - Short-term (i.e., 3 months) exercise training Increases cardiac size and mass Increased blood volume Even cured POTS in several patients • Referral - PT prescription for graded aquatherapy with transition to land - Cardiovascular rehabilitation Fu Q et al. J Am Coll Cardiol. 2010;55(25):2858-68 A Practical Guide to Dizziness and Disequilibrium April 5, 2019 HYPERADRENERGIC STATE • Troubled adrenergic symptoms (palpitations) - Beta-blockade Propranolol 20 mg daily - Sinus node ablation Not effective - Ivabradine Inhibits f-channels within the SA node - Central sympatholytic agents (clonidine) Equivocal data in POTS A Practical Guide to Dizziness and Disequilibrium April 5, 2019 9 4/5/2019 PROGNOSIS • Limited longitudinal data • Most patients have a favorable prognosis • Relapsing-remitting course A Practical Guide to Dizziness and Disequilibrium April 5, 2019 TAKE HOME POINTS • Multidisciplinary team approach - Autonomic Neurology: Testing: Clinical Neurophysiology Lab (414) 805-4269 - Comorbidities Migraines: Headache specialist Fibromyalgia: PM&R GI symptoms: GI dysmotility Interstitial cystitis: Urogynecology Inappropriate sinus tachycardia: Cardiac Electrophysiology - Joint hypermobility Orthopaedics Services (dislocations) PM&R or Pain Clinic (pain management) A Practical Guide to Dizziness and Disequilibrium April 5, 2019 10.
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