POTS. Putting the Puzzle Pieces Together. Artur Fedorowski MD, Assoc.Prof. FESC Skåne University Hospital in Malmö and Lund University Sweden
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1 POTS Putting the Puzzle Pieces Together Artur Fedorowski MD, Assoc.Prof. FESC Skåne University Hospital in Malmö and Lund University Sweden
2 1993 These patients were usually women who experienced an acute onset of persistent lightheadedness and fatigue or gastrointestinal dysmotility. In seven patients, a viral illness may have preceded the onset of symptoms
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4 POTS and vasovagal reflex syncope (woman, 24 years). Nilsson D, Sutton R, Tas W, Burri P, Melander O, Fedorowski A. (2015) PLoS ONE 10(6): e
5 Open Heart 2017;4:e doi: / openhrt
6 Is there something special with POTS?
7 Common POTS Symptoms 0 Cardio/Vasc Palpitations Lightheadedness Chest discomfort/pain Shortness of breath Exercise intolerance 0 NeuroMuscular Mental clouding (brain fog) Headaches (migraine) Sleep complaints Involuntary movements Gastrointestinal Nausea and vomiting Constipation Weight loss Chronic Fatigue Visceral and regional pain Yes, POTS is special
8 ORs log regression Q4 vs Q1 adj age sex delta HR 3 min log transformed (n=671). Normal response <3 bpm Tachycardia >15 bpm Nilsson D, Sutton R, Tas W, Burri P, Melander O, Fedorowski A. (2015). PLoS ONE 10(6): e
9 Neuroendocrine response to hypotension ACh
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11 Activated adrenergic β-receptor Nobel Prize in Chemistry for 2012 to Robert J. Lefkowitz and Brian K. Kobilka
12 GPCR: How does it work?
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14 Tissue responses to activation of specific adrenergic receptor subtypes 2010 by American Physiological Society Gerald W. Dorn II Physiol Rev 2010;90:
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16 Fedorowski et al. Europace (2017).
17 Fedorowski et al. Europace (2017).
18 Fedorowski et al. Europace (2017).
19 Neuroendocrine response to hypotension ACh
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27 How to treat POTS? Ricci F, De Caterina R, Fedorowski A. JACC 2015; 66(7):
28 Dexamphetamine Brain fog Tapentadol Buprenorphine Pain Pirydostygmine GI Symptoms Muscle fatigue Beta blockers Ivabradine CCBs How to treat POTS? Midodrine Droxidopa Pseudoephedrine Ricci F, De Caterina R, Fedorowski A. JACC 2015; 66(7):
29 Perspectives? More laboratories with access to the diagnostic tests More training about POST An objective and reproducible method of identifying autoantibodies Basic studies/ genetic studies/ biomarker studies Randomized clinical intervention trials Pharmacological interventions Immunotherapy
30 Take-home message POTS probably an old disease in a modern outfit. POTS may mimic other conditions and is difficult to diagnose and treat for an untrained practitioner. POTS may have an autoimmune etiology GPCR AAb hypothesis is the closest we can get to the answer today.
31 Take-home message Presence of AAbs against GPCRs has been demonstrated in POTS and other cardiovascular disorders. These diseases may have an autoimmune etiology. The next step is to find a way to eliminate AAbs and demonstrate improvement of symptoms.
32 Activation of MMP-10 or equivalent endo proteinase by virus/stress extr Intra ECL Proteosome degradation of the ECL Immunoprotein complex
33 THE HUMAN IMMUNE RESPONSE
34
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