Indiana University Health Bloomington Southern Indiana Physicians

1. Kyle Hornsby, MD, FACCAssistant Professor of Cardiac ElectrophysiologyInternational University Sports Federation Medical Committee Indiana University Health Bloomington Southern Indiana Physicians

2. Indiana University Health Bloomington Regional Acacademic Medical Center

3. Topics to be covered… • Postural Orthostatic Tachycardia Syndrome (POTS) • POTS review and physiology • POTS subtypes • Associated conditions • Differential diagnoses • Evaluation and management • Painful left bundle branch block (LBBB) syndrome • Brief introduction • Case study SCHOOL OF PUBLIC HEALTH-BLOOMINGTON

4. Definitions to know • Postural Orthostatic Tachycardia Syndrome (POTS) is a clinical syndrome of orthostatic intolerance with an increase in heart rate by >30-40bpm within 10 minute of standing without orthostatic hypotension (>20mmHg drop in systolic blood pressure or >10mmHg drop in diastolic blood pressure). Orthostatic intolerance is a broad term referring to symptoms such as palpitations, fatigue, cognitive disturbance, headache, nausea, pre-sncope, and syncope. Dysautonomia is a nonspecific term referring to abnormal function of the autonomic nervous system which is often normally functioning in POTS and involved with many syndromes and can be involved in orthostatic intolerance.

5. Demographics / Characteristics • Young women 20-40 years old Symptoms are more bothersome in the AM Usually preceded by a viral illness or period of bedrest Commonly associated with GI symptoms (such as bloating, nausea, diarrhea, and abdominal pain), fatigue, sleep disturbances, headache, etc… Presyncope is much more common than syncope but reflex syncope (neurocardiogenic syncope) can coexist Syndrome onset can be acute, subacute, or insidious and usually in someone who relates to a previously healthy and active lifestyle (i.e. prior athletes)

6. Normal Gravitational Physiology

7. POTS Physiology

8. Female versus Male

9. Hypovolemic Effects • Muscle sympathetic nerve activity (MSNA) in response to lower body negative pressure and volume infusions explaining why hydrations is a key in management Central hypovolemia also happens with heat stress which redirects significant volume to the skin for cooling Central hypovolemia can happen with GI symptoms

10. POTS Subtypes • >50% of patients with POTS with peripheral sympathetic denervation Controversial; may play a role 30% of patients with POTS with persistently low plasma volumes 30-60% of patients with POTS with elevated standing NE levels Controversial

11. Associated Conditions

12. Differential Diagnoses Inappropriate sinus tachycardia Orthostatic hypotension Neurocardiogenic syncope Dysautonomia Anxiety Hypovolemia Anemia Hyperthyroidism Pulmonary embolism Pheochromocytoma Medications Supraventricular tachycardia

13. Evaluation Basic Labs EKG Holter Monitor Rarely a tilt table test

14. Management • Nonpharmacologic treatment: Exercise conditioning with a recumbent bike, rowing machine, or swimming via an exercise facility or rehab program Increase blood volume with 3L of water per day (16floz prior to getting out of bed) and 5-10gms of Na per day Avoid large heavy meals, EtOH, and heat exposure Recommend compression stockings at least to the thigh and preferably to the abdomen Recommend sleeping with head of bed elevated 4-6 inches and performance of physical counter maneuvers such as leg crossing and squatting in addition to upright activity during day Behavioral and cognitive therapy may be good particularly when anxiety, hypervigilance, or catastrophizing behaviors are present

15. Exercise Program The majority of patients who complete the exercise program no longer meet criteria for POTS This exercise program was compared to propranolol in a double-blind drug trial and found to be superior to propranol at restoring upright hemodynamics and improvement of quality of life (effect persisted for >1 year) The major barrier is patient compliance with a 3 month program and the most difficult is the first few weeks due to increased fatigue Comorbid conditions with the correlating symptoms may also limit the patient and appropriate referrals should be made

16. Exercise Program cont… The program progresses from seated or horizontal exercise all the way to upright exercise over a 3 month period, but can be longer Monitoring heart rate is key and there is significant involvement with healthcare personnel to calculate heart rate zones for the training program The Rating of Perceived Exertion (RPE) is also used

17. Management

18. Painful Left Bundle Branch Block Syndrome • Characterized by the development of intermittent non-ischemic chest pain at the onset of exercise-induced or rate-related LBBB Postulated that the pain arises from dyssynchronous ventricular contraction via a potential generalized interoceptive sensitivity although the precise mechanisms remain elusive Due to rarity, unclear management which has included medical thearpy and pacing

19. Example of Interesting LBBB

20. Current Common Ventricular Pacing Techniques • RV apical pacing • Time tested and still the most common form of pacing • RV septal pacing • Due to concern related to RV apical pacing • May be better? • Biventricular Pacing • Derived from HF trials and LBBB pts

21. Why His Bundle Pacing? • Replicates true human physiology • Lead tip & body potentially within the right atrium • Could prevent lead related issues such as tricuspid regurgitation • Data not convincing for other forms of pacing • RV pacing and its detrimental effects • BiV pacing debatable in some populations (i.e. EF>35%) • Should eliminate pacing induced cardiomyopathy

22. Imaging Evaluation Imaging evaluation of implantation site of permanent direct His bundle pacing lead Vijayaraman et al. Heart Rhythm 2014

23. Example of Interesting LBBB

24. What Am I Looking At?

25. Reference Bryarly M, Phillips LT, Fu Q, Vernino S, Levine BD. Postural Orthostatic Tachycardia Syndrome: JACC Focus Seminar. J Am Coll Cardiol. 2019 Mar 19;73(10):1207-1228. doi: 10.1016/j.jacc.2018.11.059. Review. PubMed PMID: 30871704. Sheldon RS, Grubb BP 2nd, Olshansky B, Shen WK, Calkins H, Brignole M, Raj SR, Krahn AD, Morillo CA, Stewart JM, Sutton R, Sandroni P, Friday KJ, Hachul DT, Cohen MI, Lau DH, Mayuga KA, Moak JP, Sandhu RK, Kanjwal K. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015 Jun;12(6):e41-63. doi: 10.1016/j.hrthm.2015.03.029. Epub 2015 May 14. PubMed PMID: 25980576; PubMed Central PMCID: PMC5267948. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz IJ, Schondorf R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. AutonNeurosci. 2011 Apr 26;161(1-2):46-8. doi: 10.1016/j.autneu.2011.02.004. Epub 2011 Mar 9. PubMed PMID: 21393070. Narula OS. Longitudinal dissociation in the His bundle. Bundle branch block due to asynchronous conduction within the His bundle in man. Circulation. 1977;56(6):996-1006. Shvilkin A, Ellis ER, Gervino EV, Litvak AD, Buxton AE, Josephson ME. Painful left bundle branch block syndrome: Clinical and electrocardiographic features and further directions for evaluation and treatment. Heart Rhythm. 2016;13(1):226-232.