PoTS; the King s approach. Dr. Nick Gall King s College Hospital London, UK
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2 PoTS; the King s approach 2017 Dr. Nick Gall King s College Hospital London, UK
3 The King s PoTS experience Appointed in 2004 Cardiac electrophysiologist Occasional patients with PoTS / IST Anticoagulant nurse was the first recognisable patient Impotent in dealing with the issues Paucity of UK services Little help as to what to do
4 Initial (on-going) battle against myths PoTS DOESN T EXIST They re just hysterical nurses
5 A neurocardiology MDT
6 So what did we do.. Ask the expert(s) at conferences Read the articles (written by the expert(s) at conferences) Treat the patients and see what happens Ask questions Why do you get migraines? How do I treat that? Why don t you get better?
7 At last.we ll know what to do now!?
8
9 Oh if only it were that easy! So, this is what I ve learnt! STEP 1: RECOGNISING YOUR PATIENT
10 It s not always that simple! The HR changes are unfortunately variable and are perhaps not the whole story
11 Did you know? Symptoms change from day to day, hour to hour.. Tested 8-9am, fasted, medication stopped >5 half-lives before
12 The world is not divided into normal, mad and PoTS! Normal Fainty people Mad Orthostatic intolerance PoTS POTS
13 The haemodynamic changes vary! THE CLASSICAL PATTERN
14 OI
15 Normal (?!)
16 Reflex syncope is not required for the diagnosis
17 Clinical features CORRECT DEMOGRAPHIC SYMPTOMS FOR >6/12 CARDIOVASCULAR SYMPTOMS UNEXPLAINED BY OTHER CONDITIONS OFTEN WORSE WITH POSTURAL CHANGE ASSOCIATED, VARIABLE NON- CARDIAC SYMPTOMS
18 You might have the right patient IF THEY VE GOT THE RIGHT SYMPTOMS AND A SUGGESTIVE TILT
19 Is this really our patient? STEP 2: LET S MAKE SURE WE RE NOT MISSING SOMETHING!
20 The guidelines will help us?! Tiny evidence base!
21 Our approach to testing is empiric and cardiological Tilt / active stand Echo 7 day Holter CPET Respiratory function tests
22 Holter the HR trend is helpful Persistently fast Spiky More normal
23 CPET Very complex investigation Good assessment of physiology overall, exclude other conditions Assessment of deconditioning Dysfunctional breathing
24
25 Respiratory function tests
26 Other things. BLOOD TESTS FBC, ESR, CRP U&Es, LFTs, TFTs, Glc CK Ferritin, B12, folate, Vitamin D (Coeliac, autoantibodies) EBV serology (Lyme serology)
27 Results AFTs Very complex Helpful where there is uncertainty e.g. Diabetes and hypermobility Cardiovascular reflexes: Resting cardiac vagal tone (CVT): was 6.2 units in the linear vagal scale (LVS) which is a normal vagal tone, (Normal range, units in the LVS). Resting heart rate: was 78.0 beats/min, which is a normal heart rate for this level of CVT. Breathing: there was normal breathing at the rate of 14.0 breaths/min. Deep breathing: CVT was 11.5 units and the maximum CVT was 14.4 units in the LVS indicating normal respiratory effect on CVT in the brainstem during deep breathing. Carotid massage: CVT increased by 5.8 units in the LVS showing a normal cardiodepressor effect (normal increase units), blood pressure (BP) changed by mmhg indicating a normal vasodepressor effect (normal drop mmhg). Baroreflex responsiveness in isometric exercise: was 1.85 ms/mmhg but 1.42 ms/mmhg was predicted from the patient s height, indicating a normal central gain of the baroreflex system. Phenylephrine injection test: there was no measurement. Valsalva s ratio: was 2.39 indicating a high Valsalva's ratio (normal range, ). Orthostasis: Cardiac response: showed an abnormally low response in a 30:15 ratio test. BP stability: was good, systolic BP varied by mmhg, normal variation is <25 mmhg. Mean supine arterial BP was 77.5 mmhg indicating normal supine BP (the normal range of supine mean arterial BP, mmhg). Orthostatic hypotension: Postural change in diastolic BP was mmhg. Therefore, no postural hypotension was detected. Sympathetic function in general: There was no test done for postganglionic damage. Control of resistance blood vessels in skeletal muscles during isometric exercise: showed normal muscle sympathetic tone. Cardioaccelerator function in isometric exercise: showed normal cardioaccelerator function. Blood pressure response to Valsalva s manoeuvre: BP change in phase IIe was 4.9 mmhg and in phase III was 9.9 mmhg showing evidence of normal venous return. BP change in phase IIi was 48.9 mmhg indicating raised splanchnic sympathetic tone. Cutaneous sympathetic function: Sudomotor function function Emotional sudomotor function was not assessed not assessed Vasomotor Thermoregulatory vasomotor function was Interpretation: The results show evidence of normal muscle sympathetic tone, normal cardioaccelerator function and raised splanchnic sympathetic tone in the deep targets of the sympathetic division of the autonomic nervous system. There was evidence of normal venous return to the heart. In the cutaneous targets, there was no sudomotor measurement and there was no vasomotor measurement. Postganglionic sympathetic fibres were not assessed for damage. In the parasympathetic division, there was normal vagal tone. Baroreflex system had a normal central gain and there was normal respiratory effect on the CVT in the brainstem during deep breathing. There were normal cardiodepressor and normal vasodepressor effects of the carotid reflex. Of the non-specific tests, there was no postural hypotension, a high Valsalva's ratio and an abnormally low response of the heart to standing upright. HR increased from 91 to 100 bpm and there were runs of Mayer type waves which were associated with her symptoms of icy legs and headache. Clinical Interpretation: Despite the relatively modest HR change with standing the Mayer type waves were convincing and were symptomatic. This is more the picture of dysregulation rather than a major autonomic neuropathy.
28 The tilt can help though..
29 Let s get the treatment started. STEP 3: MAKING A DIFFERENCE TO THE ORTHOSTATIC INTOLERANCE
30
31 Nonpharmacological therapy IT S NOT SEXY BUT NOTHING WORKS IF THEY RE NOT DOING THIS!! Consider proving it with a 24 hour urine collection for Na+ and volume: >2.5L >170mmol Na+ REMEMBER THE DIET
32 IV Saline (1L) Acutely Decreases Orthostatic Tachycardia G Jacob et al. Circulation 1997;96:
33 Exercise Study in POTS - Design Cardiac MRI Maximal Exercise Test Blood Volume Measurement 3 months of exercise training 45-min 60 Upright Tilt Screening 45-min 60 Upright Tilt Blood Volume Measurement Maximal Exercise Test Cardiac MRI
34 Exercise in POTS Focus on Aerobic Activity Some resistance training focused on thighs Exercise training in POTS: Must be Regular Every other day (4/week) 30min/session -> 45-60min/session NO UPRIGHT EXERCISES Rowing machines Recumbent Cycles Swimming o o o o o Increases fitness levels Increases blood volume Cardiac Remodeling Normalizes Sympathetic Activity Decreases Orthostatic Tachycardia Takes 4-5 weeks to start seeing benefits Qi Fu et al., JACC 2010;55:
35 Pharmacological therapy Does it really help? Very helpful; use with care Worth a go, at low dose Very helpful in some; split doses
36 Midodrine Decreases Orthostatic Tachycardia Jacob, G. et al. Circulation 1997;96:
37 Heart Rate (bpm) Change in Heart Rate (bpm) Propranolol 20mg lowers Orthostatic Tachycardia Standing HR Orthostatic Increase in HR 130 Propranolol Placebo 40 Propranolol Placebo P Drug <0.001 P Int < P Drug < Pre 1H 2H 3H 4H Time Post Dose 0 Pre 1H 2H 3H 4H Time Post Dose SR Raj et al. Circulation 2009;120:
38 Symptoms (a.u.) Propranolol Improves Symptoms Symptoms 26 Propranolol Placebo P Int = Pre 2H 4H Time Post Dose SR Raj et al. Circulation 2009;120:
39 Symptoms Score (a.u.) but less is more 0 Propranolol 20mg Propranolol 80mg P =0.041 Wilcoxon SR Raj et al. Circulation 2009;120:
40 Heart Rate (bpm) DDAVP+H 2 O reduces standing HR DDAVP+H2O Placebo P Time = P Drug = P INT = Pre 1H 2H 3H 4H Time Post Dose ST Coffin et al., Heart Rhythm. 2012;9:
41 Heart Rate (bpm) Change in Symptom Score (au) Acetylcholinesterase Inhibition Standing Heart Rate Symptoms 135 Pyridostigmine Placebo 5 Pyridostigmine Placebo P=0.001 P= P<0.001 P< P= Pre 2H 4H -15 Time Post Dose SR Raj et al., Circulation 2005;111:
42 Heart Rate (bpm) Symptoms Score (a.u.) SNRIs make it worse! C Orthostatic Change Symptoms: 0 to 2h 40 Atomoxetine Placebo Atomoxetine Placebo 20 P Int = P = Pre 1H 2H 3H 4H Time Post Dose -6-8 SR Raj et al., AAS Presentation (2010)
43 So what do I do? Midodrine first (2.5 10mg TDS) Ivabradine second (2.5 5mg BD TDS) Then think about something else Beta blockers if high functioning (low dose) Fludrocortisone (up to 200 mcg daily) Slow sodium ( mg TDS) Anti-histamines (Pyridostigmine etc - I don t prescribe drugs I can t spell.)
44 But what about all of the other stuff? STEP 4: ALL OF THE OTHER SYMPTOMS
45 Dysfunctional breathing respiratory physio
46 Gastroenterology Often complain of: Nausea / vomiting Bloating Pain Constipation / Diarrhoea Find a helpful gastroenterologist and look for gastroparesis, SIBO, colonic dysmotility Treat whatever you can! Medications, diet (various)
47 Urology Often complain of: Weak bladders Frequency, urgency, incontinence Recurrent UTI, pain Find a helpful urologist and look for a large, insensate bladder Timed and double voiding Antibiotics Catheters etc
48 Neurology / Sleep / Audiovestibular medicine Lots of headaches esp. migraines Migraine variant balance disorder Psychophysiological insomnia Reassurance needed: Neuropathic symptoms. MS. Chiari.
49 Rheumatology Hypermobility is very common Pain, clicky joints, stretch marks, easy bruising PoTS vs hypermobility Do we need to exclude an inflammatory arthritis? Find a helpful rheumatologist Try to refer to the hypermobility experts for pain management, specialist physio etc
50 Mast cell activation syndrome
51 Mast cell activation syndrome Consider if allergies, rashes, pain Testing.. Try to find an expert (and let me know when you do ) Empirical treatment (cetirizine, ranitidine, Na+ cromoglicate etc)
52 Other stuff that comes up. STEP 4: DAY TO DAY MANAGEMENT
53 Pregnancy implications No clear suggestion of adverse consequences Symptoms may well get worse reassure Fludrocortisone and beta-blockade are OK Don t do anything differently on our account Standard analgesia and delivery in labour
54 Anaesthetic implications No adverse consequences Inform the anaesthetist that it is not a heart problem but is about managing the underfilled Lots of IV fluid TEDs Slow mobilisation Don t panic with the tachycardia
55 Other stuff LYME DISEASE SAY NOTHING WE WERE NEVER HERE I HAVE NEVER MET ANY OF YOU
56 What we really need is some sort of practical document. Perhaps with a UK focus.
57 To conclude: Recognise the patient by the symptoms more than the HR change Exclude other conditions Do the simple stuff extremely well Consider medications Treat the associated features Be honest and caring because we don t have all of the answers!
58 AND ON THAT BOMB- SHELL... THANK YOU FOR YOUR ATTENTION
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