Multi-Faceted Nature of Postural Tachycardia Syndrome (POTS)

Satish R Raj MD MSCI FACC FHRS Libin Cardiovascular Institute of Alberta University of Calgary Autonomic Dysfunction Center Vanderbilt University School of Medicine Heart Rhythm Congress (Birmingham, UK) October 1 2017

Postural Tachycardia Syndrome - Common Criteria

n  Orthostatic tachycardia ≥30 bpm q  ≥40 bpm required if <18 years

n  No consistent orthostatic hypotension q  ΔBP ≥20/10 mmHg

n  Orthostatic Symptoms q  Worse upright; better recumbent q  Some due to sympathetic activation?

n  Chronic symptoms ≥6 months

Phillip Low MD Mayo Clinic

POTS - Common Symptoms

n  Rapid Heartbeat n  Chest Discomfort n  Short of Breath n  Lightheaded

n  Exercise Intolerance

n  Mental Clouding n  Headache n  Nausea n  Tremulousness

n  Fatigue n  Sleep Complaints

Cardiac Non-Cardiac

POTS Control Heart Rate (bpm)

Blood Pressure (mmHg)

Tilt Angle (deg)

200

200 0

50

60

0

Tilt Testing

SR Raj, Indian Pacing Electrophysiol J. 2006;6:84-99

POTS: Feel awful when upright

0 10 20 30

05

101520253035

POTSControl

Tilt (60°) Time

Sym

ptom

s S

core

(au

)

SR Raj & RS Sheldon, Tilt Table Testing in S Saksena & AJ Camm Electrophysiological Disorders of the Heart 2nd Ed. (2011)

POTS – Who is affected?

n  Prevalence ½-3 million in USA n  Female (~80-85%) n  Typically aged 13-50 years

q  “women of child-bearing age”

n  Significant functional disability

Is POTS … a Psychiatric Disorder?

Vidya Raj

Is POTS … a Psychiatric Disorder?

n  Patients with POTS did not have an increased prevalence of major depression or anxiety disorders, including panic disorder, compared to the general population.

V Raj et al. , J Neurol Neurosurg Psychiatry 2009; 80: 339-344

CAARS DSM-IV Inattention Scores

Normals POTS ADHD Background0

1020304050607080

ANOVA P<0.001N vs. P: P=0.001N vs. A: P<0.001P vs. A: P=0.001P vs. B: P=0.008

T Sc

ore

V Raj et al. , J Neurol Neurosurg Psychiatry 2009; 80: 339-344

Anxiety (ASI) Scores

n  Total score 0-64 n  Population 19.1±9.1 n  Panic disorder 36.4±10.3

n  POTS vs. pop: P=0.07 n  ADHD vs. pop: P=0.001

Normals POTS ADHD Panic Population0

10

20

30

40ANOVA P<0.001N vs. P: P=0.001N vs. A: P=0.031P vs. A: P=0.504

ASI

Sco

re

V Raj et al. , J Neurol Neurosurg Psychiatry 2009; 80: 339-344

S Masuki et al., J Appl Physiol 2007; 102: 896-903

Is the HR Increase in POTS due to Blood Pooling in Legs or Anxiety?

Time (min)

Quality of Life in POTS

Kanika Bagai

Health Related Quality of Life (SF-36) – Chronic Illnesses

Physical Mental0

25

50

75

100 Back PainESRD

SF36 Sub-Scores

Scor

eDialysis

Health Related Quality of Life (SF-36) – Chronic Illnesses

Physical Mental0

25

50

75

100

POTSBack PainESRD

SF36 Sub-Scores

Scor

e

Modified from K Bagai et al., J Clin Sleep Med 2011

Dialysis

WHY do they have POTS?

… ‘final common pathway’ of hundreds of genetic and acquired autonomic and cardiovascular entities

- David Robertson

David Robertson

POTS - Pathophysiologies

n  Mast Cell Activation n  Partial Autonomic Neuropathy n  Leg Blood Flow Abnormalities n  Hypovolemia n  Hyperadrenergic

q  Increased Release q  Decreased Clearance

n  Antibodies are Evil…

A Norepinephrine Synapse

NET

Slide courtesy of Alex Nackenoff

(Vanderbilt)

Norepinephrine Synapse – NET blocked

NET

Slide courtesy of Alex Nackenoff

(Vanderbilt)

SNS Tone

POTS – What to Do?

Investigation & Treatment

POTS: Treatment Approaches n  Exercise n  Increase Blood Volume

q  Oral Water q  Increase Salt (diet vs. tablets) q  Fludrocortisone q  Octreotide q  IV Saline q  Acute DDAVP-H2O

n  Hemodynamic Agents q  Midodrine q  Propranolol q  Pyridostigmine q  Ivabradine (emerging)

n  Behavioral Therapies

Exercise in POTS - Benefits

n  Short-term exercise training in POTS q  Increases fitness levels q  Increases blood volume q  Cardiac Remodeling q  Normalizes Sympathetic Activity

q  Decreases Orthostatic Tachycardia q  Improves Quality of Life

Qi Fu et al., JACC 2010;55:2858-68

Exercise in POTS – How To? n  Focus on Aerobic Activity

q  Some resistance training focused on thighs n  Must be Regular

q  Every other day (4/week) n  30min/session -> 45-60min/session n  NO UPRIGHT EXERCISES

q  Rowing machines q  Recumbent Cycles q  Swimming

n  Takes 4-5 weeks to start seeing benefits Qi Fu et al., JACC 2010;55:2858-68

POTS: Treatment Approaches n  Exercise n  Increase Blood Volume

q  Oral Water q  Increase Salt (diet vs. tablets) – data coming q  Fludrocortisone q  Octreotide q  IV Saline q  Acute DDAVP-H2O

n  Hemodynamic Agents q  Midodrine q  Propranolol q  Pyridostigmine q  Ivabradine (emerging)

n  Behavioral Therapies n  Treat Co-Morbidities

G Jacob et al. Circulation 1997;96:575-580

IV Saline (1L) Acutely Decreases Orthostatic Tachycardia…a LOT!!

DDAVP+H2O reduces standing HR

Pre 1H 2H 3H 4H859095

100105110115120125 DDAVP+H2O Placebo

PTime=0.001

PDrug=0.001

PINT =0.001

Time Post Dose

Hea

rt R

ate

(bpm

)

ST Coffin et al., Heart Rhythm. 2012;9:1484-90

POTS: Treatment Approaches n  Exercise n  Increase Blood Volume

q  Oral Water q  Increase Salt (diet vs. tablets) q  Fludrocortisone q  Octreotide q  IV Saline q  Acute DDAVP-H2O

n  Hemodynamic Agents q  Midodrine q  Propranolol q  Pyridostigmine q  Ivabradine (emerging)

n  Behavioral Therapies n  Treat Co-Morbidities

Jacob, G. et al. Circulation 1997;96:575-580

Midodrine Decreases Orthostatic Tachycardia…a little bit.

Pre 1H 2H 3H 4H70

80

90

100

110

120

130 Propranolol Placebo

PDrug <0.001PInt <0.001

Time Post Dose

Hea

rt R

ate

(bpm

)Propranolol 20mg lowers Orthostatic Tachycardia

Pre 1H 2H 3H 4H0

10

20

30

40 Propranolol Placebo

PDrug <0.001

Time Post Dose

Cha

nge

in H

eart

Rat

e (b

pm)

Standing HR Orthostatic Increase in HR

SR Raj et al. Circulation 2009;120:725-734

Symptoms

Pre 2H 4H12

14

16

18

20

22

24

26 Propranolol Placebo

PInt =0.04

Time Post Dose

Sym

ptom

s (a

.u.)

Propranolol Improves Symptoms…

SR Raj et al. Circulation 2009;120:725-734

Propranolol 20mg Propranolol 80mg

-15

-10

-5

0

P =0.041Wilcoxon

Δ S

ympt

oms

Scor

e (a

.u.)

…but Less is More

SR Raj et al. Circulation 2009;120:725-734

Norepinephrine Transporter Inhibition (e.g. SNRI drugs)

Standing

Pre 1H 2H 3H 4H90

100

110

120

130 Atomoxetine Placebo

PInt <0.001

A

Time Post Dose

Hea

rt R

ate

(bpm

)

EA Green et al., JAHA 2013;2:e000395

Seated

Pre 1H 2H 3H 4H70

75

80

85

90

95

100

PInt =0.029

B

PlaceboAtomoxetine

Time Post Dose

Hea

rt R

ate

(bpm

)

Norepinephrine Transporter Inhibition (e.g. SNRI drugs)

Orthostatic Change

Pre 1H 2H 3H 4H15

20

25

30

35

40 Atomoxetine Placebo

PInt =0.001

C

Time Post Dose

Δ H

eart

Rat

e (b

pm)

Symptoms: 0 to 2h

Atomoxetine Placebo

-8

-6

-4

-2

0

2

4

6

P =0.028Δ

Sym

ptom

s Sc

ore

(a.u

.)

EA Green et al., JAHA 2013;2:e000395

POTS: Treatment Approaches n  Exercise n  Increase Blood Volume

q  Oral Water q  Increase Salt (diet vs. tablets) q  Fludrocortisone q  Octreotide q  IV Saline q  Acute DDAVP-H2O

n  Hemodynamic Agents q  Midodrine q  Propranolol q  Pyridostigmine q  Ivabradine (emerging)

n  Behavioral Therapies n  Treat Co-Morbidities

POTS – Take Home Messages n  POTS

q  chronic disorder associated with significant disability

q  Syndrome…not one disease n  Multiple pathophysiologies

n  Treatment q  Exercise q  Volume expansion q  Heart rate control q  Manage the “living with a chronic illness”

Questions?