Page 1
CP1278619-0
Blood Pressure Regulation & the Postural Orthostatic Tachycardia
Syndrome (POTS) Deconditioning, Pseudodeconditioning;
Both or Neither?
Blood Pressure Regulation & the Postural Orthostatic Tachycardia
Syndrome (POTS) Deconditioning, Pseudodeconditioning;
Both or Neither?
Michael J. Joyner, MDMayo Clinic
Rochester, MN
Michael J. Joyner, MDMayo Clinic
Rochester, MN
Page 2
CP1278619-1
Mayo ClinicMayo Clinic
Mayo ClinicScottsdale
Mayo ClinicJacksonville
Mayo ClinicRochester
Page 3
CP1278619-2
Mayo ClinicMayo Clinic• Emerged in late
1800’s• Practice, Research,
Education• Med school • Training programs• ~ 53,000 employees• ~ 500 mil$ research
budget
The Needs of the The Needs of the Patient Come First!Patient Come First!
Page 4
CP1278619-3
MAP=CO x TPRMAP=CO x TPR
Feedback control by BaroreflexesFeedback control by Baroreflexes
Page 5
CP1278619-4
Arterial Pressure Regulation by Baroreflexes
Arterial Pressure Regulation by Baroreflexes
Peripheralvessels
NE
Heart
Cardiovascularcenter
Baroreceptors
NE
+
+ACH-
Page 6
CP1278619-5
Integrated Baroreflex ResponseIntegrated Baroreflex Response
Page 7
CP1278619-6
Baroreflex CurveBaroreflex Curve
www.rrk-berlin.de/fvkweb/nephrology/por1.html
Page 8
CP1278619-7
Overview of TalkOverview of Talk
• What happens when we stand up?
• Definition of POTS
• Is POTS “Psychogenic”?
• A baroreflex “problem”?
• POTS & deconditioning
the same or different?
• The physiological evidence in “related syndromes”
• Ideas about how this might all fit together
• What should we do next?
• What happens when we stand up?
• Definition of POTS
• Is POTS “Psychogenic”?
• A baroreflex “problem”?
• POTS & deconditioning
the same or different?
• The physiological evidence in “related syndromes”
• Ideas about how this might all fit together
• What should we do next?
Page 9
CP1278619-8
What Happens When You Stand Up?What Happens When You Stand Up?
Page 10
CP1278619-9
Definition of POTSDefinition of POTS
• Emerged as a recognized syndrome in the 1990s
• Baseline sinus rhythm with no evidence of cardiac disease
• Sustained HR ↑
30 beats/min with 10 min of tilting
• Light-headedness, weakness, palpitations, blurred vision, breathing difficulties, nausea, or headache developing on standing or tilting and resolving with recumbency.
• No sustained or marked orthostatic hypotension
• No other explanation
• Emerged as a recognized syndrome in the 1990s
• Baseline sinus rhythm with no evidence of cardiac disease
• Sustained HR ↑
30 beats/min with 10 min of tilting
• Light-headedness, weakness, palpitations, blurred vision, breathing difficulties, nausea, or headache developing on standing or tilting and resolving with recumbency.
• No sustained or marked orthostatic hypotension
• No other explanation
Page 11
CP1278619-10
David Streeten, MB, D PhilDavid Streeten, MB, D Phil• Native of Bloemfontein, South
Africa • Medical degree 1946, the
University of the Witwatersrand in Johannesburg
• Doctorate in pharmacology from Oxford in 1951
• The main concern of his research was hypertension and orthostatic intolerance
• AAS President 1996
• Native of Bloemfontein, South Africa
• Medical degree 1946, the University of the Witwatersrand in Johannesburg
• Doctorate in pharmacology from Oxford in 1951
• The main concern of his research was hypertension and orthostatic intolerance
• AAS President 1996
http://www.upstate.edu/library/history/portraitbiogs.shtml
Page 12
CP1278619-11
Stand up
Postural OrthostaticTachycardia Syndrome (POTS)
Postural OrthostaticTachycardia Syndrome (POTS)
• Dramatic increase in HR on standing
• Absence of orthostatic hypotension
• Dramatic increase in HR on standing
• Absence of orthostatic hypotension
-120 -60 0 60 120 -120 -60 0 60 120
40
80
120
160
60
80
100
120
140
POTS
AP(mmHg)
HR(beats/min)
Time (sec)
Stand up
Control
SAP
DAP
Time (sec)
Page 13
CP1278619-12
Is POTS “Psychogenic”?Is POTS “Psychogenic”?
• Unusual presentations• No obvious “cause”
for the symptoms
• Some cross talk with CFS and/or Fibromyalgia etc
• Multiple encounters with the “Medical Industrial Complex”
• Psych drugs by the time they get to an “expert”
• Unusual presentations• No obvious “cause”
for the symptoms
• Some cross talk with CFS and/or Fibromyalgia etc
• Multiple encounters with the “Medical Industrial Complex”
• Psych drugs by the time they get to an “expert”
Page 14
CP1278619-13
Hypothesis: Anxiety Plays a Key Role in the HR Responses in POTS?
Hypothesis: Anxiety Plays a Key Role in the HR Responses in POTS?
POTS patients• Increased HR during
orthostatic stress is due to anxiety OR
• Increased HR during orthostatic stress is a baroreflex mediated response to inadequate α-adrenergic vasoconstriction
POTS patients• Increased HR during
orthostatic stress is due to anxiety OR
• Increased HR during orthostatic stress is a baroreflex mediated response to inadequate α-adrenergic vasoconstriction
Page 15
CP1278619-14
Will HR Rise During “Sham”
Venous Pooling?
Will HR Rise During “Sham”
Venous Pooling?
• “Sham”
LBNP (Halliwill
et al JAP, 1998)
• MAST pressure = 5 mmHg (relative to outside the LBNP box)
• Prevents venous pooling
• No sensation of severe pressure on legs
• Subject still feels “sucked”
into box
• “Sham”
LBNP (Halliwill
et al JAP, 1998)
• MAST pressure = 5 mmHg (relative to outside the LBNP box)
• Prevents venous pooling
• No sensation of severe pressure on legs
• Subject still feels “sucked”
into box
Page 16
CP1278619-15
MethodsMethods
Measurements• Arterial pressure: Finapres• Heart rate: ECG• Forearm blood flow: plethysmography
Measurements• Arterial pressure: Finapres• Heart rate: ECG• Forearm blood flow: plethysmography
Lower Body Negative Pressure (LBNP) withand without Medical Anti-Shock Trouser inflation
Lower Body Negative Pressure (LBNP) withand without Medical Anti-Shock Trouser inflation
Page 17
CP1278619-16
Individual RecordsIndividual Records
AP(mmHg)
HR(beats/min)
FBF(mL/100 mL/
min)
LBNP box or trouserpressure(mmHg)
-3 0 3 6 9 12
Trouser InflationTrouser InflationTrouser Inflation
12
3
No InflationNo Inflation
Time (min)
50100150
-50
10
50
100
150
LBNP box
-3 0 3 6 9 12
ControlControl POTSPOTS
Page 18
CP1278619-17
Subject CharacteristicsSubject Characteristics
• N = 14* patients F/M = 12/229 ±
2 yrs, 68 ±
2 kg, 170 ±
2 cm
• Drugs off for 5 ½
lives*• N = 10 healthy controls
• N = 14* patients F/M = 12/229 ±
2 yrs, 68 ±
2 kg, 170 ±
2 cm
• Drugs off for 5 ½
lives*• N = 10 healthy controls
Page 19
CP1278619-18
Group Responses to Real and Sham LBNPGroup Responses to Real and Sham LBNPControlControl POTSPOTS
Standard LBNPStandard LBNP
LBNP boxMAP
(mmHg)
HR(beats/min)
-3 0 3 6 9 12Time (min)
MAST InflationMAST Inflation Vacuum SoundVacuum Sound
50100150
0-3 0 3 6 9 12 -3 0 3 6 9 12
80
120
40
Time (min) Time (min)
-10 -20 -30 -40 mmHgLBNP
-10 -20 -30 -40 mmHg -10 -20 -30 -40 mmHLBNP LBNP
baseline -10 -20 -30 -40
50100150
0
80120
40
LBNP (mmHg)
MAP(mmHg)
HR(beats/min) 0
baseline -10 -20 -30 -40LBNP (mmHg)
baseline -10 -20 -30 -40LBNP (mmHg)
Page 20
CP1278619-19
Mental StressRationale
Mental StressRationale
Stroop
colored word test
• Increased HR during orthostatic stress is due to anxiety?
• Test HR response
to non-orthostatic anxiety provoking stress
• Increased HR during orthostatic stress is due to anxiety?
• Test HR response to non-orthostatic anxiety provoking stress
pink red white
Page 21
CP1278619-20
Responses to Mental StressResponses to Mental Stress
20
40
60
80
100
MAP(mmHg)
HR(beats/min)
40
60
80
100
70
80
90
110
100
-3.5 -1 0 1 2 360
70
80
90
100
Time (min) Mental stress (min)baseline 1 2 3
Mental stressInst
ControlControl POTSPOTS
Page 22
CP1278619-21
Somatic HypervigilanceSomatic Hypervigilance
Score
ControlControl POTSPOTS
0
10
15
20
25
5
0
10
15
20
25
5
* * *
0.0
1.0
1.5
2.0
0.5
Anxiety sensitivityindex
Body vigilancescale
Catastrophizingscale
Page 23
CP1278619-22
Physiology “Wins”Physiology “Wins”• HR response only happens with venous
pooling • HR response to mental stress “normal”
in
spite of increased hypervigilance • Why?
DenervationHypovolemiaCNS
• Or, is there a deconditioning element and if so how big?
• HR response only happens with venous pooling
• HR response to mental stress “normal”
in spite of increased hypervigilance
• Why?DenervationHypovolemiaCNS
• Or, is there a deconditioning element and if so how big?
Page 24
CP1278619-23
Is POTS a Baroreflex “Problem”?Is POTS a Baroreflex “Problem”?
• Same subjects
• Overnight hydration
• Upright and supine exerciseSupine exercise and cardiac filling
• Bolus doses of PE during exercise to raise BP and evoke reflex changes in HR
• Same subjects
• Overnight hydration
• Upright and supine exerciseSupine exercise and cardiac filling
• Bolus doses of PE during exercise to raise BP and evoke reflex changes in HR
Page 25
CP1278619-24
Same exercise protocol was repeated (no stand test)Same exercise protocol was repeated (no stand test)
SupineSupine
UprightUpright
Exercise ProtocolExercise Protocol
Stand test= PE infusion (μg/kg)
2550
75 W
Exercise
0 7 14 21 min
70 min break70 min break
1.5
2.02.5
3.0
AP & HRCO
Page 26
CP1278619-25
HR(beats/min)
AP(mmHg)
PP(mmHg)
50
90
Rest 25 50 75Workload (watts)
SupineSupine UprightUpright
SAP
MAP
DAP
80
120
160
*
**
80
120
160
Rest 25 50 75Workload (watts)
70
ControlControlPOTSPOTS
Hemodynamic Responses to ExerciseHemodynamic Responses to Exercise
Page 27
CP1278619-26
CO(L/min)
SV(mL)
TPR(mmHg/L/min)
Rest 25 50 75Workload (watts)
SupineSupine UprightUpright
6
8
12
80
100
Rest 25 50 75Workload (watts)
ControlControlPOTSPOTS
*
10
120
60
8
12
16
SV Responses in POTSSV Responses in POTS
Page 28
CP1278619-27
0
200
0
200
AP(mmHg)
AP(mmHg)
1 sec
Upright Exercise at 75WUpright Exercise at 75W
Control
POTS
Page 29
CP1278619-28
Frequency(%)
5
15
20
0
10
-40 -20 0 20 40
5
15
20
0
10
-40 -20 0 20 40
Distribution of PP (mmHg)
Control POTS
BP More Variable in POTSBP More Variable in POTS
Page 30
CP1278619-29
HR(beats/min)
HR(beats/min)
SAP (mmHg)SAP (mmHg)
ControlControl POTSPOTS
20
60
100
140
100 140 180 220
50W
75W
25W
Rest60
100
140
180
100 140 180 220
50W
75W
25W
Rest
Baroreflex Control of HRBaroreflex Control of HR
Page 31
CP1278619-30
-1.8
-1.2
-0.6
0
Baroflexsensitivity(beats/min/
mmHg)
Baroflexsensitivity(beats/min/
mmHg)
4040 8080 120120 160160
SupineSupine UprightUpright
Heart RateHeart Rate
ControlControl POTSPOTS
4040 8080 120120 160160
Baroreflex Control: Corrected for HRBaroreflex Control: Corrected for HR
Page 32
CP1278619-31
Δ
HR,upright —
supine
(beats/min)
Δ
HR,upright —
supine(beats/min)
RestRest 50W50W
Δ
SV, upright —
supine (mL)Δ
SV, upright —
supine (mL)
ControlControl POTSPOTS
-10
0
10
20
30
40
50
-80 -60 -40 -20 00
10
20
30
40
50
-80 -60 -40 -20 0
R2= 0.35 R2= 0.60
Change in SV vs
HRChange in SV vs
HR
Page 33
CP1278619-32
Exercise Studies Physiology Wins Again
Exercise Studies Physiology Wins Again
• Baroreflex control of HR is not fundamentally different
• Similar responses while supine
• Smaller SV while upright
• Responses are similar when SV is considered: cardiopulmonary interactions
• Small SV is a “hallmark”
of deconditioning
• Baroreflex control of HR is not fundamentally different
• Similar responses while supine
• Smaller SV while upright
• Responses are similar when SV is considered: cardiopulmonary interactions
• Small SV is a “hallmark”
of deconditioning
Page 34
CP1278619-33
Spaceflight & Regulation of MSNA What Does It Tell Us About POTS?
Spaceflight & Regulation of MSNA What Does It Tell Us About POTS?
• Cardiac atrophy
• Smaller stroke volume
• Reduced blood volume
• Can be simulated by bed-rest deconditioning
• Cardiac atrophy
• Smaller stroke volume
• Reduced blood volume
• Can be simulated by bed-rest deconditioning
Page 35
CP1278619-34
40
50
60
70
80
90
100
POTS Like Responses to Tilt After Spaceflight N=5
POTS Like Responses to Tilt After Spaceflight N=5
Levine et al J Phys 2002
Heart rate(beats/min-1)
Supine Tilt5
Tilt10
Supine Tilt5
Tilt10
Supine Tilt5
Tilt10
~72 days ~23 daysLanding dayLanding dayPreflightPreflight
* *
Page 36
CP1278619-35
Levine et al J Phys 2002
MSNA Responses After SpaceflightMSNA Responses After Spaceflight
Musclesympathetic
nerveactivity
Supine
60°
upright tilt
Landing dayLanding dayPreflightPreflight
TimeAstronaut 3
0 10 20 30 40 0 10 20 30 40
Page 37
CP1278619-36
0
20
40
60
25 50 75 100 125 150
Ventricular Volume & MSNAVentricular Volume & MSNA
Levine et al J Phys 2002
Musclesympathetic
nerveactivity
(bursts/min-1)
PreflightLanding dayPreflightLanding day
Stroke volume (mL)
*
*
Page 38
CP1278619-37
ΔH
R (b
pm)
ΔH
R (b
pm)
MSNA Responses to 45* HUT in POTS n=9MSNA Responses to 45* HUT in POTS n=9
Swift et al 2005
BaselineBaseline
30 degrees30 degrees
45 degrees45 degrees
Control 20 sControl 20 s POTS 20 sPOTS 20 s
MSN
A (%
of b
asel
ine)
MSN
A (%
of b
asel
ine)
ΔD
BP
(mm
Hg)
ΔD
BP
(mm
Hg)
0
100
200
300
0
10
20
30
0
5
10
15
20
25*P=0.03
P=0.10
*P=0.02
P=0.03P=0.66
P=0.60
45°30° 45°30° 45°30°
ControlControl POTSPOTS
Page 39
CP1278619-38
010203040506070
010203040506070
MSNA Responses to Nitroprusside
in POTS
MSNA Responses to Nitroprusside
in POTS
Bonyhay
and Freeman 2004
Burstfrequency
(bursts/min)
Burstfrequency
(bursts/min)
0102030405060
NPBaseline
POTSPOTS ControlControlΔ
=20.4±7.5Δ
=20.4±7.5 Δ
=12.1±4.1Δ
=12.1±4.1
Δ
=21.8±8.4Δ
=21.8±8.4 Δ
=14.4±5.2Δ
=14.4±5.20
102030405060
Burstincidence(bursts/
100 heart beats)
Burstincidence(bursts/
100 heart beats)
NPBaseline
Page 40
CP1278619-39
Further Evidence from the Dallas Group
Further Evidence from the Dallas Group
Page 41
CP1278619-40
0 20 40 60 80 100 120 1400
10
20
30
40
50
60
70
80
0 20 40 60 80 100 120 140
r = 0.87 ±
0.15r = 0.96 ±
0.05
MSNA and SV Relationships in POTSMSNA and SV Relationships in POTS
MSNA(bursts/min)
ControlsControlsPOTSPOTS
Stroke volume (mL)
Page 42
CP1278619-41
0 20 40 60 80
Linear Correlation Between Total Peripheral Resistance and MSNA During Orthostasis
in POTS Patients And Controls
Linear Correlation Between Total Peripheral Resistance and MSNA During Orthostasis
in POTS Patients And Controls
500
1000
1500
2000
2500
3000
3500
4000
0 20 40 60 80
r = 0.81 ±
0.19r = 0.89 ±
0.09
Totalperipheralresistance(dyne·sec·
cm-5)
ControlsControlsPOTSPOTS
Stroke volume (mL)
Page 43
CP1278619-42
SV and HR in POTSSV and HR in POTS
POTSControls
Mean±SD
Supine
30°
tilt
60°
tilt
60°
tilt5 min
10 minSupine
30°
tilt
60°
tilt
60°
tilt5 min
10 minSupine
30°
tilt
60°
tilt
60°
tilt5 min
10 minSupine
30°
tilt
60°
tilt
60°
tilt5 min
10 min
0
20
40
60
80
100
120
140
160
0
20
40
60
80
100
120
Heart rate (beats/min)Heart rate (beats/min)Stroke volume (mL)Stroke volume (mL)Group P=0.005Protocol P<0.001Group X Protocol P=0.015
Group P<0.001Protocol P<0.001Group X Protocol P=0.847
Page 44
CP1278619-43
LV Mass Increased After 3-Month of Exercise Training in POTS
LV Mass Increased After 3-Month of Exercise Training in POTS
Before
After
Healthy training
training
womenBefore
After
Healthy training
training
women
Left ventricular mass (g)
Left ventricular mass (g)
0
20
40
60
80
100
120
140 12
+40%
Page 45
CP1278619-44
50
60
70
80
90
100
110
120
50
60
70
80
90
100
110
120
Heart Rate Responses During 10-min Standing Before and After Exercise Training
Heart Rate Responses During 10-min Standing Before and After Exercise Training
1
Heart rate
(bpm)
2
+37+36
+7
+22
Supine Stand 10 min
Supine Stand 10 min
Page 46
CP1278619-45
POTS Interim Summary
POTS Interim Summary
• Physiological data looks like deconditioning
• Some evidence that training “works”
• Psych data suggests hypervigilance
• Is there a triggering “event”
followed by prolonged inactivity
• Heterogeneous syndrome, what this might not explain
• Physiological data looks like deconditioning
• Some evidence that training “works”
• Psych data suggests hypervigilance
• Is there a triggering “event”
followed by prolonged inactivity
• Heterogeneous syndrome, what this might not explain
Page 47
CP1278619-46
The Physiological Evidence & “Related Syndromes”
The Physiological Evidence & “Related Syndromes”
Is There a Similar Story for CFS and Fibromyaligia?
Is There a Similar Story for CFS and Fibromyaligia?
Page 48
CP1278619-47
HR Responses Normal During Exercise in CFS n=31
HR Responses Normal During Exercise in CFS n=31
Wallman et al 2004
Heart rate (bmp)
Heart rate (bmp)
CFSControls
WattsWatts
60
80
100
120
140
160
25 50 75 100 125 150 175
Page 49
CP1278619-48
Oxygen Uptake Responses Normal During Exercise in CFS
Oxygen Uptake Responses Normal During Exercise in CFS
Wallman et al 2004
Oxygen uptake
(mL·kg·min)
Oxygen uptake
(mL·kg·min)
CFSControls
WattsWatts
0
5
10
15
20
25
30
25 50 75 100 125 150 175
Page 50
CP1278619-49
Perception of Effort During Exercise Altered
in CFS
Perception of Effort During Exercise Altered
in CFS
Wallman et al 2004
RPERPE
CFSControls
WattsWatts
6
8
10
12
14
16
18
20
25 50 75 100 125 150 175
Page 51
CP1278619-50
Muscle Metabolism is Normal in CFS NMR Measures of ADP n=19
Muscle Metabolism is Normal in CFS NMR Measures of ADP n=19
• Quad exercise
• Cuffs to limit blood flow
• NMR measures of metabolism
• Doppler measures of flow
• Quad exercise
• Cuffs to limit blood flow
• NMR measures of metabolism
• Doppler measures of flow
McCully et al J Appl Physiol 2003
End exercise
ADP (uM)
End exercise
ADP (uM)
Cuff pressure during recovery (mmHg)Cuff pressure during recovery (mmHg)
Muscle Vmax
(mL/min)
Muscle Vmax
(mL/min)
CFS Controls
0102030405060708090
0 50 60 70 80 90 0
0102030405060708090
0 50 60 70 80 90 0
Page 52
CP1278619-51
0100200300400500600700800900
1000
-60 0 60 120 180 240 300 360 420
Muscle Blood Flow Not Grossly Abnormal In CFS
Muscle Blood Flow Not Grossly Abnormal In CFS
McCully et al J Appl Physiol 2003
Blood flow
(mL/min)
Blood flow
(mL/min)
SecondsSeconds
Free Flow60 mmHg90 mmHg
A B
Page 53
CP1278619-52
Does CFS Respond to Training?Does CFS Respond to Training?82 volunteers82 volunteers
68 subject randomized68 subject randomized
14 excluded for14 excluded fornot meeting criterianot meeting criteria
Exercise groupExercise group(n=34)(n=34)
Relaxation/flexibilityRelaxation/flexibilitygroup (n=34)group (n=34)
4 weeks4 weeks’’
baselinebaselinetestingtesting
2 exercise2 exercisesubjects withdrewsubjects withdrew
2 relaxation/flexibility2 relaxation/flexibilitysubjects withdrewsubjects withdrew
12 weeks12 weeks’’
graded exercisegraded exercisewith pacing (n=32)with pacing (n=32)
12 weeks12 weeks’’
relaxation/flexibility relaxation/flexibility (n=29)(n=29)
4 weeks4 weeks’’
postpost--intervention testingintervention testing
Page 54
CP1278619-53
1.0
1.5
2.0
0.100.15
0.200.25
1000015000200002500030000
Baseline Post-intervention
CFS Responds to TrainingCFS Responds to Training
Wallman et al 2004
Self-rated clinical global impression change scores after
completing treatment
Self-rated clinical global impression change scores after
completing treatmentGraded
Relaxationexercise
flexibilityn=32
n=29Rating
No. (%)
No. (%)
Very much better
5 (16)
2 (7)Much better
14 (44)
10 (34%)A little better
10 (31%)
10 (34%)No change
3 (9%)
6 (21%)A little worse
0
1 (3%)Much worse
0
0Very much worse
0
0
Graded
Relaxationexercise
flexibilityn=32
n=29Rating
No. (%)
No. (%)
Very much better
5 (16)
2 (7)Much better
14 (44)
10 (34%)A little better
10 (31%)
10 (34%)No change
3 (9%)
6 (21%)A little worse
0
1 (3%)Much worse
0
0Very much worse
0
0
Values are number (%) of people choosing each rating
Changes (95% CIs) in selected physicological
variables
Changes (95% CIs) in selected physicological
variables
Pow
erou
tput
(W/k
g)
RPE
/po
wer
Act
ivity
leve
l(k
J/w
eek)
Relaxation/flexibility group (n=29)Relaxation/flexibility group (n=29)Graded exercise group (n=32)Graded exercise group (n=32)
Page 55
CP1278619-54
CFS Interim Summary
CFS Interim Summary
• Physiological data looks “normal”
• Some evidence that training “works”
• Psych data suggests perception of effort is altered
• Is there a triggering “event”
followed by prolonged inactivity
• Heterogeneous syndrome, what this might not explain
• Physiological data looks “normal”
• Some evidence that training “works”
• Psych data suggests perception of effort is altered
• Is there a triggering “event”
followed by prolonged inactivity
• Heterogeneous syndrome, what this might not explain
Page 56
CP1278619-55
Same Story For FibromyaligiaSame Story For Fibromyaligia
Richards and Scott 2002
220 offered screening
196 screened• Not fibromyalgia (n=29)• Too mild (n=9)• Fibromyalgia but ineligible (n=22)
Randomized (n=136)
Exercise group (n=69) Relaxation group (n=67)
AdherenceNo of classes attended:
0 111-8
169-16
2317-24
19
AdherenceNo of classes attended:
0 111-8
169-16
2317-24
19
Page 57
CP1278619-56
Exercise Improves Symptoms in Fibromyalgia
Exercise Improves Symptoms in Fibromyalgia
Mean scores (95% CI) Mean change between groups
(95% CI)TimeRelaxation group n=67
Exercise group n=69 P
Baseline 14.0 (13.4-14.6) 14.4 (13.7-15.1) NA NA
3 months 11.8 (10.9-2.8) 10.6 (9.2-12.0) 1.1 (-0.47-2.6) 0.21
6 months 11.2 (10.0-12.3) 10.2 (8.9-11.5) 1.4 (-0.1-2.8) 0.07
1 year 12.0 (10.8-13.0) 10.2 (8.8-11.6) 2.2 (0.63-3.7) 0.019
Page 58
CP1278619-57
Summary Thoughts How This Might All Fit Together
Summary Thoughts How This Might All Fit Together
• POTS, CFS and Fibromyalgia defy a clear physiological explanation
• Triggering event
• Perceptual “mismatch”?
• Chronic deconditioning as a sustaining factor?
• “Medicalization”
as a sustaining factor?
• POTS, CFS and Fibromyalgia defy a clear physiological explanation
• Triggering event
• Perceptual “mismatch”?
• Chronic deconditioning as a sustaining factor?
• “Medicalization”
as a sustaining factor?
Page 59
CP1278619-58
What To Do Next?What To Do Next?
• Exercise based rehab
• Demedicalize
• Perceptual “retraining”
• Continued empathy for the patients with a firm consistent message
• Exercise based rehab
• Demedicalize
• Perceptual “retraining”
• Continued empathy for the patients with a firm consistent message
Page 60
CP1278619-59
AcknowledgementsAcknowledgementsN Dietz
J Eisenach
N Charkoudian
F Dinenno
W Schrage
S MasukiM Tschakovsky
K Krucker
P Engrav
S Roberts
D Wick
E MartinC Johnson
B Walker
E Snyder
K Engelke
B Wilkins
N NicholsonZ Liu
T Curry
J Halliwill
C Minson
D Proctor
L SokolnikiT Pike
A Reed
M Ceridon
L Berry
T Young
S ShastryR Kraft
M Somanju
A Issa
C Hesse
F Ramirez
P KredietT Pike
B Welch
P Sandroni
B Johnson
S Turner
M JensenJT Shepherd
BG Wallin
PA Low
N Dietz
J Eisenach
N CharkoudianF Dinenno
W Schrage
S Masuki
M Tschakovsky
K Krucker
P EngravS Roberts
D Wick
E Martin
C Johnson
B Walker
E SnyderK Engelke
B Wilkins
N Nicholson
Z Liu
T Curry
J HalliwillC Minson
D Proctor
L Sokolniki
T Pike
A Reed
M CeridonL Berry
T Young
S Shastry
R Kraft
M Somanju
A IssaC Hesse
F Ramirez
P Krediet
T Pike
B Welch
P Sandroni
B Johnson
S Turner
M JensenJT Shepherd
BG Wallin
PA Low
CP1153975-61
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CP1278619-61
If All You Have is a Hammer… Everything Looks Like a Nail
If All You Have is a Hammer… Everything Looks Like a Nail
Physician Physician PerspectivePerspective•• CardiologyCardiology•• NeurologyNeurology•• PsychPsych
Page 63
CP1278619-62
If All You Have is a Hammer… Everything Looks Like a Nail
If All You Have is a Hammer… Everything Looks Like a Nail
Physician PerspectivePhysician PerspectiveJoyner & Levine Teams Joyner & Levine Teams interested in exercise; interested in exercise; ““DetrainingDetraining”” usually on usually on the differential the differential
Page 64
CP1278619-63
0
10
20
30
40
50
60
70
MSNA Responses to HUT in POTSMSNA Responses to HUT in POTS
Supine 30°
tilt
60°
tilt
60°
tilt
5 min 10 min
Supine 30°
tilt
60°
tilt
60°
tilt
5 min 10 min
Group P=0.198Protocol P<0.001Group x Protocol P<0.001
POTSControls
MSNA (bursts/min)
MSNA (bursts/min)
Page 65
CP1278619-64
POTS Like Responses to 120 Days of HDT n=6POTS Like Responses to 120 Days of HDT n=6
Kamiya
et al Am J Physiol
Regulatory Integrative Comp Physiol
2000
Cha
nges
in M
BP
(mm
Hg)
Cha
nges
in M
BP
(mm
Hg)
Pre-HDBRPre-HDBR HDBR60HDBR60
**
Cha
nges
in to
tal M
SNA
(arb
itrar
y un
its/m
in)
Cha
nges
in to
tal M
SNA
(arb
itrar
y un
its/m
in)
****
Cha
nges
in h
eart
rate
(bea
ts/m
in)
Cha
nges
in h
eart
rate
(bea
ts/m
in)
**
HDBR120HDBR120 Rec-HDBR (n=3)Rec-HDBR (n=3)
-12
-8
-4
0
4
0
1000
2000
3000
4000
5000
0
10
20
30
Page 66
CP1278619-65
Baroflexsensitivity(beats/min/
mmHg)
Baroflexsensitivity(beats/min/
mmHg)
WorkloadWorkload
SupineSupine UprightUpright
*
*-1.8
-1.2
-0.6
0 RestRest 2525 5050 7575 RestRest 2525 5050 7575
ControlControl POTSPOTS
Page 67
CP1278619-66
∆
HR(beats/min)
∆
arterialpressure(mmHg)
-20
-10
0
10
20
30
0
10
20
30
40
50
SAP DAP MAP
ContPOTS
P=0.37 P=0.0033 P=0.18
P <0.001