Join Dr. Satish Raj and Nasia Sheikh for an overview of Initial Orthostatic Hypotension (IOH), how these patients present in the clinic, the mechanisms that underly the condition, and how IOH can be managed with a non-pharmacological approach. Despite frequent presentation in syncope clinics, Initial Orthostatic Hypotension (IOH) is a relatively understudied and under-recognized disorder. Patients with IOH are often referred for syncope or Postural Orthostatic Tachycardia Syndrome (POTS). During this webinar, Satish Raj, MD MSCI and Nasia Sheikh, MSc from the University of Calgary will briefly review IOH, including diagnostic criteria, review the differential diagnosis of IOH, and common presentations. They will share some recent research findings on the hemodynamic mechanisms underlying IOH. And they will offer some insights into non-pharmacological approaches to the management of patients with IOH from recent studies. To learn more, access additional resources, and watch the webinar, please visit: https://insidescientific.com/webinar/initial-orthostatic-hypotension-dont-blink-or-you-will-miss-it/

1. Initial Orthostatic Hypotension –
Don’t blink or you will miss it!
SATISH R. RAJ, MD MSCI
Professor of Cardiac Science
School of Medicine
University of Calgary
NASIA SHEIKH, MSc
Student Clinical Researcher
Cardiovascular & Respiratory Sciences
University of Calgary

2. Join Dr. Satish Raj and Nasia Sheikh for an overview of
Initial Orthostatic Hypotension (IOH), how these patients
present in the clinic, the mechanisms that underly the
condition, and how IOH can be managed with a non-
pharmacological approach.
Initial Orthostatic Hypotension –
Don’t blink or you will miss it!

3. Initial Orthostatic Hypotension:
Don’t Blink or You Will Miss It
Satish R Raj MD MSCI
Nasia A Sheikh MSc
Libin Cardiovascular Institute
University of Calgary
October 6, 2021

4. ~700 mL fluid shift
Decreased venous return and CO
1. Activation of low and high pressure receptors
2. Central disinhibition of CNS & CV centers
3. Increased SNS and reduce PNS
4. Restoration of stroke volume, vasoconstriction
No change in BP
Minimal increase in HR
Courtesy of Diedrich A, Gamboa A. Vanderbilt University Medical Center.
Standing, a Challenge to the ANS

5. Definition
Supine BP, HR (at least 5 minutes)
Standing BP, HR at 3, 5, 10 minutes
SBP ≥20 mmHg in SBP or
DBP ≥10 mmHg in DBP
within
3 minutes upon standing
(SBP >30 mmHg in
patients with HTN)
Orthostatic hypotension is defined as:
In AM and during fasting conditions
Classical Orthostatic Hypotension

6. Orthostatic Hypotension (OH) Is a Significant
Problem in the Elderly
Nationwide Inpatient Sample
• Total # hospitalizations = 38,661,786
• Hospitalizations with diagnosis of OH =
164,401
• OH-related hospitalizations from
nonacute causes = 80,095
• Rate: 36 per 100,000 US adults
Shibao C, et al. Am J Med. 2007;120(11):975‐980

7. Neurogenic Orthostatic Hypotension
Orthostatic Hypotension (OH)
• ↓SBP ≥20 mmHg in SBP or
• ↓DBP ≥10 mmHg in DBP within
3 minutes upon standing
Neurogenic Orthostatic Hypotension
(nOH)
• Due to dysfunction of the sympathetic
nervous system that impacts
norepinephrine release upon standing
• Inadequate vasoconstriction and
compensatory HR increase to maintain
BP can result in symptoms

8. THE SPECTRUM OF
ORTHOSTATIC HYPOTENSION
Classic Orthostatic Hypotension (cOH)
• Sustained drop in SBP ≥ 20 mmHg and/or DBP ≥ 10 mmHg
• Occurs within 30s – 3mins of active stand or HUT
Delayed Orthostatic Hypotension (dOH)
• Drop in SBP ≥ 20 mmHg and/or DBP ≥ 10 mmHg
• Occurs after 3mins of active stand or HUT
Initial Orthostatic Hypotension (IOH)
• Drop in SBP ≥ 40 mmHg and/or DBP ≥ 20 mmHg
• Occurs within 15s of active standing

9. INITIAL ORTHOSTATIC HYPOTENSION
Definition (Wieling)
• Large transient ↓ BP (within 15s) of standing
• Associated with presyncope symptoms
• Occurs during ACTIVE stand
ACTIVE
STAND
PASSIVE
STAND
W. Wieling, 2007
Mechanism
• Rapid vasodilation in contracting leg
muscles due to brief muscular effort of a
stand

10. OTHER POSSIBLE MECHANISMS
EXPLAINING INITIAL BP DROP (Wieling, 2007)
Muscle Pump
• ↑ arterial-venous pressure gradient = ↑ blood flow
• Time-course does not align with IOH
Cardiopulmonary Receptor Reflex
• Standing = compressed venous vessels = ↑ intra-abdominal pressure
• Results in ↑ RAP, activating cardiopulmonary mechanoreceptors = ↓SVR
• Time-course does not align with IOH
Rapid Vasodilation
• Brief muscle contraction = ↑ blood flow due to local mechanisms
• Currently the most convincing explanation

11. IOH Literature - Impact
Recent Syncope Study
• 2nd most common form of unexplained
syncope: IOH (van Twist, 2018)
• Common Reason for Clinic Visits
Syncope Clinics
• Frequent reason for referrals
• Referred as “syncope” or “POTS”
• Patients have travelled from other
provinces to see me for IOH

12. IOH Literature - Management
Management Options
• Sit up first, then stand
• Stand slowly
• Physical counter-maneuvers after standing (LBMT after squat)
• Wieling, 2007

13. Recap
• Occurs during ACTIVE stand
• Often does not recur after standing a second time
INITIAL ORTHOSTATIC HYPOTENSION

14. Exploring the Physiology, Underlying
Mechanism, Symptom Management
Options, and Patient Experience with IOH
Satish R Raj MD MSCI
Nasia A Sheikh MSc
Libin Cardiovascular Institute
University of Calgary
October 6, 2021

15. Is there a refractory
period to the reflex
underlying IOH?

16. Exploring the Physiology & Refractory
Period of an Active Stand in IOH
Purpose
To determine whether there is a refractory period to the muscle activation reflex
underlying IOH and if so, what the duration of that period is
Hypothesis
A stand following a SHORT 30s sit would result in a smaller BP drop compared to a
LONG 20min sit
Primary Outcome
• Dssd

17. Exploring the Physiology & Refractory
Period of an Active Stand in IOH
Refractory Period
< 2 mins

18. Exploring the Physiology & Refractory
Period of an Active Stand in IOH
IOH blunted
with SHORT
sit
B

19. Can this refractory
period be exploited
for treatment?

20. Lower Body Muscle Pre-Activation vs
Post-Tensing in Mitigating IOH
Control
LBMT
Purpose
To explore the efficacy of muscle pre-activation and post-tensing as symptom
management options in IOH
LBMP
Hypothesis
Lower body muscle pre-activation (LBMP) prior
to standing as well as lower body muscle post-
tensing (LBMT) after standing would blunt the
BP drop seen in IOH and improve symptoms

21. LBMP blunts IOH by ↑CO
Lower Body Muscle Pre-Activation vs
Post-Tensing in Mitigating IOH
B

22. Lower Body Muscle Pre-Activation vs Post-
Tensing in Mitigating IOH
LBMT blunts IOH by ↓SVR & ↑SV
B C

23. Muscle Activation: What Plays
a Bigger Role?
Muscle Contraction
vs.
Sympathetic Activation

24. Mechanistic Roles of Muscle Contraction
vs Sympathetic Activation
Purpose
To better understand the relative roles of sympathetic nervous system activation and
skeletal muscle contraction in mitigating the IOH response
Serial Seven Test
• ↑Sympathetic activity  ↑SVR, HR, and MAP via MENTAL stimulus
Cold Pressor Test
• ↑Sympathetic activity  ↑SVR, HR, and MAP via PAIN stimulus
Electrical Stimulation
• Uses small electrical currents to passively contract muscles
• Minimal sympathetic activation

25. Mechanistic Roles of Muscle Contraction
vs Sympathetic Activation
No Intervention
(NI)
Serial 7
(S7)
Function Electrical
Stimulation
(FES)
Cold Pressor
(CP)
Hypothesis
Inducing passive muscle
contractions prior to standing would
have a greater reduction in the IOH
BP drop compared to sympathetic
activation
BSL INTV BPnadir

26. Mechanistic Roles of Muscle Activation vs
Sympathetic Activation: BSL to BPnadir
S7 & CP blunts SBP drop by
blunting SVR drop
B C

27. Mechanistic Roles of Muscle Activation vs
Sympathetic Activation: INTV to BPnadir
FES blunts SBP
drop from INTV to
BPnadir

28. Exploring the Patient Experience with IOH
Purpose
To explore the patient experience living with IOH and provide a deeper
understanding of IOH
Specific Inquiries
• How does IOH affect day-to-day life?
• What are the social, emotional, and financial implications of IOH?
• What are patient priorities for living with IOH?

29. Key Findings: Day-to-Day Impact
Exploring the Patient Experience with IOH
“I would say it definitely can contribute to
some depression when I feel like I'm missing
out on my life because of my symptoms.” “I look like a relatively "young" healthy
person, but I have to move very slowly and I
can't always control the situation so that's
difficult. That's really difficult.”
“It's validating for sure. To me, once I had
a name for it, then I could actually say okay,
here's what I have, what could I do to mitigate
these effects? What strategies have people
used? How can I take back some of the
control? So yeah, that was very empowering.”

30. LIMITATIONS
• All participants in Aims 1-3 were female
• Many patients were enrolled based solely off history taking.
• Data collected in Aim 4 were all subjective, self reported data

31. FUTURE DIRECTIONS
Gaps from the Current Studies
• Future studies should include sex-matched participants
• Future studies should explore the efficacy of combining LBMP and LBMT
Knowledge Translation
• LBMT is a novel physical counter-maneuver for physicians to recommend to
their patients
• Results from these studies should aim to increase awareness for IOH
amongst the public & with physicians

32. CONCLUSIONS
• The reflex underlying IOH has a refractory period <2 minutes
• IOH can be blunted with a SHORT sit
• Both LMBP & LBMT blunt the drop in SBP & improve symptoms of
IOH
• Sympathetic activation & muscle activation blunts the IOH
response
• IOH affects many aspects of patient life, and should be a more
widely recognized disorder

33. THANK YOU
• Dr. Robert S Sheldon
• Dr. Aaron A Phillips
• Dr. Derek V Exner
• Dr. Mary Runte
• Matthey Lloyd
• Jacquie Baker
• Karolina Kogut
• Shahana Safdar
• Jessica Ng
• Kate M Bourne
• Julianna Jorge
• Lucy Y Lei
• Shaun Ranada
• Dallan McCarthy
• Mark Pineda

34. SATISH R. RAJ, MD MSCI
Professor of Cardiac Science
School of Medicine
University of Calgary
NASIA SHIEKH, MSc
Thank you for participating!
Student Clinical Researcher
Cardiovascular & Respiratory Sciences
University of Calgary
CLICK HERE to learn more and
watch the webinar