1. Beyond RDN Paul A. Sobotka, MD Professor of Medicine/Cardiology
The Ohio State University
Chief Medical Officer
Cibiem, Inc.

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Consulting Fees/Honoraria
Royalty Income
Ownership/Founder/Salary
Ardelyx Inc.
Medtronic, Inc.
Rox Medical, Inc.
Ardian, Inc.
Cibiem, Inc.

3. Next Generation Devices to Rebalance Sympathetic Activity
Renal Denervation Clones
Faster, smaller, more complete
Smörgåsbord of Tools:
Multi lead RF ablation, Ultrasound, Cryoablation Chemical Infusion
Disruptive Technology- rebalancing central sympathetic & parasympathetic tone
Baroreceptor stimulation
Carotid body modulation

4. Control of Central Sympathetic Drive
Vasoconstriction
HTN &
Insulin Resistance
Renin, AngII, Aldo
Sodium Retention
Renal Blood Flow
Dyspnea,
Exercise Intolerance,
Central Sleep Apnea
Central
Chemoreceptor
Sensitivity
Splanchnic Venous
Capacitance
Congestion
Acute HF
Obstructive Sleep Apnea
Chemosensors
carotid body
Mechanosensors
baroreceptor
Hypertrophy
Arrhythmia 4

5. Carotid Body in HF Both Increased Tonic and Chemosensitivity
resting activity (21% FiO2)
Schultz et al. ISH 2012

6. Carotid Body Function (CBF) is related to mortality in Heart Failure (CHF)
Ponikowski et al. Circulation 2001;104:
Gianonni, et al. Chemoreflex and Prognosis in HF

7. Therapeutic carotid body chemoreceptor denervation (CBD) reduces renal sympathetic nerve activity (RSNA) and arrhythmia incidence in congestive heart failure (CHF)
Adult male New Zealand White Rabbits
Paced into heart failure over the course of 3-4 weeks
Carotid bodies ablated using a fine tip forceps dipped in liquid nitrogen
Marcus, et al. Autonomic Society 2012

8. CBM normalizes RSNA in CHF Is the CB the sleep apnea link?* #
Hypoxia increases RSNA in CHF
CBM normalizes RSNA response to hypoxia in CHF

9. CBM Restores Sympathetic Balance in CHF
CHF-CBD
sham-sham
CHF-sham
2.5 sec
CBM reduces MSNA and normalizes RSNA in heart failure

10. CBM restores HRV B
Schultz et al. ISH 2012

11. CBM normalizes Ve in CHF
Hypoxia increases minute ventilation in CHF
CBM normalizes minute ventilation response to hypoxia in CHF

12. Carotid Body Modulation in CHF
Selective denervation of carotid body chemoreceptors reduces the elevation in RSNA observed in rabbit CHF.
Arrhythmia incidence is increased in rabbit CHF, and is reduced by CBD.
Surgical or device oriented ablation of carotid body chemoreceptors may reduce sympathetic outflow and restore autonomic balance to the heart in human CHF, which may in turn reduce incidence of arrhythmias.

13. CBM in Hypertension

14. Experimental Design SHR & Wistar rats 10 weeks of age
4 weeks of age carotid sinus nerve ablated
10 weeks of age
left femoral artery cannulated
11 & 13 weeks of age
ABP recorded during sleep
McBryde et al. ISH 2012

15. CBM Reduces Renal Sympathetic Activity
Days
CBM
(n=3)
% Renal SNA
Stress
RSNA
Days
McBryde, Abdala et al. ISH 2012

16. Peripheral Chemoreceptor Afferent Drive is
Pro-Hypertensive in SH Rats:
Transient Inactivation 80
100
120
140
160
180 - 1 2
Time (min)
MAP (mmHg)
Wistar
SHR
H Y P E R O X I A *
Air 3s
20mV
RSA
100% O2
SHR – Renal Sympathetic
-20
-15
-10 -5 5
∆ MAP
(mmHg)
SHR
Wistar *
% RSA
-120
-100
-80
-60
-40
-20
SHR
Wistar *
McBryde....Paton (2013)

17. Sympathetic Nerve Responses to RDN & Carotid Body Denervation in SH Rats
Lumbar
SNA (mV)
-10 -5 5 10
Day -3
Day 10
-25 25 50 2s
Renal Denervation
Renal
Carotid Body Denervation
↓22%
↓56%
-50
McBryde..... Paton (2013)

18. Changes Evoked After Renal Denervation &
Carotid Body Denervation in SH Rats
-80
-60
-40
-20
MAP
SNA (%) ** * #
* p<0.05 within-subject
* p<0.01 within-subject
# p<0.01 between-group RD
CBD
MAP (mmHg) or
SNA (%)
McBryde..... Paton (2013)

19. Human Trials Positive Surgical Control Endovascular Trials- 2013
CHF (4 unilateral, 6 bilateral completed)
FC III, IIIb; hyper chemosensitivity; optimal meds
MSNA, Chemosens, Euglycemic Insulin Clamp, Sleep Study, Exercise parameters, ECHO morphology, BNP
rHTN (4 unilateral completed)
Office & ABPM proved rHTN
MSNA, Chemo sens, Sleep Study, ABPM, oBP, HOMAir
Endovascular Trials- 2013

20. The art of making a medical device
Make it fool proof

21. Carotid Body Modulation (CBM) Restoring Sympathetic Balance
CIBIEM, Inc.

22. Terminal Thoughts A final cautionary thought.
I’ve been traveling through a lot of airline terminals lately. Here’s a diagram of several of them.
Most people looking at this diagram will conclude there are many ways to build an airport.
But I’m more cynical. I think it means we haven’t yet learned how to build one!