1. Accelerating a Revolution in the Treatment of Hypertension
Mapping the Renal Nerve:
Can We Improve Accuracy?
Jie Wang, MD, PhD
SyMap Medical Ltd
Accelerating a Revolution in the Treatment of Hypertension

2. Jie Wang, MD, PhD J Wang is a co-founder of SyMap Medical Ltd
Consult: Respicardia, Backbeat

3. Unresolved Issues in RDN
Need to increase efficacy and safety of RDN procedure:
“real world” response rates can be improved
Limit the potential side effects from “too much” denervation
Understanding the complexity of renal sympathetic nerve distribution
Significant variability in length and diameter of the renal artery
Length: LRA, cm; RRA, cm
Diameter: LRA, mm; RRA, mm
Significant variability in length and diameter of the renal artery
Length: LRA, cm; RRA, cm
Diameter: LRA, mm; RRA, mm
Can the renal sympathetic nerve be mapped using clinically relevant parameters to monitor?

4. (12) patients with difficult-to-control hypertension (45–74 yrs)
(3) patients: clinically relevant reductions in blood pressure; (7) patients: BP remained unchanged or even increased.
157±7/85±4 mm Hg vs 157±6/85±4 mm Hg
Resting MSNA : 34±2 bursts/min vs. 32±3 bursts/min
No clinical applicable readout to confirm RND
Not clear there was sufficient disruption of renal nerve

5. Question and Challenge
Can the Renal Sympathetic Nerve Be Mapped Using a Clinically Relevant Approach?
Significant variability in length and diameter of the renal artery
Length: LRA, cm; RRA, cm
Diameter: LRA, mm; RRA, mm
Can the renal sympathetic nerve be mapped using clinically relevant parameters to monitor?

6. Our Solution: Renal Mapping
We have shown that selectively stimulating nerves in renal artery can change blood pressure (BP) and heart rate (HR)
By mapping and ablating only the nerves that change BP/HR, one may optimize the renal denervation procedure

7. Proof-Of-Concept Study
Acute animal experiment: anesthetized pigs
Catheter applied electrical stimulation to at least 4 sites within left and right renal arteries
Blood pressure and heart rate measurements during electrical stimulation, recording max/min

8. Changes in Blood Pressure and Heart Rate in Response to
Right Renal Artery Stimulations

9. Changes in Blood Pressure and Heart Rate in Response to
Left Renal Artery Stimulations

10. Study Conclusion
Electronic stimulation in renal artery caused changes in blood pressure and heart rate
The changes in blood pressure and heart rate due to renal artery stimulations are site-specific
These “stimulation sites” that caused the maximum increases in blood pressure and heart rate may correlate with sympathetic innervation of renal arteries
Mapping these “stimulation sites” may provide optimal locations for renal denervation therapy
Mapping technology provides a marker to confirm RDN
Conclusion:
It is feasible to map the renal sympathetic nerve

11. IP: First to File
SyMap is “first-to-file” patents on the renal mapping concept
>10 patents have already been filed
Freedom to operate

12. CRT 2012
Best Innovation Award

13. Validated by Other Investigators
Renal Mapping Concept
Validated by Other Investigators

14. Acute, Anesthetized Dog Study
Intra-Renal Arterial Stimulation

15. Changes in BP in Responses to Intra-Renal Stimulation Before and After Renal Ablation

16. Changes in HR in Responses to Intra-Renal Stimulation Before and After Renal Ablation

17. Summary
First to demonstrate that Renal Mapping can be achieved through intra-renal stimulation, then monitoring change in BP/HR and other physiological parameters.
Renal Mapping has been validated by other investigators, will be further developed and improved.
Using mapping technologies, one may optimize the renal denervation procedure, improve its efficacy and safety
Mapping concept provides a significant differentiator in one of the most important growth market opportunities in medical device.
First-In-Human study of SyMap will be started in August 2013

18. Thank You

19. Renal Nerve Components
Neural Control of Renal Function
DIBONA GF AND KOPP UC: PHYSIOLOGICAL REVIEWS
Vol. 77, No. 1, January 1997

20. Illustrations of Changes in BP/HR in Responses to Intra-Rena Stimulation B/A Renal Ablation

21. Changes in HRV in Responses to Intra-Renal Stimulation Before and After Renal Ablation

22. Changes in EP/Norep in Responses to Intra-Renal Stimulation Before and After Renal Ablation