1. A Non-vascular Treatment for Resistant Hypertension
RICHARD R. HEUSER, MD, FACC, FACP, FESC, FSCAI
Chief of Cardiology, St. Luke’s Medical Center,
Phoenix, Arizona
Professor of Medicine Univ. of Arizona,
College of Medicine, Phoenix, Arizona

2. Richard R. Heuser, MD Consulting: Abbott Vascular and ev3, Inc.
Honoraria: Abiomed, Inc., Bard Peripheral Vascular, Inc., Medtronic, Inc. and Spectranetics Corporation
Stocks, Stock Options, other ownership interest: QuantumCor, Inc., PQBypass and CSI.

3. This paper was presented on behalf of Verve Medical and the following individuals:
Terry Buelna, President, CTO
Winton Berci, Chief Business Officer
Brad Hubbard, DVM, Managing Director,
Gateway Medical Innovation Center
Renu Virmani, MD, FACC, President and Medical
Director, CVPath Institute

4. Presenter Disclosure Information
Name: RICHARD R. HEUSER M.D.
Within the past 12 months, the presenter or their spouse/partner
have had a financial interest/arrangement or affiliation with the organization
listed below.
QuantumCor, Major Stock Holder/Medical Director;
Radius Medical, Avinger and Claret Medical, Major Stock Holder;
PQ ByPass, Founder and Major Stock Holder;
CSI, Stockholder;
Spectranetics, Abbott, Medtronic, Bard, Abiomed, Honorarium;
Medtronic, Abbott, AngioScore, Speaker;
Acist Medical Systems Grant; and
Verve Medical, Inc., Major Stockholder
Patents -- RF, Snares, Wires, Balloon Catheters, Covered
Stents, Devices for Arterial Venous Connection,
Devices for LV and RV Closure

5. Renal Nerve Actions
RAAS- Renin-Angiotensin-Aldosterone System

6. Renal Nerves

7. Ardian Tx by Renal RF Catheter
4 to 8 Ablations per Kidney
Verve Medical Inc CONFIDENTIAL

8. Verve Medical Inc. CONFIDENTIAL
Renal Artery Devices
Mercator
Maya/ Covidien
ReCor
Vessix / BSX
Ardian/Medtronic
Verve Medical Inc CONFIDENTIAL

9. Market Size $30 Billion - $40 Billion
Hypertension Market
Prevalence: 1 Billion Patients
25 % uncontrolled HTN
5% penetration
Patients: 12.5 Million
ASP: $2,400-$3,200
Market Size $30 Billion - $40 Billion
Source – St Jude Medical

10. Vascular Exclusion Vessels with renal artery aneurysms
Vessels with area of visible disease
Anatomical abnormalities
Acute angle of the take off of the renal artery
Short or no common renal artery trunk
Renal artery branches < 4mm

11. Renal Arterial Supply 55% 1 hilar artery CONFIDENTIAL
----- Meeting Notes (10/3/12 08:19) -----
Sampaio, F :Renal Anatomy Applied to Urology, Endourology & Interventional Radiology 1993
CONFIDENTIAL

12. Renal Denervation for HTN
Numerous articles show renal denervation or the interruption of renal AFFERENT nerve activity attenuates systemic sympathetic tone, lowering blood pressure
Suzanne Oparil, Prof Department of Medicine, Cardiovascular Dx Kidney International 1986 Sep;30(3) The sympathetic nervous system in clinical and experimental hypertension University of Alabama Birmhamg

13. Neuroanatomy
“ In contrast to the widespread distribution of EFFERENT Sympathetic nerve fibers in the kidney, the majority of the AFFERENT Renal Sensory nerves are located in the renal pelvic area”
Kopp UC, University of Iowa. Neural Control of Renal Function 2011

15. Verve Medical Inc. CONFIDENTIAL
Verve’s Approach
ACCESS
METHOD
THERAPY
BENEFITS
Verve
Ureter – Natural body Orifice
Catheter – Standard technique for Urologist
RF Heat
LESS-invasive
No arterial intervention/Tx
Standard Technique
Not restricted by anatomical
variances of artery
Potential Office procedure
Verve Medical Inc CONFIDENTIAL

16. Pre-Clinical Results

17. Procedural Fluoroscopy
----- Meeting Notes (10/3/12 08:19) -----
retrograde pyelogram - 3 bands
CONFIDENTIAL

18. Pathology

19. A) Image shows relation to the surrounding renal pelvis tissue
A) Image shows relation to the surrounding renal pelvis tissue. H&E B) High power showing ureteral epithelial loss and thermal injury of wall. H&E. C) High power showing adjacent vein thermal injury. Movat. D) High power showing severe nerve injury with necrosis of endineural cells and perineural thermal injury . A B C D

20. Materials and Methods
8 female swine underwent renal denervation via ureteral access
3 were euthanized after treatment
5 survived for 7 days
Renal cortical norepinephrine levels measured
Histopathology in the treated zone confirmed nerve damage

21. Reduction in Porcine Norepinephrine

22. Reduction in Porcine Norepinephrine
Mean Reduction = 70.8%

23. Reduction in Porcine Norepinephrine

24. Reduction in Porcine Norepinephrine

25. Results
Pyelography, ureterography and arterial angiography performed and unremarkable
Histopathology confirmed nerve ablation
Tissue norepinephrine levels dropped 70%and remains reduced at 30 days

26. Device design protocol being finalized for first human treatment
Chronic Swine Studies
>12 animals treated 7 – 30 day survival
Transurethral approach
Histopathology and norepinephrine levels consistently reduced
Device design protocol being finalized for first human treatment

27. Who Is Going To Do These procedures?
Primary Care (Internist)
Nephrologist Cardiologist
Urologist, Interventional Radiologist, Interventional Nephrologist or perhaps Interventional Cardiologist

28. Verve Hypertension Market
US Prevalence: 75 Million Patients
25 % uncontrolled HTN (18.8M)
30% Cannot Undergo Vascular Denervation
Patients: 5.6 Million
ASP: $2,500
Market Size $14 Billion

29. CONCLUSION Pre-Clinical Results Acute and Chronic Animal Studies
Catheter introduction requires little skill
Safe Technique, no damage to surrounding tissue
Animals returned to normal diet and uresis next day
Norepinephrine reduced 70%
First-in-man in 2013