1. Vasilios Papademetriou, MD
Sympathetic Renal Denervation: Experience with the St Jude EnligHTN Ablation System?
Vasilios Papademetriou, MD
Professor of Medicine Georgetown University
Chief Hypertension and CV Research VAMC Washington DC

2. Vasilios Papademetriou, MD, DSc
I/we have no real or apparent conflicts of interest to report. Off-Label: Experimental data in animal models

3. EnligHTN™ Multi-Electrode Renal Denervation System
EnligHTN™ Multi-Electrode Renal Denervation System* St Jude Medical: First in man study
Ablation Catheter
Multi-electrode
Radiopaque electrodes
8 F compatible
Deflectable, atraumatic tip
Femoral access
Generator
Default settings:
Power output (6 Watts)
Impedance (400Ω)
Electrode temperature (75 degrees C)
Time (90 seconds per ablation)
Temperature controlled
*CE Mark — December 2011Not for sale in the U.S.

4. Renal Procedure Goal: Effective Denervation
Transmurality*
Predictable Pattern
Acute lesion formation**
After one month**
* Atherton DS, Deep NL, Mendelsohn FO, Micro-Anatomy of the Renal Sympathetic Nervous System: A Human Postmortem
Histological Study, Clinical Anatomy 2011.
** Animal study. Results on file at St. Jude Medical

5. The PIKERMI Study J J 5

6. Porcine #2 (acute) RRA LRA Papademetriou, Tsioufis 6
>70 swine used in various experiments

7. Porcine 5– one month after denervation
Papademetriou, Tsioufis

8. Average Peak Velocity-APV
Baseline
Hyperemia
Tsioufis C, Papademetriou et al; Int J Cardiol Nov 16

9. Renal Blood Flow- RBF
Tsioufis C, Papademetriou et al; Int J Cardiol Nov 16

10. Resistive Index-RI
Tsioufis C, Papademetriou et al; Int J Cardiol Nov 16

11. Procedure Overview
Key Discussion Points:
The steps for completing an EnligHTN procedure on 1 renal artery are the following:
First the operator must establish and maintain access to the renal artery of interest. Pre-planning and preparation is essential to optimize results in this first step.
Once access has been established, the basket of the ablation catheter is positioned as distal in the artery as possible but should be proximal to the renal bifurcation.
Upon reaching this position, the basket is expanded and the operator will perform a quick diagnostic check to confirm that all 4 electrodes have good contact with the artery wall.
If this is confirmed, the ablation process is started and will take 90 seconds per electrode delivered sequentially.
Once all 4 electrodes have delivered the therapy, the basket is collapsed, pulled back 1 cm, rotated 45 degrees, re-expanded and the diagnostic / ablation process I just described is repeated.
Initial basket positioning proximal to the bifurcation
Expand basket and perform generator diagnostic check for electrode contact
Ablate – 90 seconds per electrode
For a second set of ablations the basket is collapsed, pulled back 1 cm, rotated and expanded, contact is checked and ablation sequence repeated

12. Study Design Office Systolic BP ≥ 160 mmHg
Stable use of ≥3 antihypertensive medications
* Exclusion due to renal artery anatomy therefore renal denervation was not attempted.

13. Baseline Characteristics
Gender (female)
15 (33%)
Ethnic origin (white)
45 (98%)
Body Mass Index (kg/m2)
32 (±5)
Coronary Artery Disease
9 (20%)
Hyperlipidemia
27 (59%)
Type II Diabetes Mellitus
Sleep Apnea
14 (30%)
eGFR (mL/min/1.73m2)
87 (±19)
Serum Creatinine (mmol/L)
78 (±17)
Cystatin C (mg/L)
1.14 (±0.29)
Number of Anti-Hypertensive Medications
4.1 (±0.6)
Office Systolic Blood Pressure (mmHg)
176 (±16)
Office Diastolic Blood Pressure (mmHg)
96 (±14)
Heart Rate (bpm)
71 (±12)
Two patients did not meet all inclusion criteria, but are included in the analyses
Data are mean (±SD) or number (%)

14. Results: Safety Data
The primary safety outcome was assessment of all adverse events
Serious Peri-Procedural Events: NONE
No renal artery dissections, aneurysms or new stenosis
No flow-limiting renal artery vasospasms
No major vascular access complications
Non-Serious Peri-Procedural Events:
Non-flow limiting vasospasms, puncture site hematomas, vasovagal reactions, low back pain, hypotensive episodes, transient hematuria, nausea and bradycardia
Serious device/procedure events include:
Worsening of pre-existing proteinuria (n=1)
Symptomatic hypotension (n=1)
Worsening of pre-existing renal artery stenosis (n=1)
The EnligHTN System delivers renal denervation with an acceptable safety profile through 6 months

15. Renal Function
There was no clinically significant change in renal function
No patient experienced:
a reduction in eGFR >50%,
a two-fold increase in Serum Creatinine, or
progressed to end stage renal disease
Laboratory Values:
Baseline
(n=46)
Month 1
Month 3
Month 6
(n=45)
eGFR
(mL/min/1.73m2)
87 (±19)
85 (±20)
84 (±22)
82 (±20)
Serum Creatinine
(mmol/L)
78 (±17)
79 (±19)
81 (±20)
83 ± (20)
Cystatin C
(mg/L)
1.14 (±0.29)
1.00 (±0.25)
0.97 (±0.20)
1.00 (±0.23)

16. Mean Office Blood Pressure

17. Office BP Reduction from Baseline
EnligHTN therapy delivers a rapid and significant reduction in
Office BP that is sustained through the 6M timeframe

18. 24 hr Ambulatory BP Reduction from Baseline
P values are <0.0001, except
Diastolic 1 mo p-value
Diastolic 3 mo p-value
EnligHTN therapy delivers a rapid and significant reduction in Ambulatory BP that is sustained through the 6M timeframe

19. Responder & Goal Blood Pressure Parameters
% Responders (>10 mmHg Reduction from baseline) = 76% (n=34)
At Goal SBP:
76% were responders
2/3 of patients had systolic BP<150 mmHg at 6 months
1/3 of patients normalized their Blood Pressure
Blood pressure response occurred early

20. Interesting Cases

21. Case 05 Female, 52 years old, non-smoker BMI: 24.6 Kg/m2
Hypertension diagnosed in 2005
Hx: unremarkable
SBP persistently above 160mmHg despite multiple medication
Screening for 2ndary hypertension: Negative
Office BP: 201/93mmHg, 64bpm
ABPM average: 158/86mmHg
Currently on 4 antihypertensive drugs:
Amlodipine/Valsartan/HCTZ 10/320mg/25mg OD
Metoprolol 25 mg BID
Other drugs: ASA 100mg
RBC: 4.21 , WBC: 6.91, PLT: 250
eGFR: 94ml/min/1.73m2, ACR:30mg/g
ECHO: Left ventricular hypertrophy (IVS:12.5mm)
Renal angiography performed during coronary angiography
Selective renal angiography performed during coronary catheterization
RRA D: 4.1mm, L: 45mm
LRA D: 4.6mm, L: 22mm

22. Case 05. LRA Pre-Ablation

23. Case 05. LRA Basket Inside

24. Case 05. LRA Basket Expanded

25. Case 05. LRA Post Ablation

26. Case 05. RRA Pre-Ablation

27. Case 05.RRA Basket Inside

28. Case 05. RRA Basket Expanded

29. Case 05. RRA Post Ablation

30. Case 05. Baseline ABPM

31. Case week ABPM

32. Case weeks ABPM

33. Case month ABPM

34. ARSENAL Challenging case #2 (13)
Female, age=52, BMI=43.4kg/m2, smoker with resistant hypertension
Hypertension diagnosis: 2005
Hx: Treated hypothyroidism, impaired fasting glucose
History of TIA (2006)
Extensive workup for secondary hypertension: Negative
A Office BP=223/130mmHg, OHR:97bpm
BPM average: 178/102mmHg
Currently on 6 antihypertensive drugs:
Olmesartan 40mg OD
Chlorthalidone 25mg OD
Nifedipine 60mg OD
Bisoprolol 10mg 1-0-1/2
Eplerenone 50mg OD
Clonidine 150μg TID
Other drugs: Levothyroxine
Screening for secondary hypertension: Negative
Hct=38,3%, WBC=9630, PLTs=279
Renal function: eGFR= 93ml/min/1.73m2, ACR:101mg/gr
Echo: Significant left ventricular hypertrophy (IVS:14mm)
Selective renal angiography performed during coronary catheterization
RRA D: 6.2mm, L: 37mm
LRA D: 5.5mm, L: 38mm

35. Case 13. Sharp Take off of LRA

36. Case 13. LRA Basket In

37. Case 13. LRA Basket Expanded

38. Case 13. LRA Post-Ablation

39. Case 13. Sharp take off of RRA Pre-Ablation

40. Case 13. RRA Basket In

41. Case 13. RRA Basket Expanded

42. Case 13. RRA Post-Ablation

43. Case 13. Baseline ABPM
Office BP
223/130

44. Case month ABPM
Office BP
110/70
-123/60 Office
-76/22 ABPM

45. Office BP: Change from Baseline at One month: Best 5 cases
Systolic BP
Diastolic BP HR
-19
-30
-65 75
Papademetriou, Tsioufis

46. ABPM BP: Change from Baseline at One month: Best 5 cases
Systolic BP
Diastolic BP HR
-15
-21
-37 75
Papademetriou, Tsioufis

47. EnligHTN IV: First US trial
Double Blind, multicenter, Sham controlled procedure
Patients with office SBP>160 mmHg, ABPM
Randomized to:
Optimal med Regimen
Optimal med Regimen + RNA
N=590 pts