Renal denervation: the next big push for radial approach

1. Renal Denervation:
The Next Big Push For
Radial Approach?
Sasko Kedev, MD, PhD, FESC, FACC
University Clinic of Cardiology
Skopje, Macedonia
skedev@gmail.com

2. Disclosure
Nothing to disclose

3. Hypertension Epidemiology
• Single largest contributor to death worldwide
30%
Untreated
35%
Treated but
Uncontrolled
35%
Treated &
Controlled
• Every 20/10 mmHg increase in BP correlates
with a doubling of 10-year cardiovascular
mortality
• Dramatically increases risk of stroke, heart
attack, heart failure, & kidney failure
• Only half of all treated hypertensives are
controlled to established BP targets
• High prevalence:
• Affects 1 in 3 adults
• 1B people worldwide  1.6 B by 2025
Chobanian et al. Hypertension. 2003;42(6):1206–1252.

4. Resistant Hypertension - Definition
Failure to achieve target blood pressure values:
 Standardized systolic clinic blood pressure of
≥160mmHg (or ≥150mmHg in type 2 diabetes)
 Despite triple drug regimen
(including a diuretic)
Chobanian et al. Hypertension 2003;42(6):1206–1252.

5. Renal Sympathetic Efferent Nerve Activity:
Kidney as Recipient of Sympathetic Signals
Renal Efferent
Nerves
↑ Renin Release  RAAS activation
↑ Sodium Retention
↓ Renal Blood Flow

6. Renal Afferent Nerves:
Kidney as Origin of Central Sympathetic Drive
Vasoconstriction
Atherosclerosis
Insulin
Resistance
Sleep
Disturbances
Renal Afferent
Nerves
Hypertrophy
Arrhythmia
Oxygen Consumption
↑ Renin Release  RAAS activation
↑ Sodium Retention
↓ Renal Blood Flow

7. Renal Nerve Anatomy
• Nerves arise from T10-L2
• The nerves arborize around the artery
and primarily lie within the adventitia
Vessel
Lumen
Media
Adventitia
Renal
Nerves
7

8. Anatomy of Renal Artery

9. Renal Nerve Anatomy Allows a
Catheter-Based Approach
• Standard interventional technique
• 4-6 two-minute treatments per artery
• Proprietary RF generator
– Automated
– Low power
– Built-in safety algorithms

11. Which Patients Are Suitable For
Renal Denervation?
 SBP ≥160 mmHg (≥150 mmHg Diabetes Type 2)
 ≥3 antihypertensive drugs in adequate dosage and
combination (incl. diuretic)
 Life-style modification
 Exclusion of secondary hypertension
 Exclusion of pseudo-resistance (ABPM)
 24-hour BP >130 mmHg, daytime BP >135 mmHg
 Preserved renal function (eGFR ≥45 ml/min/1.73 m2)
 Eligible renal arteries: no stenosis, no PTA/stenting
Mahfoud F et al, Eur Heart J 2013

12. Staged Clinical Evaluation
First-in-Man 
Symplicity HTN-1
Series of Pilot studies 
Symplicity HTN-2 
EU/AU Randomized Clinical Trial
USA
Approved Geographies
Symplicity HTN-3
US Randomized Clinical Trial
(Enrolment Complete)
Global SYMPLICITY Registry

13. Symplicity HTN-1 Change in Office BP
Through 36 Months (153 Patients)
P<0.01 for ∆ from BL for all time points

14. Symplicity HTN-1 % Responders Over Time
(All Patients)
(n=141)
(n=144)
(n=132)
(n=105)
(n=88)

15. Conclusions
 BP-lowering with percutaneous RDN appears to be
durable out to 36-months
 This suggests that nerve re-growth and functional reinnervation do not translate into a clinically significant
loss of BP-lowering efficacy of the procedure (at least to
this time-point); further longer-term study of these
patients required
 Analysis of key sub-groups did not demonstrate which
patients may be hyper- or non-responders to the
procedure; larger-scale studies/registry data required

16. Systolic BP (mmHg)
Renal Denervation
Randomization Offered to Control
(n = 37)
(n = 54)
(n = 52)
(n = 35)
(n = 49)
(n = 33)
(n = 31)
(n = 47)
(n = 43)
Primary Endpoint
reached*
Baseline
Esler M et al, Circulation 2012

17. Global SYMPLICITY Registry: Real-World
Clinical Outcomes
Worldwide evaluation of the safety and efficacy of treatment with the Symplicity™ renal
denervation system in real world uncontrolled hypertensive patients
Consecutive patients treated
in real world population
~ 5000 patients
GREAT Registry
N=1000
Korea Registry*
N=102
South Africa Registry*
N=400
Canada and
Mexico*
Rest of GSR
N~3500
~ 200 Global Sites
Minimum 10% randomly assigned to 100% monitoring
30% monitoring to date
Follow-up schedule
3mo
Bӧhm M, ESC 2013
6mo
1yr
2yr
3yr
4yr
5yr

18. GSR Population Characteristics
 1097 patients treated as of
June 26, 2013
 86% with SBP ≥140 mmHg
 66% of patients treated
according to ESC Consensus
paper on Renal Denervation1
 SBP ≥ 160 mm Hg (≥ 150
mmHg Diabetes II), 3+
meds, including diuretic
 13% with BP ≥180/100
mmHg
Mahfoud F et al. Expert consensus document from the European
Society of Cardiology on catheter-based renal denervation, Eur Heart
J April 2013
1
Bӧhm M, ESC 2013
Co-Morbidities Include:
•Diabetes II 38.2%
•Renal Disease 30.1%
•Sleep Apnea 16.9%
•Hx of Cardiac Disease 49.4%
•Heart Failure 9.2%
•Atrial Fibrillation 12.6%
•LVH 15.9%

19. GSR Change in Office BP According to
Baseline BP
≥ 140
≥ 160*
≥ 180†
≥ 140
Bӧhm M, ESC 2013
≥ 180† ≥ 140
6 months
3 months
n=612 n=468 n=78
≥ 160*
≥ 180†
12 months
n=391 n=313 n=51
* ≥ 150 mm Hg in Diabetes
† ≥ 100 mm Hg DBP
≥ 160*
n=91
n=79
-37
n=9
p < 0.001 for all values except;
P = 0.001 SBP ≥ 180, 12m; p = 0.0005 DBP ≥ 180, 12m

20. Conclusions
 Excellent procedural and clinical safety
profile in real world
 Treatment resembles current consensus
 Significant reduction in both office and
ambulatory BP
 Enrolment and analyses continue
Bӧhm M, ESC 2013

21. Vascular safety

22. Symplicity HTN-1
Safety Out to 36-Months
Possible Renal Artery
Stenosis
0-6
Months
> 6-18
Months
> 18-36
Months
Hemodynamically stable, no
intervention required
1
1
-
Stented without sequelae
-
-
1
Non-significant, no
intervention required
-
1
-

23. GSR Procedural Safety
 Renal artery intervention due to dissection
0.09% (n=1)
 Vascular complication at access site
Vascular complication, pseudoaneurysm
Vascular complication, hematoma
Bӧhm M, ESC 2013
0.34% (n=4)
0.09% (n=1)

24.  OCT in 32 renal arteries after RDN
 11 Symplicity & 5 EnligHTN
 Key Symplicity inclusion criteria
 All patients received heparine and aspirin
Templin C et al, Eur Heart J 2013

25. Intraluminal thrombus formation increased from 18% to 67%.
Platelet inhibition after RDN is recommended
Templin C et al, Eur Heart J 2013

26. Puncture Site for Renal Artery

27. Renal Artery Anatomy

28. Renal Artery Anatomy

29. Access Site for Renal Artery

30. Technical Consideration for TRA

31. Technical Consideration for TRA
 In general, left radial is considered as a first choice
due to two main considerations:
 the distance from access to renals is shorter and
 less catheter manipulation is usually required
since there is no need to traverse the aortic arch.
The MP guiding catheter in an artery with downward
course

32. Technique
• Treat distal to proximal .
• 4 to 6 points in each artery / Size depending
• Both arteries should be treated

33. Technical Information of Iberis

34. Less Invasive

35. How to use ?
 Guiding catheter / Guiding sheath is placed in renal artery with a
standard Guide wire
 Stability of GC or GS is essential
 Has to be used through min 6 Fr Guiding catheter of 5 Fr Destination
 For radial access long guiding catheter is needed 125 cm
 The Iberis system is advanced through GC / GS
 No guide wire is necessary to place the Iberis catheter in renal artery

36. Safety Technology
• Automatic de-activation when electrode is not apposed
• Customized program controls RF energy
• Long term safety outcome of single electrode system

37. Less-invasive patients can be discharged from the hospital earlier

38. Other RDN systems
 Medtronic : Symplicity
 Boston : Vessix V2 system
 St Jude : EnlighHTN
 Covidien : One shot
 Recor : Paradise
 Cardiosonic : TIVUS

39. Medtronic :Symplicity® Catheter System™
®

41. New Catheters

42. Medtronicʼ s Multi-Electrode :Symplicity
Spyral

43. Symplicity Spyral – FIM





Over the wire
Standardized ablation pattern
1 min ablation
Effective in 3-8 mm* diameter renal arteries
One size fits most

44. BOSTON / Vessix V2 Percutaneous RF Balloon Catheter
Renal Denervation System for Hypertension

45. Occluding RF Ballon Catheter Optimized
for Renal Denervation

46. Vessix Bipolar RF Generator

47. Safety, Flexibility and Complete
Denervation

48. St Jude Medical : EnglinHTN : Renal
Artery Ablation Catheter

49. Covidien OneShot Renal Denervation
System

50. Recor ̓ s Paradise™ System

51. Cardiosonic TIVUS™ System

52. Comparison

53. Patient Selections:
 Avoid ablating arteries with renal stents
 Potential for the future
 Lower-risk moderate hypertension
 Drug-intolerant
 Anxiety disorders
 Heart failure
 Tachyarrhythmias
 Diabetes
 Sleep apnea

54. Therapeutic Strategies in Patients With Resistant
Hypertension
Recommendations
In case of ineffectiveness of drug
treatment invasive procedures
such as renal denervation and
baroreceptor stimulation may be
considered.
Until more evidence is available
on the long-term efficacy and
safety of renal denervation and
baroreceptor stimulation, it is
recommended that these
procedures remain in the hands
of experienced operators and
diagnosis and follow-up restricted to
hypertension centers.
It is recommended that the
invasive approaches are
considered only for truly resistant
hypertensive patients, with clinic
values ≥160 mmHg SBP or
≥110 mmHg DBP and with BP
elevation confirmed by ABPM.
Classª
IIb
Level
C
Ref.
-
I
C
-
I
C
-
European Heart Journal 2013; 34: 2159–2219

55. Could This Become a Great Opportunity ?
 The disease should be frequent
 The disease should be important
 Interventionalists should have direct access to the
patients
 Should be duable without huge infrastructure
 The procedure should be:
• effective
• safe
• durable
• easy to learn

56. Implementation Issues
 The long- term efficacy and safety of the RDN
procedure beyond three years in a larger patient
population in a real-world clinical practice setting has yet
to be determined.
 It is possible that sympathetic nerve regrowth over a
period of months to years could diminish long-term blood
pressure reduction.
 More studies are required to ascertain the need for
repeat procedures and the requirement for the
continuation of antihypertensive combination therapy.