Renal Denervation:
The Next Big Push For
Radial Approach?
Sasko Kedev, MD, PhD, FESC, FACC
University Clinic of Cardiology...
Disclosure
Nothing to disclose
Hypertension Epidemiology
• Single largest contributor to death worldwide
30%
Untreated

35%
Treated but
Uncontrolled

35%...
Resistant Hypertension - Definition
Failure to achieve target blood pressure values:
 Standardized systolic clinic blood ...
Renal Sympathetic Efferent Nerve Activity:
Kidney as Recipient of Sympathetic Signals

Renal Efferent
Nerves

↑ Renin Rele...
Renal Afferent Nerves:
Kidney as Origin of Central Sympathetic Drive

Vasoconstriction
Atherosclerosis

Insulin
Resistance...
Renal Nerve Anatomy
• Nerves arise from T10-L2
• The nerves arborize around the artery
and primarily lie within the advent...
Anatomy of Renal Artery
Renal Nerve Anatomy Allows a
Catheter-Based Approach

• Standard interventional technique
• 4-6 two-minute treatments per ...
Which Patients Are Suitable For
Renal Denervation?
 SBP ≥160 mmHg (≥150 mmHg Diabetes Type 2)
 ≥3 antihypertensive drugs...
Staged Clinical Evaluation
First-in-Man 
Symplicity HTN-1
Series of Pilot studies 
Symplicity HTN-2 
EU/AU Randomized C...
Symplicity HTN-1 Change in Office BP
Through 36 Months (153 Patients)

P<0.01 for ∆ from BL for all time points
Symplicity HTN-1 % Responders Over Time
(All Patients)

(n=141)

(n=144)

(n=132)

(n=105)

(n=88)
Conclusions
 BP-lowering with percutaneous RDN appears to be
durable out to 36-months
 This suggests that nerve re-growt...
Systolic BP (mmHg)

Renal Denervation
Randomization Offered to Control

(n = 37)

(n = 54)
(n = 52)

(n = 35)

(n = 49)

(...
Global SYMPLICITY Registry: Real-World
Clinical Outcomes
Worldwide evaluation of the safety and efficacy of treatment with...
GSR Population Characteristics
 1097 patients treated as of
June 26, 2013
 86% with SBP ≥140 mmHg
 66% of patients trea...
GSR Change in Office BP According to
Baseline BP
≥ 140

≥ 160*

≥ 180†

≥ 140

Bӧhm M, ESC 2013

≥ 180† ≥ 140

6 months

3...
Conclusions
 Excellent procedural and clinical safety
profile in real world
 Treatment resembles current consensus
 Sig...
Vascular safety
Symplicity HTN-1
Safety Out to 36-Months
Possible Renal Artery
Stenosis

0-6
Months

> 6-18
Months

> 18-36
Months

Hemody...
GSR Procedural Safety

 Renal artery intervention due to dissection

0.09% (n=1)

 Vascular complication at access site
...
 OCT in 32 renal arteries after RDN
 11 Symplicity & 5 EnligHTN
 Key Symplicity inclusion criteria
 All patients recei...
Intraluminal thrombus formation increased from 18% to 67%.
Platelet inhibition after RDN is recommended
Templin C et al, E...
Puncture Site for Renal Artery
Renal Artery Anatomy
Renal Artery Anatomy
Access Site for Renal Artery
Technical Consideration for TRA
Technical Consideration for TRA
 In general, left radial is considered as a first choice
due to two main considerations:
...
Technique
• Treat distal to proximal .
• 4 to 6 points in each artery / Size depending
• Both arteries should be treated
Technical Information of Iberis
Less Invasive
How to use ?
 Guiding catheter / Guiding sheath is placed in renal artery with a
standard Guide wire
 Stability of GC or...
Safety Technology

• Automatic de-activation when electrode is not apposed
• Customized program controls RF energy
• Long ...
Less-invasive patients can be discharged from the hospital earlier
Other RDN systems
 Medtronic : Symplicity
 Boston : Vessix V2 system
 St Jude : EnlighHTN
 Covidien : One shot
 Recor...
Medtronic :Symplicity® Catheter System™

®
New Catheters
Medtronicʼ s Multi-Electrode :Symplicity
Spyral
Symplicity Spyral – FIM






Over the wire
Standardized ablation pattern
1 min ablation
Effective in 3-8 mm* diamete...
BOSTON / Vessix V2 Percutaneous RF Balloon Catheter
Renal Denervation System for Hypertension
Occluding RF Ballon Catheter Optimized
for Renal Denervation
Vessix Bipolar RF Generator
Safety, Flexibility and Complete
Denervation
St Jude Medical : EnglinHTN : Renal
Artery Ablation Catheter
Covidien OneShot Renal Denervation
System
Recor ̓ s Paradise™ System
Cardiosonic TIVUS™ System
Comparison
Patient Selections:
 Avoid ablating arteries with renal stents
 Potential for the future
 Lower-risk moderate hypertens...
Therapeutic Strategies in Patients With Resistant
Hypertension
Recommendations
In case of ineffectiveness of drug
treatmen...
Could This Become a Great Opportunity ?
 The disease should be frequent
 The disease should be important
 Interventiona...
Implementation Issues
 The long- term efficacy and safety of the RDN
procedure beyond three years in a larger patient
pop...
Kedev S - AIMRADIAL 2013 - Renal denervation
Kedev S - AIMRADIAL 2013 - Renal denervation
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Renal denervation: the next big push for radial approach

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  • Accordingly, these criteria and blood pressure thresholds should be borne in mind when selecting patients for renal nerve ablation
    Secondary forms of hypertension and pseudo-resistance, such as non-adherence with medication, intolerance of medication, and white coat hypertension should have been ruled out and 24-h ambulatory blood pressure monitoring is mandatory in this context
  • Efferent Renal Nerves: Sympathetic drive from the CNS acts on the kidney to:1) Decrease renal blood flow; 2) Increase sodium retention; 3) Stimulate renin release
    Afferent RN: The kidney is a source of central sympathetic activity, sending signals to the CNS
  • Efferent Renal Nerves: Sympathetic drive from the CNS acts on the kidney to:1) Decrease renal blood flow; 2) Increase sodium retention; 3) Stimulate renin release
    Afferent RN: The kidney is a source of central sympathetic activity, sending signals to the CNS
  • RDN: Disrupt the renal nerves, break the cycle; Simultaneously reduce both efferent &amp; afferent effects
    70% of RN are within 1.5mm of the ostium of the RA
    95% of RN are within 2.5mm of the vessel lumen
  • As there are theoretical concerns with regard to renal safety, selected patients should have preserved renal function with an estimated GFR of at least ≥45ml/min/1.73m2.
  • Long-term safety and efficacy data are limited to 3 years of follow up in small patient cohorts, thus efforts to monitor treated patients are crucial to define long term performance of the procedure.
  • Need background on the first renal artery re-intervention
  • Nickel-titanium shaft makes RA possible and easy delivery
  • 5.1 ± 1.4 antihypertensive drugs
  • While renal nerve ablation could have beneficial effects in other conditions characterized by elevated renal sympathetic nerve activity, its potential use for such indications should currently be limited to formal research studies of its safety and efficacy.
  • Kedev S - AIMRADIAL 2013 - Renal denervation

    1. 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. 2. Disclosure Nothing to disclose
    3. 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. 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. 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. 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. 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. 8. Anatomy of Renal Artery
    9. 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
    10. 10. 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
    11. 11. 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
    12. 12. Symplicity HTN-1 Change in Office BP Through 36 Months (153 Patients) P<0.01 for ∆ from BL for all time points
    13. 13. Symplicity HTN-1 % Responders Over Time (All Patients) (n=141) (n=144) (n=132) (n=105) (n=88)
    14. 14. 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
    15. 15. 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
    16. 16. 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
    17. 17. 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%
    18. 18. 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
    19. 19. 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
    20. 20. Vascular safety
    21. 21. 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 -
    22. 22. 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)
    23. 23.  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
    24. 24. Intraluminal thrombus formation increased from 18% to 67%. Platelet inhibition after RDN is recommended Templin C et al, Eur Heart J 2013
    25. 25. Puncture Site for Renal Artery
    26. 26. Renal Artery Anatomy
    27. 27. Renal Artery Anatomy
    28. 28. Access Site for Renal Artery
    29. 29. Technical Consideration for TRA
    30. 30. 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
    31. 31. Technique • Treat distal to proximal . • 4 to 6 points in each artery / Size depending • Both arteries should be treated
    32. 32. Technical Information of Iberis
    33. 33. Less Invasive
    34. 34. 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
    35. 35. Safety Technology • Automatic de-activation when electrode is not apposed • Customized program controls RF energy • Long term safety outcome of single electrode system
    36. 36. Less-invasive patients can be discharged from the hospital earlier
    37. 37. Other RDN systems  Medtronic : Symplicity  Boston : Vessix V2 system  St Jude : EnlighHTN  Covidien : One shot  Recor : Paradise  Cardiosonic : TIVUS
    38. 38. Medtronic :Symplicity® Catheter System™ ®
    39. 39. New Catheters
    40. 40. Medtronicʼ s Multi-Electrode :Symplicity Spyral
    41. 41. Symplicity Spyral – FIM      Over the wire Standardized ablation pattern 1 min ablation Effective in 3-8 mm* diameter renal arteries One size fits most
    42. 42. BOSTON / Vessix V2 Percutaneous RF Balloon Catheter Renal Denervation System for Hypertension
    43. 43. Occluding RF Ballon Catheter Optimized for Renal Denervation
    44. 44. Vessix Bipolar RF Generator
    45. 45. Safety, Flexibility and Complete Denervation
    46. 46. St Jude Medical : EnglinHTN : Renal Artery Ablation Catheter
    47. 47. Covidien OneShot Renal Denervation System
    48. 48. Recor ̓ s Paradise™ System
    49. 49. Cardiosonic TIVUS™ System
    50. 50. Comparison
    51. 51. 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
    52. 52. 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
    53. 53. 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
    54. 54. 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.

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