Kedev S - AIMRADIAL 2013 - Renal denervation
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Renal denervation is a potential treatment for resistant hypertension that involves ablating the renal nerves to lower blood pressure. The document discusses the epidemiology of hypertension and definitions of resistant hypertension. It then summarizes early clinical trial results from Symplicity HTN-1 and Symplicity HTN-2 that demonstrated reductions in blood pressure out to 3 years with renal denervation. Ongoing studies like the Global SYMPLICITY Registry aim to evaluate real-world outcomes. The document reviews technical considerations for renal denervation and compares various catheter systems for performing the procedure. Long-term data are still needed regarding durability and safety with larger and longer-term studies.
Kedev S - AIMRADIAL 2013 - Renal denervation
- 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
- 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
- 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
- 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.
Editor's Notes
- #5: 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
- #6: 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
- #7: 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
- #8: RDN: Disrupt the renal nerves, break the cycle; Simultaneously reduce both efferent & 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
- #22: 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.
- #23: 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.
- #24: Need background on the first renal artery re-intervention
- #35: Nickel-titanium shaft makes RA possible and easy delivery
- #37: 5.1 ± 1.4 antihypertensive drugs
- #54: 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.