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Catheter-Based Renal Sympathetic Denervation in the Management of Resistant Hypertension

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0 samir rafla renal denervation

  1. 1. Catheter-Based Renal SympatheticDenervation in the Management ofResistant HypertensionProf. Samir Morcos RaflaAlexandria Univ.1
  2. 2. The RenalSympatheticNervous System
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  5. 5. The European Society of Cardiology (ESC)has issued a consensus statement regardingthe use of catheter-based renal denervation forthe treatment of high blood pressure, statingthat the novel therapy can be considered atherapeutic option in patients with drug-resistant hypertension who cannot get to goalwith a combination of lifestyle andpharmacologic therapy.
  6. 6. 6The data support the concept that theradiofrequency ablation of the renal nervesreduces blood pressure and improves blood-pressure control in these difficult-to-treatpatients. The data supporting the treatmentnow extend to 36 monthsMahfoud F, et al. Expert consensus document from theEuropean Society of Cardiology on catheter-based renaldenervation. Eur Heart J 2013; DOI:10.1093
  7. 7. 7Patients are eligible for renal denervation if they meetthe following criteria:Office-based blood pressure >160 mm Hg (>150 mm Hgin patients with type diabetes).Use of three or more antihypertensive drugs in adequatedosage and combination, including use of a diuretic.Have attempted to modify blood pressure with lifestylechanges.Secondary hypertension has been excluded.Pseudoresistance has been excluded with the use ofambulatory blood-pressure monitoring.Patients have preserved renal function (glomerularfiltration rate >45 mL/min/1.732).Absence of polar or accessory arteries, no renal arterystenosis, and no prior renal revascularization.
  8. 8. 8The ESC consensus statement acknowledgesthat it is not yet clear how renal denervationworks, but the mechanism is likely the result of areduction in peripheral resistance, reduced reninrelease, and favorable changes in water and salthandling."The fact that renal denervation also reduceswhole-body sympathetic-nerve activity suggeststhat this therapy may also be beneficial in otherclinical states characterized by sympatheticnervous system activation—this may ultimatelylead to new indications,"
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  11. 11. SYMPLICITY HTN-2 (Renal Denervation inPatients With Uncontrolled Hypertension)• Background:Renal sympathetic efferent and afferent nerves are crucial for the initiation andmaintenance of systemic hypertensionDenervation of the renal sympathetic nerve to reduce BP has been attempted,unsuccessfully, by surgical means years ago• Population and treatment:106 patients with resistant hypertension (SBP >160 mm Hg, or >150 mm Hg forthose with type 2 diabetes, taking ≥ three antihypertensive drugs)Randomized 1:1 to renal denervation + previous treatment (n=52) or previoustreatment alone (n=51)• Primary outcome:BP reduction at six monthsMD Esler (Baker IDI Heart and Diabetes Institute, Melbourne, Australia)American Heart Association 2010 Scientific Sessions
  12. 12. • Average office-based BP in the renal-denervation group was reduced 32/12 mm Hg(average baseline 178/96 mm Hg) six months after the ablation• Between-group differences in BP at six months were 33/11 mm Hg (p<0.0001)• Of the patients in the ablation arm, 84% had a 10-mm-Hg or greater drop in SBP vs35% of controls (p<0.0001)• There did not appear to be any adverse events:Imaging of renal arteries for damage showed no evidence of renal artery stenosisor aneurysmal dilatation during the six-month follow-upThere were no changes in renal function, even in those with mild to moderaterenal failureSYMPLICITY HTN-2: Results
  13. 13. SYMPLICITY HTN-2: Commentary**All comments from A revolutionary road for resistant hypertension? Renal denervation in SymplicityHTN-2 (http://www.theheart.org/article/1151787.do)"This has the potential for really revolutionizing the way we treat resistanthypertension, which is an enormous clinical need."- Dr Suzanne Oparil"Ive never seen BP falls as big as this from any other treatment process, whichmakes the possibility of cure realistic; it might be within reach."- Dr Murray D Esler"My only reservation about the study is that they have not compared thedenervation with the most effective add-on drug in patients with resistanthypertension, which is spironolactone."- Dr Peter Sever
  14. 14. Anatomical Location of RenalSympathetic Nerves• Arise from T10-L1• Follow the renal artery to the kidney• Primarily lie within the adventitia
  15. 15. Anatomical Location of RenalSympathetic Nerves• Arise from T10-L1• Follow the renal artery to the kidney• Primarily lie within the adventitiaVesselLumenMediaAdventitiaRenalNerves
  16. 16. RF Ablation Approach to RenalSympathetic DenervationElectrodeInsulatedarch wireSymplicity® Catheter System,Ardian, Inc., Palo Alto, CA, USA
  17. 17. Placement of Renal RF Catheter
  18. 18. Treatment by Renal RF Catheter
  19. 19. Treatment by Renal RF Catheter
  20. 20. Treatment by Renal RF Catheter
  21. 21. Treatment by Renal RF Catheter
  22. 22. Treatment involves approximately 4 to 6applications Using low-power (8 W)radiofrequency energy. Treatments aredelivered in a helical fashion within the renalartery by rotation of the catheter andapproximately 5 mm pullback betweenablations. The generator provides theradiofrequency energy according to anautomated algorithm
  23. 23. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EEHypertension Epidemiology• Single largest contributor to deathworldwide• Every 20/10 mmHg increase in BPcorrelates with a doubling of 10-yearcardiovascular mortality• Dramatically increases risk of stroke,heart attack, heart failure, & kidney failure• Only half of all treated hypertensives arecontrolled to established BP targets• High prevalence:• Affects 1 in 3 adults• 1B people worldwide  1.6 B by 202535%Treated &Controlled30%Untreated35%Treated butUncontrolledChobanian et al. Hypertension. 2003;42(6):1206–1252.23c
  24. 24. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EERenal Sympathetic Activation: Efferent NervesKidney as Recipient of Sympathetic SignalsRenal EfferentNerves↑ Renin Release  RAAS activation↑ Sodium Retention↓ Renal Blood Flow24
  25. 25. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EEHypertrophyArrhythmiaOxygen ConsumptionVasoconstrictionAtherosclerosisInsulinResistanceRenal Sympathetic Activation: Afferent NervesKidney as Origin of Central Sympathetic DriveRenal AfferentNerves↑ Renin Release  RAAS activation↑ Sodium Retention↓ Renal Blood FlowSleepDisturbances25
  26. 26. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EE• Nerves arise from T10-L2• The nerves arborize around the arteryand primarily lie within the adventitiaRenal Nerve AnatomyVesselLumenMediaAdventitiaRenalNerves2626
  27. 27. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EERenal Nerve Anatomy Allows aCatheter-Based Approach27• Renal artery access via standardinterventional technique• 4-6 two-minute treatments per artery• Proprietary RF generator– Automated– Low power– Built-in safety algorithmsSpacing ofe.g. 5 mm.
  28. 28. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EE
  29. 29. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EEBaseline Patient Characteristics (n=153)29Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917.Demographics Age (years) 57 ± 11Gender (% female) 39%Race (% non-Caucasian) 5%Co-morbidities Diabetes Mellitus II (%) 31%CAD (%) 22%Hyperlipidemia (%) 68%eGFR (mL/min/1.73m2) 83 ± 20Blood Pressure Baseline BP (mmHg) 176/98 ± 17/15Number of anti-HTN meds (mean) 5.1 ± 1.4Diuretic (%) 95%Aldosterone blocker(%) 22%ACE/ARB (%) 91%Direct Renin Inhibitor 14%Beta-blocker (%) 82%Calcium channel blocker (%) 75%Centrally acting sympatholytic (%) 33%Vasodilator (%) 19%Alpha-1 blocker 19%
  30. 30. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EEBrief Procedure with a Low Complication rate(n=153)• 38 minute median procedure time– Average of 4 ablations per artery• Intravenous narcotics & sedatives used to manage painduring delivery of RF energy• No catheter or generator malfunctions• No major complications• Minor complications 4/153:– 1 renal artery dissection during catheter delivery (priorto RF energy), no sequelae– 3 access site complications, treated without furthersequelae30Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917.
  31. 31. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EESymplicity HTN-1: BP Reductions through3 yearsBP change(mmHg)P<0.01 for ∆ from BLfor all time points*Expanded results presented at the American College of Cardiology Annual Meeting 2012 (Krum, H.)
  32. 32. FordistributiononlyinmarketswheretheSymplicity™renaldenervationsystemisapproved.NotfordistributionintheUSAorJapan.Trademarksmayberegisteredandarethepropertyoftheirrespectiveowners.©2012Medtronic,Inc.Allrightsreserved.UC201205567EE• Therapeutic renal sympathetic denervation involves a brief,simple percutaneous procedure• No major complications were observed to either the renalartery or the kidney• Significant and sustained reductions in blood pressure wereachieved in patients with resistant hypertension• Achievement of denervation supported by significantreduction in renal norepinephrine spilloverSummary
  33. 33. ConclusionsRenal denervation offers a novel and safecatheter-based approach for selective reductionof renal sympathetic drive. We demonstrated forthe first time that selective denervation of therenal sympathetic nerves has the potential toimprove glucose metabolism and blood pressurecontrol concurrently in patients with resistanthypertension in the absence of significantchanges in body weight and alterations in lifestyleor antihypertensive medication.
  34. 34. J Clin Hypertens . 2012;14:799–801. 2012The Ohio State University, Columbus, OH;
  35. 35. 35Attenuation of sympathetic activity may have amultitude of effects beyond those directly related tohypertension. Increased sympathetic nervoussystem activity, for example, is associated withheightened risk of death among heart failurepatients. Further, salt and water retention in someforms of heart failure may be mediated in large partby renal sympathetic activity, and selective renaldenervation may play a role in treatment orprevention of heart failure and the cardiorenalsyndrome. Recent reports in patients with insulinresistance or type II diabetes mellitus,polycystic ovary syndrome, and hypertension havealso suggested improved insulin resistance andglycemic control with denervation therapy.
  36. 36. 37
  37. 37. Multi-electrode renal-denervation deviceappears safe38
  38. 38. 39RD offers a novel and safe catheter-based approachfor selective reduction of renal sympathetic drive. Wedemonstrate for the first time to our knowledge thatselective denervation of the renal sympatheticnerves in addition to lowering peripheral BPsignificantly reduces LV mass and improves diastolicfunction in patients with resistant hypertension.
  39. 39. 40•Renal denervation has been shown to reducefasting plasma glucose, fasting plasma insulin,insulin resistance, and haemoglobin A1C levelsin diabetic patients with resistant hypertension.•In patients with obstructive sleep apnoea andresistant hypertension, renal denervationresulted in improvements in glucose profiles aswell as sleep apnoea symptoms.•There is some evidence that renal denervationexerts a renoprotective effect in diabeticnephropathy.Excerpta MedicaFeb 19, 2013
  40. 40. Hints of renal-denervation side benefit:Fewer ventricular arrhythmiasRenal sympathetic denervation significantly reduces mean heart rateand exerts a favorable effect on atrial and ventricular arrhythmias inresistant hypertensives. American College of Cardiology 2013 ScientificSessions; March 9, 2013; San Francisco, CA. Abstract 1148-22.41
  41. 41. Renal-artery denervation can help to reducethe recurrence of atrial fibrillation in concertwith pulmonary-vein isolation (PVI) inpatients with drug-resistant hypertension.A randomized comparison of pulmonary vein isolation with versuswithout concomitant renal artery denervation in patients with refractorysymptomatic atrial fibrillation and resistant hypertension. J Am CollCardiol 2012; 05.03642
  42. 42. Vascular lesions induced by renal nerve ablation asassessed by optical coherence tomography: pre-and post-procedural comparison with theSimplicity(R) catheter system and the EnligHTN™multi-electrode renal denervation catheter.Eur Heart J Apr 2013;43CONCLUSION: Here we show that diffuse renalartery constriction and local tissue damage at theablation site with oedema and thrombus formationoccur after RNA and that OCT (optical coherenttomography) visualizes vascular lesions not apparenton angiography. This suggests that dual antiplatelettherapy may be required during RNA.
  43. 43. Expert Consensus Document From the EuropeanSociety of Cardiology on Catheter-Based RenalDenervation. Eur Heart J 2013; Apr 251. Hypertension is one of the most frequent chronicdiseases worldwide. It is estimated that over the nexttwo decades, up to 50% of the adult population will bediagnosed with hypertension.2. Resistant hypertension, defined as uncontrolled bloodpressure that persists despite the use of three or moreantihypertensives of different classes, including adiuretic, at maximal or the highest tolerated dose, ispresent in 5-10% of patients with hypertension.44
  44. 44. 3. Renal denervation targeting both afferent and efferentnerves has been demonstrated to reduce sympatheticnerve activity, norepinephrine spillover, and bloodpressure in patients with resistant hypertension.5. The renal artery needs to be at least 4 mm indiameter and at least 20 mm in length for successfuldenervation, and should be free of significant stenosis orcalcification.6. Transient local de-endothelialization, acute cellularswelling, connective tissue coagulation, and thrombusformation have been demonstrated to occur after renaldenervation. Use of aspirin for 4 weeks is empiricallyrecommended based on these findings.45
  45. 45. 7. Improvement in blood pressure rarely occursimmediately, and it often takes several weeks tomonths before a notable blood pressure reductionis evident. Further, a reduction in pill burden hasnot been demonstrated in the currently completedrandomized trials, although consistent reductionin blood pressure has been noted in bothrandomized and observational studies.46
  46. 46. 8. Renal denervation results in a significant dropin resting, maximum exercise, and recovery bloodpressure, whereas heart rate response duringexercise and oxygen uptake is well preserved.9. Renal denervation is currently being evaluatedfor heart failure and metabolic syndrome, withsmall studies demonstrating promising results.Further, the therapy has also been demonstratedto reduce the occurrence of atrial fibrillation andventricular arrhythmias.47