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Renal denervation in resistant hypertension, with target organ damage

Renal denervation in resistant hypertension, with target organ damage . Darrel Francis Reader in Cardiology Imperial College, London. BHS, Cambridge 2011. REACH – pilot study REnal Artery  denervation in Chronic Heart failure Imperial College London. 55 female

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Renal denervation in resistant hypertension, with target organ damage

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  1. Renal denervation in resistant hypertension, with target organ damage Darrel Francis Reader in Cardiology Imperial College, London BHS, Cambridge 2011

  2. REACH – pilot study REnal Artery  denervation in Chronic Heart failure Imperial College London 55 female Hypertension for over 20 years since the birth of her first child 15 years blood pressure >180 mm Hg tolerated well no evidence of secondary organ involvement

  3. REACH – pilot study REnal Artery  denervation in Chronic Heart failure Imperial College London Extensive review tertiary (Newcastle) and at national specialist centres (Cambridge) Excluded secondary causes of hypertension Renal artery stenosis Congenital causes Malignancy Tests Normal renal function No proteinuria CT/MRI Renal vein sampling

  4. Progressive worsening of hypertension 18 months blood pressure sustained >230 mm Hg (250-270mm Hg)episodes of blood pressure exceeding 300 mmHg 6 months heart failure – moderate-severe systolic impairment Marked decrease in exercise capacity (200 yards) 3 in-patient admissions 1 ITU admission (Pulmonary oedema) pre-syncope when blood pressure <170 mmHg

  5. Pharmacological regime

  6. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 7

  7. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 8

  8. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 9

  9. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 10

  10. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 11

  11. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 12

  12. Primary Endpoint: 6-Month Office BP ∆ from Baseline to 6 Months (mmHg) Systolic Diastolic Diastolic Systolic 33/11 mmHg difference between RDN and Control (p<0.0001) • 84% of RDN patients had ≥ 10 mmHg reduction in SBP • 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. The Lancet 2010: 376:1903-1909 13

  13. Renal Denervation – practicalities of the technique

  14. Symplicity® Catheter System™ • Low profile, electrode-tipped catheter • Delivers RF energy to treatment site • Proprietary RF generator • - Low power • - Automated • - Built-in safety control algorithms • Standard interventional technique

  15. Multiple Discrete TreatmentsMaximize Nerve Coverage Without Applying Circumferential Energy in a Single Segment

  16. 6-Month Histology (Porcine Model) Movat’s pentachrome stain cutting artifact Zone of energy delivery 20X magnification 100X magnification Findings: Minimal intimal thickening and minimal IEL injury overlying areas of mild full thickness medial fibrosis (yellow with green [proteoglycan deposition]), and adventitial fibrosis (yellow). No significant inflammatory cells are present suggesting that the healing process is complete.

  17. REACH Phase 1 7-patient safety study Investigator-led study Academic Health Science Centre, Cardiovascular Practice Group AimDetermine first-in-man safety of procedurein 7 patients with CHFInpatient monitoring for 5 days afterwardsWeekly and then monthly outpatient monitoring for 6 months

  18. REACH Phase 1 7-patient safety study Day Minus 1 AdmissionClinical assessmentQoLBloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  19. REACH Phase 1 7-patient safety study Day 0 ProcedureResearch Cath Lab AnaesthetistOn standby: Interventional Radiologist Vascular surgeon Nephrologist Post-procedure Care plan designed with Head of Nursing Patient returns to ward Team of Specialist Research Nursing Sisters Dr Justin Davies and Dr Darrel Francisare first point of contact for ward team if any queries 5-day postprocedure stay planned, with option to extend

  20. REACH Phase 1 7-patient safety study Day +1 Clinical assessmentBloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin 24-hour UrineSodium outputCreatinine outputMetanephrines24-hour ambulatory monitors BP ECG

  21. REACH Phase 1 7-patient safety study Day +2 .. +4 Clinical assessmentBloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin 24-hour UrineSodium outputCreatinine outputMetanephrines24-hour ambulatory monitors BP ECG

  22. REACH Phase 1 7-patient safety study Week +1 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  23. REACH Phase 1 7-patient safety study Week +2 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  24. REACH Phase 1 7-patient safety study Month +1 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  25. REACH Phase 1 7-patient safety study Month +2 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  26. REACH Phase 1 7-patient safety study Month +3 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  27. REACH Phase 1 7-patient safety study Month +4 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  28. REACH Phase 1 7-patient safety study Month +5 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  29. REACH Phase 1 7-patient safety study Month +6 BloodsElectrolytes, Creatinine, NT-ProBNPRenin, aldosteroneFasting glucose, insulin24-hour UrineSodium outputCreatinine outputMetanephrines Chemoreflex testingDynamic sinusoidal CO2 stimulusRebreathing CO2 stimulusExercise 6 minute walk testCardiopulmonary exercise testEchocardiography Heart rate / BP variability Recumbent spontaneousControlled breathing 24-hour ambulatory monitors BP ECG

  30. REACH – pilot patient REnal Artery  denervation in Chronic Heart failure Extensive pre-procedural preparation Admission Review by clinical pharmacology team Anaesthetic review Biochemistry / Imaging performed Echo – severe LV systolic function Detailed review of notes from previous investigations

  31. REACH – pilot patient REnal Artery  denervation in Chronic Heart failure Procedure Anaesthetic input to maintain SBP at 180 mmHg Uncomplicated denervation procedure Immediate after-care Immediate fall in blood pressure overnight to 150 mm Hg Medications temporary reduced, and then slowly restored to original levels

  32. REACH – pilot patient REnal Artery  denervation in Chronic Heart failure Discharge Reduction in 2 of her anti-hypertensive agents Blood pressure 190-200 mmHg Felt well

  33. REACH – pilot patient REnal Artery  denervation in Chronic Heart failure Follow-up (2 weeks) Large symptomatic improvement in breathlessness Blood pressure 190-200 mmHg Exercise tolerance increased from 200 m to 1 mile Medications re-introduced at full dose with the aim to slowly reduce her blood pressure

  34. REACH – pilot study REnal Artery  denervation in Chronic Heart failure Follow-up (4 months) Continues to feels well Improvement in exercise capacity persists 250-280mmHgsystolic 200-205mmHgsystolic

  35. Close enough to target most of the time

  36. Close enough to target most of the time

  37. ~2 x

  38. ~2 x ~2 x

  39. REACH – pilot study REnal Artery  denervation in Chronic Heart failure Follow-up (4 months) Continues to feels well Improvement in exercise capacity persists 250-280mmHgsystolic 200-205mmHgsystolic

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