CRT 2016 Washington Feb 20 23 2016 How

CRT 2016 Washington, Feb 20 -23, 2016 How Do I Treat Today’s Patients with Resistant Hypertension in My Practice? Horst Sievert, Laura Vaskelyte, Sameer Gafoor, Ilona Hofmann, Stefan Bertog, Predrag Matić, Markus Reinartz, Kolja Sievert Cardio. Vascular Center Frankfurt - CVC, Frankfurt, Germany

Disclosures Physician name Company Relationship Horst Sievert Abbott, Access Closure, AGA, Angiomed, Aptus, Atrium, Avinger, Bard, Biosense Webster, Boston Scientific, Bridgepoint, Carag, Cardiac Dimensions, Cardio. Kinetix, Cardio. MEMS, Cardiox, Celonova, CGuard, Coherex, Contego, Covidien, CSI, CVRx, Endo. Cross, ev 3, Flow. Cardia, Gore, GTIMD Medical, Guided Delivery Systems, Hemoteq, In. Seal Medical, Inspire. MD, Lumen Biomedical, HLT, Lifetech, Lutonix, Maya Medical, Medtronic, NDC, Occlutech, Osprey, Ostial, Pendra. Care, pfm Medical, Recor, Res. Med, Rox Medical, Sentre. Heart, Spectranetics, Square. One, Svelte Medical Systems, Tendyne, Trireme, Trivascular, Valtech, Vascular Dynamics, Venus Medical, Veryan, Vessix Consulting fees, Travel expenses, Study honoraria Cardiokinetix, Access Closure, Velocimed, Lumen Stock options, Biomedical, Stocks Coherex, SMT Grant Research Support Cook, St. Jude Medical

Preparing an invited lecture always requires some basic homework One part of this is to check how much time will be available It happened to me that I thought "10 min" and then it turned out to be 45 min

So this time I checked and found out that I have …. only 1 min

So I have to hurry up But please turn off the timer – it is not relevant for this talk!

Another important task is to define the topic • I will not talk about - How to rule out secondary hypertension • because that is always our first step in all hypertensive patients - How to rule out white coat effect and lack of compliance • because these patients do not have resistant hypertension - How to optimize medical therapy • because per definition medical therapy has already been optimized in resistant hypertension

Renal Denervation? • There is no doubt that RF does work • There is also no doubt - that there will no reimbursement - that I would have to pay it out of my pocket (patients never pay) • Therefore I don't do it with some rare exceptions

So what are the options? • Ongoing randomized studies with "old" approved devices • New renal denervation techniques in clinical trials • Other device based approaches

Devices for Renal Denervation • Radiofrequency catheters - Spiral - Medtronic St. Jude Medical Cordis Angiocare – Terumo Verve • Radiofrequency balloons - Vessix – Boston • Microwave - Denerv. XCooled • Drugs - Mercator Northwind Ablative Solutions Kipprokration Hospital, Athens • Radiation - Best Medical Int. - Cyber. Heart (Cyber. Knife) • Ultrasound - Recor Medical - Cardio. Sonic - Kona

Verve Surprisingly, some cardiovascular interventionists think that this is Transurethral denervation (Radiofrequency) invasive … … whereas urologists know that this is the simpliest thing to do • Animal results: - Tissue norepinephrine levels dropped 70% R. Heuser In humans (n=4), 1 month result

Northwind Approach • Local administration of a neurotropic agent - NW 2013: Specifically destroying nerves, leaving other tissue unaffected • Catheter-based delivery using micro-needles - 0. 014 guide wire-based, - 6 -8 F delivery system

Northwind Ambulatory BP over 3 Months N=5 p=0. 14 Mean Std. Dev. SEM 164. 2 14. 7 6. 6 145. 4 22. 8 10. 2 p=0. 07 142. 2 18. 9 8. 4

Ablative Solutions Peri. Vascular Renal Denervation (PVRD) Renal nerves Micro Needles Renal artery crosssection Ethanol or other agents Tim Fischell TRENDS 2013

Change in Office Blood Pressure SBP and DBP Reduction From Baseline Through 6 Months (Office BP) SBP and DBP Change Per Visit 200 Blood Pressure mm Hg 160 140 175 120 151 153 100 80 60 95 87 83 40 20 0 Baseline (N=16) 1 Month (N=16) SBP Blood Pressure Reduction (mm Hg) 180 1 Month (N=16) 6 Months (N=16) 0 -5 -8 -10 -12 -15 -20 -22 -24 -25 -30 Systolic BP Diastolic BP 6 Months (N=16) DBP Reduction in systolic OBP at 6 -Month = -24 ± 21 Reduction in diastolic OBP at 6 -Month = -12 ± 21 Fischell et al, in preparation

Radiation: Best Medical Int. • Radiation selectively destroys nerves • Device is based on the Novoste system for brachytherapy • Clinical trial ongoing R. Waksman

Surprisingly, some cardiovascular interventionists think that this is invasive Cyber. Heart - Cyber. Knife • Percutaneous radiation therapy • Ready for clinical trial

Ultrasound: Recor Medical • Ultrasound transducer mounted inside of a low pressure balloon • Cooled water in the balloon protects the endothelium against heat • 30 seconds of circumferential heating CE mark

Kona Medical Surround Sound. TM System • Fully non-invasive system utilizing ultrasound for targeting / tracking • Wave I, II and III trials: BP reduction 25 mm. Hg after 6 months

… and beyond renal denervation?

Approaches to modulate the Sympathetic System • Deep brain stimulation • Carotid sinus stimulation • Carotid body ablation • Bladder trigone stimulation

Surprisingly, some cardiovascular interventionists think that this is invasive Periaqueductal gray stimulation Ventral PAG 30 Hz 2 v Dorsal PAG Jonathan Hyam, TRENDS 2013

Approaches to modulate the Sympathetic System • Deep brain stimulation • Carotid sinus stimulation • Carotid body ablation • Bladder trigone stimulation

Carotid sinus stimulation - Background The Baroreflex

Electrode, implanted at the carotid bulb New Generation Lead (Unilateral) neo

Rheos Pivotal trial: SBP Reduction and Improvement in Stages of Hypertension in (N=251) 177. 6 ± 21. 9 -34. 6 ± 1. 9 p < 0. 001 143. 0 ± 28. 7 100 90 21% SBP > 160 80 70 60 % 83% 25% SBP 140 - 160 SBP <= 140 50 40 54% 30 20 10 15% 0 Enrollment 12 Months BAT • 81% of patients were responders (SBP decrease ≥ 10 mm. Hg)

Barostim has entered the ESH/ESC guidelines as an option to treat resistant hypertension

Mobius. HD concept • Implant placed in the carotid sinus • It passively amplifies the signal generated by the baroreceptors surrounding the carotid sinus - thereby signaling the Central Nervous System to lower blood pressure. Vascular Dynamics, Inc.

Case Example Jan van der Heyden, TRENDS 2014, Frankfurt

Approches to modulate the Sympathetic System • Deep brain stimulation • Carotid sinus stimulation • Carotid body ablation • Bladder trigone stimulation

What is the Carotid Body? • A small cluster of cells with chemoreceptors • located near the carotid bifurcation • It detects changes in - the partial pressure of oxygen and carbon dioxide, - p. H, - Temperature • Activation of the carotid body increases ventilation and blood pressure

• Cibiem Transvenous Procedure: Posterior IJV Measure desired depth of desired lesion • Identify desired height of treatment using fluoroscopy and Ultra ICE • • Measure desired lesion depth on Ultra ICE • • Enter desired ablation depth into Cibiem generator Parameters for ablation automatically determined Ablation time: 5 – 15 seconds

Approaches to modulate the Sympathetic System • Deep brain stimulation • Carotid sinus stimulation • Carotid body ablation • Bladder trigone stimulation

Surprisingly, some cardiovascular interventionists think that this is invasive Bladder Trigone Stimulation • Stimulation of the bladder • Reduces sympathetic activity Nephera Ltd. , Caesarea, Israel

So, in my daily practice • Clinical trials - KONA, Cibien, Ablative Solutions, Mobius • Unfortunately most patients do not qualify • Baroreceptor stimulation • Conventional renal denervation - RF or ultrasound

Thank you!