Απονεύρωση νεφρικών αρτηριών. Που βρισκόμαστε και που πάμε. Κώστας Τσιούφης ESH Secretary Εκλεγείς πρόεδρος ΕΚΕ

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1 Απονεύρωση νεφρικών αρτηριών. Που βρισκόμαστε και που πάμε Κώστας Τσιούφης ESH Secretary Εκλεγείς πρόεδρος ΕΚΕ

2 Blocking of SNS overactivity: An unmet need through time HTN 3 30 s-50 s 60 s /14 11/2014 Clinical use Research interest Time

3 Theoretical basis for catheter-based RDN treatment of HTN Renal sympathetic activation in essential hypertension Surgical renal denervation lowers BP in experimental hypertension Kidney transplantation in humans: the denervated kidney is capable of maintaining electrolyte and volume homeostasis Renal nerves are close to renal artery lumen

4 How does RDN work? Papademetriou V, Tsioufis C, Doumas M. Circulation 2014

5 Multiple Clinical Trials showed BP reduction Mean decrease of office systolic BP (mmhg) N=153 N=102 N=29 N=313 N=109 N=206 N=63 N=15 N=36 N=46 N=139 N=50 N=17 N=16 Ott C., Schmieder RE Current Review Hypertension 014 in press Medtronic EnligHTN/St Jude Vessix/Boston Sci Maya/Covidien Paradise/Recor TIVUS/Cardiosonic (1) Krum H. et al. Lancet. 2009;373: (2) Esler MD. et al. Lancet. 2010;376: (3) Walton T et al. EuroPCR 2014;14A-OP209 (4) Mahfoud F. et al. ACC Scientific Sessions 2013 (5) Persu A. et al. Journal of Human Hypertension 2014;28: (6) Mahfoud F. et al. Circulation 2013;128: (7) Vogel B. et al. Clin Res Cardiol. 2014;103: (8) Hering D. et al. J Am Soc Nephrol. 2012;23: (9) Ott C, et al. J Am Coll Cardiol. 2013;62: (10) Papademetriou V, et al. Hypertension [Epub ahead of print] (11) Sievert H et al. TCT 2013 (12) Verheye S. EuroPCR 2014;14A-OP208 (13) Zeller T. et al. EuroPCR 2014; 14A-OP205 (14) Shetty S. et al. EuroPCR 2014;14A-OP206

6 Change in Office SBP (mm Hg) Primary efficacy endpoint RDN Sham P<0.001 for change from baseline for both 2.39 mm Hg (95% CI, 6.89 to 2.12) P=0.26 Primary efficacy endpoint was not met Bhatt DL, NEJM 2014

7 Symplicity Complexity

8 Symplicity HTN 3: Methodological considerations

9 HTN 3 The procedure could be simply ineffective 111 operators did at least 1 procedure in 364 pts 31% did only 1 procedure Only 26 operators did >5 procedures No intra-procedural measure of treatment effectiveness The first patient denervated in each center was the first patient introduced into the trial by the center

10 RDN: No safety issues up to now in terms of Changes in renal function Changes in ACR Development of renal artery stenosis Vascular complications SYMPLICITY HTN I, II, III EnligHTN I Symplicity Global registry

11 HTN -3 Safety without efficacy is of value only in the context of further testing of the technology New catheter electrodes (spiral, basket or balloon mounted electrodes) could accomplish multiple ablations and ensure circumferential ablation The location of the ablation More preclinical research is needed followed by human studies incorporating randomization, blinding and sham control

12 Our view of renal nerve distribution has changed! Distal Proximal Prior concept Uniform radial distribution Distal Proximal Renal nerves may have a positional bias on radial distance from the arterial lumen: distal nerves are closer Current concept Non-uniform radial distribution

13 RDN Response: During the Procedure? C. Procedural Indexes of Success (I) Pain Renal nerve mapping: Not yet feasible Electrical stimulation of renal artery Changes in renal hemodynamics Tsiachris, Tsioufis et al, Int J Cardiol 2014 Effects of multi-electrode based RDN on RBF and RRI in swines Add approval number Tsioufis et al, Int J Cardiol 2012

14 RDN Response: During the Procedure? C. Procedural Indexes of Success (II) Number of ablations EnligHTN I :15.10 ±1.01 EnligHTN III : ± 1.01 GSR: Symplicity HTN 3: 11.2 ±28 *P value change in SBP for RDN compared with sham Data presented are mean (SD) Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Symplicity renal denervation system has been approved. Not for distribution in the USA, Japan or France Medtronic, Inc. All rights reserved. UC ML 5/14. D.Kandzari, PCR 2014

15 RDN Response: During the Procedure? C. Procedural Indexes of Success (II) Pattern of Ablation: 4 Quadrant Ablation Pattern *1 superior, 1 inferior and 2 posterior D.Kandzari, PCR 2014 Add approval number

16 Change in Blood Pressure (mmhg) EnligHTN I: Ambulatory BP Reduction from Baseline Month 1 (n=46) Month 3(n=46) Month 6(n=44) Month 12 (n=35) Month 24 (n=43) Systolic BP Diastolic BP p < % CI Worthley, Tsioufis..Papademetriou. Eur Heart J. 2013;34: Papademetriou, Tsioufis,. Worthley. Hypertension 2014 Tsioufis, Papademetriou.Worthley. submited) 16

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20 Procedural parameters of successful ablation What is the potential solution? Come back to the basics of renal nerve innervation. Understand better >The anatomy of the renal nerves (location, distribution, distance from the lumen) and >The sites for delivering the energy. >The appropriate design of the multielectrode system, >The type of energy and >The optimal ablation setting The above would guarantee RDN success even if no procedural marker of efficacy is available.

21 The burden of RDN potential effects.beyond BP lowering LVH Arterial Stiffness Albuminuria Renal hemodynamics Hypertension Arrhythmias Glucose Impairment Sleep Apnea Risk Factors Intermediate Surrogates Cardio-Renal Disease Heart Failure Chronic Kidney Disease Tsioufis C, et al, JHH 2014 Tsioufis et al, JH 2014 Tsioufis et al, Int J Cardiol 2014 RDN System Ukena C, et al. Int J Cardiol [ Brandt MC, et al. J Am Coll Cardiol Mahfoud F, et al. Circulation Mahfoud F, et al. Hypertension. 2012; Mahfoud F, et al. Eur Heart J 2014

22 EnligHTN I: Multi-center substudy Effects of RDN on BPV indexes Tsioufis et al, submitted

23 ESH/ESC guidelines 2013 Η απονεύρωση του νεφρού μπορεί να αποτελεί μέρος της κλινικής πρακτικής μόνο σε ασθενείς με επιβεβαιωμένη σοβαρού βαθμού ανθεκτική υπέρταση μετά την αποτυχία των υγιεινοδιατητικών και φαρμακευτικών μέσων και οι ασθενείς να παρακολουθούνται στα πλαίσια μιάς καταγραφής (IC) Περαιτέρω έρευνα χρειάζεται για τον κατάλληλο φαινότυπο του ασθενούς και για τον τρόπο επίτευξης της απονεύρωσης (τύπος ενέργειας, τύπος καθετήρα, σημεία της νεφρικής αρτηρίας που θα στοχεύουμε, κλπ)

24 Diagnostic and treatment algorithm for RHTN Schmieder,...Tsioufis. Eurointervention 2013

25 RDN: Future Therapeutic Targets Refractory HTN Less Severe HTN HTN- Related Disorders Disorders of SNS Excess HFPEF Systolic CHF Acute HF CKD

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