OLOMOUC I Registry. The effect of renal denervation in patients with advanced heart failure:

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1 The effect of renal denervation in patients with advanced heart failure: OLOMOUC I Registry M. Táborský, M. Lazárová, J. Václavík, D. Richter, D. Vindiš, M. Kamasová, A. Louis, J. Jarkovský * I.IKK FNOL, LF UPOL a NTMC, * IBA MUNI Brno XXI. výroční sjezd ČKS

2 RDN experimental studies in HF 1. Long-term RD in rats after MI improved LV function and restored natriuresis 2. RD increased renal blood flow in congestive HF rats by 35 % and normalised the autoregulation of renal blood flow 3. RD normalization of angiotenzin II type 1 and 2 receptors expresion in HF rabbits 1. Nozawa T et al.: Heart Vessels 2002;16: DiBona GF, Savin LL: Am J Physiol Renal Physiol 2004;F209-F Clayton S et al. Am J Physiol Renal Physiol 2010;F31-F39.

3 Heart failure and increased sympathetic activity Sobotka P, Curr Cardiol Rep, 2012.

4 Registry characteristics Single center registry on RDN in HF pts Primary purporse: treatment Estimated enrollment: 50 subjects Estimated study completion date: Q Health authority: MF and UH EC

5 Inclusion criteria Congestive heart failure, LV <0.35 NYHA III(IV) Optimal stable medical therapy (>6M) Rest heart rate>70 bpm Renal artery anatomy eligible for treatment GFR >50 ml/min/1.73m 2 Not indicated for CRT or other nonpharmacological HF treatment

6 Exclusion criteria Clinically unstable patient Renal/femoral artery anatomy not eligible for treatment Pre-existing renal disease, history of prior renal artery intervention Valve disease (HS) MI, unstable AP, stroke, TIA within 6 M Systolic BP < 100 mm Hg CRT present or eligible Age<18 y, gravidity Unable to consent

7 Primary endpoints: Registry endpoints Ventricular systolic function by echocardiography Safety of renal denervation in HF pts. Secondary endpoints: Heart rate Renal function NT-proBNP levels NYHA classification

8 Patients and follow-up 417 screened 51 randomized 26 to RDN 25 to medical therapy (OMT) Deaths: 0 Deaths: 2 12 analysed 14 analysed

9 Baseline characteristics I RDN OMT Mean age (y) Male gender (%) History of HF (m) Ischemic etiology (%) Previous MI (%) NYHA II (%) 7 8 NYHA III/IV (%) 86/7 88/4 Diabetes mellitus (%) Hypertension (%) History of stroke (%) LVEF (%) Mean HR (bpm) Mean SBP (mmhg) Mean DBP (mmhg) 70 68

10 Baseline characteristics II RDN OMT ACEIs or ARBs (%) Diuretics (%) BB (%) Aldosterone antagonists (%) Digitalis (%) Ivabradine (%) ICD (%) 14 16

11 Reality of BB therapy

12 Renal denervation protocol Definition of anatomy CT scan + 3D reconstruction Analgosedation Direct BP monitoring, O 2 sat, ACT RF energy 6F catheter and RF generator (Symplicity Renal Denervation System, Medtronic, Inc., Mountain View, CA) RF energy applications in a helical fashion (>5 mm distance), pullback (periphery ostium) Using AP, LAO and RAO projections R RA L RA Nr. of RF applications 6.2 ± ± 2.0

13 Ejekční frakce OLOMOUC I Registry: LVEF N=12* Průměr (směr. odch) Medián Min; max Před denervací 26.3 (7.0) ; měsíců po denervaci 33.8 (8.0) ; 42.0 Změna 7.5 (8.4) ; p (párový t-test) = p (Wilcoxon test) = Před denervací 6 měsíců po denervaci * Údaj není k dispozici u 3 pacientů

14 OLOMOUC I Registry: Před denervací NYHA N=15 13,3% II (N=2) III (N=13) 6 měsíců po denervaci 86,7% 6 měsíců po denervaci 13,3% Před denervací NYHA II III Celkem II 2 (13.3%) 0 (0.0%) 2 (13.3%) III 11 (73.3%) 2 (13.3%) 13 (86.7%) Celkem 13 (86.7%) 2 (13.3%) 15 (100.0%) II (N=13) III (N=2) p (McNemar test) = ,7%

15 OLOMOUC I Registry: NT-proBNP p < 0.01 p < 0.01 p = 0.12 Baseline 6 months Baseline 12 months RDN (n=12) OMT (n=14)

16 OLOMOUC I Registry: Renal function development Δ Renal function (baseline x 6 M) RDN (mean ±SD) OMT (mean ±SD) p egrf (MDRD) (ml/min/1.73m 2 ) -5±12 1±

17 OLOMOUC I Registry: Complications Type of complication RDN OMT AV fistula with surgical revision 1 - Thrombus formation during procedure (ACT 283) 1 - Transient ischemic attack 1 2 Hypotension 1 1 AP requiring coronary stenting 2 3 Death during FU 0 2

18 Conclusions HF and systolic dysfunction are associated with poor prognosis RDN increased the LV systolic function and reduced the mean heart rate (p<0.01) RDN in a pilot study with HFLEF patients is a safe procedure RDN did not change the renal function Missing long-term data

19 Variability in renal artery anatomy

20 Patients with HF and LV aneurysm: Contraindication for RDN?

21 OLOMOUC I Registry: Heart rate

22 Disclosures MT: honoraria Bayer, Boehringer- Ingelheim, Pfizer, Biotronik JV: honoraria Servier, Boehringer- Ingelheim, Bayer ML: honoraria Servier Supported by educational grant Medtronic Czechia s.r.o.

23 Registry design RDN 1 M Visit (Doppler or CT) 6 m Visit 12 m Visit Screening (0 30 days) PIC + Randomization CT scan (7 14 days) OMT 1 M Visit 6 m Visit 12 m Visit

24 Patophysiology of HF HF substantial neurohormonal activation in heart, kidney and skeletal muscle Activation of sympatetic NS and RAAS aggravating HF by increasing ventricular afterload and preload Inverse relationship between noradrenaline serum levels and mortality Renal sympatetic activation congestion (release of renin, sodium retention in prox. tubules and elevation of renal vascular resistance) Role of renin - angiotensin II on proximal tubulus and vasoconstriction of the efferent renal arteriole 1. Hasking GJ et al: Circulation 1986;73: Cohn JN et al: N Engl J Med 1984;11: DiBona GF: Am J Physiol Regul Interg Comp Physiol 2005;289:R633-R Floras JS: J Am Coll Cardiol 2009;54: Jessup M, Constanco MR: J Am Coll Cardiol 2009;53: Parati G, Esler M: Eur Heart J 2012;TBD 7. Sobotka PA et al: Clin Res Cardiol 2011;00: