Meeting of the Balkan Excellent Centers “The Greek experience of Renal Denervation in resistant hypertension” K. Dimitriadis, PhD, FESC Consultant Cardiologist First Cardiology Clinic, University of Athens, Hippokration Hospital Για την διαχρονικά σταθερή στηριξή του

Abstract The first renal denervation (RDN) procedures in Greece were performed in the First Cardiology Clinic, University of Athens, Hippokration Hospital by Prof. Costas Tsioufis in patients with severe drug-resistant hypertension.1 During the last 5 years numerous patients have undergone RDN in this center which participates in international studies and registries and important experience has been gathered regarding the safety and efficacy of this interventional therapy. In an attempt to identify responders to RDN therapy in an animal setting, we have shown that RDN causes an acute and chronic alteration in renal blood flow as well as resistive index,2 whereas stimulation of the renal arteries did not lead to augmentation of blood pressure (BP) in swines in contrast to previous reports.3 The Hippokration Hospital was also one of the few centers globally for the EnligHTN I study the first-in-human study with the use of the multielectrode RDN catheter. From this population important papers regarding the effect of RDN besides BP,4 on left ventricular mass with up to 24 months follow-up have been published.5,6 In Greece, the Hellenic Cardiological Society and the Working Group Hypertension and the Heart of the Society have organized a national registry on patients with resistant hypertension under the name Herhodotos with data on more than 300 cases providing a useful insight into the characteristics of potential candidates for RDN. Additionally, the Greek RDN registry has taken place in 4 Greek hospital centers including patients with drug resistant hypertension. In this “real-world’ multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is proven during a 12 months follow-up. Moreover, younger age and higher levels of baseline office systolic BP are independently related to better BP response to RDN.

RDN in Greece First Cases in Hippokration Hospital in 2011 2 cases of patients with RHT

Renal Sympathetic Denervation The Greek experience in the Hippocration Hospital Clinical and pre-clinical Global Simplicity Registry EnligHTN I (FIM) EnligHTN II MS study Greek RDN registry

Tsioufis C, et al. Int J Cardiol 2014 Animal studies for indentification of reliable markers of intra-procedural success Tsioufis C, Papademetriou V, Dimitriadis K et al. Int J Cardiol 2012 Tsioufis C, et al. Int J Cardiol 2014

ENLIGHTN I study

Results: LV Mass Index Tsioufis C, Papademertriou V, Dimitriadis K, et al. J Hypertens. 2015

LV hypertrophy status changes After RDN, the number of patients with concentric LV hypertrophy (decreased from 16 patients (80%) at baseline to 10 patients (50%) at 12 months, and to 7 patients (36.8%) at 24 months 8 CONFIDENTIAL-Do not distribute Tsioufis C, Papademetriou V, Dimitriadis K, et al. J Hum Hypertens 2016

RDN in MS patiens C.Tsioufis, K.Dimitriadis, A.Kasiakogias, et al. ESH 2016

The first Greek registry of patients with Resistant Hypertension Endorsed by the Hellenic Cardiac Society and the WG of Hypertension and the Heart

HERHODOTOS REGISTRY Excellence centers Till today >300 pts registered Parameter RHT pts (n=320) Age (years) 5610 Gender (males%) 51 BMI (kg/m2) 30.13.8 Waist (cm) 103.113.3 Smoking (%) 26 Creatinine (mg/dl) 10.5 Duration of hypertension (years) 14.77

Patients with resistant hypertension HERHODOTOS REGISTRY Parameter Patients with resistant hypertension (n=320) Systolic office BP(mmHg) 15717 Diastolic office BP (mmHg) 8712 Office HR (bpm) 7019 24h Systolic BP (mmHg)* 14915 24h Diastolic BP (mmHg)* 859 Home systolic BP (mmHg) 14818 Home diastolic BP (mmHg) 8410

resistant hypertension HERHODOTOS REGISTRY Parameter Patients with resistant hypertension (n=320) Number of drugs 4.4 ACE-i (%) 41 ARBs (%) 61 Renin-i (%) 9 CCBs (%) 70 Diuretics (%) 90 b-blockers(%) Aldosterone antagonists (%) α-blockers (%) Centrally acting (%) 64 19 3 31

Greek RDN registry 4 centers in Greece Athens-Hippokration Hospital C. Tsioufis Heraklion Crete M. Marketou Patras P. Davlouros Τhessaloniki A. Ziakas

Greek RDN registry: Baseline characteristics Parameter RDN pts (n=68) Age (years) 5810 Gender (males%) 49 BMI (kg/m2) 33.15 Waist (cm) 104.111.3 Smoking (%) 30 Creatinine (mg/dl) 10.4 Duration of hypertension (years) 9.14

Greek RDN registry: Baseline BP Parameter RDN pts (n=68) Systolic office BP(mmHg) 17417 Diastolic office BP (mmHg) 9513 Office HR (bpm) 7019 24h Systolic BP (mmHg) 15817 24h Diastolic BP (mmHg) 9013 24h HR (bpm)

resistant hypertension Greek RDN registry: Baseline therapy Parameter Patients with resistant hypertension (n=68) Number of drugs 4.1 RAAS blockade (%) 85 Renin-i (%) 3 CCBs (%) 78 Diuretics (%) 90 b-blockers(%) Aldosterone antagonists (%) α-blockers (%) Centrally acting (%) 68 32 5 28

Office and ambulatory SBP after RDN at 6 and 12 months -30 mmHg -29 mmHg -13 mmHg -12mmHg

Office and ambulatory DBP after RDN at 6 and 12 months -12mmHg -11mmHg -10mmHg -9mmHg

BP response to RDN 85% (59 pts) with an at least 10 mmHg office SBP reduction Patients that were RDN responders (85%, n=58), compared to non-responders were younger (57±9 vs 65±8 years, p<0.05), had higher baseline office systolic BP (176±17 vs 160±11 mmHg, p<0.05) and 24h systolic BP (159±13 vs 149±11 mmHg, p<0.05).

Correlation of office BP reduction at 12 months with baseline office BP r=0.402, p=0.008

Correlation of 24h SBP reduction at 12 months with baseline 24h SBP r=0.3673 p=0.027

ESH excellence centers Collaborate Exchange experiences In order to improve delivered therapies in the field of RDN

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