Catheter-based Renal Denervation with the Symplicity System Provides Safe and Durable Blood Pressure Reduction out to Three Years Horst Sievert1, Henry Krum2 on behalf of the Symplicity HTN-1 Investigators 1CardioVascular Center Frankfurt, Frankfurt, GERMANY, 2Monash University/Alfred Hospital, Melbourne, Australia

Horst Sievert, MD Consulting: AccessClosure, Inc., AGA Medical Corporation, Ardian, Inc., Arstasis, Inc., Atritech Atrium Medical Corporation, Avinger, Inc., Bard Peripheral Vascular, Inc., Boston Scientific Corporation, Bridgepoint, CardioKinetix Inc., CardioMEMS, Inc., Coherex, Inc., Contego, CSI, EndoCross, Endotex Interventional Systems, Epitek, Evalve, Inc. and ev3, Inc.

Horst Sievert, MD Consulting: FlowCardia, Inc., Gore, Guidant, Lumen Biomedical, Inc., HLT, Kensey Nash Corporation, Kyoto Medical, Lifetech, Lutonix, Inc., Medinol, Medtronic, Inc., NDCNMT Medical, Inc., OAS, Occlutech Osprey Medical, Inc., Ovalis, Inc., Pathway Medical Technologies, Inc., PendraCare International B.V., Pfm Medical, Inc., Rox Medical, Recor, Sadra Medical, Sorin Biomedica Cardio S.R.L.,and Spectranetics Corporation, Trireme, Trivascular and Viacor, Inc.

Horst Sievert, MD Honoraria: Veryan, Ardian, Inc., Atritech, Atrium Medical Corporation, Boston Scientific Corporation, CardioKinetix Inc., CardioMEMS, Inc., Coherex, Inc., Contego, Epitek, Evalve, Inc., Guidant,Gore,Kyoto Medical, Lutonix, Inc., Medinol, Medtronic, Inc., Pfm Medical, Inc., and Spectranetics Corporation.

Horst Sievert, MD Honoraria: Viacor, Inc., HLT, Lifetech, Recor, Trivascular, Veryan, CVRx, GDS and InSeal Medical.

Symplicity HTN-1 Initial Cohort – Reported in the Lancet, 2009: Catheter-based Renal Sympathetic Denervation for Resistant Hypertension Durability of Blood Pressure Reduction Out to 24 Months Symplicity HTN-1 Investigators* Lancet. 2009;373:1275-1281 Hypertension. 2011;57:911-917. Initial Cohort – Reported in the Lancet, 2009: First-in-man, non-randomized study conducted in Europe and Australia Cohort of 45 patients with resistant HTN (SBP ≥160 mmHg on ≥3 anti-HTN drugs, including a diuretic; eGFR ≥ 45 mL/min) All patients received bilateral renal denervation with the Symplicity™ renal denervation system Primary endpoint: change in office BP; 1, 3, 6, 9 and 12 months post-procedure Expanded Cohort – Symplicity HTN-1: Expanded cohort of patients (n=153) from 19 sites (US, Europe, and Australia) 24 and 36-month follow-up of safety and effectiveness 6

Baseline Patient Characteristics (n=153) Demographics Age (years) 57 ± 11 Gender (% female) 39% Race (% non-Caucasian) 5% Co-morbidities Diabetes Mellitus II (%) 31% CAD (%) 22% Hyperlipidemia (%) 68% eGFR (mL/min/1.73m2) 83 ± 20 Blood Pressure Baseline BP (mmHg) (n=150) 175/98 ± 17/15 Number of anti-HTN meds (mean) 5.1 ± 1.4 Diuretic (%) 95% Aldosterone blocker(%) ACE/ARB (%) 91% Direct Renin Inhibitor 14% Beta-blocker (%) 82% Calcium channel blocker (%) 75% Centrally acting sympatholytic (%) 33% Vasodilator (%) 19% Alpha-1 blocker Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917. 7

Change in Office Blood Pressure Through 36 Months* P<0.01 for ∆ from BL for all time points Reported as mean with 95% confidence intervals *Data is reported only on the patients available at each timepoint. It does not reflect the full cohort

Distribution of SBP Change at BL, 1, 12, 24, and 36 Months % Patients placeholder (N=150) (N=143) (N=132) (N=105) (N=34)

Percentage Responders Over Time Responder was defined as an office SBP reduction ≥10 mmHg (n=143) (n=148) (n=144) (n=132) (n=108) (n=105) (n=44) (n=34)

Change in Office BP by Age 12 Months 24 Months 36 Months (mmHg) Actual values to be added P<0.01 compared with BL, †p=0.19 N=98 N=34 N=78 N=27 N=29 N=5

Change in Office BP in Diabetic and Non-Diabetic Patients 12 Months 24 Months 36 Months (mmHg) Actual values to be added P<.01 Compared with BL, †p=0.03 DM (N=45) Non-DM (N=87) DM (N=31) Non-DM (N=74) DM (N=11) Non-DM (N=23)

Change in Office BP According to Baseline Renal function 12 Months 24 Months 36 Months (mmHg) ‡ Actual values to be added eGFR 45-60 (N=10) eGFR>60 (N=116) † eGFR 45-60 (N=9) eGFR>60 (N=92) eGFR 45-60 (N=2) eGFR>60 (N=30)

Vascular Complications Out to 36 months Stenosis (previously reported to 18 months) One progression of a pre-existing stenosis unrelated to RF treatment (stented without further sequelae) One new moderate stenosis which was not hemodynamically relevant , requiring no treatment No new reports of vascular complications* *Analysis includes data on all patients available through 36 months Ask Bryan – can this be included Schlaich M, TCT 2012 Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917. 14

Other Adverse Events Out to 36 months* Hypotension and Renal Failure (18 m) n=1 Due to sepsis, resolved Hypotension and Renal Failure (24 m) n = 1 Post-operative acute renal failure resolved Hypotension Episode (n = 1) No treatment, resolved 3 deaths, unrelated to procedure Myocardial Infarction - After 3-day visit Sudden death (cardiac) - After 6 months Cardio-respiratory arrest - After 18 months Ask Bryan – can this be included *Analysis includes data on all patients available through 36 months Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917. Schlaich M – TCT 2012 15

Conclusions The magnitude of clinical response is significant and sustained through 36 months Increasing responder rates indicate: Some subjects respond late to RDN No loss of treatment effect out to 36 months The treatment effect was consistent across subgroups (age, diabetes status, and baseline renal function) No late adverse events related to RDN through 36 months Analysis iincludes data on patients available through 36 months