Risk Stratification of Severe, Symptomatic Aortic Stenosis Patients AHA/ACC 2014 Guidelines Low Operative Risk (Must Meet ALL Criteria in This Column) Intermediate Operative Risk (Any 1 Criterion in This Column) High Operative Risk (Any 1 Criterion in This Column) Prohibitive STS PROM1 < 4% AND 4% to 8% OR > 8% OR Prohibited risk with surgery of death or major morbidity (all-cause) > 50% at 1 year OR Frailty2 None AND 1 Index (mild) OR > 2 Indices (moderate to severe) OR Major organ system compromise not to be improved postoperatively3 1 organ system OR No more than 2 organ systems OR > 3 organ systems OR Procedure specific impediment4 None Possible procedure-specific impediment Possible procedure- specific impediment Severe procedure- specific impediment Use of the STS PROM to predict risk in a given institution with reasonable reliability is appropriate only if institutional outcomes are within 1 standard deviation of STS average observed/expected ratio for the procedure in question. Seven frailty indices: Katz Activities of Daily Living (independence in feeding, bathing, dressing, transferring, toileting, and urinary continence) and independence in ambulation (no walking aid or assist required or 5-meter walk in <6 s). Other scoring systems can be applied to calculate no, mild-, or moderate-to-severe frailty. Examples of major organ system compromise: Cardiac—severe LV systolic or diastolic dysfunction or RV dysfunction, fixed pulmonary hypertension; CKD stage 3 or worse; pulmonary dysfunction with FEV1 <50% or DLCO2 <50% of predicted; CNS dysfunction (dementia, Alzheimer’s disease, Parkinson’s disease, CVA with persistent physical limitation); GI dysfunction—Crohn’s disease, ulcerative colitis, nutritional impairment, or serum albumin <3.0; cancer—active malignancy; and liver—any history of cirrhosis, variceal bleeding, or elevated INR in the absence of VKA therapy. Examples: tracheostomy present, heavily calcified ascending aorta, chest malformation, arterial coronary graft adherent to posterior chest wall, or radiation damage. Nishimura RA, et al. Circulation. 2014;129.

Transcatheter Therapy First explored for in-operable AS patients No other interventional options available Outcomes far superior than what was expected

Landmark PARTNER Trials High-Risk Patients: Defined by Risk of Mortality ≥ 15% Inoperable Patients: Defined by Risk of Mortality > 50% 7

Absolute Reduction in Mortality at 3 Year in Inoperable Patients Standard Rx HR [95% CI] = 0.53 [0.41, 0.68] p (log rank) < 0.0001 100% TAVR 80.9% 80% 68.0% 26.8% 60% 50.8% 25.0% 54.1% All Cause Mortality (%) 20.1% NNT = 3.7 pts 40% 43.0% NNT = 4.0 pts 30.7% 20% NNT = 5.0 pts Updated WNA to Oct 9 data Point-in-time at 2 yrs: p < 0.0001 0% 6 12 18 24 30 36 Months Numbers at Risk Standard Rx 179 121 85 62 46 27 17 TAVR 138 124 110 101 88 70 8

Reduction in Repeat Hospitalization in Inoperable Patients Rehospitalization Standard Rx HR [95% CI] = 0.39 [0.28, 0.54] p (log rank) < 0.0001 TAVR 75.7% 72.5% 53.9% 33.4% 37.6% Rehospitalization (%) 26.9 42.3% 34.9% NNT = 3.0 pts 27.0% NNT = 2.7 pts NNT = 3.7 pts Months Days Alive Out of Hospital Median [IQR] TAVR 944 [233-1096] Standard Rx 368 [147-1096] p <.0001 Numbers at Risk Standard Rx 179 86 49 30 19 11 7 TAVR 115 100 89 77 64 9

Options for Aortic Valve Replacement Surgery Low- to Moderate-Risk High Risk Greater Risk TAVR Open-Heart Surgery (AVR) Minimal Incision Valve Surgery (MIVS) Transcatheter Heart Valve Multiple treatment options are now available for patients with severe aortic stenosis. For patients at high or greater risk for open surgical therapy, transcatheter aortic valve replacement is available. High Risk Patients Defined by Risk of Mortality > 15% Surgical Heart Valve

Access Routes for TAVR

TAVR Video http://media.corporate- ir.net/media_files/IROL/25/251324/videos/CoreValve-Final- Animation-7-1-14-preview.mp4 https://www.youtube.com/watch?v=Euox0KA6uG8

TAVR Trials at SMH SURTAVI - Intermediate Risk Low Risk TAVR Trial

Low Risk TAVR Trials PARTNER 3 Medtronic TAVR Low Risk

MitraClip® Therapy Filling a Treatment Gap Medical therapy is limited to symptom management MV surgery has been the only option that reliably reduces MR A significant gap exists between medical and surgical options MitraClip® therapy is a first-in-class, percutaneous option to reduce MR* Less Invasive Medical Therapy MitraClip® MV Surgery Increased MR Reduction *Reference Source: Instructions For Use See important safety information referenced within

MitraClip® System Overview