Structural Heart Live Cases Supported by: Medtronic Inc Bard Inc Terumo Medical Corp

Disclosures Samin K. Sharma, MD, FACC None for today’s case Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, ABIOMED, CSI, Trireme Inc Annapoorna S. Kini, MD, FACC Nothing to disclose Allan Stewart, MD Nothing to disclose regarding today’s presentation Mathew R Williams, MD Nothing to disclose for today’s case

December 13th 2016 Structural Heart Live Case #13: BC, 85 yr M Presentation: Worsening dyspnea and fatigue on exertion for last few weeks, NYHA class III PMH: Severe AS, HPL, Idiopathic pulmonary fibrosis on chronic steroid use, Raynaud’s disease, OSA, BPH and hypothyroidism Medications: Aspirin, Atorvaststin, Flomax, Synthroid, Prednisolone TTE (11/14/16): Severe valvular AS; PG/MG=65/41mmHg, Doppler valve area = 0.8 cm2, Ao peak velocity = 4.03m/s, LVEF 57% EKG: Sinus rhythm with narrow QRS, PR prolongation Cath (11/29/16): 1V CAD, 60% mLAD disease, FFR negative

December 13th 2016 Structural Heart Live Case # 13 Contd…. CT Angiography: The bilateral lower extremity peripheral arterial accesses have minimal diameters 8.7mm STS risk mortality: 5.6% EuroScore II risk: 7.1% Logistic Euroscore mortality: 12.4% Course: Patient is determined to be high risk for surgical AVR due to history of age, lung disease and chronic steroid use Plan Today: Patient is planned for Medtronic EVOLUT R CoreValve TAVR (34 mm) via percutaneous femoral access and conscious sedation. SLIDE TO BE EDITED BY JK

Transthoracic Echo Severe valvular aortic stenosis; peak gradient = 65 mmHg, mean gradient = 41 mmHg, Doppler valve area = 0.79 sq cm, Ao peak CW velocity = 4.03 m/sec, LVEF 57%

CTA: Aortic Annulus Annulus Max: 27.3 mm Min: 26.8 mm Mean: 27.1 mm Perimeter = 89 mm Area = 6.1 cm2 Annular angle = 56° Annulus diameter: 27.3 x 26.8mm Annulus circumference : 89mm Annulus angle: 56°

CTA: SOV and STJ Sinus of Valsalva Mean Diameter = 38.4 mm Sino-tubular junction height (above annulus) = 20.1 mm Ascending aorta = 36 mm 39.7 mm 39.3mm 37.2 mm RCA: 19.9 mm LM: 17.1 mm

CTA: Access – 3D

Access: Iliac and common femoral arteries Rt CFA: 9.7mm Lt CFA: 9.8mm Rt CIA: 11.4mm Lt CIA: 10.5mm Calcific Left CFA

EVOLUT R 34 MM Patient Selection Matrix Aortic Root Criteria CoreValve Evolut R TAV Valve Size Selection Size 23 mm 26 mm 29 mm 34 mm Annulus Diameter 18 – 20 mm 20 – 23 mm 23 – 26 mm 26 - 30 mm Annulus Perimeter (π x Diam) 56.5 – 62.8 mm 62.8 – 72.3 mm 72.3 – 81.7 mm 81.7 – 94.2 mm Sinus of Valsalva Diameter (Mean) ≥ 25 mm ≥ 27 mm ≥ 29 mm ≥ 31 mm Sinus of Valsalva Height (Mean) ≥ 15 mm ≥ 16 mm Our patient 27.1 89.0 38.4 20.1

CoreValve™ Evolut™ R 34 mm

34 mm Delivery Catheter System 16Fr Equivalent DCS Design Same EnVeo R Delivery System technology with a 16Fr equivalent Capsule and InLine Sheath Indicated to treat vessels ≥ 5.5 mm 16Fr Equivalent (20FR OD) Capsule 12Fr Inner Shaft 15Fr Stability Layer 16Fr Equivalent (20Fr OD) InLine Sheath

Consistent Evolut R design for accurate deliverability & performance Evolut R 34 mm TAV Design Fundamentals Consistent Evolut R design for accurate deliverability & performance Wider inflow for greater oversizing (34 mm at target implant depth of 3 mm) Shorter length and outflow width for improved alignment to native annulus More gradual inflow angle to maintain target oversizing in case of deeper implant depth Evolut R 34 mm CoreValve 31 mm 23 mm 31 mm 34 mm 24 mm 38 mm 44 mm 36 mm

Evolut R Family cell Dimensions & Target Implant Depth Consistent inflow frame cell design with a target implant depth is 3 - 5 mm for all valve sizes 3 – 5 mm = midway between nodes 0 and 1 to just below node 1 6 mm 4 mm 13mm Skirt 14mm Skirt 23 mm TAV 26 mm TAV 29 mm TAV 34 mm TAV

Evolut-R 34 Study: Valve Performance Effective orifice area Mean gradient N=15 Effective Orifice Area, cm2 Mean Gradient, mm Hg CoreValve™ Evolut™ R 34 mm Up to 30mm aortic annulus size J Popma, TCT 2016

Summary of Case - 85 year old male - NYHA Class III - TTE: AS – mean gradient 41 mmHg STS mortality: 5.6% EuroScore II mortality: 1.96% Logistic Euroscore mortality: 12.4% Course: Patient is determined to be high risk for surgical AVR due to age, lung disease and chronic steroid use For 34 mm Medtronic EVOLUT R CoreValve via percutaneous femoral approach under conscious sedation.

Issues Related To The Case Outcomes of Valve-in-Valve TAVR

Valve in Valve TAVI Eggebrecht et al., JACC 2011;4:1218 18

Adverse Events Reported with Aortic Valve-in-Valve Procedures for Failed Bioprosthesis

Procedural Characteristics and Early Results Total (n=202) CoreVavle (n=124) Edwards SAPIEN (n=78) p=<0.0001 p=0.45 p=0.31 p=0.16 % p=0.11 p=0.32 p=0.64 Dvir et al., Circulation 2012;126:2335

Analysis of High Post-procedural Gradients After Valve-in-Valve Procedure Mean gradients after Edwards SAPIEN procedures – bioprosthesis size (r = 0.35, p = 0.28) Mean gradients after CoreValve procedures – bioprosthesis size (r = 0.08, p = 0.40) Dvir et al., Circulation 2012;126:2335

Clinical Outcomes at 30 Days Dvir et al., JAMA 2014;312:162

Clinical Outcomes at 1 Year Dvir et al., JAMA 2014;312:162

Time-to-Event Curves in Patients Undergoing Valve-in-Valve Procedures Mechanism of Surgical Valve Failure Dvir et al., JAMA 2014;312:162

Time-to-Event Curves in Patients Undergoing Valve-in-Valve Procedures Surgical Valve Label Size Device Used During VIV Implantation Dvir et al., JAMA 2014;312:162

Results of Valve-in-Valve Measurements Within the Edwards Perimount Sedaghat et al., Ann Thorac Surg 2016;101:118

CoreValve US Clinical Trial: TAVR for Failed Aortic Bio-prosthesis: All-Cause Mortality or Major Stroke N=107 Internal stent diameter (ID) of SAV using valve in valve application developed by Dr. Vinayak Bapat & UBQO Technology GM Deeb – on Behalf of CoreValve US Investigators, TCT 2015

CoreValve US Clinical Trial: TAVR for Failed Aortic Bio-prosthesis- All-Cause Mortality or Major Stroke N=107 All-Cause Mortality by Discharge Gradient Hemodynamic Outcomes What is driving higher gradient at discharge? -Surgical valve size -Modality of failure (> in stenosis) -Patient prosthesis mismatch What is the impact of a higher mean valve gradient? GM Deeb – on Behalf of CoreValve US Investigators, TCT 2015

Take Home Message: Outcomes of Valve-in-Valve (ViV) TAVR TAVR for failed surgical aortic bio-prosthetic valve (ViV) is feasible and is associated with acceptable death and stroke rates at 1-2 years of follow-up. Hence Valve-in-Valve TAVR is an acceptable (recommended) option in appropriate AS pts. Valve-in-Valve TAVR outcomes are strongly associated with the residual aortic gradient post procedure and mechanism of valve failure. Hence every effort should be made to decrease the residual aortic gradient to < 20mmHg.

Correct answer: C Question # 1 Following is the false statement regarding TAVR procedure in aortic bio-prosthetic failure vs native aortic valve : Higher residual aortic gradient Lower annulus rupture Lower coronary obstruction Less para-valvular regurgitation Correct answer: C

Correct answer: B Question # 2 Following statements are true about the outcomes of balloon expandable vs self expanding TAVR valve except: Lower need for PPM Lower residual aortic gradient Lower para-valvular regurgitation Similar long-term death and stroke at follow-up Correct answer: B

Correct answer: D Question # 3 Following are the usual factors responsible for higher residual aortic gradient post CoreValve ViV TAVR except: A. Modality of bio-prosthetic valve failure B. Baseline surgical valve size C. Predicted patient prosthetic mismatch D. Need for permanent pacemaker Correct answer: D