Conflicts of interests

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1 Update in Interventional Cardiology for the Internist Transcatheter valve therapies Dr Vaikom S Mahadevan Director of Structural and Adult Congenital Interventions William W Parmley Endowed Chair in Cardiology Associate Professor of Medicine University of California, San Francisco Conflicts of interests Proctor for Melody Medtronic pulmonary valve Europe Proctor for Edwards Sapien pulmonic valve Europe Proctor for Edwards Sapien TF aortic valve USA and Europe Will mention about unlicensed indications for transcatheter valves 1

2 What valves are currently available Pulmonic valve implantation Melody valve Medtronic PMA approval Edwards Sapien valve Edwards Life Sciences Not approved Aortic valve implantation Edwards Sapien valve Approved Corevalve Medtronic Approved St Jude s, Boston Scientific, Direct flow valve As part of studies Transcatheter aortic valve Replacement To offer patients with severe AS who are inoperable or very high risk for surgery, a treatment option 2

3 Simplified decision tree for patients considered for percutaneous aortic valve placement. Frederick G.P. Welt et al. Circulation. 2011;124: Copyright American Heart Association, Inc. All rights reserved. Suitable candidates for THV High Risk Patients Age No absolute age limits Combination of several commorbidities (Renal, respiratory failure, LV dysfunction ) Contra indication to surgery (Porcelain Aorta, chest radiation, ) Not too frail or too much debility TA, TAo or TF technically feasible 3

4 PARTNER Study Design Severe Symptomatic Aortic Stenosis Yes Cohort A n = 699 Assessment Operability 2 Cohorts Individually Cohort Powered A (N = 1,057) No Cohort B n = 358 Yes Assessment Transfemoral Access No Yes Assessment Transfemoral Access No TF (n = 492) TA (n = 207) Not in Study 1:1 Randomization 1:1 Randomization 1:1 Randomization TF TAVI (n = 244) vs AVR (Control) (n = 248) TA TAVI (n = 104) vs AVR (Control) (n = 103) TF TAVI (n = 179) vs Standard Therapy (Control) (n = 179) Primary Endpoint: All Cause Mortality (1 yr) (Non inferiority) Primary Endpoint: All Cause Mortality Over Length of Trial (Superiority) Co Primary Endpoint: Composite of All Cause Mortality and Repeat Hospitalization (Superiority) All Cause Mortality, % % Absolute Reduction in all cause Mortality at 1 Year at 1 yr = 20.0% NNT = 5.0 pts 50.7% 30.7% Standard Therapy Edwards THV HR [95% CI] = 0.55 [0.40, 0.74] P (log rank) <.001 No. at Risk Edwards THV Standard Therapy Months

5 All cause and CVS Mortality Rate at 30 days and 1 year All Cause p =.001 Cardiovascular Mortality, % TAVI (n = 179), 30 Days, 5 Standard Rx (n = 179), 30 Days, 2.8 TAVI (n = 179), 1 Year, 30.7 Standard Rx (n = 179), 1 Year, 49.7 Column1, 30 Days, 4.5 Column2, 30 Days, 1.7 Column1, 1 Year, 19.6 p <.001 Column2, 1 Year, 41.9 p =.41 p =.22 Edwards THV (n = 179) Standard Therapy (n = 179) Survival with TAVR and AVR AVR Mortality, % % 24.2% 10 0 HR [95% CI] = 0.93 [0.71, 1.22] P (log rank) =.62 No. at Risk Edwards THV AVR Months

6 Transfemoral, Transapical Approach / Transaortic approach Access to the aortic valve Annulus Measurement mm Vessels cannot be too Tortuous No large Ischaemic Area Coronary Angiogram 6

7 Transfemoral route General anaesthesia and TEE guidance Need bilateral femoral arterial access and one femoral venous access for temporary pacing wire With ICE support could be done without GA Transapical / Transaorticroute General anaesthesia and TOE guidance Cardiac apical / aortic access by cardiac surgeon Femoral venous access for pacing Arterial access for angiography Techniques for measurement of aortic annulus by CT Minimum and maximum diameters and average the mean Area derived diameter D= 2 X (A/ π ) Circumference derived diameter D = C/π 7

8 Based on TEE 8

9 An example of a TAVR referral 88 year old male History of prostate problems Found to have a large bowel lesion needing surgery On investigation found to have severe AS Raised STS / Euroscore Good iliac and femorals and no major coronary disease Proceeded to TF TAVI Need to minimise valve / paravalvular leak Sometimes post dilatation is required with the same balloon or a different balloon In case of significant central leak a further valve implant is required Valve in valve implant The Sapien 3 valve has decreased para leak significantly 9

10 Transaortic approach Increasingly used in patients not suitable for TF approach but high risk with TA Includes those with impaired LV function Direct aortic approach using mini sternotomy Valve delivered using transapical delivery system TF Groin management is now percutaneous Given smaller sheath sizes percutaneous groin access site management Usually 2 / 3proglides sutures predeployed Sheath removal in the cath lab with tightening of predeployed perclose sutures Immediate hemostasis and check angio via contralateral side to confirm 10

11 Edwards SAPIEN 3 Transcatheter Heart Valve The 14 French esheath 11

12 Sapien 3 implant via Tao route Octagenarian male with severe AS Multiple co morbidities with severe PVD Moderate LV dysfunction Elected for Sapien 3 implant via Tao route Home on day 5 Sapien 3 trial The SAPIEN 3 Trial Objective: To assess the safety and efficacy of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in high- and intermediate-risk patients who are eligible for surgical aortic valve replacement Primary Endpoint: All-cause mortality of the valve-implant population at 30 days post-index procedure Secondary Endpoints: Organization: Follow-Up: Technical success, safety and efficacy endpoints, echocardiographic endpoints Steering Committee, Clinical Events Committee (VARC 2), Echo Core Lab and CT Core Lab 30 days, 1 year, and annually for 5 years This analysis from The SAPIEN 3 Trial presents the 30-day outcomes of the first 150 patients who received TAVI with the Edwards SAPIEN 3 THV. 12

13 Methods The SAPIEN 3 Trial Study Design Prospective, multicenter, non-randomized study Number of Patients 150 (TF [transfemoral] = 96, TAA [transapical / transaortic] = 54) 50 high-risk patients & 100 high-risk or intermediate-risk patients Patient Selection High-risk: STS score 8 or Logistic EuroSCORE 15 Intermediate-risk: STS score 4 to < 8 or Logistic EuroSCORE 10 to < 15 Enrollment Period January 2013 to November 2013 Study Centers 16 sites in Europe and Canada Access Approach Transfemoral, transapical, or transaortic access, as determined by the Heart Team Baseline Characteristics (1) Operability Risk Assessment AT* PATIENTS (N = 150) Age (Years) 83.6 ± 5.0 Female 81 (54.0%) NYHA III/IV 130 (86.7%) Severe Pulmonary Hypertension 10 (6.7%) Severely Impaired Pulmonary Function Contradicting Surgery 8 (5.3%) Hostile Chest 3 (2.0%) Severe Liver Disease / Cirrhosis 2 (1.3%) Frailty Index VARC-2 (continuous) 1.3 ± 0.9 Patients with 1 or More Risk Factors 147 (98.0%) Non-Cardiac Conditions AT* PATIENTS (N = 150) Renal Insufficiency 60 (40.0%) Diabetes 48 (32.0%) Anemia 46 (30.7%) Pulmonary Disease COPD 40 (26.7%) Cancer 32 (21.3%) AT* PATIENTS Echo Parameters (N = 150) Effective Orifice Area (cm 2 ) 0.6 ± 0.2 Mean Gradient (mm Hg) 45.3 ± 14.3 LV Ejection Fraction (LVEF) (%) 56.3 ± 9.2 Mitral Regurgitation (Moderate to Severe) 26 (22.4%) Annular Diameter (TEE - mean) (mm) 23.2 ± 2.3 * AT, as-treated. 13

14 Procedural Characteristics (1) ACCESS APPROACH (%) VALVE SIZE (%) TF TAA 23 mm 26 mm 29 mm Note: Limited14F esheath availability during initial patient enrollment period. The 29 mm valve was introduced later in the trial. Due to a low rate of paravalvular leak a strategy of minimal oversizing evolved. Procedural Characteristics (2) Variable TF PATIENTS (N = 96) Variable ALL PATIENTS (N = 150) Femoral Access/Anesthesia General 63.5% Conscious Sedation 36.5% Procedural Outcomes Correct Placement at Intended Site 149 (99.3%) Post-dilatation 5 (3.3%) Technical Success* 94.0% Femoral Access/Closure Percutaneous/Closure Device 95.8% Surgical 4.2% Procedural Events Conversion to Conventional Surgery 1 (0.7%) Patient Required ECMO 1 (0.7%) Coronary Obstruction 0 (0.0%) Valve-in-Valve 0 (0.0%) * No procedural mortality, correct positioning, and only one valve implanted. 14

15 Clinical Outcomes at 30 Days (1) Clinical Outcome TF (N = 96) EVENT RATE IN THE AT POPULATION # PATIENTS (KM %) TAA (N = 54) Overall (N = 150) All-Cause Mortality 2 (2.1%) 6 (11.1%) 8 (5.3%) Cardiac Mortality 2 (2.1%) 5 (9.3%) 7 (4.7%) All-Stroke* 1 (1.0%) 3 (5.6%) 4 (2.7%) Disabling Stroke 0 (0.0%) 0(0.0%) 0(0.0%) Major Vascular Complication 5 (5.2%) 4 (7.4%) 9 (6.0%) Major Bleeding 19 (19.8%) 11 (20.4%) 30 (20.0%) Life-Threatening Bleeding 2 (2.1%) 3 (5.6%) 5 (3.3%) Rehospitalization 0 (0.0%) 0(0.0%) 0(0.0%) Primary Endpoint TF (N = 95) EVENT RATE IN THE VI POPULATION # PATIENTS (KM %) TAA (N = 54) Overall (N = 149) All-Cause Mortality 1 (1.1%) 6 (11.1%) 7 (4.7%) VI, valve implant = all enrolled patients who received a SAPIEN 3 implant, and retain the valve upon leaving the cath lab * Severity of the one TF stroke unknown. Rehospitaliza on for for valve related symptom or worsening of congestive heart failure. Clinical Improvement at 30 Days NYHA CLASS I II III IV ANGINA CCS CLASS None I II III IV 100% 8.7% p < p = % 100% 1.3% 5.9% 9.3% 0.8% 2.2% 11.9% 80% 80% 13.4% 45.2% 10.0% 60% 78.0% 60% 40% 40% 66.0% 85.1% 20% 48.2% 20% 0% 13.3% Baseline 30 Days 0% Baseline 30 Days N = 150 N = 135 N = 150 N =

16 Echocardiographic Data at 30 Days TOTAL AR (N=149) PARAVALVULAR AR (N=149) None/Trace Mild Moderate Severe None/Trace Mild Moderate Severe 100% 2.6% 5.1% 3.4% 100% 2.6% 5.1% 3.4% 80% 28.2% 15.4% 23.9% 80% 28.6% 15.4% 24.1% 60% 60% 40% 69.2% 79.5% 72.6% 40% 68.8% 79.5% 72.4% 20% 20% 0% TF TAA Overall N = 78 N = 39 0% TF TAA Overall N = 117 N = 77 N = 39 N = 116 Improvement in Quality of Life at 30 Days VAS EQ-5D 6-MINUTE WALK TEST 80 p < p = * 300 VAS Score Meters * Baseline 30 Days 50 Baseline 30 Days N = 146 N = 127 N = 76 N = 76 VAS, Visual Analogue Scale. * p-values from paired t-test baseline vs follow-up. 16

17 Conclusions - The SAPIEN 3 Trial Outcomes at 30 days were excellent. TF SAPIEN 3 implantation was associated with a very low mortality of 2.1%, stroke of 1.0%, and very few access-site complications. TF implantation was associated with a very low mortality of 1.1% in the valve implant population. 99.3% of valves were implanted at the intended location - due to precise SAPIEN 3 positioning. 96.6% of patients had mild PVL. There was no severe PVL. Post-implant maneuvers were rarely needed despite reduced oversizing - Procedural post-dilatation (3.3%), valve-in-valve implants (0%) The SAPIEN 3 THV may enable treatment of intermediate-risk patients with aortic stenosis. CoreValve Evolut R System Recaptureable valve and delivery catheter with loading system Catheter Delivery System 14Fr equivalent profile Loading System 23mm Transcatheter Valve Supra annular design 17

18 CoreValve Evolut R Family Evolut R 23 mm CE Approved Evolut R 26 & 29 mm Exclusively for Clinical Investigations Evolut R 3X mm Under Development 23 mm 26 mm 29 mm 3x mm Annulus Size (mm) EnVeo R Delivery Catheter Designed for 1 st Time Positioning Accuracy with Option to Fully Recapture & Reposition * Capsule Flare Nitinol Reinforced 1:1 response Self centering Nitinol capsule with flare and flexible catheter enable uniform, controlled valve expansion and self-centering 18

19 Supra Annular Design Maximizes Blood Flow Over 25% larger potential orifice area 1 Indicated for Valve in Valve Low Rates of Patient Prosthesis Mismatch Low Post-Procedural Gradients 1. Medtronic data on file. Bench testing comparison between CoreValve and Sapien XT in surgical bioprosthesis. Bench test comparison to Sapien XT, CoreValve device has a 25% larger potential orifice area when implanted in degenerated surgical bioprosthesis. 2. Dvir D, Webb JG, Bleiziffer S, et al. Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA 2014;312(2): doi: /jama CE Approval is for CoreValve Evolut R 23mm. 19

20 Pulmonic valve Device Rationale To reduce the total number of surgeries over the patient s lifetime by postponing time to surgery, while restoring pulmonic function Option to intervene earlier, providing better outcomes for patients while avoiding surgical complications Tetralogy of Fallot Anomalies of the RVOT Estimated at 20.1% of all CHD Patients With Pulmonary Stenosis With Pulmonary Atresia Truncus Arteriosus Transposition Great Arteries Others RV PA Conduit RV PA Conduit RV PA Conduit Surgical correction of outflow tract non-conduit ~ 85% of all RVOT Pts. RV PA conduit Virtually all patient will require future procedure(s) to replace the conduit and / or pulmonary valve ~ 15% 0f RVOT Patients 20

21 Melody Transcatheter Pulmonary Valve 18mm Contegra bovine jugular vein with valve segment NuMed Platinum Iridium Stent 28 mm length Crimped down to 6mm, re expanded 18mm up to 22mm Selection Criteria Objective evidence of conduit dysfunction Moderate or severe regurgitation Right ventricular outflow obstruction Clinical indication for surgical intervention Free PR with progressive or moderate severe RV dilatation / significant TR Arrythmia or decreasing ET 21

22 23 year old with d TGA, VSD and aortic coarctation repair Coarctation repair with PA banding shortly after birth 10 months Arterial switch with debanding of PA and Dacron conduit to elongate PA trunk 2 years RV PA conduit replacement with 20mm homograft 12 years Tricuspid valve repair and 19mm homograft in pulmonary position Developed progressive exertional dyspnoea and increasing RV pressures Underwent catheterisation and RV pressures greater than 2/3 rd Systemic. Conduit very adherent to sternum Underwent balloon dilation with 18mm balloon with good effect Increasing RV systolic pressure and dyspnoea, underwent stenting of conduit with 3.9cms uncovered stent on 18mm Cristal wire was used for support to deliver the stent using 11 Fr Mullins sheath 22

23 Use of TAVR in other positions Not licenced for routine use Used usually as valve in valve in tricuspid and mitral positions Transcatheter Tricuspid valve implant No licensed valve currently Used for valve in valve implant Inverted TAVI valves 38 year old female Ebstein s anamoly 14 years ago Prosthetic valve TVR Failed prosthesis replaced with bioprosthesis 12 years ago 31mm Sorin Increasing SOB with mixed valve lesion 23

24 Clinical findings Transthoracic echo revealed significant tricuspid stenosis and regurgitation Reduced exercise tolerance with reduction in peak VO2 maximum Significant RA dilatation and preserved right ventricular systolic function Mean RA pressure of 19mm Hg Mitral valve in valve Not licenced for routine clinical use Useful when there is significant disease of mitral prosthesis and surgical risks are high Can be done transapical or transeptal Can also be done in certain valve ring repairs 24

25 Mitral valve in valve 28 year old female Mitral endocarditis aged 21 with severe MR R hemiplegia with significant residual deficit Two successful pregnancies Severe bioprosthetic valve stenosis with symptoms Does not want further surgery / mechanical valve. ICE in TAVR Avoids the need for GA Via RFV using 8 or 10Fr sheath Now 3D ICE is available However sweep is low but newer systems are in progress Valve annular measurements can be made 25

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