Implantation of BalloonExpandable THVs in Native Mitral Valve

Implantation of Balloon-Expandable THVs in Native Mitral Valve with Severe MAC Mayra Guerrero MD Professor of Medicine Department of Cardiovascular Medicine Mayo Clinic Hospital CRT 2019 Washington, DC March 3 rd, 2019 © 2017 MFMER | slide-1

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship • Research Grant Support, Proctor • Consultant, Speaker’s Bureau Company • Edwards Lifesciences • Boston Scientific Off label use of products and investigational devices will be discussed in this presentation © 2017 MFMER | slide-2

Outcomes of Vi. MAC not as good as Vi. V 1 year mortality TMVR

Outcomes of Vi. R and Vi. MAC not as good as Vi. V Yoon

MITRAL Trial Mitral Implantation of TRAnscatheter va. Lves 90 patients extremely high surgical risk (STS PROM >15% or M&M >50%) Inclusion Criteria d e t n e s e r p e b l l 9 i 1 w 0 2 a Valve-in-Ring t y Valve-in-Valve a Native MV (MAC) a d M r R n=30 1 Yea C P o r u E at Severe MS (MVA ≤ 1. 5 cm 2) SAPIEN XT SAPIEN 3 NYHA II or greater Severe MR + Moderate MS 16. 6% At least Moderate-Severe MR 30 day mortality 6. 6% At least Moderate-Severe MR 3. 3% © 2017 MFMER | slide-5

Life after MITRAL Trial… Focus on Main Challenges (standardize procedure) Embolization PVL LVOT Obstruction

Technique Evolution Open Transatrial Transapical Transseptal My preferred method but not all patients are

Cardiac CT is Essential for Success “The main screening tool to prevent complications” Measure annular dimensions Determine fluoroscopy deployment angle Determine Landing zone Transeptal puncture location Estimate risk of LVOT obstruction © 2017 MFMER | slide-8

Deployment Angle & Landing Zone Deployment angle RAO 50 Landing zone for ventricular edge

Estimate Risk of LVOT Obstruction LVOT in systole Neo-LVOT with virtual valve in place

Tips to Prevent valve embolization Adequate sizing with CT (oversize THV as in TAVR or more) Must flare in the left ventricle Adding extra volume during deployment can help flare (23 mm S 3=2 ml, 26 mm S 3=3 ml and 29 mm S 3=4 ml) Post-dilate if needed Aim for final position 80/20 LV/LA © 2017 MFMER | slide-11

Tips to Prevent PVL Adequate sizing with CT Aim for final position 80/20 LV/LA

Dealing with PVL Understand mechanism Post-dilate if no central MR present PVL closure for

PVL Closure after Vi. MAC Series of 5 consecutive cases at Mayo Clinic 3 successful 1 unable to cross 1 posterior leaflet impingement, AVP-II device prolapsed through stent frame cells Al-Hijji, et al. CCI January 2019. © 2017 MFMER | slide-14

TMVR in MAC Global Registry Multivariate Cox Regression Analysis Independent Predictors of 1 -Year Mortality HR 95% CI p Technical success (yes vs no) 0. 22 0. 09 -0. 51 0. 0005 LVOT obstruction 2. 63 1. 14 -6. 06 0. 0227 Guerrero, Urena et al, JACC May 1 st. 2018; 71: 1841 -53. © 2017 MFMER | slide-15

How to Prevent LVOT Obstruction Septal Reduction Strategies Alcohol Septal Ablation Anterior Leaflet Strategies Surgical resection (MITRAL and SITRAL trials) Percutaneous laceration (LAMPOON trial) Concept generated in MITRAL trial © 2017 MFMER | slide-16

Preventing LVOT Obstruction with Alcohol Ablation Baseline Post-alcohol ablation Post-TMVR © 2017 MFMER |

Pre-emptive Alcohol Ablation to Prevent LVOT Obstruction Early Clinical Experience in a Multicenter Observational First-in-Man Study 30 patients STS 7. 2%, average 1. 6± 0. 7 ml alcohol, repeat CT 3 -4 weeks later Baseline Median Neo-LVOT=85. 1 mm 2 Median increase Neo-LVOT=111. 2 mm 2 Wang et al, In Press JACC Interv 2019 © 2017 MFMER | slide-18

Pre-emptive Alcohol Ablation to Prevent LVOT Obstruction 30 day Outcomes 2/30 deaths (6. 7%) 5/30 (16. 7%) pacemaker Alive Wang et al, In Press JACC Interv 2019 1 Dead Alive 30 day Mortality= 3/30 (10%) © 2017 MFMER | slide-19

Transatrial TMVR in MAC Single center experience, 8 patients with severe MAC and STS score 8%, 30 -Day Mortality= Zero SITRAL Trial ongoing (Surgical Implantation of TRAnscatheter va. Lves in MAC) PI Dr. Robert Smith Russell, Guerrero, et al. JACC Sept 25, 2018; 72: 1437 -48. © 2017 MFMER | slide-20

LAMPOON Laceration of the Anterior Mitral Leaflet to Prevent Outflow Obstructio. N MAC (n=15) and MVi. R (n=15) Enrollment complete Preliminary In-Hospital data presented at TCT (in-hospital mortality 7%) 30 day outcomes will presented as LBCT at CRT Monday March 4 th 11: 30 am © 2017 MFMER | slide-21

Vi. MAC 30 -day Mortality 30 25 25 21 20 15 16. 6 13 12 10 10 All-cause Cardiovascular 5 0 TMVR in MAC Global Registry (2012 -2017) n=116 TVT (2013 -2017) n=100 * Data monitoring not yet complete, may be subject to change. MITRAL Trial* (2015 -2017) n=30 Yoon=34% (real world experience) Russell= 0% LAMPOON=not reported yet 7% in-hosp m © 2017 MFMER | slide-22

Options to Prevent LVOT Obstruction Today Preemptive alcohol septal ablation Percutaneous laceration of anterior leaflet (LAMPOON) Surgical resection of anterior leaflet (transatrial TMVR) Don’t do it… Med Rx only is better than acute LVOTO! © 2017 MFMER | slide-23

Summary Vi. MAC with balloon-expandable aortic THVs is a complex procedure LVOT Obstruction, PVL and embolization are the worst complications Cardiac CT is the most important screening tool to prevent such complications Risk reduction strategies to reduce risk of LVOTO are now available Clinical outcomes have improved with adequate screening and patient selection © 2017 MFMER | slide-24