Implantation of Balloon-Expandable THVs in Native Mitral Valves with Severe MAC Mayra Guerrero, MD, FACC, FSCAI Director of Cardiac Structural Interventions NorthShore University HealthSystem CRT 2017 Washington, DC Feb 19, 2017

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 Company Research Grant Support, Proctor Consultant Speaker’s Bureau Edwards Lifesciences Tendyne Holdings/Abbott Abiomed Off label use of products and investigational devices will be discussed in this presentation

Surgical MVR for MAC Comorbidities increase risk Technically challenging Rupture of posterior wall of LV Many pts untreated due to risk Casarotto et al, G Ital Cardiol 1977;7(4):387-94. Goodney et al, Ann Thorac Surg 2003;76:1131-1136. Vohra et al, J Heart Valve Dis 2011;20(6):624-6.

TMVR in MAC Global Registry 115 patients from 48 centers in 11 countries (Sept 2012-Feb 2017) Underwent TMVR with compassionate use of aortic THV Balloon expandable 95%, Lotus+DFM 5% (TA 44%, TS 38%, atrial 18%) First 64 patients…Technical success 72%, 30-Day Mortality 29.7% Guerrero et al, J Am Coll Cardiol Intv July 2016;9:1361-71.

Patient Characteristics n (%), or mean (range) Age 73 ± 13 (39-96) Female 66% NYHA II 8.5% III 41.5% IV 50% Diabetes 38% COPD 44.8% Atrial Fibrillation 45% Renal Failure 35% Prior CABG 34% Prior AVR 47.5% STS score 14.43± 10 (1-41)

Procedural Outcomes n (%) 78/109 (76%) 16/109 (14.6%) 12/109 (11%) Technical success by MVARC criteria 78/109 (76%) Need for second valve (migration=7, MR=9) 16/109 (14.6%) LVOT obstruction with hemodynamic compromise 12/109 (11%) Valve embolization 5/109 (4.5%) Conversion to open surgery (embolization=2, LV perforation=1, LVOTO=1) 4/109 (3.6%) LV perforation (surgery=1, conservative=1) 2/109 (1.8%) Pulmonary Vein Perforation 1 (0.9%)

30 Day/Procedural Mortality 28/109 (25.6%) n (%) Cardiovascular 11/109 (10.1 %) LVOT Obstruction 3 (2.9%) LV Perforation 2 (1.9%) Complete AV block 1% MI due to air emboli / Pulmonary vein perforation Stroke PEA arrest 1 % MR Non-Cardiac 17/109 (15.5 %) Multi-organ failure 9 (8.6%) Pneumonia Thoracentesis related bleeding complication Infection

Clinical Outcomes relative to experience 104 patients from 47 centers in 11 countries (Sept 2012-April 2016) Outcome First 1/3 (n=32) n (%) Second 1/3 (n=32) Third 1/3 (n=40) Technical success * MVARC criteria 20 (62.5%) 27 (84.4%) 32 (80%) 30 Day Mortality 12 (37.5%) 7 (21.9%) 6 (15%) Complications Valve Embolization 3 (9.3%) 1 (3.1%) LVOTO 4 (12.5%) 2 (6.2%) 5 (12.5%) Need for a second valve 2 (5%) Cardiac Perforation 2 (6.25%) Conversion to open surgery EuroPCR 2016

Role of Alcohol Septal Ablation Baseline After Alcohol Ablation Courtesy of Dr. William O’Neill After TMVR Guerrero et al, CCI 2016 July 5. doi:10.1002/ccd.26649.

Alcohol Septal Ablation as bail out for LVOTO 6 patients were treated with ETOH ablation as bail out Reduction of LVOT gradient in all 6 cases One recurred the following day (suspected edema) One died of AVB and one died of MOF 3 weeks later 4 out of 6 were discharged from the hospital * Guerrero et al, In Press CCI 2017

Role of Alcohol Septal Ablation prior to TMVR Pre-ablation Post-ablation Courtesy of Dr. Dee Dee Wang 8 patients successfully treated with TMVR after alcohol ablation (TMVR in MAC Registry and MITRAL Trial)

Role of Anterior Leaflet Resection prior to TMVR

Role of Anterior Leaflet Resection prior to TMVR 6-month follow 2-17-17 NYHA I Mean MVG 4 mmHg Mean LVOT gradient 5 mmHg

Percutaneous Anterior Leaflet Laceration prior to TMVR LAMPOON Laceration of the Anterior Mitral leaflet to Prevent LVOT ObstructioN Khan et al, JACC Intv 2016;9:1835-43.

1-Year Follow-up TMVR in MAC Registry Work in Progress… Data lock scheduled May 2017 As of 2-19-17… excluding non-balloon expandable valves in registry (Lotus, DFM) 109 patients 25.6% 30-day mortality 81 Survived 30 days 8 had procedure after June 2016 73 eligible for 1-year follow-up by May 2017 11 deaths after 30 days 62 Patients 13 (1-year follow-up not due until May 2017) 49 Patients 24 (1-year follow-up due data being collected) 25 survivors with 1-year follow-up data submitted

1 valve reintervention (V-in-V for MR 9 months from index procedure) Deaths After 30 Days 11/109 (10.1%) n (%) Cardiovascular 5/109 (4.6 %) Sudden death 1 Valve thrombosis at 2 months (subtherapeutic INR) Endocarditis Stroke Heart failure Non-Cardiac 6/109 (5.5 %) C2 fracture after fall Failure to thrive GI bleed Sepsis Suspected infection 2 1 valve reintervention (V-in-V for MR 9 months from index procedure)

NYHA Class

1-Year Echocardiogram EF 51.2 (30-83) mmHg Mean MVG MVA LVOT gradient 2.02 (1.3-2.8) cm2 LVOT gradient 6.5 (0-37) mmHg Trace or mild MR 70% No MR 30%

The MITRAL Trial Inclusion Criteria www.clinicaltrials.gov Native MV (MAC) Valve-in-Ring Valve-in-Valve Calcific MS (MVA ≤1.5 cm2) Severe MR + Mod MS NYHA II or greater Not surgical candidate Failing surgical ring Severe MR or MS NYHA II or greater Not surgical candidate Failing Bioprosthesis Severe MR or MS NYHA II or greater Not surgical candidate www.clinicaltrials.gov

Surgical Implantation of TRAnscatheter vaLve in Native MAC SITRAL Trial Surgical Implantation of TRAnscatheter vaLve in Native MAC Baylor Research Institute PI Robert Smith, MD 30 patients Start April 2016 Transatrial TMVR with SAPIEN 3 www.clinicaltrials.gov

Laceration of the Anterior Mitral leaflet to Prevent LVOT ObstructioN LAMPOON Trial Laceration of the Anterior Mitral leaflet to Prevent LVOT ObstructioN PI Robert Lederman, MD NHLBI Locations: Emory University Henry Ford Hospital Evanston Hospital www.clinicaltrials.gov

Severe MV Disease and Severe MAC Prior Algorhitm… Severe MV Disease and Severe MAC Symptomatic Patient Despite Medical Treatment Surgical Candidate? Yes No MV Replacement Palliative Care

Severe MV Disease and Severe MAC Evolving Algorithm… Severe MV Disease and Severe MAC Symptomatic Patient Despite Medical Treatment Surgical Candidate? Yes No MAC related Technical Challenges? Favorable Anatomy for Transeptal TMVR with Balloon Expandable THV? No due to High Risk of LVOTO No due to inadequate calcium for anchoring No Yes Yes Tendyne compassionate use or trial when available MVR SITRAL Trial ? Alcohol Septal Ablation LVOTO risk lower? or MITRAL Trial Unfavorable Anatomy for ASA Yes No LAMPOON Trial

Severe MV Disease and Severe MAC Evolving Algorithm… Severe MV Disease and Severe MAC Symptomatic Patient Despite Medical Treatment Surgical Candidate? Yes No MAC related Technical Challenges? Favorable Anatomy for Transeptal TMVR with Balloon Expandable THV? No due to High Risk of LVOTO No due to inadequate calcium for anchoring No Yes Yes Tendyne compassionate use or trial when available MVR SITRAL Trial ? Alcohol Septal Ablation LVOTO risk lower? or MITRAL Trial Unfavorable Anatomy for ASA Yes No LAMPOON Trial

Conclusions TMVR in MAC is feasible & outcomes are improving with experience TMVR may evolve into a viable option for non-surgical patients Patients who survive TMVR with balloon-expandable aortic THVs experience sustained improvement of symptoms at 1 year THV performance is maintained at 1 year Anticoagulation post-TMVR should be considered (ideal duration ?) Prospective clinical trials are needed (MITRAL, SITRAL, LAMPOON)

Thank You mguerrero@northshore.org mayraguerrero@me.com