Cardiovascular Research Technologies The Pathoanatomy of Functional MR as It Relates to Transcatheter Therapy Ted Feldman, M.D., MSCAI FACC FESC Evanston Hospital CRT Valve – Mitral (6:30 AM – 2:30 PM) CRT 2017 Track: CRT Valve & Structural CRT Valve - Mitral Session: CRT Valve & Structural Heart for the Surgeon: Breakfast I (6:30 AM – 8:00 AM) Sunday, February 19, 2017 7:20 AM – 7:30 AM Room: Blue Room The Pathoanatomy of Functional MR as It Relates to Transcatheter Therapy Your role: Presenter RT Valve & Structural Heart for the Surgeon: Breakfast I 6:30 AM - 8:00 AM 6:30 AM Session ModeratorsModerator: Ted Feldman, MD, MSCAI Moderator: Neil Moat, MS FRCS 6:50 AM Surgical Mitral Valve Repair: What Is the Gold Standard?Presenter: Donald D. Glower, MD 7:00 AM Tricuspid Repair Indications and TechniquesPresenter: Steven F. Bolling, MD 7:10 AM How I Treat Functional Mitral Regurgitation (MR) – The Surgeon's PerspectivePresenter: Thierry G. Mesana, MD, PhD 7:20 AM The Pathoanatomy of Functional MR as It Relates to Transcatheter TherapyPresenter: Ted Feldman, MD, MSCAI 7:30 AM MAC and Transcatheter ValvesPresenter: Mayra E. Guerrero, MD, FACC, FSCAI 7:40 AM Transseptal Mitral Valve-In-Valve ImplantationPresenter: Charanjit Rihal, MD CRT Cardiovascular Research Technologies Washington D.C. February 18-21st, 2017

Ted Feldman MD, MSCAI FACC FESC Disclosure Information The following relationships exist: Grant support: Abbott, BSC, Cardiokinetics, Corvia, Edwards, WL Gore Consultant: Abbott, BSC, Edwards, WL Gore Stock Options: Mitralign Off label use of products and investigational devices will be discussed in this presentation

Key Inclusion Criteria The subject has had at least 1 HF hospitalization in the 12 months prior to enrollment and/or a corrected BNP ≥300 pg/ml or nT-proBNP ≥1500 pg/ml measured within 90 days prior to registration Subject has been adequately treated per applicable standards for CAD, LV dysfunction, MR or HF (CRT, revascularization, and/or GDMT) The primary regurgitant jet is non-commissural. If secondary MR jets exist, they must be considered clinically insignificant. CK-MB obtained within prior 14 days less than local laboratory upper limit of normal (ULN) 3

Key Exclusion Criteria Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets, or sufficient MR reduction by the MitraClip Insufficient mobile leaflet available for grasping with the MitraClip device Evidence of calcification in the grasping area Presence of a significant cleft in the grasping area Lack of both primary and secondary chordal support in the grasping area Leaflet mobility length < 1 cm MV orifice area <4.0 cm2, confirmed by the Site 90 days prior to registration

Key Exclusion Criteria Chronic Obstructive Pulmonary Disease (COPD) requiring continuous home oxygen therapy or chronic outpatient oral steroid use Physical evidence of right-sided congestive heart failure with echocardiographic evidence of moderate or severe right ventricular dysfunction, as assessed by site PASP > 70 mm Hg Tricuspid valve disease requiring surgery Aortic valve disease requiring surgery or transcatheter intervention ACC/AHA Stage D heart failure

Transseptal: DMR vs FMR Kar S, Yeow WL: CH 14 Procedural tips and tricks. In, Percutaneous Mitral Leaflet Repair: MitraClip Therapy for Mitral Regurgitation Edited by Ted Feldman & Frederick St Goar, Informa Healthcare, 2012.

Grasping: PML

CARDIOBAND Edwards PASCAL Repair System

Two-Year Outcomes of Surgical Treatment of Severe Ischemic MR Figure 1. Time-to-Event Curves for Death. Shown are the proportions of patients who died in the mitral-valve (MV) repair group and the mitral-valve replacement group at 2 years. The most frequent underlying causes of death were multisystem organ failure (in 20.8% of patients), heart failure (in 17.0%), and sepsis (in 13.2%). The tick marks indicate censored data. Goldstein D et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1512913

LV-mitral ring mismatch: recurrent ischemic MR after annuloplasty Figure 3. Proposed algorithm for applying the LV-MV ring mismatch concept to define patients at high risk for recurrence of MR after repair. LV-MV ring mismatch concept uses a simple and highly reproducible measurement that can be performed in the majority of patients. LVESd/ring size- odds ratio 2.2 per 0.5 increase was associated with 1-year MR recurrence. Figure 1. Mechanisms of recurrent MR after annuloplasty. Top, Preop echo shows LV dimension, MV leaflet tethering and lack of coaptation (left), and MR severity (right). Bottom, Postop LV dimension, posterior leaflet tethering and lack of coaptation after MV repair (left), and associated degree of MR severity (right). The dimension of the LV remained the same after surgery, whereas the anteroposterior dimension of the MV annulus was significantly decreased after MV repair. This mismatch resulted in a significant MR after repair. is associated with a significant rate of recurrent MR. Ring size is based on intertrigonal distance without consideration of left ventricular (LV) size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering before and after repair. We aimed to determine whether LV-MV ring mismatch (mismatch of LV size relative to ring size) is associated with recurrent MR in patients with IMR after restrictive ring annuloplasty. METHODS: Patients with moderate or severe IMR from the 2 Cardiothoracic Surgical Trials Network IMR trials who received MV repair were examined at 1 year after surgery. Baseline LV size was assessed by LV end-diastolic dimension and LV end-systolic dimension (LVESd). LV-MV ring mismatch was calculated as the ratio of LV to ring size (LV end- diastolic dimension/ring size and LVESd/ring size). RESULTS: At 1 year after ring annuloplasty, 45 of 214 patients with MV repair (21%) had moderate or greater MR. In univariable logistic regression analysis, larger LVESd (P=0.02) and LVESd/ring size (P=0.007) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe IMR, only LVESd/ring size (odd ratio per 0.5 increase, 2.20; 95% confidence interval, 1.05–4.62; P=0.038) remained significantly associated with 1-year MR recurrence. CONCLUSIONS: LV-MV ring size mismatch is associated with increased risk of MR recurrence. This finding may be helpful in guiding choice of ring size to prevent recurrent MR in patients undergoing MV repair and in identifying patients who may benefit from MV repair with additional subvalvular intervention or MV replacement rather than repair alone. What is new? In this analysis of 2 randomized, clinical trials focused on the surgical treatment of ischemic mitral regurgitation, we demonstrated the importance of mismatch between left ventricular size relative to mitral valve ring size, quantified as left ventricular end-systolic dimension/ring size ratio, as an inde- pendent predictor of recurrent ischemic mitral regurgitation after restrictive ring annuloplasty. The mechanistic basis that underlines this asso- ciation between left ventricular to mitral valve ring mismatch and the recurrence of mitral regurgitation after ring annuloplasty relates to the persistence of mitral leaflet tethering. What are the clinical implications? The main adverse effect of restrictive ring annulo- plasty in patients with ischemic mitral regurgitation is the high rate of recurrence of mitral regurgita- tion after surgery: up to 30% at 1 year and 60% at 2 years. The findings of this study support the potential utility of the left ventricular to mitral valve mismatch as a means of identifying preoperatively patients with ischemic mitral regurgitation who may benefit from additional subvalvular interventions to the restrictive ring annuloplasty or mitral valve replacement rather than mitral valve repair alone. Circulation. 2016;134:1247–1256

TMV Replacement Fixation/Anchoring/Migration PVL LVOT obstruction Hemolysis Calcium Apical access Transseptal access Philipp Blanke, MD