COAPT A Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation Gregg W.

COAPT A Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation Gregg W. Stone, MD On behalf of Michael Mack, William Abraham, JoAnn Lindenfeld and the COAPT Investigators

Institutional conflict
Disclosure Statement Gregg W. Stone MD Consulting fees from Neovasc, Valfix, Gore Equity/options in Ancora Institutional conflict Columbia University, my employer, receives royalties from Abbott for sale of the MitraClip

Background (i) Pts with heart failure (HF) in whom mitral regurgitation (MR) develops secondary to left ventricular dysfunction have a poor prognosis, with reduced quality-of-life, frequent hospitalizations for heart failure and decreased survival There are no proven therapies for secondary MR in HF Guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT) may provide symptomatic relief in some pts Whether correcting secondary MR improves the prognosis of pts with HF is unknown Surgery with a downsized annuloplasty ring has not been demonstrated to be beneficial for secondary MR, and has a high recurrence rate This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 2

Background (ii) By approximating the anterior and posterior mitral leaflets and forming a double-orifice valve, the MitraClip device reduces MR Registries have suggested that the MitraClip is safe and may provide symptomatic benefit to HF pts with secondary MR We therefore performed the COAPT randomized trial to evaluate the safety and effectiveness of transcatheter mitral leaflet approximation in HF pts with secondary MR who remained symptomatic despite GDMT This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 3

The COAPT Trial GDMT alone MitraClip + GDMT N=305
Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation A parallel-controlled, open-label, multicenter trial in ~610 patients with heart failure and moderate-to-severe (3+) or severe (4+) secondary MR who remained symptomatic despite maximally-tolerated GDMT Randomize 1:1* GDMT alone N=305 MitraClip + GDMT This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Stratified by cardiomyopathy etiology (ischemic vs. non-ischemic) and site 4

Key Inclusion Criteria
Ischemic or non-ischemic cardiomyopathy with LVEF 20%-50% and LVESD ≤70 mm Moderate-to-severe (3+) or severe (4+) secondary MR confirmed by an independent echo core laboratory prior to enrollment (US ASE criteria) NYHA functional class II-IVa (ambulatory) despite a stable maximally- tolerated GDMT regimen and CRT (if appropriate) per societal guidelines Pt has had at least one HF hospitalization within 12 months and/or a BNP ≥300 pg/ml* or a NT-proBNP ≥1500 pg/ml* Not appropriate for mitral valve surgery by local heart team assessment IC believes secondary MR can be successfully treated by the MitraClip This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Adjusted by a 4% reduction in the BNP or NT-proBNP cutoff for every increase of 1 kg/m2 in BMI >20 kg/m2 5

Key Exclusion Criteria
ACC/AHA stage D HF, hemodynamic instability or cardiogenic shock Untreated clinically significant CAD requiring revascularization COPD requiring continuous home oxygen or chronic oral steroid use Severe pulmonary hypertension or moderate or severe right ventricular dysfunction Aortic or tricuspid valve disease requiring surgery or transcatheter intervention Mitral valve orifice area <4.0 cm2 by site-assessed TTE Life expectancy <12 months due to non-cardiac conditions This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 6

Central Echo Core Lab and Eligibility Committee Review
A Central Echo Core Lab confirmed the presence of secondary MR Potentially eligible pts were then presented by the local site investigators on weekly calls to a Central Eligibility Committee consisting of at a minimum a heart failure specialist and expert mitral valve surgeon The CEC confirmed that all eligibility criteria were met, especially 1) use of maximally-tolerated GDMT for heart failure, and treatment with CRT, defibrillators and revascularization if appropriate, and that 2) mitral valve surgery was not considered appropriate at the treating center and would not be offered to the patient, even if randomized to control Pts not meeting these criteria were rejected, or in some cases were deferred and could be re-presented after suitable GDMT had been instituted if the pt remained symptomatic and repeat echo still showed MR This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 7

Primary Endpoints Primary effectiveness endpoint: All HF hospitalizations through 24 months* Powered for superiority of the Device group compared with the Control group Primary safety endpoint: Freedom at 12 mos from device-related complications: - Single leaflet device attachment - Device embolization - Endocarditis requiring surgery - Echo core laboratory-confirmed mitral stenosis requiring surgery - Left ventricular assist device implant - Heart transplant - Any device-related complication requiring non-elective cardiovascular surgery Powered for superiority of the Device group vs. a pre-specified OPG** This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Analyzed when the last subject completes 12 months of follow-up; **Objective performance goal 8

Sample Size and Power Analysis
Primary Effectiveness Endpoint Analyzed using a joint frailty model to account for the competing risk of death Assumptions Annualized HF hosp rates: 0.60 per pt-yr Control vs per pt-yr Device 12-month mortality rates: 27% Control vs. 22% Device 12-month attrition rate: 7.5% Power 610 randomized pts provided 80% power at a 1-sided α of 0.05 to demonstrate superiority of the Device group compared with the Control group for the 24-month rate of all HF hospitalizations Primary Safety Endpoint 305 pts in the Device group provided >95% power to demonstrate that freedom from device-related complications at 12 months is more than a pre-specified objective performance goal of 88% at a one-sided α of 0.05 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 9

Powered Secondary Endpoints
- Tested in hierarchical order1 - MR grade 2+ at 12 months All-cause mortality at 12 months2 Death and all HF hospitalization through 24 months (Finkelstein-Schoenfeld and win ratio analysis) Change in QOL (KCCQ) from baseline to 12 months Change in 6MWD from baseline to 12 months All-cause hospitalizations through 24 months NYHA class I or II at 12 months Change in LVEDV from baseline to 12 months All-cause mortality at 24 months Death, stroke, MI, or non-elective CV surgery for device-related compls at 30 days3 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 1All powered for superiority unless otherwise noted; 2Powered for noninferiority of the device vs. the control group; 3Powered for noninferiority against an objective performance goal 10

Study Leadership Principal Investigators
Michael J. Mack, MD, Baylor Scott & White Heart Hospital Plano, Plano, TX Gregg W. Stone, MD, Columbia University Medical Center, NY, NY Heart Failure Co-Principal Investigators William T. Abraham, MD, Ohio State University, Columbus, OH JoAnn Lindenfeld, MD, Vanderbilt Heart and Vascular Institute, Nashville, TN Steering Committee Gregg W. Stone, Michael J. Mack, JoAnn Lindenfeld, William T. Abraham, Steven F. Bolling, Ted E. Feldman, Paul A. Grayburn, Samir R. Kapadia, Patrick M. McCarthy Central Eligibility Committee Gregg Stone, Paul Grayburn, Scott Lim, Michael Zile, James Udelson, William Abraham, JoAnn Lindenfeld, Rakesh Suri, James Gammie, Marc Gillinov, Steve Bolling, Patrick McCarthy, Donald Glower, David Heimansohn Clinical Events Committee Cardiovascular Research Foundation, New York, NY; Steven O. Marx, MD, chair Echocardiographic Core Laboratory MedStar Health Research Institute, Hyattsville, MD; Neil J. Weissman, MD, director Cost-effectiveness and quality-of-life assessment Saint Luke’s Mid America Heart Institute, KC, MO; David J. Cohen, MD, director Sponsor Abbott, Santa Clara, CA This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 11

Study Flow and Follow-up
1576 pts with HF and MR considered for enrollment between September 25th, 2012 and June 23th, 2017 at 89 centers in the US and Canada Ineligible N=911 Eligible for enrollment N=665 Reasons for exclusion Inadequate MR or DMR (n=244) Not treated with GDMT (n=79) All inclusion criteria not met (n=85) Exclusion criteria present (n=34) Echo criteria not met (n=255) Incomplete screening or other (n=419) Roll-in cases N=51 at 34 sites Randomized N=614 at 78 sites MitraClip + GDMT N=302 GDMT alone N=312 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 12

Study Flow and Follow-up
MitraClip + GDMT N=302 GDMT alone N=312 Initial treatment MitraClip GDMT alone N=293 N=9 N=1 N=311 Withdrew 3 Lost to follow-up 1 3 Withdrew 0 Lost to follow-up N=298/302 (98.7%) 30-day follow-up N=309/312 (99.0%) Withdrew 6 Lost to follow-up 1 18 Withdrew 0 Lost to follow-up N=295/302 (97.7%) 1-year follow-up (primary endpoint minimum) N=294/312 (94.2%) Withdrew 10 Lost to follow-up 3 23 Withdrew 3 Lost to follow-up This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) N=231/244 (94.7%) 2-year follow-up (eligible patients) N=232/258 (89.9%) 13

Top 10 Enrolling Sites 1. Saibal Kar
Cedars-Sinai Medical Center, Los Angeles, CA n=46 2. Scott Lim University of Virginia, Charlottesville, VA n=30 3. Jacob Mishell Kaiser Permanente, San Francisco, CA n=29 4. Brian Whisenant Intermountain Medical Center, Murray, UT n=26 5. Paul Grayburn Baylor Heart and Vascular Hospital, Dallas, TX n=25 6. Andreas Brieke University Of Colorado Hospital, Aurora, CO n=17 6. Michael Rinaldi Carolinas Medical Center, Charlotte, NC 6. Samir Kapadia Cleveland Clinic, Cleveland, OH 6. Ian Sarembock The Christ Hospital, Cincinnati, OH 6. Vivek Rajagopal Piedmont Hospital, Atlanta, GA This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 14

Baseline Characteristics (i)
MitraClip + GDMT (N=302) GDMT alone (N=312) MitraClip + GDMT (N=302) Age (years) 71.7 ± 11.8 72.8 ± 10.5 BMI (kg/m2) 27.0 ± 5.8 27.1 ± 5.9 Male 66.6% 61.5% CrCl (ml/min) 50.9 ± 28.5 47.8 ± 25.0 Diabetes 35.1% 39.4% - ≤60 ml/min 71.6% 75.2% Hypertension 80.5% 80.4% Anemia (WHO) 59.8% 62.7% Hyperchol. 55.0% 52.2% BNP (pg/mL) 1015 ± 1086 1017 ± 1219 Prior MI 51.7% 51.3% NT-proBNP (pg/mL) 5174 ± 6567 5944 ± 8438 Prior PCI 43.0% 49.0% STS replacement sc 7.8 ± 5.5 8.5 ± 6.2 Prior CABG 40.1% 40.4% - ≥8 41.7% 43.6% Prior stroke or TIA 18.5% 15.7% Surgical risk (central eligibility committee) PVD 17.2% 18.3% - High* 68.6% 69.9% COPD 23.5% 23.1% - Not-high 31.4% 30.1% H/o atrial fibr 57.3% 53.2% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) * STS repl score ≥8% or one or more factors present predicting extremely high surgical risk 15

Baseline Characteristics (ii)
HF parameters MitraClip + GDMT (N=302) GDMT alone (N=312) Echo core lab MitraClip + GDMT (N=302) Etiology of HF MR severity - Ischemic 60.9% 60.6% - Mod-to-sev (3+) 49.0% 55.3% - Non-ischemic 39.1% 39.4% - Severe (4+) 51.0% 44.7% NYHA class EROA, cm2 0.41 ± 0.15 0.40 ± 0.15 - I 0.3% 0% LVESD, cm 5.3 ± 0.9 - II 42.7% 35.4% LVEDD, cm 6.2 ± 0.7 6.2 ± 0.8 - III 54.0% LVESV, mL 135.5 ± 56.1 134.3 ± 60.3 - IV 6.0% 10.6% LVEDV, mL 194.4 ± 69.2 191.0 ± 72.9 HF hosp w/i 1 year 58.3% 56.1% LVEF, % 31.3 ± 9.1 31.3 ± 9.6 Prior CRT 38.1% 34.9% - 40% 82.2% 82.0% Prior defibrillator 30.1% 32.4% RVSP, mmHg 44.0 ± 13.4 44.6 ± 14.0 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 16

Medication Use at Baseline
Maximally-tolerated doses MitraClip + GDMT (n=302) GDMT alone (n=312) Beta-blocker 91.1% 89.7% ACEI, ARB or ARNI 71.5% 62.8% Mineralocorticoid receptor antagonist 50.7% 49.7% Nitrates 6.3% 8.0% Hydralazine 16.6% 17.6% Diuretic 89.4% 88.8% Chronic oral anticoagulant 46.4% 40.1% Aspirin 57.6% 64.7% P2Y12 receptor inhibitor 25.2% 22.8% Statin 62.6% 60.6% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 17

Major Changes in HF Meds w/i 12 Months
MitraClip + GDMT (n=302) GDMT alone (n=312) P value ACEI, ARB or ARNI - ⇓ dose by >50% or discontinue 6.6% 4.8% 0.33 - ⇑ dose by >100% or new drug started 7.6% 7.4% 0.91 Beta-blocker 5.3% 5.1% 0.92 8.6% 3.8% 0.01 Mineralocorticoid receptor antagonist 0.7% 0.6% 1.00 2.6% 0.08 Nitrates 0.0% 1.0% 1.9% 0.51 Hydralazine 0.12 4.3% 0.77 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 18

MitraClip Procedure (n=302)
MitraClip procedure attempted 293/302 (97.0%) Clip implanted (MitraClip procedure attempted) 287/293 (98.0%) Clip implanted (all patients) 287/302 (95.0%) Mean # of clips implanted 1.7  0.7 (n=293) - 0 clips implanted 6 (2.0%) - 1 clip implanted 106 (36.2%) - 2 clips implanted 157 (53.6%) - 3 clips implanted 23 (7.9%) - 4 clips implanted 1 (0.3%) Procedure duration (mins) 162.9  118.1 - Device procedure time (mins) 118.9  63.5 - Device time (mins) 82.7  80.8 - Fluoroscopy time (mins) 33.9  23.2 TTE at discharge (n=260) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 19

Primary Effectiveness Endpoint All Hospitalizations for HF within 24 months
300 MitraClip + GDMT GDMT alone 283 in 151 pts 250 200 HF Hospitalizations (n) Cumulative 160 in 92 pts 150 100 HR (95% CI] = 0.53 [ ] P<0.001 50 3 6 9 12 15 18 21 24 Median [25%, 75%] FU = 19.1 [11.9, 24.0] mos Time After Randomization (Months) No. at Risk: This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) MitraClip 302 286 269 253 236 191 178 161 124 GDMT 312 294 271 245 219 176 145 121 88 20

Annualized rates of HF hospitalization*
Primary Effectiveness Endpoint Hospitalizations for HF within 24 months Annualized rates of HF hospitalization* NNT (24 mo) = 3.1 [95% CI 1.9, 8.2] GDMT alone 283/416.8 pt-yrs HR (95% UCL] = 0.53 [0.66] P<0.001 MitraClip + GDMT 160/446.5 pt-yrs This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Joint frailty model 21

Primary Safety Endpoint Freedom from Device-related Complications within 12 months
96.6%* MitraClip procedure attempted N=293 Device-related complications 9 (3.4%) - Single leaflet device attachment 2 (0.7%) - Device embolization 1 (0.3%) - Endocarditis requiring surgery 0 (0.0%) - Mitral stenosis requiring surgery - Left ventricular assist device implant 3 (1.2%) - Heart transplant 2 (0.8%) - Any device-related complication requiring non-elective CV surgery 94.8% [95% LCL] 88% OPC P<0.001 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *KM estimate; **Calculated from Z test with Greenwood’s method of estimated variance against a pre-specified objective performance goal of 88% 22

- Tested in hierarchical order1 - P-value 1. MR grade 2+ at 12 months 2. All-cause mortality at 12 months2 3. Death and all HF hospitalization through 24 months (Finkelstein-Schoenfeld) 4. Change in QOL (KCCQ) from baseline to 12 months 5. Change in 6MWD from baseline to 12 months 6. All-cause hospitalizations through 24 months 7. NYHA class I or II at 12 months 8. Change in LVEDV from baseline to 12 months 9. All-cause mortality at 24 months 10. Death, stroke, MI, or non-elective CV surgery for device-related compls at 30 days3 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 1All powered for superiority unless otherwise noted; 2Powered for noninferiority of the device vs. the control group; 3Powered for noninferiority against an objective performance goal 23

- Tested in hierarchical order1 - P-value 1. MR grade 2+ at 12 months <0.001 2. All-cause mortality at 12 months2 3. Death and all HF hospitalization through 24 months (Finkelstein-Schoenfeld) 4. Change in QOL (KCCQ) from baseline to 12 months 5. Change in 6MWD from baseline to 12 months 6. All-cause hospitalizations through 24 months 0.03 7. NYHA class I or II at 12 months 8. Change in LVEDV from baseline to 12 months 0.003 9. All-cause mortality at 24 months 10. Death, stroke, MI, or non-elective CV surgery for device-related compls at 30 days3 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 1All powered for superiority unless otherwise noted; 2Powered for noninferiority of the device vs. the control group; 3Powered for noninferiority against an objective performance goal 24

All-cause Mortality All-cause Mortality (%) HR [95% CI] =
100% MitraClip + GDMT GDMT alone 80% HR [95% CI] = 0.62 [ ] P<0.001 60% NNT (24 mo) = 5.9 [95% CI 3.9, 11.7] All-cause Mortality (%) 46.1% 40% 29.1% 20% 0% 3 6 9 12 15 18 21 24 Time After Randomization (Months) No. at Risk: This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) MitraClip + GDMT 302 286 269 253 236 191 178 161 124 GDMT alone 312 294 271 245 219 176 145 121 88 25

Death or HF Hospitalization
100% MitraClip + GDMT HR [95% CI] = 0.57 [ ] P<0.001 GDMT alone 80% 67.9% 60% All-cause Mortality or HF Hospitalization (%) 45.7% 40% NNT (24 mo) = 4.5 [95% CI 3.3, 7.2] 20% 0% 3 6 9 12 15 18 21 24 Time After Randomization (Months) No. at Risk: MitraClip + GDMT This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 302 264 238 215 194 154 145 126 97 GDMT alone 312 244 205 174 153 117 90 75 55 26

24-Month Death or HF Hospitalization
Subgroup MitraClip + GDMT GDMT alone HR [95% CI] HR [95% CI] P [Int] All patients All patients 45.7% (129) 67.9% (191) 0.57 [0.45, 0.71] Age (median) ≥74 years (n=317) 52.1% (78) 70.2% (100) 0.65 [0.48, 0.88] <74 years (n=297) 37.8% (51) 65.3% (91) 0.47 [0.33, 0.66] 0.13 Sex Female (n=221) 43.2% (39) 59.4% (66) 0.60 [0.40, 0.89] Male (n=393) 47.1% (90) 73.0% (125) 0.54 [0.41, 0.71] 0.76 Etiology of cardiomyopathy Ischemic (n=373) 48.1% (84) 70.0% (116) 0.57 [0.43, 0.76] Non-ischemic (n=241) 41.1% (45) 65.2% (75) 0.54 [0.37, 0.78] 0.79 Prior CRT Yes (n=224) 50.2% (55) 68.4% (69) 0.62 [0.44, 0.89] No (n=390) 42.9% (74) 67.4% (122) 0.53 [0.39, 0.71] 0.54 HF hospitalization within the prior year Yes (n=407) 44.7% (86) 67.9% (126) 0.56 [0.42, 0.73] No (n=207) 47.6% (43) 67.8% (65) 0.59 [0.40, 0.86] 0.79 Baseline NYHA class I or II (n=240) 41.1% (50) 66.9% (65) 0.56 [0.39, 0.81] III (n=322) 46.6% (67) 65.3% (99) 0.61 [0.44, 0.83] 0.92 IV (n=51) 68.3% (12) 84.4% (26) 0.56 [0.28, 1.12] STS replacement score ≥8% (n=262) 54.1% (65) 71.4% (88) 0.64 [0.46, 0.88] <8% (n=352) 39.2% (64) 65.0% (103) 0.51 [0.37, 0.70] 0.41 Surgical risk status* High (n=423) 49.7% (95) 71.5% (140) 0.58 [0.45, 0.75] Not high (n=188) 35.8% (32) 58.7% (51) 0.51 [0.33, 0.80] 0.69 Baseline MR grade 3+ (n=320) 37.5% (51) 65.3% (100) 0.48 [0.34, 0.67] 4+ (n=293) 53.4% (78) 71.4% (91) 0.62 [0.45, 0.83] 0.29 Baseline LVEF ≥30% (median; n=301) 44.1% (62) 61.2% (85) 0.60 [0.43, 0.84] <30% (median; n=274) 46.4% (56) 77.8% (99) 0.46 [0.33, 0.64] 0.32 >40% (n=103) 49.7% (22) 56.2% (27) 0.67 [0.38, 1.17] ≤40% (n=472) 44.2% (96) 71.9% (157) 0.50 [0.39, 0.65] 0.31 Baseline LVEDV (median) ≥181 mL (n=288) 48.9% (43) 68.0% (92) 0.58 [0.42, 0.80] <181 mL (n=287) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle 41.5% (54) 69.5% (92) 0.48 [0.34, 0.67] 0.42 KM time-to-first event rates *Central eligibility committee assessment 0.2 0.5 1 1.5 2.5 Favors MitraClip + GDMT Favors GDMT alone 27

Kaplan-Meier time-to-first event rates
24-Month Event Rates (i) MitraClip + GDMT (n=302) GDMT alone (n=312) HR [95% CI] P-value Death, all-cause 29.1% 46.1% 0.62 [0.46, 0.82] <0.001 - CV 23.5% 38.2% 0.59 [0.43, 0.81] - HF-related 12.0% 25.9% 0.43 [0.27, 0.67] - Non-HF-related 13.1% 16.6% 0.86 [0.54, 1.38] 0.53 - Non-CV 7.3% 12.7% 0.73 [0.40, 1.34] 0.31 Hospitalization, all-cause 69.6% 81.8% 0.77 [0.64, 0.93] 0.01 51.9% 66.5% 0.68 [0.54, 0.85] 35.7% 56.7% 0.52 [0.40, 0.67] 29.4% 31.0% 0.98 [0.71, 1.36] 0.92 48.2% 52.9% 0.91 [0.71, 1.17] 0.47 Death or HF hospitalization 45.7% 67.9% 0.57 [0.45, 0.71] This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle Kaplan-Meier time-to-first event rates 28

24-Month Event Rates (ii)
MitraClip + GDMT (n=302) GDMT alone (n=312) HR [95% CI] P-value MV intervention or surgery* 4.0% 9.0% 0.61 [0.27, 1.36] 0.23 - MitraClip 3.7% 6.6% 0.99 [0.38, 2.58] 0.99 - Mitral valve surgery 0.4% 2.5% 0.14 [0.02, 1.17] 0.07 PCI or CABG 2.8% 4.3% 0.62 [0.24, 1.60] 0.32 Stroke 4.4% 5.1% 0.96 [0.42, 2.22] 0.93 Myocardial infarction 4.7% 6.5% 0.82 [0.38, 1.78] 0.62 New CRT implant 2.9% 3.3% 0.85 [0.31, 2.34] 0.75 LVAD or heart transplant 9.5% 0.37 [0.17, 0.81] 0.01 - LVAD 3.0% 7.1% 0.34 [0.13, 0.87] 0.02 - Heart transplant 1.4% 3.6% 0.35 [0.09, 1.32] 0.12 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle *Unplanned. Kaplan-Meier time-to-first event rates 29

24-Month Event Rates (ii)
MitraClip + GDMT (n=302) GDMT alone (n=312) HR [95% CI] P-value MV intervention or surgery* 4.0% 9.0% 0.61 [0.27, 1.36] 0.23 - MitraClip 3.7% 6.6% 0.99 [0.38, 2.58] 0.99 - Mitral valve surgery 0.4% 2.5% 0.14 [0.02, 1.17] 0.07 PCI or CABG 2.8% 4.3% 0.62 [0.24, 1.60] 0.32 Stroke 4.4% 5.1% 0.96 [0.42, 2.22] 0.93 Myocardial infarction 4.7% 6.5% 0.82 [0.38, 1.78] 0.62 New CRT implant 2.9% 3.3% 0.85 [0.31, 2.34] 0.75 LVAD or heart transplant 9.5% 0.37 [0.17, 0.81] 0.01 - LVAD 3.0% 7.1% 0.34 [0.13, 0.87] 0.02 - Heart transplant 1.4% 3.6% 0.35 [0.09, 1.32] 0.12 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle *Unplanned. Kaplan-Meier time-to-first event rates 30

Change in KCCQ from Baseline to 12 Months
Adjusted change* ±28.6 ±1.8 P<0.001 ±22.7 ±23.3 ±32.0 ±1.9 n=236 n=228 n=236 n=228 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Ancova 31

Change in 6MWD from Baseline to 12 Months
Adjusted change* ±9.1 ±125.3 ±157.7 ±127.1 P<0.001 ±166.7 ±9.0 n=229 n=237 n=229 n=237 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Ancova 32

NYHA Functional Class NYHA class I II III IV HF death Ptrend I or II
P-value Baseline MitraClip (n=302) 0.3% 42.7% 51.0% 6.0% - 43.0% GDMT (n=311) 0% 35.4% 54.0% 10.6% 30 days MitraClip (n=283) 15.5% 60.8% 19.4% 3.5% 0.7% <0.001 76.3% GDMT (n=281) 5.0% 41.6% 9.6% 1.1% 47.7% 6 months MitraClip (n=263) 52.9% 21.3% 2.7% 3.8% 72.2% GDMT (n=261) 5.4% 44.8% 38.3% 8.8% 50.2% 12 months MitraClip (n=237) 16.9% 55.3% 17.7% 2.5% 7.6% GDMT (n=232) 7.8% 41.8% 28.0% 4.7% 49.6% 24 months MitraClip (n=157) 12.1% 21.7% 5.7% 17.8% 54.8% GDMT (n=153) 5.2% 28.1% 23.5% 3.3% 39.3% 33.3% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 33

MR Severity (Core Lab) MR grade ≤1+ 2+ 3+ 4+ Ptrend ≤2+ P-value
Baseline MitraClip (n=302) - 49.0% 51.0% GDMT (n=311) 55.3% 44.7% 30 days MitraClip (n=273) 72.9% 19.8% 5.9% 1.5% <0.001 92.7% GDMT (n=257) 8.2% 26.1% 37.4% 28.4% 34.2% 6 months MitraClip (n=240) 66.7% 27.1% 4.6% 1.7% 93.8% GDMT (n=218) 9.2% 28.9% 42.2% 19.7% 38.1% 12 months MitraClip (n=210) 69.1% 25.7% 4.3% 1.0% 94.8% GDMT (n=175) 11.4% 35.4% 34.3% 18.9% 46.9% 24 months MitraClip (n=114) 77.2% 21.9% 0% 0.9% 99.1% GDMT (n=76) 15.8% 27.6% 40.8% 43.4% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 34

Baseline MitraClip (n=302) - 49.0% 51.0% GDMT (n=311) 55.3% 44.7% 30 days MitraClip (n=273) 72.9% 19.8% 5.9% 1.5% <0.001 92.7% GDMT (n=257) 8.2% 26.1% 37.4% 28.4% 34.2% 6 months MitraClip (n=240) 66.7% 27.1% 4.6% 1.7% 93.8% GDMT (n=218) 9.2% 28.9% 42.2% 19.7% 38.1% 12 months MitraClip (n=210) 69.1% 25.7% 4.3% 1.0% 94.8% GDMT (n=175) 11.4% 35.4% 34.3% 18.9% 46.9% 24 months MitraClip (n=114) 77.2% 21.9% 0% 0.9% 99.1% GDMT (n=76) 15.8% 27.6% 40.8% 43.4% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 35

Baseline MitraClip (n=302) - 49.0% 51.0% GDMT (n=311) 55.3% 44.7% 30 days MitraClip (n=273) 72.9% 19.8% 5.9% 1.5% <0.001 92.7% GDMT (n=257) 8.2% 26.1% 37.4% 28.4% 34.2% 6 months MitraClip (n=240) 66.7% 27.1% 4.6% 1.7% 93.8% GDMT (n=218) 9.2% 28.9% 42.2% 19.7% 38.1% 12 months MitraClip (n=210) 69.1% 25.7% 4.3% 1.0% 94.8% GDMT (n=175) 11.4% 35.4% 34.3% 18.9% 46.9% 24 months MitraClip (n=114) 77.2% 21.9% 0% 0.9% 99.1% GDMT (n=76) 15.8% 27.6% 40.8% 43.4% 3+-4+ 7.4% 6.3% 5.3% 0.9% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 36

Limitations Because the MitraClip is visible on imaging tests, COAPT was unblinded Bias was mitigated by GDMT standardization and use of independent CEC & ECL Median FU duration was greater in the Device than the Control group In part due to improved survival However, study withdrawals were more frequent in the Control group Results were consistent using multiple imputation to account for missing data The present results apply to Rx of secondary MR with the MitraClip Whether other transcatheter or surgical approaches would have comparable results is uncertain Pts were symptomatic (NYHA II - IVa) despite maximally-tolerated GDMT (with more than one-third having undergone CRT), had true moderate-to- severe or severe MR, LVEF 20%-50%, and frequent comorbidities Whether the MitraClip would be as safe and effective in more or less critically ill pts or those with lesser degrees of MR severity is unknown This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 37

Why are the COAPT Results so Different from MITRA-FR? Possible Reasons
MITRA-FR (n=304) COAPT (n=614) Severe MR entry criteria Severe FMR by EU guidelines: EROA >20 mm2 or RV >30 mL/beat Severe FMR by US guidelines: EROA >30 mm2 or RV >45 mL/beat EROA (mean ± SD) 31 ± 10 mm2 41 ± 15 mm2 LVEDV (mean ± SD) 135 ± 35 mL/m2 101 ± 34 mL/m2 GDMT at baseline and FU Receiving HF meds at baseline – allowed variable adjustment in each group during follow-up per “real-world” practice CEC confirmed pts were failing maximally-tolerated GDMT at baseline – few major changes during follow-up Acute results: No clip / ≥3+ MR 9% / 9% 5% / 5% Procedural complications* 14.6% 8.5% 12-mo MitraClip ≥3+ MR 17% 5% *MITRA-FR defn: device implant failure, transf or vasc compl req surg, ASD, card shock, cardiac embolism/stroke, tamponade, urg card surg

Conclusions In pts with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite maximally-tolerated GDMT, transcatheter mitral leaflet approximation with the MitraClip was safe, provided durable reduction in MR, reduced the rate of HF hospitalizations, and improved survival, quality-of-life and functional capacity during 24-month follow-up As such, the MitraClip is the first therapy shown to improve the prognosis of patients with HF by reducing secondary MR due to LV dysfunction This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 39

This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 40

Back-up slides

Baseline and Follow-up Tests
Clinical: Bl, 1 wk1, 1 mo, 6 mo, 12 mo, 18 mo, 2 yrs, 3 yrs, 4 yrs, 5 yrs Labs2: Bl, d/c1, 1 mo, 6 mo, 12 mo, 18 mo, 2 yrs TEE: Bl TTE: Bl, d/c*, 1 mo, 6 mo, 12 mo, 18 mo, 2 yrs, 3 yrs, 4 yrs, 5 yrs NYHA3: Bl, 1 mo, 6 mo, 12 mo, 18 mo, 2 yrs, 3 yrs, 4 yrs, 5 yrs QOL (KCCQ and SF-36)3: Bl, 6 mo, 12 mo, 2 yrs 6MWT3: Bl, 6 mo, 12 mo, 2 yrs This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 1Device group; 2Includes BNP or NT-proBNP; 3By blinded study personnel. Bl = baseline; d/c = discharge 42

Definition of HF Hospitalization
- Meets criteria A and B and C or D or E - Hospitalization with treatment in any in-patient unit or ward in the hospital for at least 24 hours, including emergency department stay* Clinical signs and/or symptoms of HF, including new or worsening dyspnea, orthopnea, paroxysmal nocturnal dyspnea, increasing fatigue, worsening functional capacity or activity intolerance, or signs and/or symptoms of volume overload Results in IV (e.g., diuretic or vasoactive therapy) or invasive (e.g., ultrafiltration, IABP, mechanical assistance) treatment for HF Arrival in emergency department with clinical presentation meeting the criteria of HF but dies in the emergency department before hospital admission Admission for an LVAD or heart transplant Overnight stays at nursing home facilities, physical rehab or extended care facilities, including hospice, do not meet the protocol definition of hospitalization. All hospitalizations, including the index hospitalization for the MitraClip procedure, if complicated by acute worsening HF that would have prompted an admission to hospital for HF, AND requires intravenous or invasive treatment AND hospitalization is extended by 24 hours, as defined above, will also be considered a HF hospitalization. Elective HF “tune-ups” that occur following the MitraClip procedure and prolong hospitalization will not count as a HF hospitalization. This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 43

Origin of the MitraClip Primary Safety Endpoint Objective Performance Goal of 88%
The performance goal for the primary safety endpoint was developed in concert with FDA after determination of what composite risk of device-related complications might be acceptable given the expected effectiveness of the therapy. Based on prior MitraClip studies we anticipated an ~6% rate of these composite adverse events: Single leaflet device attachment - 4% Device embolization - <0.1% Endocarditis - <0.1% Mitral stenosis requiring surgery - <0.1% LVAD or heart transplant - 1% Other device-related complications that require non-elective CV surgery - <0.1% The objective performance goal of freedom from device-related complications was thus set at 88% which will be compared against the 95% CI of the lower limit of the observed safety endpoint This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 44

MitraClip Procedure (n=302)
Reasons MitraClip procedure not attempted in 9 patients - Withdrew before procedure (n=5) - Expired before procedure (n=3) - Lost-to-follow-up before procedure (n=1) Reasons no Clip implanted in 6 attempted patients - Inability to complete the trans-septal procedure (n=4) - Inability to grasp the leaflets (n=1) - Pericardial effusion (n=1) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 45

Kaplan-Meier time-to-first event rates
30-Day Event Rates (i) MitraClip + GDMT (n=302) GDMT alone (n=312) HR [95% CI] P-value Death, all-cause 2.3% 1.0% 2.43 [0.63, 9.40] 0.20 - CV 0.6% 3.64 [0.76, 17.53] 0.11 - HF-related 0.7% 1.05 [0.15, 7.42] 0.97 - Non-HF-related 1.7% 0.0% - - Non-CV 0.3% Hospitalization, all-cause 13.0% 12.6% 1.04 [0.67, 1.62] 0.86 6.7% 7.7% 0.86 [0.48, 1.6] 0.62 4.0% 6.8% 0.58 [0.29, 1.18] 0.14 3.0% 3.17 [0.86, 11.7] 0.08 5.5% 1.23 [0.64, 2.35] 0.53 Death or HF hospitalization 5.6% 7.1% 0.79 [0.42, 1.48] 0.46 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle Kaplan-Meier time-to-first event rates 46

*Unplanned. Kaplan-Meier time-to-first event rates
30-Day Event Rates (ii) MitraClip + GDMT (n=302) GDMT alone (n=312) HR [95% CI] P-value MV intervention or surgery* 1.0% 0.3% 3.13 [0.33, 30.09] 0.32 - MitraClip - Mitral valve surgery 0.0% - PCI or CABG Stroke 0.7% Myocardial infarction New CRT implant LVAD or heart transplant - LVAD - Heart transplant This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle *Unplanned. Kaplan-Meier time-to-first event rates 47

Primary Endpoints Primary effectiveness endpoint – All HF hospitalizations through 24 months Population MitraClip + GDMT GDMT alone HR [upper 95% CL] P-value Intention-to-treat* 35.8% (160/446.5)1 67.9% (283/416.8)1 0.53 [0.66] <0.0012 As-treated 34.8% (154/442.0)1 70.6% (277/392.2)1 0.44 [0.56] Per-protocol 35.4% (145/409.4)1 70.0% (257/366.9)1 0.45 [0.58] Primary safety endpoint – Freedom from device-related complications at 12 months Lower 95% CL Safety analysis* 96.6% (9)3 - 94.8% <0.0014 97.5% (7)3 95.9% 97.7% (6)3 96.1% The intention-to-treat population consists of all pts randomized in the trial, analyzed in the group randomized, regardless of the treatment actually received. The as-treated population consists of all randomized pts according to the treatment they received. Pts who experience a death or HF hospitalization prior to a MitraClip procedure are considered to be in the Control group regardless of their initial randomization. Pts who experience a death or HF hospitalization after (but not prior to) a MitraClip procedure are considered to be in the MitraClip group regardless of their initial randomization. For pts who do not experience a death or HF hospitalization at any time during follow-up, they will be assigned to the group that constituted >50% of their follow-up duration. The per-protocol population consists of all randomized pts who meet all major study inclusion criteria and none of the major exclusion criteria for the trial, are treated according to the randomized assignment, and followed consistent with all major study processes. Pts who are randomized to the Device group but do not have a MitraClip procedure attempted between 1-14 days of the randomization are excluded from the per-protocol population. For pts in the Control group who receive the MitraClip device, follow-up data after the date of the procedure will be excluded from analysis. For subjects in either group who undergo other major intervention for HF (e.g. mitral valve surgery, LVAD implant or heart transplant), follow-up data after the date of the intervention will be excluded from analysis. The safety analysis population consists of all randomized Device group subjects in whom a MitraClip procedure is attempted.1Annualized event rate (total number of events/patient-years of follow-up); 2Joint frailty model; 3Kaplan-Meier time-to-first event estimates (number of events); 4Calculated from Z test with Greenwood’s method of estimated variance against a pre-specified performance goal of 88%. *Population for the study primary endpoint. This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 48

Time to First HF Hospitalization
100% MitraClip + GDMT GDMT alone HR [95% CI] = 0.52 [ ] P<0.001 80% NNT (24 mo) = 4.8 [95% CI 3.3, 8.2] 60% 56.7% HF Hospitalizations (%) 40% 35.7% 20% 0% 3 6 9 12 15 18 21 24 Time After Randomization (Months) No. at Risk: This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) MitraClip + GDMT 302 264 238 215 194 154 145 126 97 GDMT alone 312 244 205 174 153 117 90 75 55 49

LVAD or Heart Transplant Within 24 Months
HR [95%CI] = 0.37 [0.17, 0.81] P=0.01 HR [95%CI] = 0.34 [0.13, 0.87] P=0.02 HR [95%CI] = 0.35 [0.09, 1.32] P=0.12 Stone GW et al. NEJM Sept 23.

Change in LVEDV from Baseline to 12 Months
Adjusted change* ±5.1 ±94.2 P<0.001 ±69.2 ±76.0 ±76.5 ±5.1 n=175 n=174 n=175 n=174 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Ancova 51

24-Month All HF Hospitalizations
Subgroup MitraClip + GDMT GDMT alone HR [95% CI] HR [95% CI] P [Int] All patients 35.8% (160/446.5) 67.9% (283/416.8) 0.54 [0.41, 0.70] Age (median) 0.62 [0.44, 0.88] 61.7% (129/209.2) 37.7% (86/228.0) ≥74 years (n=317) <74 years (n=297) 33.9% (74/218.5) 74.2% (154/207.5) 0.47 [0.31, 0.71] 0.29 Sex 0.77 [0.49, 1.21] 58.2% (98/168.4) 44.3% (66/149.0) Female (n=221) Male (n=393) 31.6% (94/297.5) 74.5% (185/248.4) 0.44 [0.32, 0.61] 0.0504 Etiology of cardiomyopathy 0.48 [0.34, 0.68] 66.0% (162/245.6) 30.8% (85/276.0) Ischemic (n=373) Non-ischemic (n=241) 44.0% (75/170.5) 70.7% (121/171.1) 0.62 [0.41, 0.94] 0.35 Prior CRT 0.58 [0.38, 0.89] 72.0% (107/148.7) 41.6% (68/163.3) Yes (n=224) No (n=390) 32.5% (92/283.2) 65.7% (176/268.1) 0.51 [0.36, 0.72] 0.62 HF hospitalization within the prior year 0.56 [0.41, 0.78] 69.1% (189/273.7) 38.2% (116/303.8) Yes (n=407) No (n=207) 30.8% (44/142.7) 65.7% (94/143.1) 0.48 [0.30, 0.76] 0.58 Baseline NYHA class 0.59 [0.38, 0.92] 53.4% (80/149.9) 31.5% (62/197.1) I or II (n=240) 0.66 0.52 [0.36, 0.75] 68.9% (158/229.4) 34.6% (78/225.5) III (n=322) IV (n=51) 83.4% (20/24.0) 113.0% (40/35.4) 0.77 [0.34, 1.75] STS replacement score 0.51 [0.34, 0.77] 80.3% (132/164.4) 39.6% (68/171.7) ≥8% (n=262) <8% (n=352) 33.5% (92/274.8) 59.8% (151/252.4) 0.57 [0.40, 0.80] 0.70 Surgical risk status 0.49 [0.35, 0.68] 76.3% (215/281.8) 36.5% (106/290.4) High (n=423) Not high (n=188) 33.1% (51/153.9) 50.4% (68/135.0) 0.67 [0.41, 1.08] 0.28 Baseline MR grade 0.48 [0.31, 0.74] 58.8% (137/232.9) 27.3% (62/227.0) 3+ (n=320) 4+ (n=293) 44.6% (97/219.5) 80.1% (146/182.4) 0.57 [0.40, 0.80] 0.53 Baseline LVEF 0.49 [0.32, 0.76] 60.3% (123/204.0) 29.0% (66/227.7) ≥30% (median; n=301) 0.50 [0.34, 0.72] 82.2% (153/186.1) 40.1% (76/189.6) <30% (median; n=274) 0.96 0.65 [0.33, 1.27] 51.0% (35/68.6) 32.9% (26/79.0) >40% (n=103) ≤40% (n=472) 34.3% (116/338.3) 75.0% (241/321.5) 0.47 [0.34, 0.64] 0.34 Baseline LVEDV (median) 0.44 [0.31, 0.64] 80.4% (162/201.5) 35.1% (73/207.9) ≥181 mL (n=288) <181 mL (n=287) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle 32.9% (69/209.4) 60.4% (114/188.7) 0.56 [0.36, 0.85] 0.44 Annualized rates *Central eligibility committee assessment 0.2 0.5 1 1.5 2.5 Favors MitraClip + GDMT Favors GDMT alone 52

24-Month All-cause Mortality
Subgroup MitraClip + GDMT GDMT alone HR [95% CI] HR [95% CI] P [Int] All patients All patients 29.1% (80) 46.1% (121) 0.61 [0.46, 0.82] Age (median) 0.68 [0.48, 0.97] 52.3% (71) 35.9% (53) ≥74 years (n=317) <74 years (n=297) 21.3% (27) 39.0% (50) 0.51 [0.32, 0.82] 0.34 Sex 0.61 [0.35, 1.05] 34.0% (37) 22.8% (20) Female (n=221) Male (n=393) 32.0% (60) 53.7% (84) 0.59 [0.42, 0.82] 0.94 Etiology of cardiomyopathy 0.63 [0.44, 0.89] 48.1% (75) 30.8% (53) Ischemic (n=373) Non-ischemic (n=241) 26.5% (27) 43.1% (46) 0.59 [0.37, 0.95] 0.84 Prior CRT 0.75 [0.48, 1.16] 47.5% (44) 33.4% (36) Yes (n=224) No (n=390) 26.6% (44) 45.3% (77) 0.54 [0.37, 0.78] 0.28 HF hospitalization within the prior year 0.60 [0.42, 0.85] 46.6% (81) 29.0% (54) Yes (n=407) No (n=207) 29.2% (26) 45.0% (40) 0.65 [0.40, 1.07] 0.79 Baseline NYHA class 0.58 [0.36, 0.92] 45.3% (40) 27.6% (31) I or II (n=240) 0.91 0.68 [0.45, 1.00] 43.7% (62) 28.5% (41) III (n=322) IV (n=51) 46.7% (8) 62.9% (19) 0.64 [0.28, 1.46] STS replacement score 0.74 [0.51, 1.07] 57.1% (67) 42.6% (51) ≥8% (n=262) <8% (n=352) 19.1% (29) 37.5% (54) 0.49 [0.31, 0.76] 0.19 Surgical risk status* High (n=423) 33.9% (64) 50.5% (93) 0.67 [0.49, 0.92] Not high (n=188) 17.5% (14) 35.6% (28) 0.43 [0.23, 0.82] 0.25 Baseline MR grade 0.58 [0.37, 0.89] 39.1% (57) 24.8% (32) 3+ (n=320) 4+ (n=293) 33.5% (48) 54.5% (64) 0.62 [0.43, 0.90] 0.79 Baseline LVEF 0.67 [0.45, 1.00] 43.3% (56) 30.4% (42) ≥30% (median; n=301) <30% (median; n=274) 25.4% (30) 53.2% (63) 0.46 [0.30, 0.71] 0.23 0.47 [0.22, 0.98] 43.6% (20) 25.3% (11) >40% (n=103) ≤40% (n=472) 28.8% (61) 49.0% (99) 0.58 [0.42, 0.80] 0.62 Baseline LVEDV (median) 0.67 [0.45, 1.01] 45.1% (56) 30.4% (39) ≥181 mL (n=288) <181 mL (n=287) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. Top row, second from left The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. Small white rectangle 26.1% (33) 50.6% (63) 0.47 [0.31, 0.72] 0.23 KM time-to-first event rates *Central eligibility committee assessment 0.2 0.5 1 1.5 2.5 Favors MitraClip + GDMT Favors GDMT alone 53

COAPT vs. MITRA-FR: 12-Month Death or HF Hosp
Death or HF Hospitalization (%) Months 100% 90% 80% 60% 20% 0% 50% 40% 30% 10% Control Group Device Group No. at Risk: 70% 312 302 3 244 264 6 205 238 9 174 215 12 153 194 HR [95% CI]= 0.63 [0.49–0.82] P<0.001 MitraClip + GDMT GDMT alone 33.9% 46.5% 100% MitraClip + MT 90% MT alone 80% OR [95% CI]= 1.16 [0.73–1.84] P=0.53 70% 60% 54.6% Death or HF Hospitalization (%) 50% 51.3% 40% 30% 20% 10% 0% 2 4 6 8 10 12 Months No. at Risk: Control Group Device Group 152 151 123 114 109 95 94 91 86 81 80 73 73 67 Obadia JF et al. NEJM Aug 27. doi: /NEJMoa Stone GW et al. NEJM Sept 23.

COAPT vs. MITRA-FR: MR, LV Volumes and Function
COAPT (n=614) MITRA-FR (n=304) EROA, mm2 (mean ± SD) 41 ± 15 31 ± 10 - <30 mm2 14% (80/591) 52% (157/301) - 30 – 40 mm2 46% (270/591) 32% (95/301) - >40 mm2 41% (241/591) 16% (49/301) LVEF, % (mean ± SD) 31 ± 9 33 ± 7 LVEDV, mL/m2 (mean ± SD) 101 ± 34 135 ± 35 Obadia JF et al. NEJM Aug 27. doi: /NEJMoa ; Stone GW et al. NEJM Sept 23.

LVEDVI >96 ml/m2 (N=130; 23.7%)
Impact of EROA and LVEDV: EROA >40 mm2 All-cause mortality or HF hospitalization through 12 months LVEDVI >96 ml/m2 (N=130; 23.7%) LVEDVI ≤96 ml/m2 (N=92; 16.8%) We are examining EROA as a continuous variable. We have begun the work and its work in progress… We are committed to doing the analysis, per FDA recommendation… The work shows

LVEDVI >96 ml/m2 (N=88; 16.1%)
Impact of EROA and LVEDV: EROA >30-40 mm2 All-cause mortality or HF hospitalization through 12 months LVEDVI >96 ml/m2 (N=88; 16.1%) LVEDVI ≤96 ml/m2 (N=131; 23.9%) We are examining EROA as a continuous variable. We have begun the work and its work in progress… We are committed to doing the analysis, per FDA recommendation… The work shows

LVEDVI >96 ml/m2 (N=56; 10.2%)
Impact of EROA and LVEDV: EROA ≤30 mm2 All-cause mortality or HF hospitalization through 12 months LVEDVI >96 ml/m2 (N=56; 10.2%) LVEDVI ≤96 ml/m2 (N=51; 9.3%) We are examining EROA as a continuous variable. We have begun the work and its work in progress… We are committed to doing the analysis, per FDA recommendation… The work shows

COAPT vs. MITRA-FR: MitraClip Outcomes
COAPT (n=302) MITRA-FR (n=152) MitraClip attempted 293 (97.0%) 144 (94.7%) ≥1 Clip implanted 287 (95.0%) 138 (90.8%) Procedural complications 25/293 (8.5%) 21/144 (14.6%) - Device implant failure 6 (2.0%) 6 (4.2%) - Transfusion or vasc compl requiring surgery 16 (5.5%) 5 (3.5%) - ASD 2 (0.7%) 4 (2.8%) - Cardiogenic shock 1 (0.3%) - Cardiac embolism/stroke 2 (1.4%) - Tamponade 2 (1.5%) - Urgent cardiac surgery 0 (0%) Acute result: MR ≥3+ 5% 9% 12-month result: MR ≥3+ 17% Stone GW et al. NEJM Sept 23; Obadia JF et al. NEJM Aug 27. doi: /NEJMoa

COAPT A Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation Gregg W.

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COAPT A Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation Gregg W.

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Presentation on theme: "COAPT A Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation Gregg W."— Presentation transcript:

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