How I treat Functional Mitral Regurgitation: The Surgeon’s perspective Thierry MESANA, MD, PhD President and CEO Professor Cardiac Surgery Valve Surgery Research Chair University of Ottawa Heart Institute Ottawa, Ontario, Canada

I have no relevant financial relationships

GUIDELINES for Surgery in FMR not clear Symptomatic despite optimal medical management J Am Coll Cardiol. 2014;63(22):e57-e185 European Heart Journal 2012;33:24151-96 US : Uncertain benefit if moderate MR and need severe symptoms for isolated MV surgery EU : CABG + MV with EF > 30 % But Below 30% look forViability ISOLATED ? Need to have symptoms ++ No specification of type of surgery

FACT: RECURRENT MR FOLLOWING REPAIR IS COMMON and no clear advantage on survival

No significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes.

FACT: UNDERSTANDING FUNCTIONAL MR IS CHALLENGING “ALL FMR ARE NOT EQUAL”

CARPENTIER Functional Classification Type I Dilated LV, Ischemic or non Ischemic Free edge of the leaflets are at or below the annulus level Leaflet tethering, MV tenting ANNULAR DILATATION with often a LOW EJECTION FRACTION ++ Ø     Type I: Normal Leaflet Motion Regurgitation can still occur with normal leaflet motion due to annular Dilation or leaflet perforation. One disease state typically causing Type I is dilated cardiomyopathy. Techniques of valve repair for this type of functional problem may include the following:   1.      Implantation of an annuloplasty ring 2.      Annular reduction 3.      Closure of leaflet defect

CARPENTIER FUNCTIONAL ANATOMY Restricted Leaflet(s) : Type III b PL Restriction from posterior MI Posteromedial PM displacement Relatively anterior leaflet prolapse NOT NECESSARILY LOW EF NOT NECESSARILY LARGE MV ANNULUS ASYMETRICAL ANNULAR DEFORMATION (P2-P3) BASAL DYSKINESIA (RELATIVELY ANEURYSMAL) Ø     Type IIIa: Restricted Leaflet Motion   Restricted leaflet motion often results in stenosis although regurgitation may also occur. Restricted leaflet motion may be due to one or more of the following: 1.      Commissural fusion 2.      Chordal fusion 3.      Leaflet thickening One disease state typically causing Type IIIa restricted motion is rheumatic disease.

Measuring leaflet tenting (angles, lenghts, surfaces) GEOMETRY OF FMR Measuring leaflet tenting (angles, lenghts, surfaces) N-51 consecutive patients; preoperative echos and postoperative echos performed at a mean of 9 days. Magne et al. Circulation 2007;115:782-791

FACT : SURGICAL REPAIR STRATEGIES ADDRESSING RESTRICTION ARE LIMITED

Alternatives/Additional solutions ANNULAR. Rigid vs. flexible Full vs. partial 2d vs. 3D rings CHORDS. Second chord cutting (Messas, Borger) Neochords for false AL prolapse PAPILLARY MUSCLE . Posteromedial PM relocation to MV annulus right (Kron), “Ring and String” (Langer-Schaeffers) : Goretex from PM to aortic annulus “Ring and Sling” (Hvass) : Goretex suture encircling both PM LEAFLET STRATEGIES. Posterior Leaflet extension Edge-to-Edge

Carpentier-McCarthy-Adams IMR Etlogix ring . Figure 1. The new asymmetrical Carpentier-McCarthy-Adams IMR Etlogix ring (CMA IMR ETlogix ring). This new ring is undersized with a 14% reduction in the postero-medial dimension (D2, D3 dimension). Note that this ring has a slight dip at P2-P3 (left) and a narrower dimension at P2-P3 (right; D2, D3). Daimon M et al. Circulation. 2006;114:I-588-I-593 Copyright © American Heart Association, Inc. All rights reserved.

LEAFLET EXTENSION FOR IIIb MITRAL REGURGITATION Parsonnet score of 38 Mean LVEF 33% 44 patients > initial results operated 2004-2007 From P2 to PM commissure- 1cm high and 4-5 cm long 90 % freedom of moderate /severe MR at 2 years De Varennes et al. Circulation 2009;119:2837-2843

Annuloplasty + Edge-to-Edge suture “Alfieri technique augment leaflet coaptation when more tethering” Advantage : Simple, Fast, Teachable, Reproduceable

Figure 4. Freedom from recurrence of MR of grade 3 to 4+ in the edge-to-edge and in the ring-only groups. Figure 4. Freedom from recurrence of MR of grade 3 to 4+ in the edge-to-edge and in the ring-only groups. De Bonis M et al. Circulation. 2005;112:I-402-I-408 Copyright © American Heart Association, Inc. All rights reserved.

No annuloplasty with E-to-E technique Freedom from recurrence of mitral regurgitation (MR) of grade 3 to 4+. Freedom from recurrence of mitral regurgitation (MR) of grade 3 to 4+. De Bonis M et al. Circulation. 2014;130:S19-S24 Copyright © American Heart Association, Inc. All rights reserved.

Most Reliable Surgical Alternative today VS. MV Replacement with chordal preservation if : Less experience with repair Imperfect /uncertain immediate result “Good replacement better than a bad repair” Most of these patients do not do well with residual MR…

Mitral Valve Surgery Operative Risk Alternatives to surgery in selected patients with a high EuroSCORE II and the STS risk score Risk calculators do not accurately predict outcomes for a high volume center of MV surgery Mitraclip should be developed by Heart teams in centers of excellence with high volumes of MV disease refferral and surgical expertise Percutaneous therapies are a viable alternative to surgery in selected patients with a high estimated perioperative risk. The 2 most commonly utilized risk calculators include the EuroSCORE II and the STS risk score. These risk calculators were developed based on data from large registries and have been extensively validated. Although well designed, these risk scores have certain limitations. Specifically, they may not accurately predict outcomes in under represented patient groups, such as those undergoing mitral surgery.

Low Surgeon volume + low hospital volume : 5.6 % The effect of hospital volume on outcomes in MV surgery is also driven by individual surgeon within this hospital 30-day Mortality Low Surgeon volume + low hospital volume : 5.6 % Low surgeon volume + high Hospital Volume : 3.3% High surgeon volume + low Hospital volume : 2.3% High surgeon volume + high hospital volume : 2.0% Kilic et al . JTCVS 2013:146:638-46 (J Hopkins, Baltimore)

Observed & EuroSCORE II Predicted Mortality All procedures including Mitral valve Surgery Ottawa Heart Institute series 2001-2011 (Annals TS, July 2014) EuroSCORE II Quartile N Observed Mortality Predicted Mortality Lower Limit (%) Upper Limit (%) 1 285 1 (0.4%) 0.5 0.9 2 291 2 (0.7%) 1.7 3 288 3 (1.1%) 1.8 3.9 4 290 5 (1.7%) 31.1 Patients were also grouped into quartiles according to their EuroSCORE II. Again, Overall O:E ratio 0.3

MitraClip Therapy Broad Spectrum of Experience EVEREST II (Randomized Controlled Trial) EVEREST II (High Risk Cohort^) ACCESS EU (Europe) MitraClip in clinical trials In EVEREST II RCT patients are adjudicated through two years In EVEREST II High Risk Cohort patients are adjudicated through 1 year Remember pointing out to them the etiology mix in EVEREST II and show the progression in patient etiology with time Look at the real world and how we can impact FMR Note Device time improvements: implantation efficiency increases with experience Implant rate: Patient screening and implantation experience improve implant rates Valve etiology of treated patients: Unmet need in FMR has driven driven commercial adoption of MR Rx (see section 3) 178 patients Device time – 146 minutes Implant rate – 89% 211 patients Device time – 127 minutes Implant rate – 95% 567 patients Procedure time – 117 minutes Implant rate – 99% = DMR = FMR 22

MITRACLIP UOHI EXPERIENCE Total Cases: 101 patients Average # of Clips per procedure: 1.62 Average MR reduction: -2.11 Average Clip Time: 133 minutes

Average MR after Implant FMR MR Grade Post-Clip (74 pts) Intra-Op TEE (Pre Implant) Post Implant In Hospital Echo 1 Month Echo 6 Month Echo 1 Year Echo 2 Year Echo 3 Year Echo 74 72 71 62 38 36 23 11 3.64 1.53 1.62 1.65 1.71 1.69 1.87 1.45 DEG MR Grade Post-Clip (21 pts) 21 19 20 16 10 8 1 3.76 1.84 1.88 1.82 1.70 1.75 2 Mixed MR Grade Post-Clip (6 pts) 6 3.17 1.17 1.67 1.5 X

Mitral Regurgitation Grade at 5 Years DMR FMR MitraClip (N=130) Surgery (N=62) MitraClip (N=48) Surgery (N=18) p<0.005 p<0.005 p<0.05 p=0.82 81% 100% 86% 86% 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=85 25

Our indications for FMR Severe, Isolated FMR in DCMP:MITRACLIP is the preferred choice if medical therapy fails. Moderate or severe FMR with associated cardiac surgery (CABG, AVR): MV procedure repair or replacement depending of anatomy and surgical comfort. Simpler is better Severe Ischemic MR with no further revascularization : Clip or medical. Previous CABG ++

1- As these technologies become available for patients with degenerative or functional MR, it will be important for experienced referral centers and cohesive heart teams to guide their deployment into clinical practice. 2- As well, the short- and long-term technologies must be evaluated through dynamic registry supported by relevant stakeholders. JACC 2014:840-52

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CABG alone # CABG+ mitral Valve repair The trial did not demonstrate a clinically meaningful advantage to the routine addition of MVr to CABG . Longer-term follow-up is ongoing: will the lower incidence of moderate or severe MR at one-year translate into a net clinical benefit for patients undergoing CABG + mitral repair?

Our experience of Edge-to Edge + annuloplasty in FMR Mitral valve replacement is a viable alternative to mitral valve repair for ischemic mitral regurgitation: A case-matched study Vincent Chan, MD, MPH; Marc Ruel, MD, MPH; Thierry G. Mesana, MD ,PhD Ann Thorac Surg. 2011 Oct;92(4):1358-65; discussion 1365-67 Our experience of Edge-to Edge + annuloplasty in FMR 29% recurrent 2+ MR after one year echo FU 4% MR 3+ or 4+ Same survival at 5 years Limited Clinical impact of residual 2+ MR