Adjunct Professor Emory University School of Medicine

Ziyad Ghazzal MD, FACC, FSCAI Professor of Medicine Deputy to the Vice President/Dean Associate Dean for Clinical Affairs American University of Beirut Adjunct Professor Emory University School of Medicine

Organic (or primary), if there is an intrinsic valve disease Functional (or secondary), if the valve is structurally normal but leaks as a result of an extravalvular abnormality, such as an alteration in LV chamber geometry and/or dilatation of the mitral annulus that adversely affects normal coaptation of the mitral valve leaflets during systole Ischemic MR may be organic (ruptured or ischemic papillary muscle) and/or functional because of LV chamber dilatation Nonischemic MR may be organic (e.g., rheumatic) or functional (e.g., dilated cardiomyopathy)

Percutaneous Mitral Repair Caution: Investigational Device. Limited by Federal (US) Law to Investigational Use

1 clip 2 clips

Key Anatomic Eligibility Criteria Journal of the American College of Cardiology, Volume 54, Issue 8, 2009, 686-694

EVEREST I & II EVEREST II ONLY Ted Feldman, EVEREST I PI, EVEREST II PI Evanston Northwestern Hospital, Evanston, Patrick L Whitlow The Cleveland Clinic, Cleveland, OH Hal Wasserman/Bill Gray Michael Rinaldi Columbia University, New York, NY; Danville, CT Sanger Clinic, Charlotte, NC Howard Herrmann Richard W Smalling University of Pennsylvania, Philadelphia, PA Houston Health Sciences Center, Houston, TX Bill Gray/Mark Reisman Peter Block/Ziyad Ghazzal Swedish Medical center, Seattle, WA Emory University Hospital, Atlanta, GA Paul Kramer Shawnee Mission Medical Center, Shawnee Mission, KS Steven Bailey University of Texas Health Sciences Center, San Antonio, Andrew C Eisenhauer Brigham and Women Hospital, Boston, MS Saibal Kar Cedars Sinai Medical Center, Los Angeles, CA James Hermiller The Care Group, Indianapolis, IN Tanvir Bajwa St. Luke s Medical Center, Milwaukee, WI Vish Bhoopalam Nebraska Heart Institute, Lincoln, NE Andrew Berke Tim Byrne St. Francis Hospital, Long Island, NY Banner Good Samaritan Medical Center, Phoenix, AZ John Carroll University of Colorado, Denver, CO Peter Fail Terrebonne General Medical Center, Houma, LA Eric Fretz Victoria Heart Institute Foundation, Victoria BC, Canada Paul Grayburn Kenny Kent Baylor Univrsity Medical Center, Dallas, TX Washington Hospital Center, Washington DC Robert Kipperman John Lasala Oklahoma Heart Hospital, Okalahoma City, OK Washington University Medical Center, St. Louis, MO D. Scott Lim University of Virginia, Charlottesville, VA Reginald Low University of California at Davis, Sacramento, CA James Maddux/Mark Sanz St. Patrick's Hospital & Health Science Center, Missoula, M Michael O'Donnell St. Joseph s Mercy Hospital, Ypsilanti, MI Wesley Pedersen Minneapolis Heart Institute, Minneapolis, MN Stephen R Ramee Eric Horlick Ochsner Clinic Foundation, New Orleans, LA Toronto General Hospital, Toronto, ON, Canada James Slater Andrew Wang NYU Medical Center, New York, NY Duke University, Durham, NC Brian Whisenant Latter Day Saints Hospital, Salt Lake City, UT Chiu Wong Cornell Weill Medical Center, New York, NY George Hanzel William Beaumont Hospital, Royal Oak, MI Raymond Leung Ramon Quesada Royal Alexandra Hospital, Edmonton, AB, Canada Baptist Hospital of Miami, Miami, FL Elyse Foster, Echocardiographic Core Laboratory University of California at San Francisco, San Francisco, CA Donald D Glower, EVEREST II Co-PI (Surgery) Duke University, Durham, NC

At 4 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in the intention-to-treat population was 39.8% in the percutaneous repair group versus 53.4% in the surgical groups (p<0.070)

Death were 17.4% versus 17.8% (p=0.914) 3+ or 4+ MR was present in 21.7% versus 24.7% (p=0.745) at 4 years of follow-up, respectively Surgery for mitral valve dysfunction, however, occurred in 20.4% versus 2.2% (p < 0.001) at 1 year and 24.8% versus 5.5% (p < 0.001) at 4 years

Patients treated with percutaneous repair of the mitral valve more commonly required surgery to treat residual MR However, after the first year of follow-up, there were few surgeries required after either percutaneous or surgical treatment and no difference in the prevalence of moderatesevere and severe MR or mortality at 4 years

ACCESS-EUROPE Phase I A Post Market Study of the MitraClip System for the Treatment of Significant Mitral Regurgitation in Europe: Analysis of Outcomes at 1 Year Wolfgang Schillinger, MD on behalf of the ACCESS EU investigators European Society of Cardiology Congress 2012 Munich, Germany

Demographics and Co-morbidities EVEREST II RCT Device Patients N=178 EVEREST II High Surgical Risk Cohort N=211 ACCESS EU MitraClip Patients N=567 Mitral Regurgitation Grade 3+, (%) 96 86 98 Ejection Fraction < 40%, (%) 6 28 53 Functional MR, (%) 27 71 77 Ischemic NA NA 42 Non-ischemic NA NA 58 Degenerative MR, (%) 73 29 23

30 Days 97.4% 95.6% 96.6% 1 Year 86.4% 76.3% 81.8% p<0.05 Logistic EuroSCORE <20% (N=314) Logistic EuroSCORE 20% (N=253) All Patients (N=567) At Risk 0 Day 30 Days 180 Days 360 Days All Patients 567 534 475 415 Logistic EuroSCORE <20% 314 296 264 235 Logistic EuroSCORE 20% 253 238 211 180

27 patients (4.8%): Single leaflet device attachment. All but 1 case were diagnosed within 6 months from the index procedure. 10 underwent a second MitraClip procedure, no action was taken in 11 patients, 6 patients had mitral valve repair or replacement surgery, and 1 patient had additional MitraClip devices implanted during the index procedure. There have been no reports of MitraClip device embolization in the ACCESS-EU Study.

Thirty-six subjects (6.3%) underwent a mitral valve surgery within 12 months after the MitraClip implant procedure. Nineteen patients (3.4%) underwent a second intervention to place an additional MitraClip device to reduce MR. Of the 19 attempts to further reduce MR with a second intervention to place a MitraClip device, 14 (74%) were successful.

The MitraClip device (Abbott Vascular, Santa Clara, California) was approved October 24, 2013, for the reduction of significant ( 3+), symptomatic, degenerative MR in highly anatomically selected patients considered by an experienced heart team to be at prohibitive risk for mitral valve surgery.

Mod/severe MR Etiology: Degenerative (prolapse); ischemic(+/-) with non-dilated annulus functional (if annulus <4.5cm) Central jet of MR (A2/P2) LVEF > 30% No LA thrombus NSR helps but not necessary Must have reason to repair MR --- ( LV dilation, development of AF, symptoms)

World-class Training & Regular use Produce Excellent Learning Curves Device Times - UKE Hamburg, DE Device Time 6:00 4:48 3:36 2:24 1:12 0:00 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65 Implants - blue 1 clip, white 2 clips Avg. 1 clip 1:20 2 clips 1:55 Device Times - Ospedale Ferrarato, Catania, IT 3:21 Avg. 1 clip 1:00 2 clips 2:04 Device Time 2:52 2:24 1:55 1:26 0:57 0:28 0:00 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Implants - blue 1 clip, white 2 clips

European Heart Journal (2015) 36, 1651

Leaflets Annulus Supporting structures Left ventricle

Discontinuation of the mitral-ventricular continuity results in maladaptive remodelling and impaired LV performance The mitral valve regulates the flow pattern within the LV Preservation of anterior leaflet mobility and asymmetric flow may be associated with better LV performance

CARILLON Mitral Contour System Designed to be positioned, adjusted, and gently anchored in the coronary sinus/great cardiac vein to reshape the annulus around the mitral valve to reduce mitral regurgitation

53 patients were enrolled 36 patients underwent successful permanent device implantation. Significant benefit in reductions in quantitative measures of functional MR Positive clinical outcomes: improvement in 6-min walk test, functional class, and quality of life In 17 of the 53 patients, the device could not be permanently implanted, due to difficulty cannulating the coronary sinus, ineffective reduction in MR, or compression of a coronary artery. The Carillon device received CE mark approval in Europe in 2011.

Is the Coronary Sinus the answer? or the question? The CS problem Annular plane

Valtech Cardioband CE mark approved

CARDIOBAND European Heart Journal (2015) 36, 1651

Valtech Cardioband 40 high-risk patients with significant secondary MR 93% had NYHA class III-IV symptoms, with a mean LV ejection fraction of 33.3%. Acute procedural success, defined as successful implantation with acute MR reduction to grade < 2+, was achieved in all but three patients (92%).

Valtech Cardioband At 30 days, the mortality rate was 5.0%. None of the deaths were considered device-related. NYHA Class I-II at 6 months (80%) and 12 months (70%) MR grade 2+ (85% and 94% at 6 and 12 months, respectively). Improvements in quality of life as assessed with the Minnesota Living With Heart Failure Questionnaire

Figure 6. Direct annular plication concept. Masson J, Webb J G Circ Cardiovasc Interv 2009;2:140-146 Copyright American Heart Association

CE mark approval is expected 51 patients with moderate to severe functional mitral regurgitation LVEF 34±8% 30-day rates for all-cause mortality, stroke and myocardial infarction were 2.8%, 5.9% and 2.0%, respectively; the six-month death rate was 12.2%. Echocardiography: significant reduction of anterior-posterior and septal-lateral dimensions of the mitral annulus http://www.pcronline.com/eurointervention/w_issue/17

Implanted pledget

European Heart Journal (2015) 36, 1651

Comparison of transcatheter mitral valve implantation and transcatheter mitral valve repair European Heart Journal (2015) 36, 1651