Clinical Pearls: Takeaway Points for Aortic Stenosis and Mitral Regurgitation Management in 2014

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1 Clinical Pearls: Takeaway Points for Aortic Stenosis and Mitral Regurgitation Management in 2014 Hemal Gada, MD, MBA Assistant Professor of Medicine Rutgers Robert Wood Johnson Medical School

2 A Hot 20 Minutes Aortic Stenosis Indications for valve replacement are expanding Access requirements for TF TAVR are getting smaller Multiple TAVR devices mean more options and better patient care Mitral Regurgitation Degenerative (primary) mitral regurgitation needs early surgical referral Repair vs replace for medically-optimized symptomatic ischemic mitral regurgitation will be driven by surgeon expertise Percutaneous mitral valve repair indications will continue to evolve and expand into the realm of functional mitral regurgitation

3 INDICATIONS FOR AORTIC VALVE REPLACEMENT ARE EXPANDING

4 ACC/AHA Valve Guidelines Surgery for AS Vmax 4.0 m/sec -OR- MG 40 mmhg Symptomatic (Stage D1) AVR (I) LVEF < 50% (Stage C2) Other Cardiac Surgery Vmax 5 m/sec -OR- MG 60 mmhg Low surgical risk (Stage C1) Abnormal ETT AVR (IIa) ΔVmax > 0.3 m/sec/y Low surgical risk (Stage C1) AVR (IIb) Asymptomatic (Stage C) Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

5 ACC/AHA Valve Guidelines TAVR for AS For patients in whom TAVR or high-risk surgical AVR is being considered, members of a Heart Valve Team should collaborate to provide optimal patient care TAVR is recommended in patients who meet an indication for AVR for AS who have a prohibitive surgical risk and a predicted post-tavr survival > 12 mos COR I I LOE C B TAVR is a reasonable alternative to surgical AVR in patients who meet an indication for AVR and who have high surgical risk IIa B Percutaneous aortic balloon dilation may be considered as a bridge to surgical or transcatheter AVR in severely symptomatic patients with severe AS IIb Nishimura RA et al. J Am Coll Cardiol 2014;63:e C

6 Heart Valve Team Surgeon Cath lab/or staff Nurses, NPs, PAs Consultants Research staff Social work, PT Geriatricians Coordinators Hospital administrators Anesthesia Patient Valve clinic Case selection Cardiologist Multi-modality imaging (access site, valve size) TAVR procedure (cath lab/or) Post-op care and FU Imaging Specialist

7 All-Cause Mortality (%) All-Cause Mortality (ITT) Crossover Patients Censored at Crossover Standard Rx (n = 179) TAVR (n = 179) 80.9% 87.5% 93.6% 68.0% 71.8% 50.8% 64.1% 53.9% 43.0% 30.7% HR [95% CI] = 0.50 [0.39, 0.65] p (log rank) < Months * In an age and gender matched US population without comorbidities, the mortality at 5 years is 40.5%. Kapadia S. TCT 2014

8 STS Score Evolution in Patient Selection in U.S. TAVR Clinical Trials 14% Inoperable (extreme risk) High-Risk 12% 10% 11.2% 11.0% 10.3% 10.3% 9.0% 11.8% 10.9% 8% 7.0% 7.3% 6% 5.0% 4% 2% 0% PARTNER B TAVR PARTNER IIB SAPIEN PARTNER IIB SAPIEN XT CoreValve ER Iliofemoral CoreValve ER Continued Access TVT Registry SAPIEN TF PARTNER A TAVR PARTNER TF Continued Access CoreValve HR TVT Registry SAPIEN TF

Frailty Assessment Frailty Characteristic Shrinking: Weight loss, sarcopenia Weakness Poor endurance: Slowness Exhaustion Low activity Positive for frailty phenotype Cardiovascular Health Study Fried

9 Frailty Assessment Frailty Characteristic Shrinking: Weight loss, sarcopenia Weakness Poor endurance: Slowness Exhaustion Low activity Positive for frailty phenotype Cardiovascular Health Study Fried Measure Self-report 10lb weight loss Grip strength: lowest 20% (by gender, BMI) Walking time/15 feet: slowest 20% (by gender, height) Exhaustion report Kcal/week: by activity 3 or more criteria present PARTNER Measure Albumin less than 3.5 g/dl Same Same Symptomatic AS Katz ADL impairment Same P. Green, TVT 2012 Courtesy of J. Popma

Clinical Use ~10% High Risk Extr Risk* Too Sick irresponsible,

10 Futile The Role for TAVR Operable AS patients Surgery (AVR) ~65% Low Risk ~25% Intermed Risk TAVR or AVR Current TAVR TAVR Clinical Use ~10% High Risk Extr Risk* Too Sick irresponsible, reckless TAVR in 2014 equipoise OK No * Extreme risk = inoperable

11 ACC/AHA Valve Guidelines Surgery for AS Vmax 3 m/sec-3.9 m/sec -OR- MG mmhg Symptomatic Asymptomatic (Stage B) LVEF < 50% Ye s DSE with AVA 1 cm 2 and Vmax 4 m/sec (Stage D2) No AVA 1 cm 2 and LVEF 50% (Stage D3*) Other cardiac surgery AS likely cause of symptoms AVR (IIa) Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

12 Paradoxical Low-Flow Low-Gradient AS AVR is reasonable in symptomatic patients with LVEF 50% Calcified aortic valve with significantly reduced leaflet motion Vmax < 4 m/sec or MG < 40 mmhg AVA 1.0 cm 2 Provided that: Stroke volume index < 35 ml/m 2 Indexed AVA 0.6 cm 2 /m 2

Treatment Comparison in Normal EF (NEF), Low-flow (LF), Low-gradient (LG) AS 2-Year Death (%) 90% 80% 70% LF NEF LG A - TAVR LF NEF LG A - Surgery LF NEF LG B - TAVR LF NEF LG B - Std Rx log rank p=

13 Treatment Comparison in Normal EF (NEF), Low-flow (LF), Low-gradient (LG) AS 2-Year Death (%) 90% 80% 70% LF NEF LG A - TAVR LF NEF LG A - Surgery LF NEF LG B - TAVR LF NEF LG B - Std Rx log rank p= % 60% 50% 40% 30% 20% 56.5% 41.1% 39.7% 10% 0% Numbers at Risk Days A TAVR A Surgery B TAVR B Std Rx Herrmann HC et al. Circulation 2013;127:

14 ACCESS REQUIREMENTS FOR TF TAVR ARE GETTING SMALLER

15 (%) Larger Sheath Size Can Contribute to Major Vascular Complications A Sheath to Femoral Artery Ratio (SFAR) 1.05 is a Predictor of both VARC Major Vascular Complications and 30-Day Mortality Sapien or Sapien XT (n = 102) CoreValve (n = 28) Sensitivity Specificity Hayashida K et al. J Am Coll Cardiol CV Int 2011;4:851-8

Vascular Complications/Bleeding: PARTNER 2B Sheath Size Comparison Valve Valve Size Sheath ID Sheath OD Minimum Vessel Diameter SAPIEN THV 23mm 22F 25F (8.4mm) 7.

16 Vascular Complications/Bleeding: PARTNER 2B Sheath Size Comparison Valve Valve Size Sheath ID Sheath OD Minimum Vessel Diameter SAPIEN THV 23mm 22F 25F (8.4mm) 7.0mm SAPIEN XT THV 23mm 18F 22F (7.2mm) 6.0mm SAPIEN THV 26mm 24F 28F (9.2mm) 8.0mm SAPIEN XT THV 26mm 19F 23F (7.5mm) 6.5mm 33% reduction in CSA Leon M. ACC 2013

17 Vascular Complications/Bleeding: PARTNER 2B at 30 days (AT) SAPIEN (n=271) SAPIEN XT (n=282) Events n % n % p-value Vascular: Major Minor Bleeding: Disabling Major Patients with transfusions Leon M. ACC 2013

18 Edwards esheath The Edwards expandable sheath (1) features a fold that expands as the NovaFlex catheter moves through (2,3). Toggweiler S et al. J Am Coll Cardiol CV Int 2013;6:643-53

Edwards esheath Valve SAPIEN 3 26 mm 14F 16F 18F 20F SAPIEN XT 23 mm SAPIEN XT 26 mm SAPIEN XT 29 mm Sheath ID Unexpanded 4.7 mm 5.3 mm 6.0 mm 6.7 mm Sheath OD Unexpanded 6.0 mm 6.7 mm 7.2 mm 8.

19 Edwards esheath Valve SAPIEN 3 26 mm 14F 16F 18F 20F SAPIEN XT 23 mm SAPIEN XT 26 mm SAPIEN XT 29 mm Sheath ID Unexpanded 4.7 mm 5.3 mm 6.0 mm 6.7 mm Sheath OD Unexpanded 6.0 mm 6.7 mm 7.2 mm 8.0 mm Expanded w/valve 8.0 mm 8.9 mm 8.9 mm 9.9 mm Rec Minimum Diameter 5.5 mm 6.0 mm 6.5 mm 7.0 mm SFAR Unexpanded Expanded w/ valve Binder RK et al. J Am Coll Cardiol CV Int 2013;3:

20 Terumo SoloPath Dimitriadis Z et al. J Am Coll Cardiol CV Int 2013;26:84-9

21 Terumo SoloPath Re-collapsible Sheath Size (Based on Expanded ID) Features 5.3Fr tip diameter Insertion Profile OD 19Fr 23Fr 25 or 35 cm working length 13.5Fr 22Fr 26Fr 20 or 30 cm expandable length 15Fr 24Fr 28.5Fr ~30% reduction in profile once recollapsed 15Fr

22 Increasing TF Options for the Future Vessel Diameter in mm Fr Sheath 14 Fr Sheath 13 Fr Sheath SFAR <= <SFAR<=1.2 SFAR>1.2 Babaliaros V. TVT 2013

23 MULTIPLE TAVR DEVICES MEAN MORE OPTIONS AND BETTER PATIENT CARE

centers these two (very around different) the

24 The Great TAVR Device Debate Current Generation Devices >100,000 >95% of TAVR patients patients treated have thru been 2014 in treated >750 interventional with either of centers these two (very around different) the world! devices! Edwards Lifesciences Medtronic CoreValve

25 The Great TAVR Device Debate What s important? Differences in major clinical outcomes (definitely death and stroke; possibly PVR, bleeding, and vascular complications) Differences in softer secondary clinical endpoints (e.g. conduction disturbances) Preferences based upon specific anatomic situations (e.g. horizontal Ao, high rupture risk), technical device differences, and operator ease-of-use issues I use it because I know it well, I like it, and I get good outcomes!

26 Mortality (%) No Differences in Mortality at 1 Year in High Risk and Inoperable Patients TVT Registry FRANCE 2 SOURCE XT SOURCE Coh2 SOURCE Coh1 ADVANCE UK Italian CV Extreme Risk PRAGMATIC CV High Risk PARTNER 1A PARTNER 2B PREVAIL TA PREVAIL EU PARTNER 1B PREVAIL JAPAN 40 SAPIEN Family CoreValve Rate, Number of Patients , , , , , , , , , , , , , , , , , , , , Leon M. TVT 2014

27 TVT Registry SOURCE XT SOURCE Coh2 SOURCE Coh1 ADVANCE UK Italian-TA CV Extreme Risk PRAGMATIC CV High Risk PARTNER 1A PARTNER 2B PREVAIL EU ADVANCE II Italian PARTNER 1B PREVAIL TA S3 TF PREVAIL JAPAN Stroke* (%) No Differences in All Strokes at 30 days in High Risk and Inoperable Patients SAPIEN Family CoreValve Rate, Number of Patients , , , , , , , , , , , , , , , , , , , , 64 0 *Rate of All Stroke or Major Stroke + Minor Stroke Leon M. TVT 2014

28 Individualized Device Approach in TAVR: SAPIEN XT or CoreValve Dissimilarities in clinical outcomes after TAVR using SAPIEN XT or CoreValve in different annular zones* * Favorable aortic annulus zones were defined as those that may enable 5-20% area oversizing or % perimeter oversizing in SAPIEN XT procedures and 20-35% area oversizing or % perimeter oversizing in CoreValve procedures. Dvir D, et al. TVT 2014

29 CoreValve zone SAPIEN XT zone CoreValve 23 mm CoreValve 26 mm CoreValve 29 mm CoreValve 31 mm SAPIEN XT 20 mm SAPIEN XT 23 mm SAPIEN XT 26 mm SAPIEN XT 29 mm Aortic Valve Annulus Area (mm 2 ) Dvir D, et al. TVT 2014

30 DEGENERATIVE MITRAL REGURGITATION NEEDS EARLY SURGICAL REFERRAL

31 ACC/AHA 2014 Valve Guidelines Treatment of MR First decision Mitral Regurgitation Primary MR Secondary MR Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

32 ACC/AHA 2014 Valve Guidelines Primary vs. Secondary MR Definition of Severe MR Primary MR Secondary MR EROA 0.4 cm cm 2* Regurgitant volume 60 ml 30 ml Regurgitant fraction 50% 50% Vena contracta 0.7 cm - Jet area Central jet >40% LA or holosystolic eccentric jet - * Measurement of the proximal isovelocity surface area by 2D TTE in secondary MR underestimates the true ERO due to the crescentic shape of the proximal convergence Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

33 ACC/AHA 2014 Valve Guidelines Surgery for Primary MR Primary MR Severe MR Vena contracta 0.7 cm R Vol <60 ml RF 50% ERO 0.4 cm 2 LV dilation Symptomatic (stage D) Asymptomatic (stage C) Progressive MR (stage B) Vena contracta <0.7 cm R Vol <60 ml RF <50% ERO <0.4 cm 2 LVEF >30% LVEF 30% to 60% or LVESD 40 mm (stage C2) LVEF >60% and LVESD <40 mm (stage C1) New onset AF or PASP >50 mm Hg (stage C1) NO YES Likelihood of successful Repair >95% and Expected mortality <1% YES NO MV Surgery (llb) MV Surgery (l) MV Repair (lla) Periodic Monitoring Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

34 Survival (%) Surgery in Asymptomatic Severe Chronic Primary MR Suri et al. JAMA. 2013;310: Risk of CHF (%) MIDA registry (6 international centers) between 1980 and ,021 asymptomatic pts with flail leaflets causing severe MR with LVEF>60% and LVESD<40 mm MV surgery w/i 3 mos (median 14 d; 93% repair; 22% concomitant CABG) vs. med Rx (with MV surgery in 59% at median of 1.65 years, 87% repair); 10 yr median FU Outcomes in 324 propensity matched pairs were compared Survival CHF HR [95%CI] = 0.52 [ ] P= % 53% Follow-up (years) Medical management Early surgery HR [95%CI] = 0.44 [ ] P=0.003 Medical management Early surgery 24% 11% Follow-up (years)

35 All-cause Mortality (%) Cardiac Mortality (%) MACE (%) Surgery in Asymptomatic Severe Chronic Primary MR 2 S. Korean centers from asymptomatic pts 85 yo with severe MR (ERO 0.4 cm 2 ) with LVEF>60%, LVESD<40 mm Treated with MV surgery w/i 6 mos (94% repair; 10% concomitant CABG) vs. med Rx (with censoring when indications for surgery developed) Outcomes in 207 propensity matched pairs were compared (median 8 yr FU) Conservative MV surgery Conservative MV surgery Conservative MV surgery HR (95%CI) = 0.51 ( ) P=0.08 Time after Baseline, years No. at risk CONV OP % 6% HR (95%CI) = 0.11 ( ) P=0.03 Time after Baseline, years No. at risk CONV OP % 1% HR (95%CI) = 0.22 ( ) P=0.002 Time after Baseline, years No. at risk CONV OP MACE = cardiac death, repeat MV surgery, and HF hospitalization Kang et al. J Am Coll Cardiol. 2014;63: % 4%

36 FDA MitraClip Approval October 24, 2013 The MitraClip is approved for treatment of patients with primary (degenerative) MR (DMR) who are at prohibitive risk for mitral valve surgery and are likely to benefit from MR reduction

37 HF Hospitalization Rate per Patient-Year MitraClip in Prohibitive-risk DMR Relationship between Discharge MR Grade and 1-year HF Hospitalizations* % reduction 28% increase % reduction MR 1+ N=65 MR = 2+ N=35 MR = N=18 * with death counted as a HF hospitalization Lim SD et al. J Am Coll Cardiol 2014;64:182 92

38 Survival MitraClip in Prohibitive-risk DMR 127 pts from EVEREST studies Mean age 82 yrs, 87% NYHA III/IV, mean STS score 13.2%. MitraClip success 95.3% 1-year survival 75.2%; survival according to d/c MR: Survival at 1 year 83.3% 80.0% MR severity at discharge: 1+ (n=66) 2+ (n=35) 3+/4+(n=22) Survival at 1 year (unadjusted): p=0.61 for 1 vs 2+ at discharge p=0.001 for 1 vs 3+/4+ at discharge p=0.02 for 2+ vs 3+/4+ at discharge 52.4% Days Lim SD et al. J Am Coll Cardiol 2014;64:182 92

39 ACC/AHA 2014 Valve Guidelines TMVR for DMR Transcatheter MV repair may be considered for severely symptomatic pts (NYHA class III/IV) with chronic severe primary MR (stage D) who have a reasonable life expectancy but a prohibitive surgical risk because of severe comorbidities COR LOE Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

40 REPAIR VS REPLACE FOR MEDICALLY- OPTIMIZED SYMPTOMATIC ISCHEMIC MR WILL BE DRIVEN BY SURGEON EXPERTISE

41 ACC/AHA 2014 Valve Guidelines Surgery for Secondary MR Secondary MR CAD Rx HF Rx Consider CRT Symptomatic severe MR (Stage D) Asymptomatic severe MR (Stage C) Progressive MR (Stage B) Persistent NYHA Class III-IV symptoms MV Surgery (IIb) Periodic Monitoring Nishimura RA et al. J Am Coll Cardiol 2014;63:e57 185

42 Survival Is MV Surgery Beneficial in FMR? 4,989 pts with CAD and mod/sev ischemic MR at Duke between Treated with MED only (1,800; 36%), PCI only (1,295; 26%), CABG only (1,651; 33%) and CABG + MV repair or replacement (243; 5%) Propensity adjusted multivariable outcomes at median FU 5.4 yrs: No. at risk Medical treatment PCI CABG only CABG + MVRR PCI vs Med: Adj HR (95%CI) = 0.83 ( ), P= CABG vs. Med: Adj HR (95%CI) = 0.56 ( ), P< CABG+MVRR vs. Med: Adj HR (95%CI) = 0.69 ( ), P< P for interaction for MR severity = Castleberry AW et al. Circulation 2014;129: Medical treatment PCI CABG only CABG + MVr/R Median adj survival 5.6 years 6.8 years 9.7 years 8.1 years

43 Meta-analysis of Repair vs. Replacement for Ischemic MR 12 non-randomized studies, 2,508 pts, 64% repair, 36% replacement Random effects meta-analysis: Repair vs. replacement Endpoint (n studies) HR (or OR) [95%CI] P value Hospital death (11) 0.56 [0.38, 0.85] Studies after 1988 (7) 0.70 [0.44, 1.12] 0.14 Long-term death (11) 0.86 [0.66, 1.13] Propensity adjusted (4) 1.05 [0.92, 1.19] 0.46 Recurrent MR 2+ (5) 7.51 [3.70, 15.23] < Reoperation (4) 1.49 [0.91, 2.46] 0.16 Dayan V et al. Ann Thorac Surg 2014;97:758 66

44 Follow -up Enrollment Allocation Analysis Acker MA et al. NEJM 2013;45: Severe MR (SMR) Trial Design 251 pts with severe ischemic FMR Randomized to MV repair with complete rings vs. chordal-sparing MV replacement Mean EROA ~0.40 cm 2 ; 86% concomitant procedures (75% CABG, TV repair, Maze) Assessed for Eligibility (n=3458) Randomized (n=251) Excluded (n=3207) Did not meet inclusion criteria (n=3011) Refused to participate (n=131) Other (n=65) Allocated to Mitral Valve Repair (n=126) Received MV Repair (n=115) Received MV Replacement (n=11) Allocated to Mitral Valve Replacement (n=125) Received MV Replacement (n=124) Received MV Repair (n=1) Withdrawal before month 12 (n=3) Death before month 12 (n=18) Withdrawal before month 12 (n=1) Death before month 12 (n=22) Primary Endpoint Analysis (n=126) Excluded from Analysis (n=0) 2 year FU planned Primary Endpoint Analysis (n=125) Excluded from Analysis (n=0)

45 Median Change in LVESVI (mm/m 2 ) Acker MA et al. NEJM 2013;45: SMR Trial: 1 Endpoint 251 pts with severe ischemic FMR Randomized to MV repair with complete rings vs. chordal-sparing MV replacement Mean EROA ~0.40 cm 2 ; 86% concomitant procedures (75% CABG, TV repair, Maze) 1 EP = Median Change in LVESVI from baseline to 1 year P= Repair (All pts) Replacement (All pts) Repair (Survivors) Replacement (Survivors)

46 Recurrent MR (%) Acker MA et al. NEJM 2013;45: SMR Trial: Recurrent MR 251 pts with severe ischemic FMR Randomized to MV repair with complete rings vs. chordal-sparing MV replacement Mean EROA ~0.40 cm 2 ; 86% concomitant procedures (75% CABG, TV repair, Maze) Recurrent MR at 1 year 32.6% 4.2 P< % Severe Moderate Repair (n=126) Replacement (n=125) There were no significant 1-year differences in: LVESVI NYHA SF-36 scores MLwHF scores MV reoperation Death MACE

47 Mean LVESVI Acker MA et al. NEJM 2013;45: SMR Trial: Impact of Recurrent MR 251 pts with severe ischemic FMR Randomized to MV repair with complete rings vs. chordal-sparing MV replacement Mean EROA ~0.40 cm 2 ; 86% concomitant procedures (75% CABG, TV repair, Maze) Mean Change in LVESVI P< Δ=6.8 ml 10 0 Baseline Replacement 12 mos Repair without recurrent MR Repair with recurrent MR

48 PERCUTANEOUS MV REPAIR INDICATIONS WILL CONTINUE TO EVOLVE AND EXPAND INTO THE REALM OF FUNCTIONAL MR

49 Management of 3-4+ MR with HF % of Patients 1,095 pts* with 3+/4+ MR and HF between 2000 and 2008 (74% FMR, 21% DMR). Rx before 10/2011: DMR pts (n=226): 84% MV surgery, 16% med Rx FMR pts (n=814): 36% MV surgery (77% w/cabg), 64% med Rx Un-operated pts had lower LVEF (mean 27% vs. 42%, p< and higher STS score (median 5.8 vs. 4.0, p<0.001) compared with operated pts. Prognosis of unoperated pts with 3-4+ MR and HF Mortality Surviving pts hospitalized for HF Years of 474 (36%) un-operated pts with FMR and good echos would have been eligible for MitraClip based on published criteria * Excluded MVA 2 cm 2, AR 2+, aortic peak velocity 2.5 m/s, HCM, endocarditis, concomitant AV, Ao or pericardial surgeries, LVAD or OHT. Goel SS et al. JACC 2014;63,:185 90

50 What are the anatomic criteria for MitraClip? Non-rheumatic MR originating from the central 2/3 of the valve Etiology: degenerative or functional Sufficient leaflet tissue for mechanical coaptation >2mm <11mm Protocol anatomic exclusions Flail gap >10mm Flail width >15mm LVIDs >55mm <10mm MVA <4 cm 2 15mm

51 Worldwide MitraClip Experience Study Population N* EVEREST I (feasibility) Feasibility 55 EVEREST II (pivotal) Roll-in 60 EVEREST II (pivotal) Randomized 184 EVEREST II (pivotal) Non-randomized high-risk 78 REALISM continued access Non-randomized 899 Compassionate/emergency Non-randomized 66 ACCESS Europe Phase I Non-randomized 567 ACCESS Europe Phase II Non-randomized 286 Commercial Use Commercial 14,232 Total 16,427 Data as of 08/31/2014. Source: Abbott Vascular

MitraClip RCTs in Functional MR COAPT RESHAPE-HF Mitra-Fr N patients, sites 430 @ 75 US sites 800 @ 50 EU sites 288 @ 18 French sites Control arm Medical Rx Medical Rx Medical Rx FMR grade Sev (EROA

months; MV surgery is not local standard of care HF hosp within 12 months or BNP 350 pg/ml or nt-probnp 1400 pg/ml within 90 days; not eligible for MV surgery HF hosp within 12 months; not eligible

52 MitraClip RCTs in Functional MR COAPT RESHAPE-HF Mitra-Fr N patients, sites 75 US sites 50 EU sites 18 French sites Control arm Medical Rx Medical Rx Medical Rx FMR grade Sev (EROA >20 mm² + Rvol >30 ml) by ECL NYHA class II, III, or ambulatory IV III or ambulatory IV II - IV Other inclusion criteria HF hosp within 12 months or BNP 300 pg/ml or nt-probnp 1500 pg/ml within 12 months; MV surgery is not local standard of care HF hosp within 12 months or BNP 350 pg/ml or nt-probnp 1400 pg/ml within 90 days; not eligible for MV surgery HF hosp within 12 months; not eligible for MV surgery LVEF 20% - 50% 15% - 40% 15% - 40% LV volumes LVESD 70 mm LVEDD 55 mm - Primary efficacy endpoint (superiority) Primary safety endpoint (noninferiority) 3+ (EROA 30 mm² and/or Rvol >45 3+ (EROA 30 mm² and/or Rvol >45 3 trials randomizing ml by ECL) 1,518 ml by ECL) patients with heart failure and secondary (functional) MR to MitraClip vs. GDMT As of September 10 th, 2014, 207 patients had been randomized: - COAPT pts Recurrent HF hospitalization at 12 months SLDA, device embolizations, endocarditis/ms/device-related complications requiring non-elective CV surgery, LVAD, OHT Death or recurrent HF hospitalization at 12 months - RESHAPE-HF - 37 pts - Mitra-Fr - 46 pts Death or recurrent HF hospitalization at 12 months - - Health economics Assessed Assessed - Follow-up 5 years 2 years 2 years

53 A Hot 20 Minutes Aortic Stenosis Indications for valve replacement are expanding Access requirements for TF TAVR are getting smaller Multiple TAVR devices mean more options and better patient care Mitral Regurgitation Degenerative (primary) mitral regurgitation needs early surgical referral Repair vs replace for medically-optimized symptomatic ischemic mitral regurgitation will be driven by surgeon expertise Percutaneous mitral valve repair indications will continue to evolve and expand into the realm of functional mitral regurgitation

Reshape/Coapt: do we need more? Prof. J Zamorano Head of Cardiology University Hospital Ramon y Cajal, Madrid

Reshape/Coapt: do we need more? Prof. J Zamorano Head of Cardiology University Hospital Ramon y Cajal, Madrid Patient records 76 y.o. male Hypertension. Dyslipidemia. OPLD. Smoked in the past. Diabetes