How to Identify the RIGHT (and WRONG) Patient for Transcatheter Mitral RepairANITAW. ASGARMD, MSC, FRCPC, FACCPROFESSEURAGGREGÉ, UNIVERSITÉDEMONTREALINSTITUTDECARDIOLOGIEDEMONTREAL

How to Identify the RIGHT (and WRONG) Patient for Transcatheter Mitral RepairANITAW. ASGARMD, MSC, FRCPC, FACCPROFESSEURAGGREGÉ, UNIVERSITÉDEMONTREALINSTITUTDECARDIOLOGIEDEMONTREAL DISCLOSURES •Abbott Structural: Consulting, Honoraria, Research Support•Medtronic: Consulting, Proctor, Honoraria•Edwards: Consulting, Honoraria OBJECTIVES•Understand the diagnostic pathway for determining patient eligibility for percutaneous mitral interventions•Discuss discrepant results that have been reported in recent mitral intervention studies•Review the routine follow-up of patients post-mitral clip procedures CASEPRESENTATION•72 year old male followed in the Heart Failure Clinic with ischemic cardiomyopathy, NYHA Class III•Previous History•IHD: Previous PCI LAD and Cx•Hypertension•Diabetes•Dyslipidemia •Chronic Atrial Flutter-on Coumadin•Anemia•CRF: creat306•COPD CASE PRESENTATION•Medical therapy:•Lasix 80mg BID•Zaroxylyn2.5 mg die•Bisoprolol 7.5mg•Aldactone 25 mg die•Imdur 60 mg die•Hydralazine 25 mg TID•Eprex•Crestor 10 mg die•Insulin •Echocardiogram:•LVEF 33%•LV 64/50•PAP 46mmHg•MR 4/4•TR 1/4•Normal RV function CASEPRESENTATION Is this a reasonable patient for transcatheter mitral repair? QUESTION#1What is NOT an important factor to consider when selecting a patient for transcatheter mitral repair (MitraClip)?A.Ejection FractionB.Severity of Mitral regurgitationC.Etiology of cardiomyopathyD.Current medical therapyE.Severity of Pulmonary HypertensionF.Severity of TR EVALUATIONOFAPATIENTFORMITRACLIP•Clinical evaluation•Is the patient symptomatic?•Is there a reasonable chance that treating FMR will improve quality of life? Are the comorbidities prohibitive?•Transthoracic Echo•Severity of MR, LV Function, Coexistent valvular heart disease•RV function•Transesophageal Echo•Mechanism of MR•Mitral valve area CASEPRESENTATION •Patient discussed at Heart Team meeting decision made to propose COAPT Trial•Patient consented for participation in the COAPT Trial (12/2016) and randomized to medical therapy CASEPRESENTATION•Twelve months following randomization to Medical Therapy in COAPT:•Hospitalized for decompensated heart failure on 18separate occasions (January 2017-December 2017)•Renal function deteriorating, creat400•NYHA IV Theodor Seuss "Ted" Geisel(1904-1991) SECONDARYMITRALREGURGITATION MITRA-FRAugust 2018 COAPTSeptember 2018 QUESTION#2What does the evidence from MITRA-FR and COAPT suggest about the utility of MitraClip in secondary MR?A.There is no benefit of MitraClip in secondary MRB.Treatment with MitraClip reduces HF hospitalizations in ALL patients with secondary MRC.Treatment with MitraClip reduces all cause mortality in ALL patients with secondary MRD.There is benefit of MitraClip in selected patients with secondary MRE.Proportionately severe MR is a characteristic of those who benefit from MitraClip PercutaneousRepairwiththe MitraClipDevicefor SevereSecondaryMitral Regurgitation PrJean François OBADIA -LYONon behalf of the MITRA-FR Investigators AcademicStudy* *Obadiaet al. Eurointervention2015;10:1354-1360 Primary Endpoint “Composite”All-Cause Deaths or Unplanned rehospitalisationfor Heart failure at 12 months Inclusion Criteria•Symptomaticdespite Optimal Treatment (NYHA ≥II).•At least one hospitalization for HF within 12 months preceding randomization•Severe Secondary MR èERO > 20 mm² orR.vol>30 mL/beat •15% < EF < 40%•Not eligible for surgery “Heart Team”•Centralized echocardiographic Corelab 16 452 Patients 307 Randomized 152 Patients152 Patients 145 not eligible 3 consent Issues Intention To Treat15 Exclusions 43 Exclusions MitraclipControl Follow-up > 99% Per-protocol Analysis109 Patients137 Patients Medical therapy in both arms was per “real-world” practice 17 Baseline characteristicsCharacteristicsPercutaneous Repair Group (n=152)Optimal Medical Treatment Group (n=152)P valueAge year mean (±SD) 70.1±10.170.6±9.90.69>75 year n (%)51 (33.6)59 (38.8%)0.40Males n -(%) 120 (78.9)107 (70.4%)0.11Ischemic Cardiomyopathy n -(%)95 (62.5)85 (56.3%)0.29NYHA Class II n -(%) 56 (36.8)44 (28.9%)0.27NYHA ClassIII n -(%) 82 (53.9)96 (63.2%)NYHA Class IV n -(%) 14 (9.2)12 (7.9%)LVEF mean (±SD) 33.3±6.532.9±6.70.79Effect regurg. Orif. area -mm2 mean (±SD) 31 ±1031 ±110.42 60% EF=33%S=31mm2 2/3 months15212310994 86807315111495918173 67 Primary composite endpoint (99% follow-up)-All-Cause Death-Unplanned rehospitalizationfor HF Mitraclip + Med. treat.Medical treatment OR = 1.16 (0.73-1.84)P = 0.53 19 PrespecifiedSecondary EndpointsMR Grade evolution Corelab MITRA-FR supplementary Appendix 40 / 49 8.3 Figure S3: Mitral regurgitation grade in the percutaneous mitral repair group at baseline and 12 months. Change in mitral regurgitation severity is shown at b a s e l i n e a n d 1 2 m o n t h s , u s i n g p a i r e d analysis. There was a reduction in mitral regurgita tion severity between baseline and 12 months. P values are not shown because of multiple analysis limitation. 83% The COAPT Trial Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral RegurgitationA 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 GDMTRandomize 1:1* GDMT aloneN=305MitraClip + GDMTN=305*Stratified by cardiomyopathy etiology (ischemic vs. non-ischemic) and site Key Inclusion Criteria 1.Ischemic or non-ischemic cardiomyopathy with LVEF 20%-50% and LVESD ≤70 mm2.Moderate-to-severe (3+) or severe (4+) secondary MR confirmed by an independent echo core laboratory prior to enrollment (US ASE criteria)3.NYHA functional class II-IVa(ambulatory) despite a stable maximally-tolerated GDMT regimen and CRT (if appropriate) per societal guidelines4.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* 5.Not appropriate for mitral valve surgery by local heart team assessment6.IC believes secondary MR can be successfully treated by the MitraClip Adjusted by a 4% reduction in the BNP or NT-proBNPcutoff for every increase of 1 kg/m2in BMI >20 kg/m2 Key Exclusion Criteria 1.ACC/AHA stage D HF, hemodynamic instability or cardiogenic shock 2.Untreated clinically significant CAD requiring revascularization3.COPD requiring continuous home oxygen or chronic oral steroid use 4.Severe pulmonary hypertension or moderate or severe right ventricular dysfunction 5.Aortic or tricuspid valve disease requiring surgery or transcatheter intervention6.Mitral valve orifice area <4.0 cm2by site-assessed TTE7.Life expectancy <12 months due to non-cardiac conditions Primary Endpoints *Analyzed when the last subject completes 12 months of follow-up; **Objective performance goal Primary effectiveness endpoint: All HF hospitalizations through 24 months*Powered for superiority of the Device group compared with the Control groupPrimary safety endpoint: Freedom at 12 mosfrom 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 surgeryPowered for superiority of the Device group vs. a pre-specified OPG** 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 MitraClip + GDMTN=302GDMT aloneN=312 Reasons for exclusionInadequate 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 screeningor other (n=419)RandomizedN=614 at 78 sites IneligibleN=911 Roll-in casesN=51 at 34 sites Eligible for enrollment N=665 Baseline Characteristics ( i ) Baseline Characteristics (ii) HF parametersMitraClip +GDMT (N=302)GDMT alone(N=312)Echo core labMitraClip + GDMT (N=302)GDMT alone(N=312)Etiology of HFMR severity-Ischemic60.9%60.6%-Mod-to-sev(3+)49.0%55.3%-Non-ischemic39.1%39.4%-Severe (4+)51.0%44.7%NYHA classEROA, cm20.41 ±0.15 0.40 ±0.15 -I 0.3%0%LVESD, cm5.3 ±0.9 5.3 ±0.9 -II 42.7%35.4%LVEDD, cm6.2 ±0.7 6.2 ±0.8 -III51.0%54.0%LVESV, mL135.5 ±56.1 134.3 ±60.3 -IV6.0%10.6%LVEDV, mL194.4 ±69.2 191.0 ±72.9 HF hospw/i1 year58.3%56.1%LVEF, %31.3 ±9.1 31.3 ±9.6 Prior CRT38.1%34.9%-£40%82.2%82.0%Prior defibrillator30.1%32.4%RVSP, mmHg44.0 ±13.4 44.6 ±14.0 Medication Use at Baseline Maximally-tolerateddosesMitraClip + GDMT (n=302)GDMT alone (n=312) Beta-blocker91.1%89.7%ACEI, ARB or ARNI71.5% 62.8%Mineralocorticoid receptor antagonist50.7% 49.7%Nitrates6.3%8.0%Hydralazine16.6%17.6%Diuretic89.4%88.8%Chronic oral anticoagulant46.4% 40.1%Aspirin 57.6% 64.7%P2Y12 receptor inhibitor25.2% 22.8%Statin 62.6% 60.6% MitraClip Procedure (n=302) TTE at discharge(n=260) 82,3 12,73,51,5 0%10%20%30%40%50%60%70%80%90%100% MR grade≤1+2+3+4+ 95% MR 2+ or less Primary Effectiveness Endpoint All Hospitalizations for HF within 24 months HR (95% CI] =0.53 [0.40-0.70]P<0.00103691215182124 50100150200250300 0 MitraClip + GDMTGDMT alone 160in 92 pts 283in 151 pts CumulativeHF Hospitalizations (n) Time After Randomization (Months)MitraClipGDMT30228626925323619117816112431229427124521917614512188 No. at Risk: Median [25%, 75%] FU= 19.1 [11.9, 24.0] mos Primary Effectiveness Endpoint Hospitalizations for HF within 24 months Annualized rates of HF hospitalization* *Joint frailty model 35,8% 67,9% 0%10%20%30%40%50%60%70%80% GDMTalone MitraClip+ GDMT HR (95% UCL] =0.53 [0.66]P<0.001160/446.5 pt-yrs 283/416.8 pt-yrs NNT (24 mo) = 3.1 [95% CI 1.9, 8.2] Powered Secondary Endpoints 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 -Tested in hierarchical order1-P-value1. MR grade £2+ at 12 months 2. All-cause mortality at 12 months23. Death and all HF hospitalization through 24 months (Finkelstein-Schoenfeld)4. Change in QOL (KCCQ) from baseline to 12 months5. 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 months10. Death, stroke, MI, or non-elective CV surgery for device-related complsat 30 days3 Powered Secondary Endpoints 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 -Tested in hierarchical order1-P-value1. MR grade £2+ at 12 months <0.0012. All-cause mortality at 12 months2 <0.0013. Death and all HF hospitalization through 24 months (Finkelstein-Schoenfeld)<0.0014. Change in QOL (KCCQ) from baseline to 12 months<0.0015. Change in 6MWD from baseline to 12 months <0.0016. All-cause hospitalizations through 24 months 0.037. NYHA class I or II at 12 months <0.0018. Change in LVEDV from baseline to 12 months 0.0039. All-cause mortality at 24 months<0.00110. Death, stroke, MI, or non-elective CV surgery for device-related complsat 30 days3<0.001 All-cause Mortality All-cause Mortality (%)0% 20% 40% 60% 80% 100% Time After Randomization (Months)03691215182124 46.1%29.1% HR [95% CI] = 0.62 [0.46-0.82]P<0.001 MitraClip + GDMTGDMT alone30228626925323619117816112431229427124521917614512188No. at Risk: MitraClip + GDMTGDMT alone NNT (24 mo) =5.9 [95% CI 3.9, 11.7] MitraClip + GDMTGDMT alone All-cause Mortality orHF Hospitalization (%)0%20%40%60%80%100% Time After Randomization (Months)03691215182124 67.9%45.7% MitraClip + GDMTGDMT alone30226423821519415414512697312244205174153117907555No. at Risk: HR [95% CI] = 0.57 [0.45-0.71]P<0.001 NNT (24 mo) =4.5 [95% CI 3.3, 7.2] Death or HF Hospitalization Major Changes in HF Meds w/ i 12 Months 24-Month Death or HF Hospitalization 0.130.760.790.540.79 0.410.690.29 0.57 [0.45, 0.71]0.47 [0.33, 0.66]0.54 [0.41, 0.71]0.54 [0.37, 0.78]0.53 [0.39, 0.71]0.59 [0.40, 0.86] 0.56 [0.28, 1.12]0.51 [0.37, 0.70]0.51 [0.33, 0.80]0.62 [0.45, 0.83] 67.9% (191)65.3% (91)73.0% (125)65.2% (75)67.4% (122)67.8% (65) 84.4% (26)65.0% (103)58.7% (51)71.4% (91) 45.7% (129)37.8% (51)47.1% (90)41.1% (45)42.9% (74)47.6% (43) 68.3% (12)39.2% (64)35.8% (32)53.4% (78) All patients 0.310.50 [0.39, 0.65]71.9% (157)44.2% (96) 0.320.46 [0.33, 0.64]77.8% (99)46.4% (56) 0.420.48 [0.34, 0.67]69.5% (92)41.5% (54) All patientsAge (median)SexEtiology of cardiomyopathyPrior CRTHF hospitalization within the prior yearBaseline NYHA class STS replacement scoreSurgical risk status*Baseline MR gradeBaseline LVEF 0.65 [0.48, 0.88]70.2% (100)52.1% (78)≥74 years (n=317)<74 years (n=297) 0.60 [0.40, 0.89]59.4% (66)43.2% (39)Female (n=221)Male (n=393) 0.57 [0.43, 0.76]70.0% (116)48.1% (84)Ischemic (n=373)Non-ischemic (n=241) 0.62 [0.44, 0.89]68.4% (69)50.2% (55)Yes (n=224)No (n=390) 0.56 [0.42, 0.73]67.9% (126)44.7% (86)Yes (n=407)No (n=207) 0.56 [0.39, 0.81]66.9% (65)41.1% (50)I or II (n=240) 0.920.61 [0.44, 0.83]65.3% (99)46.6% (67)III (n=322)IV (n=51) 0.64 [0.46, 0.88]71.4% (88)54.1% (65)≥8% (n=262)<8% (n=352) 0.58 [0.45, 0.75]71.5% (140)49.7% (95)High (n=423)Not high (n=188) 0.48 [0.34, 0.67]65.3% (100)37.5% (51)3+ (n=320)4+ (n=293) 0.67 [0.38, 1.17]56.2% (27)49.7% (22)>40% (n=103)≤40% (n=472) 0.60 [0.43, 0.84]61.2% (85)44.1% (62)≥30% (median; n=301)<30% (median; n=274)Baseline LVEDV (median) 0.58 [0.42, 0.80]68.0% (92)48.9% (43)≥181 mL (n=288)<181 mL (n=287) P [Int]HR [95% CI]GDMT aloneMitraClip + GDMTSubgroup HR [95% CI] 0.20.511.52.5Favors MitraClip + GDMT Favors GDMT aloneKM time-to-first event rates*Central eligibility committee assessment MR Severity (Core Lab) MR grade≤1+2+3+4+Ptrend ≤2+P-value BaselineMitraClip (n=302)--49.0%51.0%---GDMT (n=311)--55.3%44.7%-30 daysMitraClip (n=273)72.9%19.8%5.9%1.5%<0.00192.7%<0.001GDMT (n=257)8.2%26.1%37.4%28.4%34.2%6 monthsMitraClip (n=240)66.7%27.1%4.6%1.7%<0.00193.8%<0.001GDMT (n=218)9.2%28.9%42.2%19.7%38.1%12 monthsMitraClip (n=210)69.1%25.7%4.3%1.0%<0.00194.8%<0.001GDMT (n=175)11.4%35.4%34.3%18.9%46.9%24 monthsMitraClip (n=114)77.2%21.9%0%0.9%<0.00199.1%<0.001GDMT (n=76)15.8%27.6%40.8%15.8%43.4% MR Severity (Core Lab) MR grade≤1+2+3+4+Ptrend ≤2+P-value BaselineMitraClip (n=302)--49.0%51.0%---GDMT (n=311)--55.3%44.7%-30 daysMitraClip (n=273)72.9%19.8%5.9%1.5%<0.00192.7%<0.001GDMT (n=257)8.2%26.1%37.4%28.4%34.2%6 monthsMitraClip (n=240)66.7%27.1%4.6%1.7%<0.00193.8%<0.001GDMT (n=218)9.2%28.9%42.2%19.7%38.1%12 monthsMitraClip (n=210)69.1%25.7%4.3%1.0%<0.00194.8%<0.001GDMT (n=175)11.4%35.4%34.3%18.9%46.9%24 monthsMitraClip (n=114)77.2%21.9%0%0.9%<0.00199.1%<0.001GDMT (n=76)15.8%27.6%40.8%15.8%43.4% Change in LVEDV from Baseline to 12 Months 194,1 211,4 196,2192,2 180 185 190 195 200 205 210 215 Baseline12 Months LVEDV (mL) GDMT aloneMitraClip + GDMT œ76.0œ69.2 Adjusted change* *Ancova 17,1 -3,7 -10 -5 0 5 10 15 20LVEDV change from BL to 12 mo(DLSM ±SE) œ5.1 œ5.1 P<0.001 n=175n=174n=175n=174 œ94.2 œ76.5 MORTALITYBENEFITSOFTHERAPIESFORHFREF ICDMineralocorticoidreceptorantagonists ACEInhibitoror ARB 10% 20% 30% 40% 0% Sacubitril/valsartan CRTBeta-blockersHydralazineIsordil % Decrease in Mortality MitraClip Courtesy of Joann Lindenfeld There is a clear BENEFITof MitraClip in addition to maximally tolerated guideline-directed medical therapy in reducing all-cause mortality in appropriate patients. SECONDARYMITRALREGURGITATION MITRA-FRAugust 2018COAPTSeptember 2018 VS. COAPT VS. MITRA-FR: 12 - M ONTH D EATH OR HF H OSP Stone GW et al. NEJM. 2018 Sept 23. COAPT Death or HF Hospitalization (%)Months 100%90%80% 60% 20% 0% 50%40%30% 10% Control GroupDevice GroupNo. at Risk: 70% 0 312302 3 244264 6 205238 9 174215 12 153194 HR [95% CI]=0.63 [0.49–0.82]P<0.001 MitraClip + GDMTGDMT alone 33.9%46.5% MITRA-FR ObadiaJF et al. NEJM. 2018 Aug 27. doi: 10.1056/NEJMoa1805374 Death or HF Hospitalization (%)Months 100%90%80% 60% 20% 0% 50%40%30% 10% Control GroupDevice GroupNo. at Risk: 70% 0 152151 2 123114 4 10995 6 9491 8 8681 10 8073 12 7367 54.6%51.3% OR [95% CI]=1.16 [0.73–1.84]P=0.53 MitraClip + MTMT alone COAPT VS. MITRA-FR: MR, LV VOLUMESANDFUNCTIONCOAPT (n=614)MITRA-FR (n=304)EROA, mm2(mean ±SD)41 ±1531 ±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 ±933 ±7LVEDV, mL/m2(mean ±SD)101 ±34135 ±35ObadiaJF et al. NEJM. 2018 Aug 27. doi: 10.1056/NEJMoa1805374; Stone GW et al. NEJM. 2018 Sept 23. COAPT VS. MITRA-FR: MITRACLIPOUTCOMESCOAPT (n=302)MITRA-FR (n=152)MitraClip attempted293 (97.0%)144 (94.7%)≥1 Clip implanted287 (95.0%)138 (90.8%)Procedural complications25/293 (8.5%)21/144 (14.6%)-Device implant failure6 (2.0%)6 (4.2%)-Transfusion or vasccomplrequiring surgery16 (5.5%)5 (3.5%)-ASD 2 (0.7%)4 (2.8%)-Cardiogenic shock1 (0.3%)4 (2.8%)-Cardiac embolism/stroke1 (0.3%)2 (1.4%)-Tamponade1 (0.3%)2 (1.5%)-Urgent cardiac surgery 1 (0.3%)0 (0%)Acute result: MR ≥3+5%9%12-month result: MR ≥3+5%17%Stone GW et al. NEJM. 2018 Sept 23; ObadiaJF et al. NEJM. 2018 Aug 27. doi: 10.1056/NEJMoa1805374 WHYARETHECOAPT RESULTSSODIFFERENTFROMMITRA-FR?POSSIBLEREASONSMITRA-FR (n=304)COAPT (n=614)Severe MR entry criteriaSevere FMR by EU guidelines: EROA ERO >20 mm2OR RV >30 mL/beatSevere FMR by US guidelines: EROA >30 mm2OR RV >45 mL/beatEROA (mean ±SD) 31 ±10 mm2 41 ±15 mm2LVEDV (mean ±SD) 135 ±35 mL/m2 101 ±34 mL/m2 GDMT at baseline and FUReceiving 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+ MR9% / 9%5% / 5%Procedural complications*14.6%8.5%12-mo MitraClip ≥3+ MR 17% 5% IMPACT OF EROA AND LVEDV: EROA >40 MM2ALL-CAUSE MORTALITY OR HF HOSPITALIZATION THROUGH 12 MONTHS 47 LVEDVI >96 ml/m2(N=130; 23.7%)LVEDVI ≤96 ml/m2 (N=92; 16.8%) IMPACT OF EROA AND LVEDV: EROA >30-40 MM2ALL-CAUSE MORTALITY OR HF HOSPITALIZATION THROUGH 12 MONTHS 48 LVEDVI >96 ml/m2(N=88; 16.1%)LVEDVI ≤96 ml/m2 (N=131; 23.9%) IMPACT OF EROA AND LVEDV: EROA ≤30 MM2ALL-CAUSE MORTALITY OR HF HOSPITALIZATION THROUGH 12 MONTHS 49 LVEDVI >96 ml/m2(N=56; 10.2%)LVEDVI ≤96 ml/m2 (N=51; 9.3%) SECONDARYMITRALREGURGITATION •KEY MESSAGES:•Populations were different (very dilated LV vs. less dilated)•MR Severity was different (moderate MR vs. severe MR)•Aggressive medical therapy titration was utilized in COAPT with no significant differences in medical therapy between groups•There was greater MR reduction in COAPT, 95% vs 83% with 2+ or less residual MR•Clinical benefit was seen in those patients with severe MR and dilated LV but not end-stage severe dilatation•In those patients with end-stage LV dilatation, treatment of moderate MR does not provide benefit (? Too late) COAPTVS.MITRA-FR DISPROPORTIONATEVS. PROPORTIONATEMR DISPROPORTIONATEVS. PROPORTIONATEMR •For any given regurgitant fraction, the EROA is dependent on both the left ventricular end-diastolic volume (LVEDV) and the left ventricular ejection fraction (LVEF) DISPROPORTIONATEVS. PROPORTIONATEMR •Regurgitant volume is very dependant on LVEF in the setting of severe MR (RF 50%)•When the LVEDV is 220 to 250 ml, severe MR (defined by a regurgitant fraction of 50%) corresponds to a regurgitant volume of 45 ml when the LVEF is 40%, 35 ml when the LVEF is 30%, and <25 ml when the LVEF is 20%. DISPROPORTIONATEVS. PROPORTIONATEMR•COAPT enrolled patients with disproportionatelysevere MR •MITRA-FR enrolled patients with proportionatelysevere MR•The totality of available evidence suggests that patients with chronic heart failure respond favorably to transcatheter mitral valve repair IF they exhibit degrees of MR that are disproportionately greater than might be expected from the degree of LV chamber enlargement. THESPECTRUMOFSECONDARYMR guidance on communication techniques to support these decisions. Its goal is primarily to help healthcare providers of all types integrate these concepts into their routine practice to promote the delivery of effective, safe, efficient, timely, equitable, and patient-centered care. 12 We recognize that major barriers to the implementation of these concepts are time, training, and resources. We also recognize the limited and inequitable access to experts with formal training in heart failure and palliative care, which leaves many of these responsibilities to be borne by healthcare providers in a general medical setting. If the goals of this document are to be realized, however, the healthcare system will need to make a fundamental commitment to shared decision making, with realignment of incentives to support the tailoring of advanced care to individual patients. Without changes in the structure of the healthcare team and associated reimbursement, these recommendations will remain an unfunded mandate that are unlikely to be fully realized in most practice settings. Expectations for the Future ● Attention to the clinical trajectory is required to calibrate expectations and guide timely decisions. ● Predictive models can target high-risk populations but leave wide uncertainties around estimates of survival for an individual. ● Difficult discussions now will simplify difficult decisions in the future. ● Uncertainty is inevitable and should be included in discus- sions with patients and family. Estimating Prognosis in Heart Failure Assessment of prognosis is the foundation for selection among therapies for life-threatening disease, but this is particularly challenging for heart failure. The clinical course varies dramatically across the spectrum of disease severity and is relatively unpredictable for individual patients (Figure 1). 19,21 This contrasts with the more linear decline of patients with advanced cancer, which has traditionally been the model for approaches to end-stage disease. Even late in heart failure, patients often enjoy “good days” and brief interludes of apparent stability, which can lull them and their care provid- ers into postponing vital decisions. Prognosis is further clouded by the unique contrast between unexpected sudden death (ie, lethal arrhythmia) and lingering death with conges- tive symptoms (ie, progressive pump failure). Frequent reap- praisal of the clinical trajectory helps calibrate expectations, guide communication, and inform rational decisions. More than 100 variables have been associated with mor- tality and rehospitalization in heart failure. 22–27 Examples of prognostic factors include demographics (age, sex, race, insurance status), functional status (New York Heart Associ- ation functional class and health-related quality-of-life scores), exercise capacity (peak oxygen consumption, 6-minute walk), cardiac structure and function (cardiac cham- Figure 1. A depiction of the clinical course of heart failure with associated types and intensities of available therapies. Black line: Patients tend to follow a progressive, albeit nonlinear, decline in health-related quality of life as the disease progresses; this course can be interrupted by sudden cardiac death caused by arrhythmia or can end in a more gradual death caused by progressive pump failure. Gray line: At disease onset, multiple oral therapies are prescribed for cardiac dysfunction and/or treatment of comorbidities. As disease severity increases, the intensity of care may increase in parallel, with intensification of diuretics, addition of an implantable cardioverter- defibrillator/cardiac resynchronization therapy for those eligible, and increasing interaction with the medical system through ambulatory visits and hospitalizations, until the time when standard therapies begin to fail (transition to advanced heart failure). Dotted line: Pallia- tive therapies to control symptoms, address quality of life, and enhance communication are relevant throughout the course of heart fail- ure, not just in advanced disease; palliative therapies work hand in hand with traditional therapies designed to prolong survival. The critical transition into advanced heart failure from the medical perspective is often followed by a transition in goals of care from the patient and family perspective, wherein palliative therapies may become the dominant treatment paradigm (for the majority of patients in whom transplantation and mechanical circulatory support are not an option). Clinicians must recognize the transition to advanced heart failure so that therapeutic options can be considered in a timely fashion and patients are able to proactively match medical deci- sions to clinical realities. CHF indicates chronic heart failure; MCS, mechanical circulatory support. Modified from Lanken et al; 21 reprinted with permission of the American Thoracic Society. Copyright © 2012, American Thoracic Society. 1930 Circulation April 17, 2012 Downloaded from http://ahajournals.org by on September 4, 2018 MITRA-FRERO > 20mm2LVEDVi 135 ml/m2 COAPTERO > 40mm2LVEDVi 100ml/m2 CASEPRESENTATION•Twelve months following randomization to Medical Therapy in COAPT:•Hospitalized for decompensated heart failure on 18separate occasions (January 2017-December 2017)•Renal function deteriorating, creat400•NYHA IV CASEPRESENTATION•Following discussion with the Heart Team and treating physician, decision was made to perform protocol deviation and perform the MitraClip procedure•COAPT Trial protocol deviation accepted•Patient electively admitted for MitraClip procedure performed on January 18, 2018 CASEPRESENTATION CASEPRESENTATION•Follow Up (12 months)•Clinic visit 16/12/2018•Patient doing well, walking daily•NYHA Class 1-2•Echocardiogram:•EF 33%•MR 1+•No further admissions for heart failure since January 2018 WHOAREIDEALCANDIDATESFORMITRACLIPTHERAPYFORFMR?•Severe symptomatic secondary mitral regurgitation•Optimally medically treated as per HF Guidelines including device therapy (CRT) as required•LVEF >20%•NO evidence of severe end-stage LV dilatation•Procedure may be successful but unlikely to change natural history of the disease•Procedure judged feasible by an experienced MitraClip teamGOAL OF THERAPY: MAXIMAL reduction of MR 61/30 EVALUATIONOFOUTCOMESOFMITRACLIPFORTHETREATMENTOFLOWEJECTIONFRACTIONANDFUNCTIONALMITRALVALVEREGURGITATION-MODERATEMR MR STUDY DESIGNRandomized trial of medical therapy vs. MitraClip in HF patients with MODERATE MR 62 CHANGING PRACTICE…EVOLVE-MRMulticenter trial in Canada that will identify the optimal strategy to treat patients with Heart Failure and Moderate Mitral Regurgitation to improve left ventricular remodelling and the quality of life 63VERSION 12-JAN-2016 135 9 101 21 75 30 0 20 40 60 80 100 120 140 160 Baseline LVEDV (ml/m2)Di fference LVEDVMITRA-FRCOAPTEVOLVE-MR * Hypothesized results based on EVOLVE-MR inclusion criteria:LVEDVi 75-110 ml/m2 * LV Remodelling in RCT of MitraClip SHOULDWEINTERVENEEARLIERFORMODERATESECONDARYMR? guidance on communication techniques to support these decisions. Its goal is primarily to help healthcare providers of all types integrate these concepts into their routine practice to promote the delivery of effective, safe, efficient, timely, equitable, and patient-centered care. 12 We recognize that major barriers to the implementation of these concepts are time, training, and resources. We also recognize the limited and inequitable access to experts with formal training in heart failure and palliative care, which leaves many of these responsibilities to be borne by healthcare providers in a general medical setting. If the goals of this document are to be realized, however, the healthcare system will need to make a fundamental commitment to shared decision making, with realignment of incentives to support the tailoring of advanced care to individual patients. Without changes in the structure of the healthcare team and associated reimbursement, these recommendations will remain an unfunded mandate that are unlikely to be fully realized in most practice settings. Expectations for the Future ● Attention to the clinical trajectory is required to calibrate expectations and guide timely decisions. ● Predictive models can target high-risk populations but leave wide uncertainties around estimates of survival for an individual. ● Difficult discussions now will simplify difficult decisions in the future. ● Uncertainty is inevitable and should be included in discus- sions with patients and family. Estimating Prognosis in Heart Failure Assessment of prognosis is the foundation for selection among therapies for life-threatening disease, but this is particularly challenging for heart failure. The clinical course varies dramatically across the spectrum of disease severity and is relatively unpredictable for individual patients (Figure 1). 19,21 This contrasts with the more linear decline of patients with advanced cancer, which has traditionally been the model for approaches to end-stage disease. Even late in heart failure, patients often enjoy “good days” and brief interludes of apparent stability, which can lull them and their care provid- ers into postponing vital decisions. Prognosis is further clouded by the unique contrast between unexpected sudden death (ie, lethal arrhythmia) and lingering death with conges- tive symptoms (ie, progressive pump failure). Frequent reap- praisal of the clinical trajectory helps calibrate expectations, guide communication, and inform rational decisions. More than 100 variables have been associated with mor- tality and rehospitalization in heart failure. 22–27 Examples of prognostic factors include demographics (age, sex, race, insurance status), functional status (New York Heart Associ- ation functional class and health-related quality-of-life scores), exercise capacity (peak oxygen consumption, 6-minute walk), cardiac structure and function (cardiac cham- Figure 1. A depiction of the clinical course of heart failure with associated types and intensities of available therapies. Black line: Patients tend to follow a progressive, albeit nonlinear, decline in health-related quality of life as the disease progresses; this course can be interrupted by sudden cardiac death caused by arrhythmia or can end in a more gradual death caused by progressive pump failure. Gray line: At disease onset, multiple oral therapies are prescribed for cardiac dysfunction and/or treatment of comorbidities. As disease severity increases, the intensity of care may increase in parallel, with intensification of diuretics, addition of an implantable cardioverter- defibrillator/cardiac resynchronization therapy for those eligible, and increasing interaction with the medical system through ambulatory visits and hospitalizations, until the time when standard therapies begin to fail (transition to advanced heart failure). Dotted line: Pallia- tive therapies to control symptoms, address quality of life, and enhance communication are relevant throughout the course of heart fail- ure, not just in advanced disease; palliative therapies work hand in hand with traditional therapies designed to prolong survival. The critical transition into advanced heart failure from the medical perspective is often followed by a transition in goals of care from the patient and family perspective, wherein palliative therapies may become the dominant treatment paradigm (for the majority of patients in whom transplantation and mechanical circulatory support are not an option). Clinicians must recognize the transition to advanced heart failure so that therapeutic options can be considered in a timely fashion and patients are able to proactively match medical deci- sions to clinical realities. CHF indicates chronic heart failure; MCS, mechanical circulatory support. Modified from Lanken et al; 21 reprinted with permission of the American Thoracic Society. Copyright © 2012, American Thoracic Society. 1930 Circulation April 17, 2012 Downloaded from http://ahajournals.org by on September 4, 2018 MITRA-FRERO > 20mm2LVEDVi 135 ml/m2 COAPTERO > 40mm2LVEDVi 100ml/m2 EVOLVE-MR THANKYOUFORYOURATTENTION