Mitraclip στη θεραπεία της καρδιακής ανεπάρκειας. Βλάσης Νινιός Επεμβατικός Καρδιολόγος Κλινική Άγιος Λουκάς

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1 Mitraclip στη θεραπεία της καρδιακής ανεπάρκειας Βλάσης Νινιός Επεμβατικός Καρδιολόγος Κλινική Άγιος Λουκάς

2 Mitraclip στη θεραπεία της λειτουργικής ανεπάρκειας ΜΒ (FMR) που σχετίζεται με την καρδιακή ανεπάρκεια

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5 HF and Mitral surgery The role of isolated mitral valve surgery in patients with severe functional mitral regurgitation and severe LV systolic dysfunction (LVEF > 30%) who cannot be revascularized or have non-ischaemic cardiomyopathy is questionable, and in most patients conventional medical and device therapy are preferred. In selected cases, repair may be considered in order to avoid or postpone transplantation. The decision should be based on comprehensive evaluation (including strain echocardiography or magnetic resonance imaging and discussed within the heart team. In patients with HF with moderate-severe, secondary mitral regurgitation

6 HF and edge-to-edge repair In patients with HF with moderate-severe, secondary mitral regurgitation who are judged inoperable or at high surgical risk, percutaneous mitral valve intervention (percutaneous edge-to-edge repair) may be considered in order to improve symptoms and quality of life, although no RCT evidence of improvement has been published, only registry studies.

7 Gaps in evidence Non-surgical (percutaneous) correction of functional mitral and tricuspid regurgitations

8 ΑΝΕΠΑΡΚΕΙΑ ΜΙΤΡΟΕΙΔΟΥΣ ΑΝΑΤΟΜΙΚΗ ΑΝΕΠΑΡΚΕΙΑ ΛΕΙΤΟΥΡΓΙΚΗ ΑΝΕΠΑΡΚΕΙΑ

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10 ΕΡΩΤΗΜΑΤΑ Είναι συχνή η FMR σε ασθενείς με ΚΑ; Επηρεάζει την πρόγνωσή τους; Είναι εύκολη η διάγνωσή της; Είναι εύκολη η θεραπεία της; Είναι αποτελεσματική η θεραπεία της;

11 HF Long Term 12,440 patients from 211 centres of 21 ESC Countries Total population n pts Acute HF n pts Follow-up not available n. 304 pts (4.1%) Chronic HF n pts Echo not available n pts Without MR n pts (73%) Study population n pts With MR n pts (27%) (Maggioni. ESC 2014)

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13 ΕΡΩΤΗΜΑΤΑ Είναι συχνή η FMR σε ασθενείς με ΚΑ; Επηρεάζει την πρόγνωσή τους; Είναι εύκολη η διάγνωσή της; Είναι εύκολη η θεραπεία της; Είναι αποτελεσματική η θεραπεία της;

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15 ΕΡΩΤΗΜΑΤΑ Είναι συχνή η FMR σε ασθενείς με ΚΑ; Επηρεάζει την πρόγνωσή τους; Είναι εύκολη η διάγνωσή της; Είναι εύκολη η θεραπεία της; Είναι αποτελεσματική η θεραπεία της;

16 The Dynamic Nature of Secondary MR Underlying LV systolic dysfunction Transient increase in MR May cause acute pulmonary oedema Exercise-induced changes in the severity of MR, LVEF, and PAP (Pierard et al. N Engl J Med 2004;351: )

17 ΕΡΩΤΗΜΑΤΑ Είναι συχνή η FMR σε ασθενείς με ΚΑ; Επηρεάζει την πρόγνωσή τους; Είναι εύκολη η διάγνωσή της; Είναι εύκολη η θεραπεία της; Είναι αποτελεσματική η θεραπεία της;

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19 ΕΡΩΤΗΜΑΤΑ Είναι συχνή η FMR σε ασθενείς με ΚΑ; Επηρεάζει την πρόγνωσή τους; Είναι εύκολη η διάγνωσή της; Είναι εύκολη η θεραπεία της; Είναι αποτελεσματική η θεραπεία της;

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26 Recurrent MR 1y = 32,6% 2y = 46% 3458 pts 447 Randomized Acker et al. NEJM ;1

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28 Μεγάλο Θεραπευτικό κενό Τελικά η FMR είναι αναστρέψιμος παράγοντας επιδείνωσης της ΚΑ ή απλά ένα σημείο κακής πρόγνωσης η αναστροφή του οποίου αδυνατεί να επιφέρει βελτίωση στην πρόγνωση των ασθενών. Η διαδερμική επιδιόρθωση με το Mitraclip μπορεί να αλλάξει το τοπίο με την αυτονόητη μείωση του επεμβατικού κινδύνου σε σχέση με το χειρουργείο, ή απλά περιορίζεται στην βελτίωση των συμπτωμάτων

29 Edge-to Edge repair with the MitraClip (Abbott Vascular)

30 Randomized Clinical Trials in FMR: The Long Wait Capodanno Eurointervention 2017

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35 ISCHEMIC CARDIOMYOPATHY FMR

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37 EXTREME FMR- NO COAPTATION

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42 LAP PRE LAP 3 nd clip

43 Percutaneous Repair with the MitraClip Device for Severe Secondary Mitral Regurgitation Pr Jean François OBADIA - LYON on behalf of the MITRA-FR Investigators

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45 Inclusion Criteria Symptomatic despite Optimal Treatment (NYHA II). At least one hospitalization for HF within 12 months preceding randomization Severe Secondary MR ERO > 20 mm² or R.vol>30 ml/beat 15% < EF < 40% Not eligible for surgery Heart Team Centralized echocardiographic Corelab

46 452 Patients 145 not eligible 307 Randomized 3 consent Issues Mitraclip Control 152 Patients Intention To Treat 152 Patients 43 Exclusions Follow-up > 99% 15 Exclusions 109 Patients Per-protocol Analysis 137 Patients 9

47 Baseline characteristics Characteristics PercutaneousRepair Group(n=152) OptimalMedical TreatmentGroup (n=152) Pvalue Ageyearmean(±SD) 70.1± ± >75yearn(%) 51(33.6) 59(38.8%) 0.40 Malesn-(%) 120(78.9) 107(70.4%) 0.11 IschemicCardiomyopathyn-(%) 95(62.5)6 0%85(56.3%) 0.29 NYHAClassIIn-(%) 56(36.8) 44(28.9%) NYHAClassIIIn-(%) 82(53.9) 96(63.2%) 0.27 NYHAClassIVn-(%) 14(9.2) 2/3 12(7.9%) LVEFmean(±SD) 33.3±6.5 EF 32.9±6.7 =33%

48 Baseline characteristics Characteristics Percutaneous RepairGroup OptimalMedical TreatmentGroup Pvalue NTproBNP-ng/Lmedian[IQR] 3407[1948;6790] 3292[1937;6343] 0.97 Implantablecardioverter-defibrillator 90(59.2%) 82(53.9%) 0.42 Diuretics 151(99.3%) 149(98.0%) 0.62 Beta-blockers 134(88.2%) 138(90.8%) 0.57 ACE-inhibitor/ARB 111(73.0%) 113(74.3%) 0.55 MineralocorticoidReceptorAntagonist 86(56.6%) 80(53.0%) 0.56 ARBandNeprilysinInhibitor 14(10.0%) 17(12.1%) 0.70 SystolicBloodPressuremmHgmean(±SD) 109±16 108±

49 *Safety Prespecified Secondary Endpoints Periproceduralcomplications Urgentconversiontoheartsurgery 0 Peri-proceduralMortality(at3days) 0 Vascularcomplicationrequiringsurgery /Hemorrhagetransfusion 5(3.5%) Cardiacembolism(Gasembolism/Stroke) 2(1.4%) Tamponade 2(1.4%) *EfficacyProceduralSuccessMVARC 138(94%) - 1 Clip 46% - 2 Clips 45% - 3+ Clips 9% 12

50 EverestII N=279 MITRA-FR N=304 AccessEurop N=567 SentinelPilot N=628 TRAMI N=740 SecondaryMR 27% 100% 77% 72% 71% MeanAge 67y 70y 74y 74y 76y MeanEF 60% 33% NA 43% NA Proceduralsuccess 77% 94% 91% 95% 97% 30daysMortality 1% 2.3% 3.4% NA 4.5% 1yearFollow-up 73% >99% NA NA NA 1yNYHAI/II 98% 72% 71% 74% 63% 1yMRGradeIII/IV 18% 17% 21.1% NA NA 1yMortality 6.1% 24.3% 17.3% 15.3% 20.3%

51 Prespecified Secondary Endpoints MR Grade evolution Corelab 83% 14

52 100% Baseline Prespecified Secondary Endpoints NYHA evolution ( 123 paired data) 12 months 75% 50% 25% 0% N = 114 P<0.001 N=114 15

53 Prespecified Secondary Endpoints NYHA evolution ( paired data) 100% Baseline 12 months Baseline 12 months 100% 75% 75% 50% 50% 25% 25% 0% N = 114 P<0.001 N=114 0% N = 112 P<0.001 N=112 P = NS 16

54 Primary composite endpoint (99% follow-up) - All-Cause Death - Unplanned rehospitalization for HF Medical treatment Mitraclip + Med. treat. OR = 1.16 ( ) P = 0.53 months

55 Dilative Cardiomyopathy Non-Compaction Myocarditis Hypertrophic Cardiomyopathy Restrictive Cardiomyopathy Right Ventricular Dysfunction Mitral Regurgitation Left atrial Disease Amyloidosis

56 The Clinical Course of Heart Failure Acute HF MitralClip No go Zone A CE-I/ARNI BB MRA ICD/CRT /

57 The Timing of Drugs, Device and Interventions in Heart Failure A CE-I/ARNI BB MRA ICD/CRT Acute HF Mitral Interventions Acute HF Advanced HF MCS VAD TX Ruschitzka HFA 2018 mod. after Allen Circulation / 2012

58 (R)evolution of Heart Failure Treatment Palliative Drugs Neurohormonal Drugs Devices ARNI Pre s 1990s 2000s 2010s 2016 Digitalis Diuretics ACE-I ICDs b -Blockers Transplantation CRT, CRT-D LVAD MR-Antagonists Ivabradine Sensing Devices ARNI Ruschitzka HFA 2016

59 Define the Sweet Spot! CARE-HF EchoCRT Cleland J, et al. NEJM 2005 Ruschitzka F., et al. NEJM 2013

60 The Do`s and Don`ts of CRT NO Yes LBBB Morphology NON-LBBB Morphology EHJ/EJHF 2016

61 Am Heart J 2018 COAPT: Randomized Trial Design 610 patients at 78 sites Significant FMR ( 3+ by echo core lab), already on OMT Not appropriate for MV surgery. Meets specific anatomic criteria Randomize 1:1 MitraClip (N=305) Control group Standard of care (n=305) Clinical and TTE follow-up: Baseline, Treatment, 1-week (phone), 1, 6, 12, 18, 24, 36, 48, 60 months Principal Investigators: Gregg Stone, Michael Mack Heart Failure Co-Principal Investigators: William Abraham, JoAnn Lindenfeld

62 Functional Mitral Regurgitation: Key Differences between the 3 RCT s Cat COAPT MITRA-FR RESHAPE-HF2v3.2 G StudySponsor Abbottsponsoredandfunded HospicesCivilsdeLyonsponsored,French governmentfunded GoettingenUniversityHosptsponsored;partlyAbbottfunded G PIs GStone,MMack,WAbraham,JLindenfeld J-FObadia PPonikowski,SAnker G Studypurpose Regulatoryapprovalformoderate-to-severe orseveresecondarymr. Determinesafety&efficacy.French 0 reimbursementforseverefmris2 G Planned/Enrolled 610/ / Clinicaldataforguidelineson chronichfwithsignificantfmr G Sites,randomization 78USsites,1:1ratio 304@~35Frenchsites,1:1ratio 75Europeansites,1:1ratio G Totalfollow-up 5years 2years 2years G PrimaryEffectiveness Endpoint RecurrentHFhospitalizations through24months,analyzedwhenlast subjectcompletes12months(allevents) All-causedeathorrecurrent HFhospitalizationat12months st (1event) Cardiovasculardeathor recurrenthf hospitalizationthrough24 mos,analyzedwhenlastsubject completes12months(allevents) G PrimarySafety Endpoint CompositeofSLDA,deviceembolizations, endocarditisandmitralstenosisrequiring surgery,lvad,openhearttransplant,and device-relatedcomplicationsrequiringnonelectivecvsurgery --- Compositeofall-causemortality, stroke,mi,newrenalreplacement therapy,non-electivecvsurgeryfor devicerelatedcomplications 17 G Secondaryendpoints 10pre-specifiedpoweredendpoints+ multipledescriptiveendpoints Alldescriptive(unpowered)endpoints Somepoweredsecondary 0 endpoints,testedonlyif1ismet

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64 Conclusions Mitraclip is an efficient therapy in reducing FMR in patients with HF However the first of the three RCTs (MITRA-FR) failed to meet the primary end point This could be either due to very sick population and/or design issues with the trial COAPT is round the corner and RESHAPE-HF2 is expanding numbers so. Stay tuned..