Τελικά επιδιόρθωση, αντικατάσταση ή clip στην ισχαιμική ανεπάρκεια Μιτροειδούς; ΒΛΑΣΗΣ ΝΙΝΙΟΣ MD MRCP ΚΛΙΝΙΚΗ ΑΓΙΟΣ ΛΟΥΚΑΣ

Transcription

1 Τελικά επιδιόρθωση, αντικατάσταση ή clip στην ισχαιμική ανεπάρκεια Μιτροειδούς; ΒΛΑΣΗΣ ΝΙΝΙΟΣ MD MRCP ΚΛΙΝΙΚΗ ΑΓΙΟΣ ΛΟΥΚΑΣ

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4 Carpentier MV Classification- Leaflet Mobility Normal Increased Decreased Mobility Perforation Prolapse/Flail Systole & Diastole Systole Annular dilation SBE; DCM Degenerative RHD/Carcinoid IHD/DCM

5 ΑΝΕΠΑΡΚΕΙΑ ΜΙΤΡΟΕΙΔΟΥΣ ΑΝΑΤΟΜΙΚΗ ΑΝΕΠΑΡΚΕΙΑ ΛΕΙΤΟΥΡΓΙΚΗ ΑΝΕΠΑΡΚΕΙΑ

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9 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)

10 HF Long-Term Baseline characteristics MR (1672 pts) No MR (4419 pts) Age, years, median [IQR] < Ischaemic aetiology, % < Treated hypertension, % < History of AF, % < Prior stroke, % Renal dysfunction, % < COPD, % p (Maggioni. ESC 2014)

11 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: )

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13 IMR PRE

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25 251 Patients Randomized Primary endpoint- LVESVI at One Year November 18, 2013, at NEJM.org.

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27 Percent with moderate or severe recurrent MR Recurrent MR at 1 year 35 Moderate or Severe Recurrent MR 32, p < ,3 0 Repair Replacement

28 Mean LVESVI LVESVI with Recurrent MR Mean LVESVI for Patients Undergoing Repair p < Baseline 12 Months Repair with MR Repair without MR CTSN SMR Trial

29 PLA >45Degrees Magne et al. Circulation 2007; 115:

30 Predictors of Recurrence Tenting Area Tenting Height Anterior and Posterior Leaflet Angles

31 J Thorac Cardiovasc Surg 2015; 149:

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34 Chronic Severe Secondary Mitral Regurgitation: Intervention Recommendations COR LOE MV surgery is reasonable for patients with chronic severe secondary MR (stages C and D) who are undergoing CABG or AVR MV surgery may be considered for severely symptomatic patients (NYHA class III-IV) with chronic severe secondary MR (stage D) MV repair may be considered for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery Repair or Replacement not stipulated IIa IIb IIb C B C

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

38 EVEREST II Randomized Clinical Trial Study Design 279 Patients enrolled at 37 sites Significant MR (3+-4+) Specific Anatomical Criteria Randomized 2:1 Device Group MitraClip System n=184 Control Group Surgical Repair or Replacement n=95 Echocardiography Core Lab and Clinical Follow-Up: Baseline, 30 days, 6 months, 1 year, 18 months, and annually through 5 years

39 30 Day Modified * MAE Intent to Treat, Hierarchical Events 50 p SUP < % 30 Day Modified MAE (%) % Major Bleeding Complication* GI Complication New Onset Atrial Fibrillation Ventilation >48hrs Urgent CV Surgery Stroke Death 0 Device Device Control Control *Major bleeding requiring transfusion 2U, or surgical intervention.

40 Primary Effectiveness 50% Per Protocol Cohort (n=217) Event rate (%) 40% 30% 20% Device Group (n=137) Control Group (n=80) 16,4% 10% 0% 6,8% 6,7% 4,5% 2,7% 2,7% Death 1 st Surgery Re-operation MR > 2+

41 Kaplan-Meier Freedom from MV Surgery in MitraClip group or Re-operation in Surgery group All Treated Patients (N = 258) Landmark Analysis Surgery (N = 80) MitraClip (N = 178) 98.7% 97.1% 97.2% 96.3% 1 year 2 years 95.6% 95.5% 3 years Surgery Non-High Risk (N = 80) RCT MitraClip Non-High Risk (N = 178) RCT Surgery Non-High MitraClip Risk (N Non-High = 80) Risk (N = 178) Days Post Index Procedure

42 Patients (%) Mitral Regurgitation Grade at 5 Years Patients (%) 100% 80% 60% 40% 20% 0% MitraClip (N=130) Surgery (N=62) Degenerative MR BL 5 Years BL 5 Years 100% 80% 60% 40% 20% 0% MitraClip (N=48) Functional MR Surgery (N=18) BL 5 Years BL 5 Years N=85 N=34 N=21 N=7 N = survivors with paired data; p-values for descriptive purposes only

43 EVEREST High Risk Registry EVEREST II High Risk Registry N=78 REALISM Continued Access High Risk Arm N=273 EVEREST II High Surgical Risk Cohort N=351 99% Follow-Up Compliance 30-Day Visit N=342 Withdrawals = 5 Missing visit = 4 98% Follow-Up Compliance 1-Year Visit N=327 Withdrawals = 11 Missing visit = 8 Subset for Durability Analysis 2-Year Visit N=211 Follow-up to 2 years is ongoing All high surgical risk patients were enrolled using the same inclusion / exclusion criteria

44 Baseline Demographics and Co-Morbidities

45 Baseline Demographics and Co-Morbidities

46 Observed 30-day Mortality Lower than Predicted Surgical Mortality p < Matched Data N=351 p < *Protocol-specified Source: EVEREST II High Risk Cohort

47 Mitral Regurgitation Grade p< p< p< Patients (%) % % 87% Baseline Discharge Baseline 1 Year Baseline 2 Years Paired data (N=325) Paired data (N=221) Paired data (N=109)

48 Patients (%) NYHA Functional Class 100% I p < p < % II 18% I I 60% 86% 83% III 40% II II 20% 0% IV III III IV IV Baseline 30 Days 1 Year Paired data (N=233)

49 HF Hospitalization Rate Per Patient Year Hospitalizations for Heart Failure 1,0 0,8 48% reduction p< ,6 0, , All treated 0,0 1 Year Prior to MitraClip 1 Year Post Discharge

50 So Where Are We Now? Ventricular element Atrial element

51 Worldwide Experience Using the MitraClip Study Population N* EVEREST I (Feasibility) Feasibility patients 55 EVEREST II (Pivotal) Pre-randomized patients 60 EVEREST II (Pivotal) EVEREST II (Pivotal) Non-randomized patients (High Risk Study) Randomized patients (2:1 Clip to Surgery) Clip 95 Surgery REALISM (Continued Access) Non-randomized patients 899 Compassionate/Emergency Use Non-randomized patients 66 ACCESS Europe Phase I Non-randomized patients 567 ACCESS Europe Phase II Non-randomized patients 286 Commercial Use Commercial patients >20,000 Total >20,000

52 ACCESS EU - Real-World Clinical Mitral Regurgitation Grade Reduction p< Experience 79% MR 2+ at 1 Year Demonstrated safety with low adverse event rates Description of Event Death 19 (3.4) Stroke 4 (0.7) Myocardial Infarction 4 (0.7) Renal Failure 27 (4.8) Respiratory Failure 4 (0.7) Need for Resuscitation 10 (1.8) Cardiac Tamponade 6 (1.1) Site Reported Safety Events at 30 Days As assessed by sites (N=327, matched) Bleeding Complications 22 (3.9) Significant NYHA Functional Class Improvements I II p< I Functional Improvement in 6-Minute Walk Test p< meter improvement III II 79% NYHA Class I or II at 1 Year IV (N=343, matched) III IV (N=216, matched)) Data presented as mean ±95% confidence intervals (44.5, 74.6) Source: Schillinger, W. 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. ESC 2012; August 25-29, 2012; Munich, Germany.

53 TRAMI Registry 486 Patients Analysis 486 patients, a majority (93%) with severe MR, 93% in NYHA class lll-lv, 67% with FMR In this high surgical risk group MR was significantly reduced and NYHA functional class improved using MitraClip Despite high surgical risk, in-hospital mortality was low (2.5%) no patient died in the operating room Mitral Regurgitation Grade Reduction Significant NYHA Functional Class Improvements P< % MR 2+ acutely I II III p< I II 62% NYHA Class I or II at follow-up IV III (total patients cohort) (total patients cohort) Baldus et. al. TRAMI Registry EHJ 2012

54 % Event free GRASP Registry 117 Patients Analysis..PMVR with the MitraClip technique was shown to be safe and reasonably effective in 117 patients from a real-world setting.. MR 3+ elderly patients at high risk for surgery Overall Freedom from death, surgery or MR 3+ at 1 year was 75.8% 100% of patients achieved MR 2+ post procedure Baseline characteristics Age FMR ethiology (%) 76 LVEF (%) NYHA lll-lv (%) 80% % Logistic EuroSCORE (%) Coronary Artery Disease (%) 49% Days Post Index Procedurde (N=117) Changes in MR severity from baseline to after MitraClip implantation *GRASP = Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation Grasso et. et. al. al. One- One- and and twelve-month twelve-month safety safety and efficacy and efficacy outcomes outcomes of patients of undergoing patients undergoing edge-to-edge edge-to-edge percutaneous mitral percutaneous valve repair mitral (from valve the GRASP repair Registry). (from the Am GRASP J Cardiol. Registry). Am J Cardiol May 2013 May

55 Severe LV Dysfunction Refractory to Medical Therapy 51 patients with MR 3+: adverse MV morphology and/or severe LV dysfunction in 69% Procedural success achieved in 96% of patients Reduction in MR, although moderate in most patients, was acceptable given high surgical risk and corresponding clinical benefits Mitral Regurgitation Grade Reduction P= Significant NYHA Functional Class Improvements p< % MR 2+ at discharge I II III I II 67% NYHA Class I or II at discharge IV III As assessed by sites (N=49) (N=49) Mitral valve repair using the MitraClip system was shown to be feasible in patients at high surgical risk primarily determined by an adverse mitral valve morphology and/or severe LV dysfunction. Franzen O, Baldus S, Rudolph V, et al. Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: Emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. 2010; 31:

56 Severe HF, Despite Optimal Medical Therapy Retrospective analysis of 50 patients with LVEF 25%, MR >3+ and NYHA III or IV Significant clinical improvements reported at 6 months Cumulative survival at 6 months in NYHA-lll and NYHA-IV patients was 81.2% and 64.2% respectively Baseline characteristics 50 patients Age 70±11 EuroSCORE (%) 34±21 FMR etiology (%) 100 Ischemic Cardiomyopathy (%) 56 NYHA lll-lv (%) 100 LVEF (%) 19±5 Patients with end-stage heart failure and marked LV dysfunction can be treated by the MitraClip as successful therapy promotes clinical benefits at 6 months. Franzen O, et al. MitraClip(R) therapy in patients with end-stage systolic heart failure. Eur J Heart Fail 2011; 13(5):

57 PERMIT-CARE CRT Non-responders Prospective survey of 51 CRT non-responders, with FMR and NYHA III or IV Implant rate of 95% At discharge 73% patients had an improved functional NYHA class; the proportion of NYHA I &II increased over time LVEF significantly increased at 6 and 12 months Reverse LV remodeling occurred even in the presence of MR 2+ - reduced LV volume in 70% of patients Auricchio A et al; PERMIT-CARE Investigators. Correction of Mitral Regurgitation in Nonresponders to Cardiac Resynchronization Therapy by MitraClip Improves Symptoms and Promotes Reverse Remodeling. J Am Coll Cardiol Nov 15;58(21):

58 SECONDARY (FUNCTIONAL) MR THE COAPT TRIAL Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk

59 RESHAPE-HF2 TRIAL RANDOMISED INVESTIGATION OF THE MITRACLIP DEVICE IN HEART FAILURE: 2 ND TRIAL IN PATIENTS WITH CLINICALLY SIGNIFICANT FUNCTIONAL MITRAL REGURGITATION

60 Objective To study the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in symptomatic patients with chronic heart failure in NYHA Functional Class II, III or IV. 1 Objective and Background

61 Primary Endpoint Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death 1 Objective and Background

62 Secondary Endpoints Mitral Regurgitation (MR) severity reduction to mild or mildto-moderate at 12 and 24 months; Change in 6 Minute Walk Test (6MWT) distance at 6, 12 and 24 months; Rate of recurrent CV hospitalizations and CV death; Change in Quality of Life (QoL) overall score at 12 months; Change in NYHA Functional Class at 6, 12 and 24 months; Change in Patient-reported Global Assessment (PGA) of well-being at 6, 12 and 24 months. 1 Objective and Background

63 Key Inclusion Criteria (1) Age between 18 years and 90 years old. Clinically significant FMR (moderate-to-severe or severe) as defined by European Association of Echocardiography, within 90 days prior to randomization. Optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks prior to randomization. (Note: Significant dose changes are considered to be present, if a new drug class was started or when the dose of an exisiting drug class was increase >100%) 3 Pre-Randomization

64 Key Inclusion Criteria (2) NYHA Class II, III or IV, despite optimal standard of care therapy, within 30 days preceding randomization. Hospitalization for heart failure (acute care admission or emergency room visit) within 12 months preceding randomization OR BNP 300 pg/ml or NT-proBNP 1000 pg/ml within 90 days preceding randomization. (Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate) 3 Pre-Randomization

65 Key Inclusion Criteria (3) LVEF of 15% to 35%, if in NYHA Class II OR LVEF of 15% to 45%, if in NYHA Class III or IV, as determined by TTE, contrast ventriculography, gated blood pool scanor, cardiac magnetic resonance within 90 days prior to randomization. Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness. 3 Pre-Randomization

66 TWO CENTERS IN GREECE ΤΜΗΜΑ ΔΙΑΔΕΡΜΙΚΩΝ ΒΑΛΒΙΔΙΚΩΝ ΠΑΘΗΣΕΩΝ- ΥΓΕΙΑ ΑΘΗΝΑ ΚΛΙΝΙΚΗ ΑΓΙΟΣ ΛΟΥΚΑΣ-ΘΕΣΣΑΛΟΝΙΚΗ ΞΕΚΙΝΗΣΑΜΕ..

67 Mitraclip: St. Luke s experience We started 2 years ago (9/2013) 15 patients (12 male- 1 female) Age: years old Successful procedure: 14 patients Inability to deliver clip: 1 patient In Hospital Mortality: 0% 30 day mortality: 0% Total mortality: 0%

68 Patients per year Number of procedures per year Σειρά 1

69 MR GRADE 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Baseline days

70 NYHA class 100% 90% 80% IV III 70% 60% IV II NYHA IV 50% NYHA III 40% NYHA II 30% NYHA I 20% I 10% 0% III Baseline 30 days

71 6-min walk (meters) Baseline months

72 Device time 04:30 04:00 03:30 03:00 02:30 02:00 01:30 01:00 Average device time 03:0 0 02:3 0 02:0 0 01:3 0 Average device time 00:30 00: St Luke Hospital- 01:0 0 00:3 0 00:0 0 -EMEA high volume centers- Tota l Linear (Total) 2014 Abbott. All rights reserved. Internal Use only. p11/15

73 CASE 1 71 Y. OLD PATIENT CABG 10 YEARS AGO PATENT GRAFTS RECENT PULMONARY OEDEMA

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83 CASE 3 68 Y OLD MALE CABG 2 TIMES SEVERE COPD SYMPTOMS OF LEFT AND RIGHT HEART FAILURE

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90 Conclusions Mitral valve surgery may still have a (limited) role in FMR (ischemic). During CABG and absence of high risk features for recurrence of MR. MV REPLACEMENT may be an alternative if High risk of MR recurrence is expected BUT do not expect significant LV remodelling Mitraclip therapy is SAFE, effective and durable and may be used in the absence of revascularisation as a stand alone procedure BUT still the mortality data are not available (so wait for COAPT and RESHAPE-HF 2)