Mitral Valve Disease James Hermiller, MD, FACC, FSCAI St Vincent Heart Center Indianapolis, IN
Disclosures Affiliation/Financial Relationship Consulting Fees/Honoraria Speaker Bureau Company Abbott, BSC, Medtronic, Edwards and St Jude Medicines Company, Astra-Zeneca
Outline Introduction Transcatheter Repair MitraClip Annular Approaches TMVR Summary/Conclusions
Complexity Mitral Valve Aortic Valve Complex Simple
Euro Heart Survey: Surgery for Functional Mitral Regurgitation Not an Option Isolated MR (n=877) No Severe MR (n=331) Severe MR (n=546) No Symptoms (n=144) Symptoms (n=396) Mirabel et al, European Heart J 2007;28:1358-1365 No Intervention (n=193) 49% Intervention (n=203) 51%
Outline Introduction Transcatheter Repair MitraClip Annular Approaches TMVR Summary/Conclusions
Edge-to-Edge Technique Ottavio Alfieri Maisano. JACC 2011;58:2174-82.
In the Beginning: Lost
In the Beginning: Confused Steerable Sleeve Guiding Catheter Delivery Catheter MitraClip
In the Beginning: Off Target
Ahah!!!!
Transseptal 30 0 MEDIAL 60 0 FOSSA P3 A3 A2 P2 POSTERIOR AO A1 P1 30 0 ANTERIOR LAA LATERAL
Essential: 3D Imaging 3D TEE
Lining up the Clip: Trajectory Aligning the Clip so the DC shaft is perpendicular to the plane of the mitral valve
Grasping Leaflets Systematic Confirmation of Grasp Success Slow Pull-Back Leaflets Fall In
Confirming: Leaflet Grasp Wait Look
MitraClip
MitraClip Surgical candidates- 5 year EVEREST II randomized trial High risk global experience Improved symptoms, procedural safety, short stays Decreased heart failure hospitalizations Expanded anatomic substrates High risk FMR US COAPT Trial Randomized MitraClip vs GDMT ± CRT
CONCLUSIONS Although percutaneous repair was less effective at reducing mitral regurgitation than conventional surgery, the procedure was associated with superior safety and similar improvements in clinical outcomes.
Percent of patients 5 year Follow-Up Mitral Regurgitation Grade EVEREST II RCT All Treated Patients (N=258) 100 80 60 40 20 0 3+ 2+ Residual MR with MitraClip 1+ Baseline MitraClip 5 Years 2+ 1+ 0 Surgery 5 Years 4+ 3+ 2+ 1+ 0
Mean SLAD diast (cm) Mean SLAD diast (cm) 5 p<0.05 Stability of Mitral Annular Dimensions DMR MitraClip (N=130) p=0.18 Diastolic SLAD 5 p=0.07 FMR MitraClip (N=48) p=0.20 4 4.0 3.9 4.0 3.9 4 3.7 3.6 3.7 3.8 3 3 2 2 1 1 0 BL 1 Year BL 5 Years N=92 N=72 N = survivors with paired data; p-values for descriptive purposes only 0 BL 1 Year BL 5 Years N=32 N=18
Long-Term MitraClip Device Safety EVEREST II RCT Through 1 Year # (%) of patients 1 Year to 5 Years # (%) of patients Single Leaflet Device Attachment (SLDA) 10 (6.3%) 0 (0.0%) MV stenosis 1 (0.6%) 0 (0.0%) Device Embolization 0 (0.0%) 0 (0.0%) Based on N=158 who were implanted with 1 or 2 MitraClip devices
Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery Group Surgery MitraClip 97.1% 98.7% 1 year 91.4% 93.7% 5 years 6-Month Landmark Analysis EVEREST II RCT
Endovascular Valve Edge-to-Edge REpair STudy Subgroup Analyses for the Primary End Point at 12 Months Feldman T et al. N Engl J Med 2011;364:1395-1406
The percutaneous mitral valve device significantly reduced MR, improved clinical symptoms, and decreased LV dimensions at 12months in this high-surgical-risk cohort. Glower, et al. J Am Coll Cardiol 2014;64:172 81
The EVEREST II High Surgical Risk Cohort n=351 Age 76 ± 11 Predicted Surgical Mortality Risk, (%) 18.2±8.4 NYHA Functional Class III or IV 85% Atrial Fibrillation 69% Mitral Regurgitation Grade 3+ 86% Left Ventricular Ejection Fraction (%) 47.5 ± 14.2 Functional MR 70% 30 day Mortality 6.8% Home ± home health care 91.7 % MR Grade I-II at 2 years 87% Decrease LV EDV/ESV at 1 year 17.9 / 8.1 ml Event Free Survival 1 year 77.1%
Mean Volume (ml) Left Ventricular Volumes Left Ventricular End Diastolic Volume Left Ventricular End Systolic Volume 180 160 Mean = -17.9 ml 97.5% UCB = -13.5 ml p<0.0001 90 85 Mean = -8.1 ml 97.5% UCB = -4.8 ml p<0.0001 140 80 120 100 160.5 142.6 75 70 87.0 78.9 80 65 60 60 Baseline 1 Year Baseline 1 Year Paired data (N=203) Paired data (N=202)
HF Hospitalization Rate Per Patient Year Hospitalizations for Heart Failure 1.0 0.8 48% reduction p<0.0001 0.6 0.4 0.79 0.2 0.0 1 Year Prior to MitraClip 0.41 N=351 N=338 1 Year Post Discharge All treated
Lim SD et al. J Am Coll Cardiol 2014;64:182 92 TMVR in prohibitive surgical risk patients is associated with safety and good clinical outcomes, including decreases in rehospitalization, functional improvements, and favorable ventricular remodeling, at 1 year.
Baseline Demographics and Comorbidities Characteristic Age (mean ± SD) Prohibitive Risk DMR N = 127 82 ± 9 years Patients over 75 years of age 84% Male Gender 55% Coronary Artery Disease 73% Prior Myocardial Infarction 24% Previous Cardiovascular Surgery 48% Atrial Fibrillation History 71% Prior Stroke 10% Diabetes 30% Moderate to Severe Renal Disease 28% Chronic Obstructive Pulmonary Disease 32% STS Mortality Risk (mean ± SD) [v2.73, replacement] 13.2 ± 7.3% SF-36 QoL Physical Component Score (mean ± SD) 32.0 ± 8.7 SF-36 QoL Mental Component Score (mean ± SD) 46.1 ± 12.5
Post-Procedural and Discharge Results Post-Procedural and Discharge Results Post-Procedural (mean ± SD) ICU/CCU duration Length of hospital stay Prohibitive Risk DMR N = 127 1.4 ± 1.8 days 2.9 ± 3.1 days Discharge MR, (%) MR 2+ at Discharge 82% MR 1+ at Discharge 54% Discharged home, (%) 87% MitraClip implant success 95.3%;
MitraClip in Prohibitive-risk DMR Pts 141 pts from EVEREST studies. Mean age 82 years, 87% NYHA III/IV, mean STS score 13.2%. MitraClip implant success 95.3%; hospital stay 2.9 ± 3.1 days. 30-Day Adverse Events: Death* 6.3% Myocardial infarction* 0.8% Non-elective CV surgery for adverse events* 0.8% Stroke* 2.4% New onset of permanent AF* 0% Renal failure 1.6% Ventilation >48 hours* 3.1% GI complication requiring surgery* 0.8 Major vascular complications 5.5% Major bleeding ( 2U or surgery for rebleeding) 12.6% Non-cerebral thromboembolism 1.6% Heart block/arrhythmia requiring perm pacemaker 0% Atrial septal defect 1.6% Mitral stenosis 0% Lim SD et al. J Am Coll Cardiol 2014;64:182 92 *CEC adjudicated.
Patients (%) MitraClip in Prohibitive-risk DMR Pts MR Grade Through 1 Year Patients With Data Available at Follow-Up (Completers Analysis) 100 2+ 80 1+ 1+ 60 40 3+ 2+ 2+ MR 2+ in 83% of surviving pts at 1 year 20 0 4+ Baseline N=124 3+ 4+ Discharge N=123 3+ 1 Year N=84 Lim SD et al. J Am Coll Cardiol 2014;64:182 92
MitraClip in Prohibitive-risk DMR Pts 141 pts from EVEREST studies. Mean age 82 years, 87% NYHA III/IV, mean STS score 13.2%. LV Remodeling, Functional Class and Rehospitilization for CHF
MitraClip Systematic Review MitraClip vs Surgery 30 Day Outcomes High Risk Patients 70 60 50 59 MitraClip Surgery n=3198 n=3265 40 36.3 30 26 20 16.2 15 10 0 3.3 1.1 4.5 4.2 1.7 3 7 Death Stroke Bleeding Prolonged Vent ICU Days Hospital Days 21 studies PhilipF et al, Cathet Cardiovasc Intervent 84:581, 2014
FDA MitraClip Approval October 24 th, 2013 The MitraClip is approved for treatment of patients with 3+-4+ primary (degenerative) MR who are at prohibitive risk for mitral valve surgery and are likely to benefit from MR reduction
History 87 year old man with a history of moderate MR and MVP Stable when he developed flash pulmonary edema 3 months prior to presentation Echo revealed 4+ MR with a flail leaflet; EF 60%; Flow reversal in Pas Refractory CHF Turned down for OHS Offered Hospice He declined
Pre-TEE
Pre TEE
Pre TEE Intercommisural
Pre-Imaging 3D
Clip To Valve Trajectory Orientation Location
2 nd Clip
Confirm Grasp, R/O MS, and Release 2 nd Clip
Follow Up Home following day Uneventful hospital course 6 months Echo 1+ mild MR Functional class 1 Back golfing Walking 3 miles
Therapy for MR Degenerative Functional Low Surgical Risk Surgical Mitral Repair? High Surgical Risk Commercial MitraClip COAPT
Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk ~430 patients enrolled at up to 75 US sites Significant FMR 3+ core lab; EF<50%; CHF hospitalization or BNP>300 High risk for mitral valve surgery- Local Heart Team Specific valve anatomic criteria Randomize 1:1 MitraClip Control group Standard of care Safety: Composite death, stroke, worsening renal function, LVAD implant, heart transplant at 12 months Effectiveness: Recurrent heart failure hospitalizations Protocol conditionally approved by FDA July 26, 2012
COAPT Inclusion Symptomatic functional MR ( 3+) Cardiomyopathy ischemic or non-ischemic LVEF 20% and 50% HF hospitalization 12 months and/or a corrected BNP 300 pg/ml or NT-proBNP 1500 pg/ml 90 days TTE on optimal therapy 30 days after: any change in GDMT revascularization and/or implant of CRT Version 5.1 November 11, 2013
Case History 79 year old man s/p prior CABG with a 6 month history of refractory CHF and severe MR, despite maximum medical therapy. No LBBB. Several comorbidities including Creatinine or 2.0 mg/dl, atrial fibrillation, DM, prior CVA (complete recovery) Echo revealed 4+ MR caused by functional valve disease and EF of 25%; turned down by two surgeons
Baseline Echo: FMR
MitraClip Placement
Follow Up Single Clip
Follow Up Trace MR after one clip Device time 43 min Home the following day No rehospitalizations 2 Year follow up EF 30-35% with mild 1+ MR; Functional Class II
Follow Up Echo
Outline Introduction Transcatheter Repair MitraClip Annular Approaches TMVR Summary/Conclusions
Percutaneous Mitral Repair Devices Already gone PTMA Monarc Mobuis leaflet repair Recor RF annular remodeling Coapsys Still developing Leaflet repair CS annuloplasty Direct annuloplasty Cerclage Mitral spacer Midle Peak Chordal replacement Valve replacement
Coronary Sinus- Indirect Annuloplasty CARILLON Mitral Contour System
TITAN Trial CARILLON Mitral ystem for FunContour Sctional MR 40% reduction in MR Reverse remodeling Functional improvement Implanted Non-Implanted n=36 n=17 Eur J Heart Fail. 2012 Aug;14(8):931-8
Update from European CARDIOBAND Trial 35 patients results 2/3/2015 Septo Lateral Dimension 24/33 Patients with MR Mild at 6 Months FU Mean Age 72 (56-81) STS Repair 7 (1-34)
DIRECT ANNULOPLASTY Mitralign Procedure Steps Wire Delivery Pledget Delivery Plication & Lock
Direct Annuloplasty - Transventricular Approach Mitralign System Wire Placement Pledget Delivery
CE Mark Study 30-Day Performance: Core Lab Adjudicated Ventricular Changes Baseline (n) 30 Day (n) 30 Day Change Paired (n) 30 Day Change P-Value LVIDd (cm) 6.35 (44) 6.10 (38) -0.21 (36) 0.004 LVIDs (cm) 5.37 (44) 5.15 (38) -0.21 (35) 0.079 LVEDv (ml) 186.4 (44) 169.0 (38) -20.1 (31) < 0.001 LVESv (ml) 122.8 (44) 110.5 (38) -13.1 (31) 0.008 Annular Changes Baseline (n) 30 Day (n) 30 Day Paired Change (n) P-Value A-P Dia. (cm) 3.58 (44) 3.27 (38) -0.39 (31) < 0.001 S-L Dia. (cm) 3.55 (44) 3.34 (38) -0.26 (33) < 0.001 N=64 Investigational Device Only: Not Available in the EU or US
.J Am Coll Cardiol. 2015;65:1190 5
Suture bicuspidization of the tricuspid valve vs ring annuloplasty for functional tricuspid regurgitation Midterm results of 237 consecutive patients Kay bicuspidization procedure Suture bicuspidization is performed by placement of a 2-0 pledget-supported mattress suture from the antero-posterior to the posteroseptal commissures along the posterior annulus. J Thorac Cardiovasc Surg 2007;133:117-126
Schofer et al. J Am Coll Cardiol. 2015;65:1190 5
JAmCollCardiol2015;65:1190 5 First Human Report on Percutaneous Repair for Functional Tricuspid Regurgitation with the Mitralign System Schofer et al. J Am Coll Cardiol. 2015;65:1190 5
Outline Introduction Transcatheter Repair MitraClip Annular Approaches TMVR Summary/Conclusions
Mitral Replacement Technologies CardiaAQ Neovasc TIARA Tendyne Edwards FORTIS Endovalve M-Valve Medtronic Valtech Lutter MitrAssist Caisson MitraSeal Twelve HighLife Others.
Mitral Replacement FIRSTS IN HUMAN CardiaAQ 2012 Tendyne implants 2013 Temp Neovasc Tiara January 2014 Edwards FORTIS February 2014
Transcatheter mitral valve implantation (TMVI) using the Edwards FORTIS device Bapat V: EuroIntervention 2014;10:U120-U128
Outline Introduction Transcatheter Repair MitraClip Annular Approaches TMVR Summary/Conclusions
Conclusion Unmet need in high risk patients with MR MitraClip safe and effective Less MR reduction than surgical repair Approved in US for high surgical-risk patients with degenerative MR >80% have <2+ MR, short hospital duration, fewer repeat hospitalizations, favorable LV remodeling and functional/qol outcomes Functional MR enroll in COAPT Annular approaches Early TMVR even earlier - Infancy
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