The Development of Interventional Cardiology for the Treatment of Degenerative Aortic Valve Stenosis: a 20 Years Odyssey

Transcription

1 The Development of Interventional Cardiology for the Treatment of Degenerative Aortic Valve Stenosis: a 20 Years Odyssey Andreas Gruntzig lecture, ESC 2010, Stockholm, 29 Aug 2010 Alain Cribier, MD University of Rouen, France

2 Speaker s name: Alain CRIBIER, MD I have the following potential conflicts of interest: Consulting Edwards Lifesciences

3 Department of Cardiology Rouen University Hospital 72 beds 12 ICU beds 3 cath-labs (B. Letac: Former Head of Dpt) Fellowship at Beth Israel, Boston A. Cribier: Current Head of Dpt (Fellowship at Cedars Sinaï, LA) Hélène Eltchaninoff: Head of Interv. Cardiol Unit Christophe Tron: Fabrice Bauer: Frederic Anselme: (fellowship at Cleveland Clinic) Head of I.C.U, Interv. Cardiologist (fellowship at Saint-Louis, Miss) Head of Echocardiography Unit (Fellowship at Cleveland Clinic) Head of Electrophysiology Unit (Fellowship at Beth Israel, Boston)

4 Rouen: from 1985 Development of innovative technologies and F.I.M. in the field of valvular disease «Don t undertake a project unless it is manifestly important and nearly impossible» Edwin Land «One doesn t discover new lands without consenting to lose sight of the shore for a very long time» 1985 Balloon Aortic Valvuloplasty 1999 Mitral Commissurotome André Gide 2002 Transcatheter Heart Valve

5 Degenerative aortic valve stenosis is the most common acquired valvular disease in adults 26% of the population above the age of 65 years has mild, moderate or severe aortic stenosis 2% are symptomatic and should require treatment It is estimated that within 15 years, the number of AS patients will nearly double!

6 Valvular Aortic Stenosis In Adults (Average Course) In an elderly population (> 80-yrs) the prognosis is even worst: 30% of deaths within 3 months in patients on the waiting list for TAVI Surgical intervention should be performed promptly once even minor symptoms occur Ross J Jr, Braunwald E. Aortic stenosis. Circulation The prognosis of AS not significantly changed since the 60 s

7 Surgical valve replacement has been the standard of care for decades In standard risk patients, mortality after AVR is low (2-5%) Mortality and morbidity increase in patients with associated risk factors: age, depressed ejection fraction, combined CABG, co-morbidity After successful valve replacement, patient s lifespan returns to that of general population

8 Severe Symptomatic Aortic Stenosis Percent of patients undergoing intervention No AVR AVR Cardiac reasons: Decrease Sx after treatment «end-stage» cardiac disease Extra-cardiac reasons: Age, comorbidities Patient refusal Bouma 1999 Iung 2004 EuroHeart Survey, Pts in 92 centers, 25 countries Pellika 2005 No operation in 31.8% Charlson 2006 Bach 2006 Spokane prelim. Vannan Pending

9 Steps towards Transcatheter Aortic Valve Replacement in Rouen Patients older than 75-y, with or without comorbidities were declined for AVR Age per-se was a contra-indication to AVR

10 In the early 80 s, in Rouen as everywhere else, most symptomatic AS patients >75-yrs were declined for surgery and left untreated! Need for an alternative treatment Percent of patients operated on Proportion de pts opérés de Rao in au Rouen CHU de between Rouen entre and 1985 selon classe d'âge Dilating the aortic valve with a 18% 1985 according to age balloon catheter was investigated 2% by us 8% 72% < >80 as a possible way of palliating the symptoms of these «non operable» patients

11 ROUEN: Sept 1985 F.I.M. BALLOON VALVULOPLASTY 72 y-old female, AS + CAD Severely symptomatic: Daily syncopal attacks NYHA grade 3 Angina Declined by surgeons 20mm Balloon Uneventful procedure Total relief of symptoms Return to normal life Death at 2 years (AMI) THE LANCET, Jan 11, 1986

12 Specific balloon catheter for BAV developed with Mansfield / Boston Scientific The «Cribier-Letac Balloon Catheter»

13 Enthusiastic response of the interventional cardiologists worldwide Rouen, 1986: First International meeting on BAV with Live Demonstrations

14 BAV: how does it work? Post-23mm balloon 23 mm balloon Fracturing calcified nodules Splitting fused commissures Stretching the aortic valve annulus Requires high balloon pressures E.O.A. should be increased by 100%

15 Balloon Aortic Valvuloplasty in the 90th Initial enthusiasm of the medical (less surgical!) community: the clinical need was there! Thousands of cases performed wordwide Impressive number of registries, and publications Clear cut immediate hemodynamic and symptomatic improvement generally observed Important limitations: - Technical issues (vast disparity in skill, techniques and end-points); Complications EARLY VALVULAR RESTENOSIS (80% at 1 y)

16 BAV: death and revival Due to its limitations, more particularly the short lasting results, BAV was progressively abandoned in the majority of centers Since 2000, BAV is rising again from its ashes due to the aging population and the onset of transcatheter valve implantation

17 In 2010, BAV has become a simpler and safer percutaneous technique Balloon inflation/deflation Rapid ventricular pacing Balloon size: 20, 23, 25mm Smaller size sheaths (10F) Preclose technique Local anesthesia / sedation 3 days of hospitalization

18 Balloon Aortic Valvuloplasty From 1986 to 2008 Complications (Severe) Mansfield Registry ( ) n=492 CHU Rouen ( ) n=321 Death during procedure 4,9% 2,1% Stroke (with sequelea) 2.2% 1.9% Pericardial Tamponade 2,2% 0% Grade 3-4 AI 1,1% 1,5% Complete Heart block 1.2% 0,9% Vascular complication 11% 0.9% Total 22.6% 7.3% (AHA 2009)

19 Current indications for BAV ESC Guidelines Class II b evidence C: «Bridge» to surgery in hemodynamically unstable patients - Class II b evidence C: Symptomatic pts who require urgent noncardiac surgery - Occasionnally as a palliative measure in individual pts with contraindication for surgery and/or severe comorbidities Additional Indications in As part of the TAVI procedure -As a screening tool - to assess the myocardial contractility reserve in pts with low EF/low gradient before AVR/TAVI - to test the impact of afterload relief on symptoms, and even on overall patient status

20 Impact of Balloon Aortic Valvuloplasty Direct In non-operable patients: Transitory improvement of hemodynamical and clinical status (can be repeated in case of restenosis) Quality of life Decreases the number of hospitalizations for CHF No effect on mortality Indirect Pushed forward the frontiers of interventional cardiology Called the cardiologist s attention to a major cardiac disease of the elderly Forced the surgeons to demonstrate their skill and efficacy in operating on older and sicker patients

21 The concept of Percutaneous Expandale Heart Valves Prosthesis - Several concepts launched since 1965 for the treatment of valvular diseases (mainly AI) - Personal challenging concept: A possible way to improve the BAV results and solve the problem of post-bav valvular restenosis in degenerative aortic stenosis

22 First dreams of implantable prosthetic heart valves 1965: Davis catheter mounted valve 1971: Monopoulos (catheter-mounted aortic valve) 1976: Phillips (balloon-mounted valve) 1992: Matsubara (balloon-mounted valve) No human application

23 Henning Rud Andersen Experimental valve - Porcine valve in a self-made stent - First implantation in pig : First publication EHJ Patent issued: 1995 No further development

24 Philipp Bonhoeffer Pulmonary valve -Bovine jugular vein valve within a balloon expandable stent 2000: First human implantation of a transcatheter valve in a RV to pulmonary artery conduit

25 Usual Stepsobservation: towards transcatheter Whatever the severity aortic of valvular valve calcification, replacement a balloon in Rouen can be fully inflated within the aortic valve! A stent with high radial force might be expanded within the aortic valve to keep it open and A valvular prevent valvular structure restenosis. should be added to the stent The diseased native valve would be used as a support to anchor the stent

26 Post-mortem study: Validation of the concept of intra-valvular stent Respect of adjoining structures Coronary ostia Post-BAV: Stented-Valve Implantation Heigth: 14mm 1994 Post-BAV: 23mm balloon Post-Stent 23mm Palmaz Stent IV Septum Mitral Valve Post-Stent Longitudinal cut A. Cribier More than 2kg of traction force to dislodge the stent

27 Steps to transcatheter valve replacement in Rouen 1985: First balloon valvuloplasty for calcific AS 1994: Post-mortem studies on cadavers : Looking for a company interested in the project of stented valve Comments of experts «Interesting but not a priority» «Major / impossible technical and anatomical issues» «Will never be approved by FDA» «Surgery covers the needs. No indication «Most stupid project ever heard»

28 1999 Foundation of «Percutaneous Valve Technologies» Laboratory tests >100 animal implantation (sheep) Percutaneous Valve Technologies Aortic Heart Valve 6 mths follow-up obtained in the systemic circulation Polyurethane valve PVT s founders Stan Rowe Alain Cribier Stan Rabinovich Martin Leon Assaf Bash Engineer 6 mos follow-up Aran, Caesarea, Israel 23mm max diameter Bovine pericardium / Stainless steel stent

29 Rouen, April 16, 2002 F.I.M THV implantation 57 y/o male Cardiogenic Shock LVEF: 12% Multiple comorbidities No arterial access Trans-septal approach

30 Rouen, April 16, 2002: F.I.M THV implantation Trans-septal approach Circulation, 2002;106: min post-implantation 8 days post-implantation

31 compassionate cases Equine Pericardial Valve Trans-septal approach (success 80%) 7 cases retrograde (3 failures) -23mm valve size too small in a number of pts Pilot (post-tavi study paravalvular I-REVIVE AR grade 3 RECAST in 25%) 4 pts (11 months) - Feasibility of TAVI confirmed - Several technical and clinical limitations of the trans-septal approach 16 patients (11 months) Single size 23mm 20 patients (5 months)

32 New valves, New delivery 2004 systems New PVT techniques for TAVI Edwards Transfemoral retrograde Cribier-Edwards 23mm J. Webb Edwards SAPIEN 23mm, 26mm F. Mohr T. Walter M. Mack Retroflex Transapical Equine pericardium Bovine pericardium Anti-Ca Tfx Ascendra

33 Transcatheter AVR (TAVI) Edwards Clinical Pathways PTCA TAVI Compassionate Low risk patients Cases 8 years CE Mark FIM, Proof of concept Small series Safety/efficacy Larger series+ F.U. From 2007 Post-market registries High Risk Patients 5 Pivotal / FDA approval? Randomized study USA

34 THV development A long road: 20 Years from concept to real world CoreValve Since Edwards Lifesciences TF & TA Feasibility Studies (antegrade) F.I.M. THV implantation «Percutaneous Valve Technology» (prototypes) Post-mortem studies of intra-valvular stenting F.I.M. Balloon Aortic Valvuloplasty FDA Approval? CE mark commercialization International TF and TA Feasibility Studies > valves Animal implantations(sheep) implanted worldwide Ew PARTNER US Pivotal Post market registries

35 2009 New opinion of experts «When a distinguished scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong» 1972 A.C. Clarke

36 Edwards Transcatheter Aortic Valve Adjudicated Clinical Investigations First-in-Man Procedural success in humans I-REVIVE (TF) RECAST Eu (TF) TRAVERCE (TA) Feasibility Demonstrate reasonable safety & effectiveness REVIVE II (TF) REVIVAL II (TF) PARTNER EU (TF & TA) Post-Market Evaluate transition to commercial use Long-term follow-up SOURCE Registry TF & TA (EU) Randomized Studyl Effectiveness vs. control (AVR & medical therapy) PARTNER-US IDE study TF & TA vs AVR or Med Tt > 200 pts >330 pts 1038 pts 1240 pts All patients with high surgical risks or contra-indications to conventional valve replacement

37 Procedural success rate EDWARDS studies COREVALVE (worldwide) FIM irevive/recast Vancouver REVIVAL II REVIVE II PARTNER EU TF SOURCE

38 30-day mortality and complications Edwards 1472 pts PARTNER SOURCE WEBB FRANCE N=130 N=1038 N=138 N=166 CoreValve Worldwide* 2300 pts, Mortality TF 8.1% 6.3% 8% 8.4% 9.2% TA 18.8% 10.3% 18.2% 16.9% - Stroke 3% 2.5% 4.2% 3.6% 3.7% PM 3% 7% 5.4% 5.4% 29.9% Maj. Vasc. 10% 7% 6.6% 6% 7.8% * Eberhard Grube, Worldwide TF TAVI Experience, TCT 2010

39 Freedom from Death All Cause Mortality Transfemoral and Edwards: Early Studies % Partner EU Revival Revive Recast I-Revive Months past Procedure

40 1 year survival Edwards & CoreValve: Recent Registries Edwards (SOURCE registry, 1038 pts): TF: 81.1% TA: 72.1% CoreValve (Worldwide*, 1476 pts): TF: 78% * Eberhard Grube, Worldwide TF TAVI Experience, TCT 2010

41 No change in EOA and gradient over time 42 Edwards pooled monitored studies

42 YES YES Randomization TF THV vs PARTNER U.S. Pivotal Trial Cohort A Femoral access evaluation Y/N Surg. AVR High risk patients Surgical assessment Randomization TA THV August 2009 vs NO Surg. AVR NO Cohort B Inclusions completed Randomization TF THV Femoral access evaluation Y/N 24 centers, 1040 pts YES First results expected: Cohort B: Oct 2010 vs Not in Study Medical management NO NON INFERIORITY of TAVI SUPERIORITY of TAVI

43 TAVI What is known in 2010? Early prosthetic valve performance similar to surgical valve replacement Current indications Decreased mortality and complications with the Severe and symptomatic AS combination of more experience, optimal training and proctoring, improved High surgical devices risk and or non procedural operable techniques, better patient patients screening and imaging modalities Patient frailty as assessed by the Marked improvement in LV function and symptoms at good clinical sense of a multidisciplinary team of physicians mid-term Still some device related complications (vascular events, complete AV block)

44 A new era of partnership for patients screening, performance of the procedure and assessment of the results Radiologist Anesthesiologist The Heart Team Echocardiographist Nurses Technicians Cardiac surgeon Geriatrician Cardiologist

45 TAVI Where are we in 2010? LCA RCA Septum Edwards-Sapien Balloon-Expandable Valve (Transfemoral or transapical) CoreValve Self-Expandable Valve (Transfemoral or subclavian)

46 PERSPECTIVES Where do we go? Improved THV and delivery systems Upcoming registries & controled trials in specific subsets of pts Assessment of Valve + Platform durability THV and procedural cost / reimbursement Expanded clinical indications?

47 From PVT to Edwards balloon expandable Valves Edwards Valves : PVT Valve Percutaneous Heart Valve Cribier Edwards Edwards Sapien Edwards Sapien XT Bovine pericardium Stainl. steel frame 23mm Equine pericardium Stainl. steel frame 23mm Treated bovine peric Stainl. steel frame. 23 and 26mm Treated Next bovine to comeperic. Cobalt 20mm Chrom. / 29mm frame 23 and 26mm 24F 24F 22F, 24F TF sheath sizes 18F, 19F

48 Edwards Sapien XT Valve (since 2009 in EU) Strong frame radial force Circumferential stent opening Leaflets matching technology Enhance leaflets design Anticalcification Thermafix process Lower crimp profile Percutaneous approach Local anesthesia Preclose technique (ProStar) PREVAIL Trial ungoing in EU Pivotal PARTNER 2 US pending

49 Self expandable Medtronic CoreValve Generation 1 25F Generation 2 21F Generation 3 18F Generation 4 18F From ? Pure percutaneous technique Preclosing with ProStar Local anesthesia / sedation Porcine pericardium valve Nitinol stent Improved device?

50 New TAVI Technologies Direct Flow Sadra AorTx GOALS Jena Valve Recoverable / repositionable HLT Lower profile systems ABPS PercValve No perivalvular leaks EndoTech More accurate positioning Percutaneous access and closure Ventor Embracer Symetis

51 Expanded Clinical indications to Medium or normal Risk AS? Lower EuroSCORE is associated with better results Data on long term durability after TAVI are missing. Most registries report on < 2-yrs F.U. Valve 1 yr + Survival platform in durability the SOURCE should Registry be > 10 yrs for standard risk patients Log EuroSCORE > < 20 NeedSurvival for rigourous59.2% trial methodology 73.5% 78.4% with clear end-points definition, 100% in database, and randomized trials vs AVR in most-important subsets (standard risk patients)

52 Expanded Clinical indications to Medium or normal Risk AS? Additional requirements Improve precision and consistency of THV positioning (adjunctive imaging) Reduce para-valvular leak (THV sizing, technique, and other device adjustments) Reduce peri-procedural strokes (e.g. embolic protection devices) Reduce vascular complications (case selection and lower profile - < 18 Fr delivery systems) Decrease pacemaker requirements Protect coronary access for further PTCA

53 TAVI for Bioprosthetic Valve Failure Endless Possibilities! Trans-apical Approach Trans-apical MVR (valve-in-valve + TAVI on AS) Webb JG, et al. Circulation 2010;121:151-6 Aortic (n=10), mitral (n=7), pulmonary (n=6), and tricuspid (n=1) Courtesy of Dr. John Webb Edwards-Sapien

54 Conclusions After a 20 years odyssey, the dream has come true The feasibility of TAVI has been fully demonstrated TAVI is already increasingly accepted as a valuable alternative to AVR in high surgical risk AS patients Careful patients screening, excellent training and proctoring and an optimal partnership in the field of a Heart Team are the key of success The devices and procedures are steadily improving and an extension of indications can be anticipated

55 Conclusions TAVI is here to stay In 2011, with technological advancements the number of centers and procedures should continue to expand in high surgical risk patients In 2012, depending on the PARTNER-US pivotal trial driven FDA s decision, TAVI might explode in USA and worldwide in this subset of high risk patients Within 5 years, expansion of indications to other subsets of patients such as less severely ill /younger patients can be expected. Less invasive procedures (stent like) might be used in > 70% of the cases

56 Conclusions TAVI is here to stay Within 10 years, it is likely that most patients with degenerative aortic stenosis will be treated using less invasive techniques than open-chest AVR. If you want a happy ending, that depends of course, on where you stop! Orson Welles ( )

57 THV: My Dream Team in Rouen H. Eltchaninoff C. Tron F. Bauer A. Troniou Interv. Cardiologists Echocardiographist Study Coordinator

58 Our Cardiac Surgeons Pr Jean-Paul Bessou Dr Pierre-Yves Litzler

59 Whatever the future development of this technology, we will have with my group the immense satisfaction of having contributed to a significant progress in interventional cardiology for the benefit of a number of patient up to then untreated