Trans Aortic Valve Replacement Update: 2016 & Beyond

Transcription

1 Trans Aortic Valve Replacement Update: 2016 & Beyond Rajiv Jauhar, MD, FACC, FSCAI Chief of Cardiology Director of Cardiac Cath Labs Northshore University Hospital, Manhasset 1

2 DISCLOSURE POLICY Northwell Health adheres to the ACCME s New Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by Northwell for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations.

3 None. FACULTY DISCLOSURES

4 Aortic Stenosis Pathology Normal Degenerative Calcified Bicuspid Rheumatic

5 Aortic Stenosis: Changing Epidemiology Normal Degenerative Calcified Bicuspid X Rheumatic

6 Severe Symptomatic Patients Require Urgent Attention Surgical intervention should be performed promptly once even. minor symptoms occur Chart: Ross J Jr,, Brunwald,E. Ciculation 1968;38 (suppl. 1) C.M. Otto Heart 2000

7 At least 30-40% Of Cardiologists AS Patients Go Untreated Severe Symptomatic Aortic Stenosis Percent of Cardiology Patients Treated No AVR AVR Bouma 1999 Iung* 2004 Pellikka 2005 Charlson 2006 Bach Spokane (prelim) Vannan (Pub. Pending)

8 Percent Mortality in Standard Rx Perspectives 5 Year Survival: Metastatic Cancer % 28% 23% 23% 5% 5% 12% 12% 30% 28% 3% * Breast Breast Lung Lung Colorectal Colorectal Prostate Prostate Ovarian Ovarian Severe Severe Inoperable Inoperable AS * Constant Hazard Model 3% * AS Courtesy of Murat Tuzcu, Interventional PI, CCF

9 Northwell Health TAVR Highlights Over 900 cases have been done at 4 sites Active sites are NSUH, SSH, and LHH SIUH soon to launch Flexibility of implant teams 24 actively implanting CTS and IC across the system Broad experience in multiple platforms and access options Experience proctoring cases in the US and abroad

10 All-Cause Mortality (%) All-Cause Mortality Building the Evidence for TAVR 100% 80% 60% 40% 20% 0% PARTNER Cohort B Standard Rx (n = 179) TAVR (n = 179) 50.8% 30.7% 93.6% 71.8% % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% TAVR SAVR PARTNER Cohort A HR [95% CI] = 1.03 [0.85, 1.24] p (log rank) = % 69.3% PARTNER trial established that TAVR improves survival in extreme risk patients with AS and is an alternative to surgery in high risk patients Key points to remember Enrollment started in <100 TAVRs performed in US and only 6 sites had experience prior to trial First generation device used (24F sheath, no nosecone on delivery catheter and original SAPIEN device used)

11 Surgery is Scary

12 Is TAVR Superior to Surgery? CoreValve US Pivotal High Risk Cohort Surgical Transcatheter 19.1% 14.2% 4.5% P = 0.04 for superiority 3.3%

13 Is TAVR Superior to Surgery? The evidence builds Smith, ACC 2016

14 Is TAVR Superior to Surgery? The evidence is clear Thourani, ACC 2016

15 TAVR Current Landscape and Limitations Stroke Paravalvular leak Pacemaker Minimalist Approach

16 All Strokes at 30 Days 20% PARTNER I Trial and PARTNER II Trial 15% Neurologist Evaluations (Pre- and Post) 10% 7.3% 5% 4.4% 4.1% 4.3% 1.4% 0% PARTNER I B (TF) PARTNER I A (Overall) PARTNER II B (TF) PARTNER II B (TF) PARTNER II High-Risk & Inop (TF) SAPIEN Valve SAPIEN XT Valve SAPIEN 3 Valve

17 PARTNER II Sapien 3 Trial Unadjusted Clinical Outcomes Events (%) 30 Days 1 Year TAVR Surgery TAVR Surgery Death All-cause Cardiovascular Neurological Events Disabling Stroke All Stroke All-cause Death and Disabling Stroke

18 CoreValve High Risk Trial

19 TAVI stroke is mostly periprocedural Timing of Cerebrovascular Events (CVE) in FRANCE-2 Registry (n=3,191) CVE most frequently occur day 0-1 >50% are major strokes Median time to major stroke is 1 day Multi-center cohort of 1,061 TAVI patients CVE most frequently occur day 0-1 >50% are major strokes >95% of strokes are ischemic Tchétché et al. J Am Coll Cardiol Intv 2014; 7(10) Nombela-Franco et al., Circulation 2012;126:

20 Rodes- Cabau 2011 Ghanem 2010 Arnold 2010 Kahlert 2010 Astarci 2011 DEFLECT III control Bijuklic 2015 CLEAN-TAVI control arm PROTAVI-C NeuroTAVR New cerebral lesions are found in the vast majority of patients following TAVI Ghanem, et. al, JACC % of TAVR patients affected Most patients have multiple infarcts Silent infarcts associated with 1,2,3 2-4-fold risk of future stroke >3-fold risk of mortality >2-fold risk of dementia Cognitive decline Dementia 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1. Sacco et al., Stroke Vermeer et al., Stroke Vermeer et al., New Engl J Med 2009 % of TAVR patients with new cerebral lesions on DW-MRI

21 CLEAN-TAVI shows the promise of protection The Problem Control group (no filters) The Promise Test group (filters) Representative slices from each of the orthogonal planes showing new lesions at 2d from each arm of CLEAN-TAVI randomized trial of cerebral embolic protection in TAVI using Claret dual-filter Cerebral Protection Systems Claret Montage Cerebral Protection System significantly reduces new cerebral lesion number and volume at 2 & 7 days, as measured by DW-MRI CLEAN-TAVI (manuscript in review) CAUTION: Investigational device. Limited to investigational use by United States law.

22 CLEAN-TAVI shows Claret filters significantly reduce lesion number and volume Lesion Number per Patient Total Lesion Volume per Patient Claret Montage Cerebral Protection System significantly reduces new cerebral lesion number and volume at 7 days, as measured by DW-MRI

23 TAVR Current Landscape and Limitations Stroke Paravalvular leak Pacemaker Minimalist Approach

24 All-Cause Mortality (%) Severity of PVR at 30 Days and All-cause Mortality at 2 Years - PARTNER 2A Moderate/Severe Mild None/Trace Overall Log-Rank p = Mod/Sev (reference = None/Trace) p (Log-Rank) < % Mild (reference = None/Trace) p (Log-Rank) = % 13.5% Months from Procedure

25 Moderate / Severe PVL At 30 Days Edwards SAPIEN Valves 50% PARTNER I Trial and PARTNER II Trial 40% 30% 24.2% 20% 10% 12.0% 13.2% 17.3% 2.5% 0% PARTNER I B (TF) PARTNER I A (Overall) PARTNER II B (TF) PARTNER II B (TF) PARTNER II High-Risk & Inop (TF) SAPIEN Valve SAPIEN XT Valve SAPIEN 3 Valve

26 Design Changes Enable Low Delivery Profile 2 1 Outer Sealing Skirt Designed to minimize paravalvular (PV) leak 3 2 Frame Design Enhanced frame geometry for low delivery profile Cobalt-chromium 1 3 Bovine Pericardial Tissue Outer sealing skirt virtually eliminates moderate-severe PV leak*

27 % Patients with Mod/Severe PVL 1-Month Moderate/Severe PVL TAVI Clinical Trials Month Mod/Severe PVL CoreValve ADVANCE 1 CoreValve High Risk 2 Evolut R 3 Portico SAPIEN 3 SAPIEN 3 CE Study 4 EU 5 PARTNER II S Direct Flow DISCOVER LOTUS REPRISE II & EXT 8 LOTUS RESPOND* 9 N=639 N=356 N=58 N=75 N=116 N=1504 N=74 N=177 N=465 *7d/Discharge; 30d angiography not mandated per protocol; Results from different studies are not directly comparable. Information provided for educational purpose only. 1 Linke A, PCR Adams D, N Engl J Med 2014; 370: Meredith I, ACC Manoharan, et al. TCT Webb J, JACC 2014;64: Kodali S, ACC Schofer, JACC Meredith I, London Valves Falk, PCR LV Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

28 % Patients with Mod/Severe PVL 12-Month Moderate/Severe PVL TAVI Clinical Trials Month Mod/Severe PVL SAPIEN XT PARTNER II 1 SAPIEN PARTNER II 1 SAPIEN PARTNER B 2 CoreValve ADVANCE 3 SAPIEN PARTNER A 4 CoreValve High Risk 5 CoreValve Ext Risk DirectFlow DISCOVER 7 LOTUS REPRISE II/II EXT 8 STS Score: N: Results from different studies are not directly comparable. Information provided for educational purpose only. 1 Leon M, ACC Leon, NEJM Linke A, PCR Smith, NEJM Adams D, N Engl J Med Popma J, JACC Lefevre, et al. JACC Ian Meredith, PCR LV Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

29 TAVR Current Landscape and Limitations Stroke Paravalvular leak Pacemaker Minimalist Approach

30 * Leon et al, NEJM 2016 Siontis et al. JACC 2014 Relationship of the Aortic Valve Complex and the Cardiac Conduction System Ferreira et al. PACE 2010;33: Conduction disturbances are not limited to TAVR (PPM incidence after SAVR was 6.9% in PIIA*) PPM incidence after TAVR is device specific (ESV 6%, MCV 28% ) Changes to device design and procedural technique (higher implantation, less oversizing, no BAV) may reduce PPM rate going forward

31 TAVR Current Landscape and Limitations Stroke Paravalvular leak Pacemaker Minimalist Approach

32 Medical and Marketing Necessity Lessons learned and not learned from stent history Lower risk patients Cost savings Complications Better equipment Comfort level

33 What s Next? Efficiency and Economics: Minimalist TF TAVR Sept 2007 Simplify procedure May 2012 No General Anesthesia, No TEE Maintain superior outcomes, short and long term Decrease resource utilization and cost Courtesy Emory

34 Some Data with EW Sapien

35 Mid-Term Mortality with Minimalist Approach

36 Cost Saving with Minimalist Approach $45,485 ± 14,397 $55,377±22,587

37 Who Is a Minimalist Candidate? Emory Approach Eligibility confirmed by the Heart Team Straightforward Vascular Access? NO STANDARD TAVR Weight < 100kg? Coronary arteries acceptable height? Any barriers to emergent intubation if required? Chronic pain? Mental status appropriate? YES MINIMALIST TAVR Conscious sedation

38 Complementary Therapies TAVR Heart Team Approach 38

39 Analysis Outcomes of Minimalist from TVT registry Courtesy Jay Giri, UPENN Moderate Sedation General Anesthesia Odds Ratio P-value 30-Day Mortality 2.96% 4.01% 0.72 P< Day Death/Stroke 4.80% 6.36% 0.69 P<0.001

40 TAVR in 2016 New performance benchmarks for high-risk AS patients 30 days) All-cause mortality < 3% Major (disabling) strokes < 3% Major vascular complications < 5% Major bleeding complications <5% Mod-severe para-valvular regurgitation < 5%

41 What is the impact of this data? Evolving Risk Thresholds

42 Futile Role of the Heart Team Assessing Risk Operable AS patients Surgery (AVR) ~65% Low Risk irresponsible, reckless TAVR or AVR ~25% Intermed Risk TAVR in 2015 equipoise Current TAVR TAVR Clinical Use ~10% High Risk OK TAVR Extr Risk* preferred Too Sick No

43 Lotus Case Example 23mm Lotus Valve retrieval and exchange for 25mm Lotus Valve 23mm 25mm Borderline 23mm had moderate PVL despite repositioning Valve was exchanged for a 25mm, final result no PVL Videos courtesy of Ted Feldman, MD. Case study not necessarily representative of all cases. Results in other cases may vary. Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

44 Ongoing Clinical Challenges in TAVR Patient selection Identifying Cohort C Severe MR Minimizing vascular complications Minimizing stroke Eliminating PVL

45 Research Opportunities EPS Post TAVR arrhythmias Pre and Post TAVR PPM predictors Timing of AICD consideration post TAVR ECHO Post TAVR LVEF recovery CT Anatomic predictors of PVL post TAVR MRI Quantification of PVL Anticoagulation regimens and post TAVR bleeding Challenging case submissions

46 TAVI 2016 Final Thoughts Clinical need for TAVI in high risk AS patients is greater than anticipated TAVI is well beyond proof of concept or feasibility already being integrated into AS clinical Rx paradigms in many parts of the world Clinical outcomes have improved and stabilized in experienced hands (<5% mortality at 30 days), with late mortality reflecting underlying co-morbidities Stroke and vascular complications remain a concern albeit less

47 The Essence of Our Being!!!

48 YOU CAN ALWAYS CONTACT me at Department of Cardiology,

49 Questions