The Sentinel Dual Filter Device Design Features & EU Clinical Trial Results Nicolas M. Van Mieghem, MD, PhD, FESC Director of Interventional Cardiology Thoraxcenter, Erasmus MC Rotterdam
Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Grant/Research Support Consulting Fees/Honoraria Company Abbott Vascular, Medtronic, Boston Scientific; Claret Medical Claret Medical All TVT 2016 faculty disclosures are listed online and on the app.
Recent Trials and any stroke @ 30 days % Patients with Strke at 30 Days 8% 7% 6% 5% 4% 3% 2% 4.0% 3.9% 5.5% 6.8% 7.0% 3.3% 4.1% 2.5% 4.9% 4.3% 1.5% 2.7% 5.5% 1% 0% CoreValve Extreme Risk N=489 Extreme Risk LOTUS RESPOND N=500 Portico CE Study N=103 LOTUS REPRISE II + Ext N=249 Direct Flow DISCOVER N=75 Extreme/High Risk 0.0% Evolut R CE Study N=60 Evolut R IDE N= 241* SAPIEN PARTNER IIB N=276 SAPIEN TVT HR N=12182 CoreValve High Risk N=390 High Risk SAPIEN XT PARTNER IIB N=284 SAPIEN 3 SAPIEN 3 PARTNER IIPARTNER II HR S3i N=583 N=1078 SAPIEN XT PARTNER IIA N=1011 Intermediate Risk * Disabling Stroke Meredith, et al., presented at PCR London Valves 2014; Adams, et al., N Engl J Med 2014; 370: 1790-8; Leon, et. al. presented at ACC 2013; Lefevre et al., J Am Coll Cardiol 2016; 1:; Popma, et al., J Am Coll Cardiol 2014; 63: 1972-81; Linke, et. al. presented at London Valves 2015; Van Mieghem, et al., presented at EuroPCR 2015; Kodali, et al., presented at ACC 2015; Holmes, et al., JAMA 2015; 313: 1019-28; Meredith, et al., presented at ACC 2015, 1 Williams, et. al. presented at ACC 2016; Thourani, et al, presented at ACC 2016
Next Gen TAVR & Major Stroke Meta-analysis of ~20 non-randomized, mostly FIM, valve-company sponsored studies 2.4% major stroke at 30-days Athappan, et al. A systematic review on the safety of second-generation transcatheter aortic valves. EuroIntervention 2016; 11:1034-1043
Stroke Timing post TAVI 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 D. Tchetche et al. JACC CV Int. 2014;7:1138-1145 Multi-center cohort of 1,061 TAVI patients CVE most frequently occur day 0-1 >50% are major strokes >95% of strokes are ischemic Nombela-Franco et al., Circulation 2012;126:3041-53
Sentinel EU Trials CLEAN TAVI SENTINEL - H MISTRAL - C
CLEAN TAVI A. Linke, MD, PhD - Presented @ TCT 2014
CLEAN TAVI Endpoints A. Linke, MD, PhD - Presented @ TCT 2014
MRI Findings Total Lesion Volume Lesion Number A. Linke, MD, PhD - Presented @ TCT 2014
MISTRAL-C Design: multi-center double-blind randomized trial enrolling patients with symptomatic severe aortic stenosis and 1:1 randomization to TAVI with or without Sentinel EPD Aim: does Sentinel EPD affect new brain lesions & neurocognitive performance after TAVI Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
MISTRAL-C From January 2013 August 2015 65 patients were enrolled TAVI Procedure Day 0 TAVI 1 Day Randomization Sentinel vs. Control Transcranial Doppler Pathology TAVI + 5 Days Consent for TAVI & MISTRAL-C study 3T Neuro-MRi Neurocognitive testing 3T Neuro-MRi Neurocognitive testing Clinical neurological exam Clinical neurological exam Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
Brain MRI n=37 Lesions @ baseline MRI: 11% Median number of days to MRI: 5 (IQR 5-5) No FU MRI: 43% Perspective Other 14% Dead / Unstable 18% Reason for MRI dropout Delirium 11% Patient refused 21% Pacemaker 36% N=28 Dropout in other studies DEFLECT-I 24% DEFLECT-II 21% DEFLECT-III 41% PROTAVI-C 33% CLEAN TAVI @D2 7% CLEAN TAVI @D30 22% Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
Lesion Volume Overall 600 Lesion volume in mm3 500 400 300 200 100 95 P=0,171 197 0 Sentinel (n=22) No Sentinel (n=15) 600 Anterior 600 Posterior Lesion volume in mm3 500 400 300 200 100 0 0 Sentinel (n=22) P=0,057 76 No Sentinel (n=15) Lesion volume in mm3 500 400 300 200 100 0 56 Sentinel (n=22) P=0,571 76 No Sentinel (n=15) Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
Number o lesions 16 14 12 10 8 6 4 Number of Lesions Overall P=0,274 2 0 Anterior 2 2 Sentinel (n=22) No Sentinel (n=15) Posterior Number of lesions (median) 16 14 12 10 8 6 4 2 0 0 Sentinel (n=22) P=0,065 1 No Sentinel (n=15) Number of lesions (median) 16 14 12 10 8 6 4 2 0 P=0,586 1 1 Sentinel (n=22) No Sentinel (n=15) Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
100% No new lesions Overall Proportion of patients (%) 50% 0% p=0,312 27% 13% Sentinel (n=22) No Sentinel (n=15) Anterior Posterior Proportion of patients (%) 100% 50% 0% p=0,065 50% 20% Sentinel (n=22) No Sentinel (n=15) Proportion of patients (%) 100% 50% 0% p=0,850 36% 33% Sentinel (n=22) No Sentinel (n=15) Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
Deterioration in neurocognitive status ITT 100% 90% Claret (n=28) No Claret (22) Proportion of patients (%) 80% 70% 60% 50% 40% 30% 20% 10% 0% p=0,017 p=0,248 p=0,105 p=0,272 27% 26% 25% 13% 8% 4% 5% 0% MMSE worsening MoCA worsening CES-D worsening NIHSS worsening Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
Histopathology of Retrieved Filters (n=31) Van Mieghem NM et al. EuroIntervention 2016 In Press July Issue
SENTINEL H Study Prevalence and etiopathology of thromboembolic debris during transcatheter interventional aortic valve replacement C.J. Jensen 1, A. Wolf 1, T. Schmitz 1, T. Schmidt 2, C. Frerker 2, T. Thielsen 2, U. Schäfer 3, N. Schofer 3, F. Deuschl 3, P. Frambach 4, D. Wagner 4, C. Kaiser 5, R. Jeger 5, E.J. Parker 6, M. Romero 7, E. Ladich 7, R. Virmani 7, C.K. Naber 1 1 Contilia heart and vascular center, department of cardiology and angiology, Elisabeth hospital, Essen, Germany; 2 AK St. Georg, Hamburg, Germany; 3 UKE Hamburg, Germany; 4 INCCI LUXEMBURG, Luxemburg; 5 Universitätsspital BASEL, Switzerland; 6 Haukeland clinic Bergen, Norway; 7 CV Path Institute, Inc., Gaithersburg, USA Jensen CJ et al. Presented @ EuroPCR 2016
SENTINEL-H Prospective, multi-center, international all-comer study TAVI + Sentinel CPS Germany Luxemburg Suisse Norway Multiple TAVR designs SAPIEN S3 88 Sapien XT 8 Edwards Centera 1 BSC Lotus 37 Direct Flow 42 STJ Portico 10 Medtronic CV 9 Medtronic EvolutR 16 Symetis 1 Jena Valve 1 Histopathology by independent core lab CVPath (Gaithersburg, USA) Jensen CJ et al. Presented @ EuroPCR 2016
Van Mieghem NM et al. Circulation 2013;176:2194-2201 Van Mieghem NM et al. JACC CV Int. 2015;8:718-24
Results N = 217 patients, mean age 83.7 years 98% transfemoral TAVI Procedural success (defined as both filters successfully deployed and retrieved) was 211/217 = 97% Remaining 6 patients all had the BCC Filter deployed In 98% of cases, there was no or insignificant interference with the TAVR device There were no cases of a dislocation of the Sentinel Device by the TAVI delivery catheter The median time to place Sentinel: 4 minutes Average contrast media to place Sentinel: 15±5 ml Jensen CJ et al. Presented @ EuroPCR 2016
Debris Presence
Histopathology Proximal & Distal Filter
Debris per THV Design Overall BE SE ME BE (96) = Sapien 3 (88) + Sapien XT (8) SE (38) = EvolutR (16) + CoreValve Classic (9) + Portico (10) + Symetis (1) + Jenavalve (1) + Centera (1) ME (79) = Lotus (37) + Direct Flow (42) *The error bars represent 95% confidence intervals (+/- 1.96 x SE)
In Conclusion Filter based cerebral protection with Sentinel during TAVR will capture debris en route to the brain in virtually all patients Debris etiology is diverse (thrombus and tissue) Small randomized trials hint towards reductions in new brain lesions by MRI neurocognitive preservation less brain insults SENTINEL US IDE Trial results are eagerly awaited