Leading the Way Investing in Clinical Evidence

Study Principal Investigator Location # Patients Trial Type Procedure Data
First in Man Prof. Christoph Naber 3 centers in Brazil & Germany 40 Registry TAVI
(CoreValve & Sapien)
EuroIntervention
March 2012
MISTRAL-I Dr. Nicolas van Mieghem Rotterdam, Netherlands 40 Registry TAVI
(CoreValve & Sapien)
Circulation
October 2013
CLEAN-TAVI Prof. Axel Linke Leipzig University, Germany 100 Randomized TAVI (CoreValve) JAMA
August 2016
MISTRAL-C Dr. Nicolas van Mieghem 4 centers in Netherlands 74 Randomized TAVI
(Sapien 3)
EuroIntervention July 2016
SENTINEL IDE Drs Susheel Kodali, Samir Kapadia, & Prof. Axel Linke 17 centers in USA & 2 in Germany 363 Randomized TAVI
(Sapien XT, Sapien 3, CoreValve, EvolutR)
JACC
January 2017
SENTINEL-H Prof. Christoph Naber 10 centers in Europe 220 Registry TAVR
(All-comers)
Presented at
EuroPCR 2016
TEVAR – Essen Prof. R Alexander Jánosi West German Heart & Vascular Center, Essen Germany 5 Pilot Study TEVAR Presented at
LINC 2016
TEVAR – London Dr. Mo Hamady & Dr. Gagandeep Grover Imperial College, London England 8 Pilot Study TEVAR Presented at
ISET 2016
LAAO – Hamburg Prof. Felix Meincke AK St Georg, Hamburg Germany 5 Pilot Study LAAO Presented at
TCT 2015
V-in-V Dr. Tobias Schmidt & Dr. Christian Frerker AK St Georg, Hamburg Germany 15 Registry Aortic and Mitral
V-in-V
BMJ
May 2016
MitraClip Dr Christian Frerker et al. AK St Georg, Hamburg Germany 14 Registry Mitral-Clip JACC Intv
January 2016
Sentinel-Ulm Dr. Jochen Wöhrle University of ULM, Ulm Germany 560 Prospective All-Comers TAVI
(all commerc. avail)
JACC Intv ePrint Sept 2017

Transcatheter Aortic Valve Implantation (TAVI)

Recent studies have shown that almost 1 in 10 TAVI patients show overt signs of ischemic brain injury as a result of TAVI procedure.1 The Sentinel Cerebral Protection System (CPS) has been shown to reduce strokes by 63% in the first 72 hours after TAVI, when most strokes occur2 and is corroborated by a reduction in TAVI stroke, and stroke or mortality by 70%.3 In clinical studies, Sentinel CPS removed visible debris headed towards the brain in 99% of TAVI cases,1 regardless of replacement valve used and with virtually no added risk.

Simple and Safe

The Sentinel has been found safe and compatible to use with all commercially-available TAVI valves.1 It is simple to use, and has demonstrated 99% deployment success in a median deployment time of four minutes.1

Sentinel CPS is securely positioned away from the aortic arch, avoiding extended contact with potentially calcified tissue, minimizing interference with TAVI catheters, and enabling physicians to put all their focus on the TAVI procedure itself.

Thoracic Endovascular Aortic Repair (TEVAR)


Image source: Grover, G. “Cerebral Embolic Protection in Thoracic Aortic Stent Grafting”, ISET 2016

Currently, thoracic endovascular aortic repair (TEVAR) is a procedure that is becoming more popular as a minimally-invasive alternative to surgery among older patients in certain countries. In TEVAR, bulky devices are inserted and placed near the atherosclerotic aortic arch that can liberate debris towards the brain circulation. Because of this, TEVAR patients are at a particularly high risk of brain injury, which may result in cognitive deficit after treatment, such as loss of memory or a reduction in executive function.

Data is emerging that there is a significant cerebral embolization rate and stroke rate associated with TEVAR. One UK study showed a silent cerebral infarction rate with TEVAR of 68%,4 while a neuroimaging study from Germany reported a silent cerebral infarction rate of 63% in patients who underwent TEVAR.5 The same UK study found an overt stroke rate of 13% with TEVAR,1 while another study showed the risk of clinically apparent, periprocedural stroke after TEVAR ranging from 1.9-5.8%.5

The result of this cerebral damage is worrisome. One study of TEVAR patients showed that 88% of patients experienced neurocognitive decline post-procedure.4

Clinically evident strokes and silent cerebral infarctions can be caused by embolic debris, released during certain procedures, that travel through the great vessels to the brain. The first study to examine embolic debris released during TEVAR showed that debris was captured by the Sentinel Cerebral Protection System (CPS) in 100% of procedures. The most prevalent types of debris were pieces of arterial wall, along with acute thrombus and foreign material consistent with hydrogel coatings common in several devices used during the TEVAR procedure.

Despite all of this evidence, embolic protection has not been routinely used in TEVAR to date. However, the clinical community is beginning to take action. Spurred by the landmark CLEAN-TAVI and MISTRAL-C trials, a feasibility study of the Sentinel CPS used during TEVAR incorporated pre- and post-procedural MRI and neurocognitive testing of patients. Results showed that when the Sentinel CPS was used, half the patients were free of lesions, the remaining half had very small-volume lesions, and 0% of patients exhibited any cognitive deficit. The learning curve for the physicians using the Sentinel CPS was also shown to be rapid, with deployment and retrieval of the device taking 16 minutes in the first case, and only two minutes by the fourth case.

Investigators concluded that the use of the Sentinel CPS in TEVAR is feasible and appears to not only reduce silent cerebral infarcts, but to also exhibit a trend towards protecting patients from neurocognitive decline. Based on this early data, they recommended that the device be tested in a randomized clinical trial.

Pilot Studies

  • Gagandeep Grover, Rudarakanchana N, Perera A, Gibbs R; Mo Hamady, Imperial College London, Thoracic Aortic Stent Grafting
  • R. Alexander Jánosi, FESC West-German Heart and Vascular Center Essen University of Duisburg-Essen, Germany, Cerebral Protection against Embolization during Thoracic EndoVascular Aortic Repair

Left Atrial Appendage Occlusion (LAAO)


Image Source: Meinke, F. “Rationale of Cerebral Protection Device”, TCT 2015.

Periprocedural stroke is a rare, but potentially devastating, event complicating left atrial appendage (LAAO) occlusion procedures. The PROTECT-AF study showed a clinically-evident stroke rate of 0.9%,6 while the PREVAIL study showed a rate of 0.7%.7 However, the rate of silent cerebral infarction is likely significantly higher, as is the case in many other minimally invasive cardiovascular procedures, such as TAVR and TEVAR. Early work is being done to explore the use of the Sentinel Cerebral Protection System (CPS) in LAAO procedures.

In an early study of five consecutive patients undergoing routine LAAO, the Sentinel CPS was used to protect patients’ brains. Even though thrombus in the atrial appendage was ruled out prior to the procedure by TEE, embolic debris was found in 100% of the procedures post-procedure, with the most common type of debris found being acute and organizing thrombus.

In the study, the Sentinel CPS showed 100% procedural success, with no periprocedural complications and no neurological abnormalities present after the procedure.

The study investigators agreed that a larger study was warranted to investigate the long-term effects of silent cerebral infarct and the impact of Sentinel CPS use during LAAO on mechanistic MRI and clinical outcomes.Investigators concluded that the use of the Sentinel CPS in TEVAR is feasible and appears to not only reduce silent cerebral infarcts, but to also exhibit a trend towards protecting patients from neurocognitive decline. Based on this early data, they recommended that the device be tested in a randomized clinical trial.

Pilot Studies

  • Felix Meincke, Tobias Spangenberg, Felix Kreidel, Elena Ladich, Oscar Sanchez, Karl-Heinz Kuck, Alexander Ghanem Asklepios Klinik St. Georg, Cardiology Department, Hamburg, Germany, Rationale of Cerebral Protection

Transcatheter Mitral Valve Repair and Implantation


Example of debris captured in one of the Claret filters.18 Data on File.

Mitral valve disease is the second most common manifestation of valvular heart disease in adults.8 A minimally-invasive approach to challenging mitral valve surgery has been developed in the form of the MitraClip, a transcatheter technology.

The incidence of stroke or TIA after a MitraClip procedure has been shown to be up to 2.6%.9 However, the clinically evident stroke rate does not tell the whole story.

The Mitral Valve Academic Research Consortium (MVARC) has stated that transcatheter mitral valve therapies may predispose patients to the formation of thrombus.10 Acute thrombus can develop at the transseptal sheath, as well as the guiding catheter and the clip delivery system due to the stasis phenomenon predisposing them to thrombogenic behavior. Maleki et al.11 reported up to 9% thrombus formation on regular transseptal sheaths despite adequate anti-coagulation and irrigation.

In addition, Feld et al.12 have shown that the Brockenbrough transseptal needle used during the MitraClip procedure generates potentially embolic particles when advanced through the dilator and transseptal sheath. Incidences of 0.2% to 2.6% have been reported.9, 13, 14 Blazek et al.15 showed that the MitraClip procedure without cerebral protection resulted in new ischemic cerebral lesions on diffusion-weighted magnetic resonance imaging (MRI) in 86% of patients. While most of the MRI-detected cerebral lesions remained clinically silent, other studies have shown that clinically silent cerebral lesions were associated with neurocognitive impairment and the development of dementia.16, 17

In an initial experience with 14 high surgical risk patients at two German centers using the Sentinel Cerebral Protection System (CPS) during MitraClip implantation, the Sentinel CPS demonstrated 100% procedural success. No transient ischemic attacks, strokes, or deaths occurred peri-procedurally or during a median follow-up interval of 8.4 months in patients protected with the Sentinel CPS.

In the study, embolic debris was identified in all 14 patients. The most common debris types were acute thrombus and small fragments of non-polarizable basophilic foreign material that were morphologically consistent with hydrogel, a material coating several devices used during the MitraClip procedure, including the transseptal sheath for transseptal puncture and the guide catheter for the MitraClip system.

No evidence was found of foreign material arising from the Sentinel CPS or its coating in this study; in fact, even after investigators manually scraped the surface of the Sentinel filters, no foreign material was observed under high-magnification microscopy.

The study’s investigators recommended that further studies are warranted to assess the impact of cerebral protection on the incidence of cerebrovascular events after MitraClip therapy.

Pilot Studies

  • Christian Frerker, MD, Michael Schlüter, PHD, Oscar D. Sanchez, MD, Sebastian Reith, MD, Maria E. Romero, MD, Elena Ladich, MD, Jörg Schröder, MD, Tobias Schmidt, MD, Felix Kreidel, MD, Michael Joner, MD, Renu Virmani, MD, Karl-Heinz Kuck, MD, Cerebral Protection During MitraClip Implantation

Valve-in- Valve Procedures


Debris captured in Sentinel CPS

Bioprosthetic heart valves typically last 10-15 years, and when they fail, they require replacement. The emergence of transcatheter heart valve procedures has enabled “valve-in-valve” procedures, where a transcatheter aortic valve is implanted within the existing implanted valve.

The Sentinel Cerebral Protection System (CPS) has been initially studied19 in 21 patients undergoing transcatheter aortic valve-in- valve procedures, where histopathological analysis of captured debris was performed on a sub-set of nine patients. The histology showed that debris was captured and removed in 100% of the procedures. Acute thrombus was the most common type of debris, found in 89% of procedures, while calcification was found in 56% of procedures.

The investigators concluded that the company’s Cerebral Protection System can protect the brain from embolic debris with a 0% stroke rate for valve-in- valve procedures.

References

TAVI

  1. Kapadia S, Kodali S, Makkar R, et al. Protection against cerebral embolism during transcatheter aortic valve replacement. JACC. 2017;69(4): 367-377.
  2. Data from SENTINEL Trial, included in device’s Instructions for Use (IFU). To view IFU, click here.
  3. To view Ulm registry results in JACC CVI, click here.

TEVAR

  1. Grover G, Rudarakanchana N, Perera A, Gibbs R, Hamady M. Cerebral Embolic Protection in Thoracic Aortic Stent Grafting, as presented at ISET 2016.
  2. Kalhert et al, Ann Thorac Surg 2014

LAAO

  1. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Clinical Trial and the Continued Access Registry Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) Safety of Percutaneous Left Atrial Appendage Closure: Results From the Watchman Left Atrial Appendage Closure Device. Circulation. 2011;123:417-424.
  2. Holmes DR, Kar S, Price MJ et al. Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy: The PREVAIL Trial. J Am Coll Cardiol. 2014;64:1–12.

Mitral Valve

  1. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005-11
  2. Glower DD, Kar S, Trento A, et al. Percutaneous mitral valve repair for mitral regurgitation in highrisk patients: results of the EVEREST II study. J Am Coll Cardiol 2014;64:172–81.
  3. Stone GW, Adams DH, Abraham WT, et al. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: A consensus document from the Mitral Valve Academic Research Consortium. J Am Coll Cardiol 2015;66:308–21.
  4. Maleki K, Mohammadi R, Hart D, Cotiga D, Farhat N, Steinberg JS. Intracardiac ultrasound detection of thrombus on transseptal sheath: incidence, treatment, and prevention. J Cardiovasc Electrophysiol 2005;16:561–5.
  5. Feld GK, Tiongson J, Oshodi G. Particle formation and risk of embolization during transseptal catheterization: comparison of standard transseptal needles and a new radiofrequency trans- septal needle. J Interv Card Electrophysiol 2011; 30:31–6.
  6. Feldman T, Foster E, Glower DD, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364:1395–406.
  7. Nickenig G, Estevez-Loureiro R, Franzen O, et al. Percutaneous mitral valve edge-to- edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011–2012 Pilot European Sentinel Registry. J Am Coll Cardiol 2014;64:875–84.
  8. Blazek S, Lurz P, Mangner N, et al. Incidence, characteristics and functional implications of cerebral embolic lesions after the MitraClip procedure. EuroIntervention 2015;10:1195–203.
  9. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215–22.
  10. Ghanem A, Müller A, Nähle CP, et al. Risk and fate of cerebral embolism after transfemoral aortic valve implantation: a prospective pilot study with diffusion-weighted magnetic resonance imaging. J Am Coll Cardiol 2010;55:1427–32.
  11. Frerker, et al. Cerebral Protection During MitraClip Implantation, J Am Coll Cardiol Intv. 2016;9(2):171-179.

Valve-in- Valve Procedure

  1. Schmidt, T, et al. Cerebral protection device for transcatheter valve-in- valve procedures — the ALSTER data. TCT 2015.
The Sentinel CPS has received the CE Mark and is commercially available in Europe.