The therapeutic landscape continues to evolve. While stroke rates have been reduced in certain procedures with the advent of cerebral protection – such as carotid artery stenting – the issue is just beginning to come to the forefront of other procedures, such as aortic valve replacement.
Clinical evidence is showing that cerebral embolic debris is generated in the vast majority of patients undergoing TAVR1, which can range up to one centimeter in size and has been captured during the use of a variety of different transcatheter valves and interventional approaches.2,3
This cerebral embolic debris causes new cerebral lesions, which are found in the vast majority of patients who have undergone TAVR.9 In fact, ischemic cerebral damage has been shown to occur in more than 84% of TAVR patients.4
Ischemic cerebral lesions may lead to clinically apparent strokes or they may cause cerebral infarcts with no overt “visible” neurological dysfunction, which are often referred to as “silent” cerebral infarcts5. These “silent” infarcts are associated with adverse neurological and cognitive consequences, including impaired mobility, physical decline, depression, cognitive dysfunction, and dementia.5 Results from the SENTINEL trial showed that the size and number of new ischemic cerebral infarcts correlate to cognitive outcomes and with the protection of Sentinel CPS, incremental ischemic infarcts to the brain were reduced by 42%.6
These “silent” infarcts are only visible using neurological imaging – such as 3 Tesla DW-MRI – which is reviewed and assessed by a team of specialized radiologists and neurologists. As such, silent infarcts have not been recognized as significant by the cardiovascular surgeons or cardiologists until very recently. In fact, one of the key findings of the recent SENTINEL trial showed that including a neurologist in the process of assessing patients after the TAVR procedure is critical to fully appreciate the nuanced presentation of clinical stroke. It also showed that the stroke rate, when assessed proactively by a neurologist, is 9.1% in those patients who were not protected with the Sentinel CPS.6
A meta-analysis that examined a number of prospective TAVR studies using neurological assessments showed that new ischemic brain lesions were detected in 77.5% of unprotected TAVR patients. This meta-analysis also assessed the overall use of cerebral protection systems in TAVR and found there is a significant reduction in total lesion volume with the use of filter embolic protections systems, including the Sentinel CPS, versus deflection embolic protection systems.7
While the Sentinel CPS is designed to capture and remove cerebral debris during TAVR to minimize the risk of stroke, another possible technique being investigated to prevent the release of cerebral debris is the use of new anticoagulation therapies during TAVR procedures. The BRAVO-MRI study investigated new pharmacologic approaches during TAVR and found these new anticoagulation regimes were not sufficient for preventing TAVR procedural stroke.8
In light of this evidence, cerebral protection is expected to become a standard of care to better protect the neurocognitive and neurological well-being of patients.
- Van Mieghem et al. Circulation, 2015
- Van Mieghem et al. Circulation, 2013
- Shafer et al. DGK 2014
- Daneault et al. JACC, 2011
- Sacco, et al. Stroke, 2013
- Kodali, et al. TCT, 2016
- Pagnesi et al. International Journal of Cardiology, 2016
- Van Belle, et al. JACC, 2016
- Van Mieghem, et al. J Am Coll Cardiol Intv, 2015
Cerebral Embolic Debris Generated in Vast Majority of TAVR patients
Cerebral embolic debris has been captured in 90 – 100%1-3 of TAVR patients using a variety of transcatheter valves and interventional approaches, and can range up to a centimeter in size. A spectrum of embolic debris has been shown to be released into the cerebral vasculature, including thrombus, tissue, calcium and foreign material.1-3
- Haussig, et al. JAMA, 2016
- Van Mieghem, et al. EuroIntervention, 2016
- Kapadia, et al., JACC 2019
The SENTINEL randomized study using the Claret Sentinel cerebral protection system included a variety of TAVR valves:
n = 103
- CoreValve (3)
- Evolut R (23)
- Sapien 3 (55)
- Sapien XT (22)
- Kapadia, et al. JACC, 2016
Lesion Volumes are Associated With Stroke
Larger lesion volumes residing in the brain, as determined by total diffusion-weighted MRI (DWI), are associated with a significantly higher risk of clinically evident stroke.1
- Bonati et al. Lancet Neurol. 2010;9:353–62
Stroke Related to TAVR is a Significant Issue
Stroke continues to be a significant complication of TAVR, leading to a three-fold increase in 30-day mortality.1
Majority of TAVR Stroke is Peri-Procedural
Cerebrovascular events as a result of TAVR are shown to occur most frequently at Day 0-1, with the median time to major stroke being 1 day. More than 50% of identified strokes are classified as major, with more than 95% of those being ischemic.2,3
Cerebral Damage More Pervasive Than Originally Thought
When neurologists examine TAVR patients’ brains post-procedure, they are seeing more damage than has been reported to-date. Neurological deficit has been observed in 28% of TAVR patients that did not receive cerebral protection as evaluated by a neurologist two days post-procedure. In addition, protected patients have shown a significantly lower ataxia* rate when compared to unprotected patients (9% vs. 24%, respectively) two days post-procedure.4
Past clinical studies on surgical valve replacement have reported stroke rates as determined by cardiovascular surgeons. When neurologists are part of the Heart Team that clinically examines the patient following surgery, clinical stroke is shown to occur more frequently than previously thought. A de novo surgical aortic valve replacement study found that the surgeon-reported stroke rate was 6.6%, which rose to 17% upon clinical and MRI review by a neurologist.5
*Ataxia is a lack of coordination and steadiness of muscle movement most often associated with damage to the brain.
- Eggebrecht H, et al. Risk of Stroke After Transcatheter Aortic Valve Implantation (TAVI): A Meta-Analysis of 10,037 Published Patients. EuroIntervention. 2012;8:129-138
- Tchétché et al. J Am Coll Cardiol Intv. 2014;7(10):1138-45
- Nombela-Franco et al. Circulation. 2012;126:3041-53
- Linke A. CLEAN-TAVI: A Prospective, Randomized Trial of Cerebral Embolic Protection in High Risk Patients with Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement. Transcatheter Cardiovascular Therapeutics (TCT). 2014
- Messé SR et al. Circulation. 2014;129:
“Silent” Stroke Not So Silent
The American Heart Association and the America Stroke Association defines stroke as a diverse disease that includes both cerebral hemorrhages and various types of ischemic stroke.1
Due to advances in brain imaging techniques, the previous 24-hour inclusion criterion for determination of cerebral infarction is no longer accurate, and is in fact, misleading – since we now know that permanent brain injury can occur within a matter of minutes.
Therefore, the presence of persistent clinical signs or symptoms is not necessary to establish a diagnosis of cerebral infarction. As a result, the definition of stroke also includes imaging evidence of lesions despite the absence of overt “visible” neurological dysfunction, often referred to as “silent” cerebral infarcts.
Blinded analysis of first 78 patients (control and treatment arms), CLEAN-TAVI, presented by Robert Zivadinov at TCT 2014.
“Silent” Lesions Common After TAVR
“Silent” cerebral infarcts are associated with several diverse neurological and cognitive consequences regardless of the type of cardiovascular procedure including:
- Impaired mobility, physical decline, depression cognitive dysfunction, dementia.
- Even lesions only visible on DW-MRI are associated with increased risk of acute and late neurological events and cognitive deterioration. 1, 2
The Sentinel CPS has received the CE Mark and is commercially available in Europe. It is limited to investigational use in the United States.