Neurocognitive Assessment in TAVI (NEAT TAVI)
Research type
Research Study
Full title
The Influence of Cerebral Protection on Neurocognitive Outcomes Following Transcatheter Aortic Valve Implantation (TAVI)
IRAS ID
293716
Contact name
Sandeep Arunothayaraj
Contact email
Sponsor organisation
Brighton & Sussex University Hospitals NHS Trust
Duration of Study in the UK
2 years, 1 months, 1 days
Research summary
Summary of Research
Severe aortic stenosis is a common heart condition affecting elderly patients. Degeneration of the aortic valve (one-way valve between the heart and the aorta) causes high resistence to blood flow, resulting in strain on the heart and the potential for heart failure and death. Treatment of aortic stenosis has traditionally been with open heart surgery. A new procedure called transcatheter aortic valve implantation (TAVI) allows new aortic valves to be implanted through the femoral arteries, resulting in equivalent outcomes to open surgery with a more rapid recovery. Some complications remain present however, including the risk of debris released during the valve implantation being carried by the blood stream into the brain. This may lead to strokes and a loss of mental capacity. Devices that filter the blood stream and capture this debris have now been developed but are of uncertain benefit. We plan to investigate the brain function of patients who have been randomly assigned to the TAVI procedure with and without the use of filters to see if there are any cognitive benefits to the use of this technology.
Patients who are enrolled in the BHF PROTECT-TAVI trial will be invited to partcipate in this trial. They will have already been randomly assigned to TAVI with or without cerebral filter use. We will perform a series of bedside clinical tests (lasting ~40 minutes) involving questionnaires, pen & paper and computer-based tasks. These will be performed both pre- and post-TAVI. There is no change to routine patient care. Data will be analysed with the assistance of trained neuropsychologists and will provide a valuable insight into the performance and role of the cerebral filter for TAVI patients in the future.Summary of Results
NEAT TAVI was an observational study conducted at the Royal Sussex County Hospital in Brighton, United Kingdom. The Chief Investigator was Dr Sandeep Arunothayaraj and the Sponsor was University Hospitals Sussex NHS Foundation Trust. Funding was provided by Terumo Medical Corporation and The Australian Government Research Training Program Scholarship.
Transcatheter aortic valve implantation, or TAVI for short, is a procedure in which a new aortic valve is inserted into the body through a blood vessel. This is required when a patient’s own aortic valve is diseased, and either does not open easily, or has a large leak. TAVI places the body under less stress than the traditional method of surgical valve replacement through a large chest incision. The recovery from TAVI is also much quicker. These are important factors as those who require a new aortic valve are often elderly and may not tolerate major surgery.
Despite these benefits, TAVI still carries some risks, such as stroke. Stroke occurs due to acute brain damage, leading to problems such as loss of control of an arm or leg, inability to understand or speak and loss of vision. Studies have shown that for every 100 patients who undergo a TAVI, approximately 2-3 will experience a stroke at the time of the procedure, or shortly after. About half of these patients will have permanent limitations following a stroke.
Stroke after TAVI is mostly caused by small fragments of calcium and blood clots being dislodged from the diseased aortic valve. Debris that enters the blood stream can travel to the brain and block the blood supply to important areas. If this debris can be trapped and removed from the blood stream before it reaches the brain, it is hoped that the chance of stroke will be greatly reduced. The Sentinel device is manufactured by Boston Scientific for this purpose. It consists of two filter baskets that can be placed in blood vessels that supply the brain. When fully deployed, approximately 75% of the brain is protected by this device. In almost every use, microscopic debris is captured within the baskets. Whether this means that the risk of stroke is reduced, and by how much, is still uncertain.
The BHF PROTECT study was designed to answer this question. Patients who chose to participate are randomly assigned to standard TAVI with no filter use, or TAVI with the Sentinel device. The rate of stroke after the procedure is determined for both groups, to see if there is a benefit with use of the Sentinel. Because stroke is rare, a very large number of people need to participate in this study to detect a reduction. This means the study will take many years to complete.
Another method to determine benefit from the use of Sentinel is to assess for cognitive changes after TAVI. Cognition refers to the ability of the brain to perform complex tasks such as maintaining attention, problem solving, and creating memories. Strokes that lead to disturbance in language or physical ability generally require a large amount of brain tissue to be injured. In contrast, slight changes in cognition may be seen with smaller amounts of injury. This is because cognition requires multiple areas of the brain to work together and can be affected by injury to any one part. We believe that we can use detailed cognitive tests in a smaller group of people to search for benefit from using the Sentinel device.
Many tests have already been developed to detect changes to cognition that result from damage to blood vessels (a condition called vascular dementia). In NEAT TAVI, a range of established and new tasks were gathered into an 8-test panel that could be performed before TAVI, after TAVI as an inpatient and several months later as an outpatient. These were trialled on a group of 25 volunteers to ensure they were easy to understand, yet challenging enough to properly measure various cognitive areas.
Following ethical approval from the Health Research Authority, participants were invited to be recruited into NEAT TAVI if they were undergoing TAVI at the Royal Sussex County Hospital between May 2021 and June 2022. During this time, patients who consented were undergoing randomisation as part of the BHF PROTECT trial. This meant that cognitive testing was performed on a group of patients who were randomly assigned to the use of Sentinel, or a standard TAVI. Importantly, both groups of patients were similar across a range of important factors such as age, level of education, previous stroke and procedural duration.
Changes in cognitive function from before to 24-hours after TAVI were found in most tests. While scores are usually expected to improve when repeating a task because of the practice effect, only 2 out of 8 tasks showed a measurable improvement. 5 tasks showed measurable deterioration, suggestive of brain stress post-TAVI. In the 6 tests with measurable changes after TAVI, 4 demonstrated significantly better results in those patients who received a Sentinel. These tasks assessed language, processing speed, short term memory and problem solving. Importantly, there were no tasks in which patients assigned to the Sentinel filter performed worse than control patients.
Only a small number of participants were able to complete longer-term follow-up testing by email. This meant that any long-term cognitive impact of TAVI or Sentinel use could not be confidently measured. Overall, there was no sign of any significant change in cognition from baseline at an average of 10 months after TAVI, and no impact of Sentinel use at this point.
This study is one of the largest to examine the results of cognitive testing in patients undergoing TAVI with the Sentinel device and is the first to demonstrate evidence of benefit. These results support the theory that collection of debris released from the aortic valve during TAVI can prevent damage to the brain. This supports the continuation of the BHF PROTECT study to determine if this translates to a reduction of stroke. It should be noted that the Sentinel device does not offer complete protection of the brain, but there are other devices in development that may be able to. The cognitive panel used in this study may also be of benefit to assess their effectiveness.
In summary, NEAT TAVI suggests that use of the Sentinel filter device has a protective effect on short-term cognition after TAVI. Further research is ongoing to examine the clinical benefits of cerebral protection. The chief investigator, study team and sponsor would all like to thank the trial participants for making this study possible.
REC name
London - Central Research Ethics Committee
REC reference
21/PR/0443
Date of REC Opinion
5 May 2021
REC opinion
Further Information Favourable Opinion