March 19, 2015 — An investigational device that deflects debris away from the brain during transcatheter aortic valve replacement (TAVR) seems to improve in-hospital safety outcomes and cognitive scores at discharge, according to preliminary findings from the small, randomized DEFLECT III study presented at the American College of Cardiology (ACC) 2015 Annual Scientific Session.
TAVR dislodges minute particles from calcified valves that embolize through the bloodstream. Much of this debris travels “downstream” from the heart, but about a quarter of the debris moves “upstream” to the brain, where it can trigger a stroke. These microscopic scraps are a likely contributor to the high stroke rates seen up to a year after TAVR and to the high rates of subclinical brain injury — damage less severe than a stroke that can affect mental functions.
The Keystone Heart TriGuard device was studied in the DEFLECT III trial. It was designed to reduce the risk of brain damage during TAVR and other procedures that release potentially hazardous debris by covering the three arteries that lead to the brain with a temporary mesh shield. Patients were reviewed after the procedure with diffusion weighted (DW) MRI, which found single and maximum brain lesion volume was reduced by about 40 percent as compared to control patients who did not have TriGuard protection. Based on changes in NIH Stroke Scale, patients protected with TriGuard had 10 percent absolute reduction in stroke (4.9 vs. 14.3 percent).
Preliminary data are available for 83 patients with complete in-hospital safety and efficacy measures. Thirty-day data are being gathered and are expected to be reported in May. Target enrollment for the trial is 86 patients recruited from 15 centers in Europe and Israel.
The novel device demonstrated benefit on several endpoints in this small patient population. For in-hospital procedure safety, defined as a hierarchical composite of major adverse cardiovascular and cerebrovascular events up to seven days after TAVR, the rates were 22.2 percent for patients with the device and 31.6 percent for patients in the control group.
Death rates from all causes were 2.2 percent for the device group and 5.3 percent for the control group. For both stroke and life-threatening or disabling bleeding, rates were 2.2 percent for the device group and 5.3 percent for the control group. No safety concerns were seen in two categories: rates of acute kidney injury were 2.2 percent for the device group compared with zero for the control group — one patient vs. none; and rates of major vascular complications were 15.6 percent for the device group and 15.8 percent for the control group.
“Protecting the brain has become a priority to improve our patients’ outcomes, and this is a new focus in interventional cardiology,” said Alexandra Lansky, M.D., director of the Yale Cardiovascular Research Program, Yale School of Medicine and the study’s lead author. DEFLECT III is the first multicenter randomized clinical trial of a brain-protection device.
Lansky said patients in the protected group performed better than the control on two cognitive tests, the Montreal Cognitive Assessment, which takes a broad look at all domains of neurocognition, and the Cogstate test, a computerized assessment of mental processing. Diffusion weighted MRI, used as a surrogate endpoint for subclinical brain injury, showed that fewer patients in the device group had new brain lesions and that the volume of the lesions was lower than in the control group.
Patients will be followed for 30 days, and all neurocognition and weighted imaging measures will be repeated at that point to determine whether the early benefits continue. The FDA has approved a definitive Investigational Device Exemption trial called REFLECT, which is expected to start enrollment during the second quarter of 2015.
TriGuard is specifically designed to provide full coverage to all aortic arch takeoffs. The device has CE mark for use in Europe, but is not yet commercially available in the United States.
This trial was sponsored by Keystone Heart Ltd. Lansky has a minor ownership in the company.
For more information: acc.org