BERLIN, GERMANY — The full findings of the CLEAN-TAVI trial are now available but will do little to resolve the debate over whether cerebral-protection devices should be routinely used during transcatheter aortic-valve replacement (TAVR).
The report in the August 9, 2016 issue of the Journal of the American Medical Association includes new procedural and MRI data (eg, single lesion volume) and expanded statistical analyses. It also has results first reported by heartwire from Medscape in 2014 showing that the Claret Montage Dual Filter System (Claret Medical) reduces the volume and size of new brain lesions on MRI 2 days post-TAVR.
The stroke rate, however, was similar between patients randomized to the embolic filter and those in the control group, although the study was not powered for clinical outcomes.
Neurological and neurocognitive outcomes are also only hypothesis generating, especially as they weren't performed by a neurologist and no routine neurological assessment was performed at 3 months, the investigators, led by Dr Stephan Haussig (University of Leipzig, Germany) note.
Without hard neurologic end points, however, it is unclear whether reducing silent brain lesions translates into better neurological outcome over the long term.
"When it comes to the heart, people go crazy over little increases in troponin because it's been shown to have a prognostic impact, and here you have morphologic evidence of silent infarcts, millions of neurons and billions of synapses killed, and people ask you why this is important," coauthor Dr Axel Linke (University of Leipzig) told heartwire .
That said, he added that CLEAN-TAVI is just a proof-of-concept study and that there is much work to be done. It is still not known how much redundancy is in the brain or why some people will have a big stroke and recover and others have a small stroke and are comatose. "I think it's not only the volume of the stroke, it's also the number of lesions and the location of the lesions that might impact on the neurological long-term outcomes."
In an accompanying editorial, Dr Steven Messé (University of Pennsylvania, Philadelphia) and Dr Michael J Mack (Heart Hospital Baylor Plano, TX) point out that acute lesions, although small, were found in virtually all patients post-TAVR (98% in both groups). Although the dual-filter design of the Claret Montage leaves the left vertebral artery unprotected, the second-generation device was associated with reduced infarct burden in all brain territories.
"Whether that reduction translates to a meaningful improvement in clinical outcomes will require more study, but the findings represent a compelling and encouraging start," they write.
The CLEAN-TAVI data are generally in line with the DEFLECT 3 pilot trial, in which successful deployment of the TriGuard HDH embolic-deflection device (Keystone Heart) resulted in fewer brain infarcts but did not significantly reduce the composite primary end point, which included stroke.
The editorialists note that several trials are nearing completion that should shed new light on periprocedural brain injury and the feasibility of neuroprotection. This includes the SENTINEL trial examining total new lesion volume as well as neurocognitive outcomes with Claret's Sentinel cerebral-protection device, already approved in Europe in 2013.
Also on deck is the Neuroprotection in Patients Undergoing Aortic Valve Replacement trial, comparing the Embol-X embolic protection device (Edwards Lifesciences) and CardioGard Emboli Protection Cannula (CardioGard Medical) using standardized postoperative MRI assessment, serial neurological evaluations, and comprehensive neurocognitive testing.
In noting the mixed results from prior trials, the editorialists call for a standardized approach for clinical and radiographic assessment of neurological and cognitive outcomes to improve study validity and cross-trial comparisons.
Cost is one element that will also play into routine adoption of these devices. Linke said that in Germany using a filter would not be associated with additional costs for healthcare providers since the potential use of a cerebral-protection device has already been incorporated in the TAVR diagnosis-related group. However, the costs for the filters in Germany are around €2500 to €3000 ($2822–$3386).
The study was supported by a grant to the Leipzig Heart Center from Claret Medical and Medtronic. Linke reports speaker honoraria or consultancy for Medtronic, St Jude Medical, Claret Medical, Boston Scientific, Edwards Lifesciences, Symetis, and Bard; and ownership of stock options from Claret. Disclosures for the coauthors are listed in the article. Messé reports compensation as a consultant for and receiving grant support from GlaxoSmithKline. Mack reports no relevant financial relationships.
Heartwire from Medscape © 2016 Medscape, LLC
Cite this: Jury Still Out on TAVR Cerebral Protection: Full CLEAN-TAVI Data Published - Medscape - Aug 16, 2016.