Background: Neurological events associated with transcatheter aortic valve implantation are major contributors to morbidity and mortality. Choosing an appropriate endpoint to determine neuroprotection device efficacy is a key difficulty inhibiting the translation of the innovation from the laboratory to the bedside. Cost and sample size limitations inhibit the feasibility of using the rate of clinical (such as stroke or other cerebral) events as the primary efficacy endpoint. This paper focuses on consensus opinions from the 2013 Yale-University College London (UCL) Device Innovation Summit.
Discussion: Neuroimaging, specifically diffusion-weighted magnetic resonance imaging (DW MRI), may serve as a surrogate endpoint for clinical studies detecting cerebral events in which cost and sample-size limitations prohibit the use of clinical outcomes. A major limitation of using imaging to prove efficacy in cardiac device studies is that no standardized endpoint exists. Ongoing trials investigating cerebral protection devices for transcatheter aortic valve implantation are utilizing and reporting various qualitative and quantitative DW MRI values; however, single lesion volume, number of new lesions, and total lesion volume have been found to be the most reproducible and prognostically important imaging measures.
Summary: DW MRI may be a useful surrogate endpoint for clinical studies detecting cerebral events to determine the device's success in neurological protection. Consensus from the 2013 Yale-UCL Device Innovation Summit specifically recommends the reporting of mean single lesion volume, number of new lesions, and total volume, and encourages European Union (EU)-US regulatory consensus in the guidance of implementing this endpoint.