TransCranial Doppler for REDUCtion of Silent strokE During MitraClip Implantation (TCD-REDUCE)

The primary goal of the TCD-REDUCE study is to demonstrate the effectiveness of continuous transcranial Doppler sonography ("sonolysis") on the reduction of the ischemic stroke volume during MitraClip implantation.

Cardiac procedures are associated with new cerebral ischemic lesions detected on diffusion-weighted MRI (Bendszus et al., 2006). A previous study suggests that sonolysis (continuous transcranial Doppler sonography using a 2-MHz diagnostic probe) can reduce the risk of new cerebral ischemic lesions during carotid endarterectomy and carotid angioplasty / stenting (Skoloudik et al., 2015). Currently, it is unknown whether sonolysis can also reduce the risk of new cerebral ischemic lesions during MitraClip implantation - a percutaneous treatment option in patients with moderate / severe mitral regurgitation. In this study, patients will receive cerebral MRI and clinical neurological / neuropsychological examination before and after MitraClip implantation. During MitraClip implantation, all patients will receive continuous transcranial Doppler sonography using a 2-MHz diagnostic probe with maximal diagnostic energy administered through either the left or the right transtemporal window (computer-generated 1:1 randomization). The primary endpoint is the median ischemic lesion volume detected on diffusion-weighted MRI after MitraClip implantation in the sonolysis group and in the control group.

Continuous transcranial Doppler sonography (TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy

median volume (in ml) of new ischemic lesions detected on diffusion-weighted MRI after MitraClip implantation in the sonolysis and in the control group

new ischemic lesions (occurrence, number and location) detected on diffusion-weighted MRI after MitraClip implantation

new cerebral microbleeds detected on T2*-weighted MRI after MitraClip implantation (occurrence, number and location)

new clinically overt stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) after MitraClip implantation

functional outcome will be evaluated using the modified Rankin scale (mRS). The mRS ranges from 0 to 6 with 0 indicating no functional deficit (best score) and 6 indicating deaths (worst score).

delirium will be evaluated using the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)

days of hospital stay from admission to hospital to discharge from hospital including direction of discharge (home, another hospital)

Inclusion Criteria: Patients with mitral regurgitation that are assigned to the MitraClip implantation by an interdisciplinary heart team according to current guidelines. Exclusion Criteria: contraindication to MRI examination (e.g. pace-maker, implanted metal material, claustrophobia) pregnancy unable to consent no transtemporal window

Skoloudik D, Kuliha M, Hrbac T, Jonszta T, Herzig R; SONOBUSTER Trial Group. Sonolysis in Prevention of Brain Infarction During Carotid Endarterectomy and Stenting (SONOBUSTER): a randomized, controlled trial. Eur Heart J. 2016 Oct 21;37(40):3096-3102. doi: 10.1093/eurheartj/ehv492. Epub 2015 Sep 28.