1. Ghanem et al., J Am Coll Cardiol 2010;55:1427–32.

2. Background Aortic valve replacement is recommended in patients with symptomatic severe valvular stenosis. Transfemoral aortic valve implantation (TAVI) offers a therapeutic option for high-risk patients with multiple comorbid conditions. Vahanian et al., European Journal of Cardiothoracic Surgery 34 (2008)

3. Background TAVI-related stroke is an important complication (1-10%). The risk of silent cerebral embolism is not elucidated yet. Diffusion-weighted MRI allows detection and localization of acute - apparent and silent - ischemic cerebral lesions. DW-MRI studies are of potential interest for pre- interventional risk stratification, peri-interventional anticoagulation management... Grube et al., JACC (2007), Webb et al., Circulation (2008), Zajarias et al., JACC (2009)

4. Background TAVI-related stroke is an important complication (1-10%). The risk of silent cerebral embolism is not elucidated yet. Diffusion-weighted MRI allows detection and localization of acute - apparent and silent - ischemic cerebral lesions. DW-MRI studies are of potential interest for pre- interventional risk stratification, peri-interventional anticoagulation management... Grube et al., JACC (2007), Webb et al., Circulation (2008), Zajarias et al., JACC (2009) Aim of the study: Prospective investigation of peri-interventional cerebral embolism (3 rd generation Corevalve™- Prosthesis) with DW-MRI and its relationship with clinical (NIHSS) and serological (NSE) parameters of brain injury.

5. Study design Inclusion criteria: –severe, symptomatic aortic stenosis with or without regurgitation and high peri-operative risk or –explicit patient‘s request and –aortic valve annulus diameter >20 and <27 mm, and –diameter of the ascending aorta <45 mm at the sinotub. junction. Exclusion criteria: –Age < 18 years –Pregnancy / lactation period –Contraindications to MRI (PM, ICD, Claustrophobia …)

6. Study design Evaluation Clinical and neurological assessment (NIHSS) Lab - Tests (incl. Lactate, NSE) MRI TAVI Clinical and neurological assessment (NIHSS) Lab - Tests (incl. Lactate, NSE) MRI Clinical and neurological assessment (NIHSS) Lab - Tests (incl. Lactate, NSE) MRI E1 E2 E3

7. Protocol E1 E2 E3 Death (n=2) New onset of claustrophobia (n=1) Hemodynamic instability (n=1) PM-Therapy (n=4) TAVI DW-MRI NIHSS (n=30) NSE DW-MRI (n=22) NIHSS NSE DW-MRI (n=22) NIHSS NSE

8. Clinical data Age, years ± SD79.3 ± 4.8 Male, n (%)8 (36.4) Body-mass-index, kg/m ² ± SD26 ± 6.2 Log. EuroScore, % ± SD19.4 ± 13.5 STS - score mortality, % ± SD6.2 ± 4.2 STS - score permanent stroke, % ± SD2.8 ± 1.3 NYHA ± SD3 ± 0.5 Comorbidities Hypertension, n (%)21 (95) Diabetes, n (%)5 (23) Dyslipidemia, n (%)20 (91) Prior stroke, n (%) // Prior TIA, n (%)6 (27) // 3 (14) Peripheral vascular disease, n (%)15 (68) Aortic atheroma ≥ 4 mm, n (%)11 (50) CHADS 2 – score ± SD3.1 ± 1.1 Baseline characteristics

9. Serology E1E2E3E1E2E3

10. MRI

11. Lesion localisation and size Vascular territories DW-MRI lesion volume range [cm ³ ] Anterior cerebral artery 0.1 – 59.2 Middle cerebral artery 0.1 – 4.5 Posterior cerebral artery 0.1 – 8.6 Vertebro- basilary arteries 0.1 – 1.6

12. NIHSS E1E2E3

13. DW-MRI lesions absentpresent Clinical datan=6n=16P Age, years ± SD79.7 ± 579.2 ± 4.90.84 Male, n (%)1 (17)7 (44)0.26 Body-mass-index, kg/m ² ± SD26.1 ± 825.9 ± 5.70.95 Log. EuroScore, % ± SD19.0 ± 9.219.6 ± 150.62 STS - score mortality, % ± SD6.5 ± 2.66.1 ± 4.70.81 STS - score permanent stroke, % ± SD2.7 ± 0.82.9 ± 1.50.64 NYHA ± SD3 ± 0.63 ± 0.51.0 Comorbidities Hypertension, n (%)5 (83)16 (100)0.27 Diabetes, n (%)1 (17)4 (25)1.0 Dyslipidemia, n (%)5 (83)15 (94)0.48 Prior stroke, n (%) // Prior TIA, n (%)1 (17) // 0 (0)5 (31) // 3 (19)0.63 Peripheral vascular disease, n(%)2 (33)13 (81)0.054 Cerebral vascular disease, n (%)1 (17)7 (44)0.35 Aortic atheroma ≥ 4 mm, n (%)2 (33)9 (56)0.63 Atrial fibrillation, n (%) // flutter, n (%)2 (33) // 1 (17)7 (44) // 1 (6)1.0 CHADS 2 – score ± SD2.8 ± 0.83.2 ± 1.20.5

14. DW-MRI, but not NSE, detects cerebral embolic lesions. Silent cerebral embolism is freuquent following TAVI (73%) The incidence of apparent cerebral embolism is low (3.6%). Results

15. Pilot study, small sample size, single site data collection, no multivariate analysis for risk factors. The incidence of silent and apparent embolism may differ with the Edwards-SAPIEN prosthesis. DW-MRI following transapical AVI could help elucidating the influence of retrograde passage of the aortic arch and valve as potential embolic sources. Limitations

16. Conclusions The incidence of clinically silent peri- interventional cerebral embolic lesions is high. However, in this cohort of 30 patients, the incidence of persistent neurological impairment was low. Further studies are needed to evaluate independent risk factors for peri-interventional cerebral embolism.