8/9/2016 Disclosures Biosense-Webster International: investigator- - PDF document

8/9/2016 Disclosures • Biosense-Webster International: investigator- NOVEL VT THERAPIES: initiated research grant HIGH-INTENSITY ULTRASOUND • The devices and technologies in this AND LINEAR RF ABLATION presentation have not been FDA-approved for clinical use. Babak Nazer, MD Cardiac Electrophysiology Fellow Assistant Professor of Medicine and Biomedical Engineering University of California San Francisco Oregon Health & Sciences University 1 2 Lamin A/C VT High-Intensity Ultrasound VT Ablation Catheter 3 4 1

8/9/2016 5 6 Epicardial scar in NICMP Septal scar in NICMP Hutchinson MD, et al. Circulation Arrhythmia EP, 2011. Haqqani H, et al. Circulation Arrhythmia EP, 2011. 7 8 2

8/9/2016 NICMP VT ablation: Long-term outcomes NICMP VT ablation: Long-term outcomes • 144 patients referred for VT ablation • 59 patients undergoing epicardial VT ablation – Median follow-up 362 days • 47% VT recurrence rate at one year • Endo: 67% recurrence at one year • Endo-Epi: 64% recurrence at one year Tung R, et al. Heart Rhythm, 2013. Schmidt, et al. Heart Rhythm, 2010. 9 10 Rationale for HIFU VT Catheter High-Intensity Focused Ultrasound Midmyocardial RF limitations: Epicardial 1) Poor depth of (Non-ischemic) penetration (5 mm) 1) Cannot ablate through epicardial fat or coronaries LAD 2) Cannot reach deep septal substrate from either side Fat Lynn JG, et al. Journal of General Physiology 1942. 11 12 3

8/9/2016 Rationale for HIFU VT Catheter Epicardial Catheter: Collaborators • HIFU characteristic • Benefit – Spares immediately – Ablate through coronaries adjacent tissue and epicardial fat – Side-facing – Avoid phrenic, pericardial, pulmonary injury – Deep penetration of acoustic energy – Ablate mid-myocardial VTs – Ablate septal VTs – Ablate epicardial VTs endocardially • Vasant Salgaonkar, PhD • Peter Douglas Jones, BS 13 14 Epicardial In-Vivo Ablation Epicardial Catheter • 12 Fr OD nylon catheter housing Radiopaque A-mode HIFU orientation imaging ablation marker transducer transducer Internal irrigation balloon 16 4

8/9/2016 Fluoroscopy A-mode US Fluoroscopy A-mode US Heart Heart Device position Device position and aiming and aiming away from heart toward heart M-mode processing A-mode tracing A-mode tracing M-mode processing HIFU In-Vivo Ablation: Methods Representative Lesions • 8 swine ablated by HIFU, 5 by RF • Epicardial HIFU sonications of left ventricle (LV) performed at 15, 20 and 30W for 60 seconds • RF ablations with ThermoCool SF at 30W, titrating power to achieve >10 Ω impedance drop 10 mm Nazer B, et al. Circulation Arrhythmia EP, 2015. 19 20 5

8/9/2016 Lesion Volume Lesion Depth *** *** *** *** *** ns HIFU HIFU *** p < 0.001 compared with RF ns not significant, *** p < 0.0001 compared with RF 21 22 Epicardial Sparing HIFU Mean Lesion Sizes *** *** ** RF 15W 20W 30W 5 mm HIFU 23 ** p < 0.001, *** p < 0.0001 compared with RF Nazer B, et al. Circulation Arrhythmia EP, 2015. 24 6

8/9/2016 HIFU Coronary Ablation HIFU Coronary Ablation: LCX • Over LCX (30 W) and LAD (20 W) 1 mm 10 mm 250 μ m 25 26 HIFU Coronary Ablation: LAD HIFU Ablations in Scar Gross infarct Epicardial map (0.5 – 1.5 mV) Endocardial map (0.5-1.5 mV) ] 10 mm 1 mm 27 7

8/9/2016 HIFU Lesions in Scar Future of HIFU VT Ablation • Endocardial use – Decrease catheter caliber – Incorporate steerability • Increase focusing (and thus coronary sparing) • Commercialization & Regulatory Approval – Industry Partner – Humanitarian Device Exemption 29 30 Linear ablation for scar-based VT Linear RF Ablation Catheter • 56 RF applications/patient • 4.5 lines/patient Marchlinski, et al. Circulation 2000. 31 32 8

8/9/2016 Substrate Modification / Scar Homogenization Core Isolation of Scar • Mean procedure time 4.2 hours • Mean procedure time 5.4 hours • Mean RF time 68 minutes • Mean 111 RF applications per patient Di Biase L, et al. JACC 2015. Tzou WS, et al. Circulation EP 2015. 33 34 nMARQ Catheter LINEAR Catheter • 7 irrigated 3 mm RF ablation electrodes • 7 irrigated 3 mm RF ablation electrodes • 5 mm spacing • 5 mm spacing • 25 W max power • 25 W max power Biosense-Webster International Biosense-Webster International 35 36 9

8/9/2016 Linear LV ablation LIN vs FOC Ablation A LIN FOC B • LIN (nMARQ) – 7 swine – 22 endo lines – 18 epi lines • FOC (Thermocool) – 5 swine – 7 endo lines (9.4 +/- 2.2 lesions/line) – 8 epi lines (8.0 +/- 1.4 lesions/line) 37 38 Ablation parameters Pre- and post-endo ablation FOC LIN p-value Total RF 496.5 56.3 p < 0.0001 time (s) Irrigation 77.7 39.4 p < 0.0001 volume (ml) Power (W) 26.7 22.8 p < 0.0001 Impedance 17.2 19.9 p = 0.049 drop ( Ω ) 40 10

8/9/2016 Pre- and post- epi ablation FOC lesion gaps FOC LIN 1 cm 1 cm 41 42 LIN lesion histology Linear Lesion Length 1 mm 1 mm 43 11

8/9/2016 Linear Lesion Volume Linear Lesion Depth Acknowledgements Conclusions • Gerstenfeld Lab • Diederich Lab HIFU Ablation Linear RF Ablation – Tomos Walters – Vasant Salagaonkar • Effective tool for: • Reduces procedure and – Srikant Duggirala – Peter Jones RF time – septal VTs – Qi Fang • Fewer gaps – mid-myocardial VTs – Rich Sievers – Epicardial VTs (from endo) • Improved steerability – Yasuaki Tanaka may improve • Catheter steerability and endocardial ablation greater focusing needed • American Heart Association • Industry partner needed • Biosense-Webster International 47 48 12

8/9/2016 B A Supplementary Slides LIN (857 points) Multi-spline (929 points) % difference Volume (ml) 178.7 217.5 -17.8 Surface area (cm 2 ) 181.6 214.9 -15.5 Scar area < 1.5 mV (cm 2 ) 57.5 72.3 -20.5 Scar area < 0.5 mV (cm 2 ) 20.2 28.2 -28.4 Fractionated EGMs (%) 18.0 21.1 -3.1 Late potentials (%) 1.5 2.6 -1.1 Very late potentials (%) 0 0.43 -0.43 49 A B LIN (1141 points) Multi-spline (2277 points) % difference Volume (ml) 168.5 231.4 -27.2 Surface area (cm 2 ) 216.1 233.2 -7.3 Scar area < 1.0 mV 16.6 40.8 -59.3 (cm 2 ) Fractionated EGMs (%) 15.2 9.7 +5.5 Late potentials (%) 3.2 3.0 +0.2 Very late potentials (%) 0.3 0.4 -0.1 13