Coronary Physiology 2019 Covering All Your Physiologic Bases

Coronary Physiology 2019: Covering All Your (Physiologic) Bases CRT Conference, Washington, DC, March 03, 2019 - Luncheon Symposium Sponsored by Opsens

AGENDA 12: 10 pm Introduction. The Latest Advancements in Invasive Coronary Physiology FFR & Resting Indices -------- Morton KERN 12: 22 pm When to Use FFR & When to Use a Resting Index ------- Javier ESCANED 12: 34 pm Diagnose & Confirm with Physiologic Assessment ----- Barry URETSKY 12: 46 pm Getting the Most from My Pressure Guidewire - Challenging Case Review ------------------- Jon GEORGE 12: 58 pm Panel & Audience Discussion & Closing 1: 10 pm Adjourn

The Latest Advancements in Invasive Coronary Physiology FFR & Resting Indices Morton J. Kern, MD, MSCAI Chief of Medicine, VA Long Beach HCS Professor of Medicine, University California Irvine, Orange, California 030319@1200

Disclosure: Morton J. Kern, MD Within the past 12 months, the presenter or their spouse/partner have had a financial interest/arrangement or affiliation with the organization listed below. Company Name Abbott / St Jude Philips / Volcano Acist Opsens Heartflow Cath. Works Relationship Speaker/Consultant Speaker

The Universe of Coronary Physiology Hyperemia Angio. FFRs Resting flow d. PR RFR ΔP DPR Kern MJ, and Seto HS. JACC 2017; 70: 2124 -2127

Latest Advancements in Invasive Coronary Physiology Hardware Software Piezo Resistive Wires FFR, c. FFR Optical Fiber Wires NHPR (i. FR, Pd/Pa, d. PR, DFR, RFR) Micro Rx Catheter Doppler Wire Thermodilution CFR, IMR Absolute Flow Co-Registration Pullback pressure recordings

Issues and Solutions for Pressure Wire Sensor Systems Problem or Issue with FFR work Solution Standard Piezo Wire Fiber-optic Wire Set up, zero, drift Automatic zero, plug/play, signal stability + +++ No adenosine Pd/Pa, c. FFR, NHPRs + + Mediocre pressure wire handling New nitinol wires and micromonorail catheters + +++ Multiple wire manipulations New nitinol wires and microand exchanges monorail catheters + +++ Pullback accuracy Angiographic co-registration + ++ Complex anatomy, multi lesion, bifurcations One wire start to finish + +++

2019 Technology: New Pressure Sensor Wires & Microcatheter Piezoelectric Pressure Wire (Abbott & Philips) 1 st gen Fiber Optic Pressure Wire and Microcatheter (Boston & Acist) 2 nd Generation Fiber Optic Pressure Wire (Opsens) Optical fiber 3 electrical cables

Nitinol-Based Construction Enhances Guidewire Performance and 2 nd Generation Optical Pressure Sensor Opto. Wire - Opsens Handle 2 meter cable FOIC optical connector to Opto. Monitor

Pressure Wire Handling and Torqueability Opto. Wire has a large nitinol core, allowing for a unique balance of torqueability, flexibility, and kink resistance 1200 Output Rotation (Degrees) 1000 800 Torque transmission of the Opto. Wire II similar to that of a BMW workhorse guidewire 600 400 Ideal Opto. Wire II (n=10) OW (n=10) Abbott BMWBMW (n=5) Philips/Volcano (n=5) Example of guidewire spinning without (left) and with (right) concentric design 200 Abbott/St-Jude (n=5) Abbott/St. Jude (n=5) Philips/Volcano (n=5) Boston Sci. (n=1) Boston Scientific (n=1) Source: Opsens company data 0 0 200 400 600 Input Rotation (Degrees) 800 1000 1200

R. Tateshi, Japan 1 N = 235 pts Severe drift occurrence (≥ 3 mm. Hg) Frequency of Drift N. Curzen, Comet study², N = 279 vessels Severe drift occurrence comparison (≥ 3 mm. Hg) Drift: ≥ 3 mm. HG Severe drift: ≥ 3 mm. HG 46. 5% p = NR 35. 8% 57% reduction p < 0. 001 33. 3% Piezoelectric pressure guidewire (Abbott Aeris™) 14. 2% 2 nd generation fiber optic pressure guidewire (Opsens Opto. Wire™) 2 nd Gen Fiber Optic Pressure Guidewires Reduce Drift vs Piezoelectric Pressure Guidewire Piezoelectric pressure guidewire (Abbott Aeris™) 1 st generation fiber optic pressure guidewire (Boston Scientific Comet™) 1 st Gen Fiber Optic Pressure Guidewires Don’t Reduce Drift vs Piezoelectric Pressure Guidewire 1. Tateishi R, et al. . European Heart Journal (2018) 39 (Supplement), 1141 2. Stables RH, et al. Euro. Intervention. Online October 30 2018.

Translesional Coronary Pressure Measurements 2019 Hyperemic Non-Hyperemic Pressure Ratios (NHPR) Sub max Hyperemic Whole-Cycle FFR All Systems c. FFR All Systems Pd/Pa All Systems ≤ 0. 80 ≤ 0. 83 ≤ 0. 91 DFR™ BSC Diastolic/Sub-Cycle i. FR® Volcano RFR™ ABT ≤ 0. 89 d. PR OPS DPR tbd

Non-Hyperemic Pressure Ratios (NHPR) Pa Mean Pd/Pa RFR Pd i. FR WFP d. PR DFR

Adenosine-Free Indices Summary Cutoff value Correlation vs. FFR Correlation vs. i. FR Pd/Pa c. FFR i. FR™ (Philips) d. PR* (Opsens) RFR™ (Abbott) DFR™ (Boston Scientific) 0. 911 0. 832 0. 89¹ 0. 893 0. 894 0. 895 81. 5%1 85. 8%2 80. 4%1 983 97. 4%4 98%5 * Opsens d. PR is currently used in clinical practice in Japan, Canada, Europe and Australia and pending approval in the US 1. 2. 3. 4. 5. Jeremias, J et al. Am Coll Cardiol, 2014. Johnson N, et al. J Am Coll Cardiol Intv 2016. Van’t Veer, M, et al. J Am Coll Cardiol. 2017. Svanerud J, et al. Eurointervention 2018. Oldroyd K, Euro. PCR 2018.

Kaplan-Meier Curves (B) Resting Pd/Pa (A) FFR 20 12. 7% ≤ 0. 80 10 >0. 80 5 0 365 730 ≤ 0. 92 >0. 92 5 7. 0% 0 365 (D) d. PR ≤ 0. 89 >0. 89 5 0 1095 >0. 89 5 6. 9% 730 Days 1095 Deferred Lesion Failure, % 10 365 20 Log-Rank P<0. 01 15 ≤ 0. 89 10 9. 5% >0. 89 7. 1% 5 0 730 (F) DFR Log-Rank P<0. 01 ≤ 0. 89 11. 0% 0 6. 9% Days 20 Log-Rank P<0. 01 15 10. 8% 10 (E) RFR 20 Deferred Lesion Failure, % 730 Log-Rank P<0. 01 15 Days 0 10. 3% 10 0 1095 Log-Rank P<0. 01 15 0 365 730 Days 1095 Deferred Lesion Failure, % 0 5. 9% 20 Deferred Lesion Failure, % Log-Rank P<0. 01 15 Deferred Lesion Failure, % 20 (C) i. FR ≤ 0. 89 12. 3% 15 10 >0. 89 5 0 6. 8% 0 365 730 1095 Days Ahn, J-M, et al. IRIS-FFR Registry: Prognostic Performance of 5 Resting Pressure- Derived Indexes of Coronary Physiology. TCT 2018.

Predictors of Discordance Between i. FR/FFR: Stenosis Location, Severity, HR, Age, and BB’s (FFR+/i. FR-)=69/587 (FFR-/i. FR+)=52/587 Derimay F, et al. Cath and CV Interven 2019: 1 -8.

Major Adverse Cardiac Events in LAD and Non-LAD Deferral based on IFR and FFR LAD FFR i. FR Non-LAD FFR i. FR Sen S, et al. JACC 2019; 73: 444 -453.

Complex Clinical Scenarios Key points Outcome Studies? Bifurcation Lesions FFR/NHPR Deceptive angio, difficult access Yes Ostial, LM FFR IV adeno for ostial, LM. LM+LAD use FFR >0. 6. IVUS for <0. 6 Yes Diffuse/Serial Disease Pullback Pressure ΔP hyperemia/rest w co-registration No FFR/NHPR MVD not need CABG of all vessels. SVG biology trumps physiology but assessment correct. DANAMI-3 -PRIMULTI and COMPAREACUTE say YES to non-culprit if <0. 8. IMR >40 worse outcomes CABG FFR Yes STEMI/NSTEMI FFR/NHPR, IMR CTO FFR Δmyoc bed and collateral flow indices TAVR FFR/NHPR CBF increases after TAVR, FFR decreases No Yes

FFR from CCTA: Improving Workflow for Better Decisions – The PACIFIC trial Driessen RS, et al. J Am Coll Cardiol. 2019; 73(2): 161 -73.

Latest Advances in Invasive Coronary Physiology - 2019 • FFR/NHPR - demonstrate better decisions • Fiber optic technology – less drift, better handling • FFR/i. FR discordance related to location, HR, BB, age • For complete vessel assessment, consider pressure pullback w angio co-registration