Primary Results of the Assessment of Catheter-based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement Study

Transcription

1 Primary Results of the Assessment of Catheter-based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement Study The ACIST-FFR Study William F. Fearon, MD, Jeffrey W. Chambers, MD, Arnold H. Seto, MD, Ian J. Sarembock, MD, Ganesh Raveendran, MD, Charlotte Sakarovitch, PhD 1, Lingyao Yang, MS, Manisha Desai, PhD 1, Allen Jeremias, MD, and Matthew J. Price, MD for the ACIST-FFR Study Investigators

2 Speaker's name: Matthew J. Price I do not have any potential conflict of interest I have the following potential conflicts of interest to report: Consultant: AstraZeneca, ACIST Medical, Boston Scientific, Medtronic, St. Jude Medical, and The Medicines Company. Other(s): Speaker s fees from AstraZeneca, Abbott Vascular, Medtronic, St. Jude Medical, Terumo, Chiesi USA and The Medicines Company.

3 Background FFR guidance to identify and treat functionally significant lesions reduces the risk of MACE and saves healthcare resources compared with angiographic guidance alone. Two different technologies to measure FFR are commercially available: a pressure wire (0.014 ), or microcatheter (0.022 ). While more convenient, a potential disadvantage of the microcatheter is that the larger profile may influence coronary hemodynamics, an effect which might also depend on lesion and vessel characteristics. To date, these issues have not been investigated in a large, multicenter, prospective fashion across a spectrum of vessel and lesion types and utilizing an independent core laboratory.

4 Aim Study Objective: To assess the differences between FFR measured by a microcatheter and commercially available 0.014" pressure wires in the setting of clinically relevant vessel diameters and lesion lengths

5 Catheter-based FFR: Navvus MicroCatheter Delivered over a standard guidewire Marker band located 2.5mm from tip Fiber-optic sensor 2.5mm from marker band (5mm from tip) Profile comparable to diameter at lesion site

6 Study Design Design: Prospective, open-label, observational study Primary endpoint: Difference in agreement between microcatheter and PW FFR by Bland-Altman Core laboratory assessed FFR and QCA (CRF, NY, NY) Independent analyses performed by Stanford University Enrollment Stable angina or ischemia Indicated for FFR RVD 2.25 mm Resting Pd/Pa PW Alone Deliver Navvus over PW Measure with both systems Navvus FFR Check PW FFR Navvus drift check Navvus removed Pressure Wire FFR With PW Alone PW Drift Check

7 Major Inclusion & Exclusion Criteria Inclusion Criteria De novo lesion with clinical indication for FFR measurement TIMI flow = 3 RVD of the target lesion 2.25 mm by visual estimation Exclusion Criteria STEMI or NSTEMI NYHA Class 4 heart failure Thrombus Target lesion is within a bypass graft Angiographic evidence of a dissection prior to initiation of PW measurements. Target vessel with excessive tortuosity or calcification

8 Subject Enrollment: 245 Patients at 11 Sites in United States Center Investigator Location Mercy Medical Center J. Chambers Coon Rapids, MN Long Beach Veteran Hosp. A. Seto Long Beach, CA Scripps Clinic M. Price La Jolla, CA Stanford University Hosp. W. Fearon Stanford, CA Christ Hospital I. Sarembock Cincinnati, OH University of Minnesota Hosp. G. Raveendran Minneapolis, MN Columbia University Hosp. J. Moses New York, NY St. Louis University Hosp. M. Lim St. Louis, MO Washington Hospital Center I. Ben Dor Washington DC University of Chicago Hosp. S. Nathan Chicago, IL Iowa Heart Center M. Ghali Des Moines, IA

9 Study Flow Chart 245 Subjects Enrolled 13 Subjects consented but FFR not measured 9 Subjects had FFR measured but no drift assessed 13 Subjects with FFR attempted but not measured because of failure to cross or device malfunction 210 Subjects with Paired FFR 41 Subjects excluded by the core lab: Ventricularization Dampening of the proximal pressure tracings Drift from one or both of the systems without proper re-measurement 169 Subjects with Core Lab Approved FFR

10 Baseline Clinical Characteristics Characteristic N=169 Age 68 ± 9 years Male Sex 133 (79%) Body Mass Index, kg/m 2 31 ±7 Hypertension 140 (83%) Dyslipidemia 127 (75%) History of Diabetes 63 (37%) Tobacco Use 23 (14%) Prior Myocardial Infarction 53 (31%) Prior PCI 75 (44%) Prior CABG 13 (8%)

11 Baseline Angiographic Characteristics (Core Lab Assessed) Patients Baseline Angiographic Characteristics Lesion Location N=169 Left Main 4 (2%) LAD 87 (52%) Left Cx 31 (18%) RCA 44 (26%) % Diameter Stenosis 47±9 Lesion Length (mm) 15.3±8 RVD (mm) 2.8±0.5 ACC/AHA Classification A 51 (30%) B1 74 (44%) B2 34 (20%) C 10 (6%) Pressure Wire FFR 0.83±0.1 40% 35% 30% 25% 20% 15% 10% 5% 0% Reference Vessel Diameter (mm)* 2% 28% 37% 24% 9% < , > 3.5

12 Primary Endpoint: Microcatheter vs. Pressure Wire FFR, Core Lab Values, by Bland Altman Analysis FFR Difference (Microcatheter-PW) N=169 Upper 95% LOA: Bias: Bias: (95%CI: , ) Lower 95% LOA: Mean FFR

13 Secondary Endpoint: Difference in PW FFR with and without the Microcatheter On the Pressure Wire N= Upper 95% LOA: FFR Difference 0.00 (MC/PW-PW) Bias: (95%CI: , ) Lower 95% LOA: Mean FFR MC/PW: microcatheter over pressure wire

14 Sensitivity Analysis: Microcatheter vs. Pressure Wire FFR, Site Reported Values N=221 FFR Difference (Microcatheter-PW) Upper 95% LOA: Bias: Bias: (95%CI: ,-0.016) Lower 95% LOA: Mean FFR

15 Correlation Between Microcatheter and Pressure Wire FFR 1.0 N=169* FFR from Microcatheter Pearson coefficient = P<0.001 Sensitivity: 88% (95% CI: 76-96%) Specificity: 78% (95% CI: 69-85%) Diagnostic Agreement: 81% (95% CI: 75-87%) FFR from PW 5 cases (2.9%) where PW FFR >0.80, microcatheter FFR <0.75 *Core laboratory values

16 Predictors of Bias on Univariate and Multivariate Analysis Variable Bias mean (SD) Univariate p-value Multivariate p-value Vessel Size based on RVD (0.05) > (0.04) Lesion Length mm (0.05) >15mm (0.05) End Stage Renal Disease No (0.05) Yes (0.03) FFR from Navvus (0.174, 0.287) <0.001 <0.001

17 Magnitude and Rate of Drift 7.4% 3.5% p=0.10 Mean Signal Drift Clinically Significant Drift (>0.03) Microcatheter Pressure Wire

18 Conclusions A pressure-monitoring microcatheter provides a modestly lower FFR value compared with a traditional pressure wire, with an average bias of On univariate analysis, RVD and lesion length tend to predict a lower FFR measured by the microcatheter However, upon multivariate analysis, lower FFR as measured by the microcatheter is the only predictor of a greater difference between the two measurements, independent of vessel and lesion characteristics The amount of bias is related to the microcatheter FFR value alone Since the bias is less at higher FFR values (e.g., the gray zone and above), the clinical impact of this difference appears minimal