The Latest on CT Fractional Flow Reserve. Dimitris Mitsouras, Ph.D.

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1 The Latest on CT Fractional Flow Reserve Dimitris Mitsouras, Ph.D. Assistant Professor of Radiology Harvard Medical School Director, Applied Imaging Science Lab Brigham and Women s Hospital

2 Disclosures Career Development Grant: NIH NIBIB EB Research Grant: Toshiba America Medical Systems Research Grant: Vital Images Speakers Bureaus: Toshiba Canada, Vital Images

3 Anatomic Severity is a poor predictor of ischemia 35% of lesions FFR<0.8 80% of lesions FFR<0.8 96% of lesions FFR<0.8 Tonino PAL et al. JACC, 2015;55:2816-

4 Anatomic Lesion Severity is Insufficient to Guide PCI 2287 pts >70% stenosis & ischemia or >80% stenosis randomized to PCI or medical therapy Boden WE et al, NEJM 2007;356:

5 The FFR Standard for Lesion-Specific Ischemia Distal P FFR= Proximal P At max hyperemia P a FAME I, Tonino et al, NEJM 2009 P d

6 Lesion-Specific Ischemia with CTA using HeartFlow FFR-CT CT FFR-CT Invasive FFR Measurement FFR CT = FFR= FFR CT = FFR=

7 CTA FFR-CT How Does it Work? Boundary Conditions Q in Q out-d1 Q out-d2 Q out-lad Q out-om CFD Simulation

8 CTA FFR-CT How Does it Work? Boundary Conditions Q in 90 mmhg Pressure 61 mmhg Q out-d1 Q out-d2 Q out-lad Q out-om FFR-CT= 0.68 CFD Simulation

9 The HeartFlow FFR-CT Model Flow proportional to vessel diameter to the 3 rd power (Murray law) Taylor CA et al. JACC, 2013

10 2011: DISCOVER-FLOW n=103 Koo B-K et al. JACC 2011;58: HeartFlow FFR CT - Results 2012: DeFACTO, n=252 Min et al. JAMA 2012;308: : NXT, 254 Patients Norgaard BL et al. JACC 2014;63: Sensitivity: CT 94% FFR-CT 93% CT 84% FFR-CT 90% CT 94% FFR-CT 86% Specificity: 25% 82% 42% 54% 34% 79% Accuracy: 61% 81% 64% 73% 53% 81%

11 2011: DISCOVER-FLOW n=103 Koo B-K et al. JACC 2011;58: HeartFlow FFR CT - Results 2012: DeFACTO, n=252 Min et al. JAMA 2012;308: : NXT, 254 Patients Norgaard BL et al. JACC 2014;63: Sensitivity: Specificity: Accuracy: CT 94% 25% 61% FFR-CT 93% 82% 81% CT 84% 42% FFR-CT 90% 54% 64% 73% - Core Lab CT reads - 75% NGT CT 94% 34% FFR-CT 86% 79% 53% 81% - Site CT reads - 13% CTAs excluded (quality) - 30% excluded total - 99% NGT - Improved algorithm

12 Beta-blockers & NGT (DeFACTO) Leipsic J et al. AJR 2014;202:989-

13 FFR-CT Reproducibility n=28 pts, 58 vessels Gaur S et al. JCCT 2014;8:307-

14 Influence of Coronary Calcification on FFR-CT NXT Substudy, n=214 (n=53 w CAC score >415) Norgaard BL et al. JACC Cardiovasc Imaging 2015;8:1045- Agatston Score 739 FFR-CT, CAC score 0-415: AUC = 0.92 FFR-CT, CAC score : AUC = 0.86 CTA, CAC score 0-415: AUC = 0.82 CTA, CAC score : AUC = 0.72 NS

15 Virtual Stenting Noninvasive FFR-CT Taylor CA et al. JACC, 2013; 61:2233-

16 Virtual Stenting Noninvasive FFR-CT Noninvasive FFR-CT After Simulated Stenting Taylor CA et al. JACC, 2013; 61:2233-

17 Virtual Stenting Diagnostic Accuracy to predict Residual Ischemia after PCI: 96% Kim KH et al. JACC Interventions, 2014; 7:72-

18 FFR Serial Stenoses (& Virtual Stenting) NXT Substudy, n=18 vessels Tanaka K et al. Annals of Biomedical Engineering, 2015; available on-line

19 FFR Serial Stenoses (& Virtual Stenting) NXT Substudy, n=18 vessels Tanaka K et al. Annals of Biomedical Engineering, 2015; available on-line

20 Serial Stenoses (& Virtual Stenting) NXT Substudy, n=18 vessels Tanaka K et al. Annals of Biomedical Engineering, 2015; available on-line

21 On-line FFR-CT (Siemens cffr) Sensitivity: Specificity: Accuracy: n=106 pts CTA 81.3% 37.6% 56.1% Segmentation Time: Computation Time: cffr 87.5% 65.1% 74.6% 30-2 hrs 5-10 min Coenen A et al. Radiology, 2015;274:674- Baumann S et al. Eur Radiol 2014;25:1201-

22 On-line FFR-CT (Siemens cffr) Segmentation Time: Computation Time: 30 min-2 hrs 5-10 min Sensitivity: Specificity: Accuracy: n=106 pts CTA 81.3% 37.6% 56.1% cffr 87.5% 65.1% 74.6% Coenen A et al. Radiology, 2015;274:674- Baumann S et al. Eur Radiol 2014;25:1201-

23 Angiography-based virtual FFR Morris PD et al. JACC Interventions, 2015; available on-line

24 Role of CT Perfusion in the FFR-CT Era CTA >50% Stenosis N=381 Prevalence = 38% CTP Defect Reference Standard: ICA 50% & SPECT-MPI defect Rochitte CE et al. Eur Heart J, 2014; 35:1120-

25 Role of CT Perfusion in the FFR-CT Era Meta-Analysis of Diagnostic Performance of CCTA, CTP, and FFR-CT vs FFR - 18 studies, 1535 patients Gonzalez JA et al. Am J Cardiol, 2015; available on-line

26 Summary FFR-CT is an accurate, reproducible technique to predict coronary lesion hemodynamic significance - Empowers CTA to be used as a single-test gatekeeper for downstream testing without requiring pharmacologic stress agents or additional radiation - Offers opportunities beyond prediction, such as PCI planning - Likely to be performed in a real-time setting in the near future - Does not apply to everyone (prior PCI, CABG?), and may not be applicable for some patients (~30%?) - CT Perfusion is a competitive approach to detect ischemia by CT but requires additional radiation and pharmacologic stress - However, it may be used in those patients where FFR-CT does not apply

27 FFR-CT Future Directions Same overall flow but different subtended myocardial demand assumed for each branch 439 ml/min 439 ml/min Q in Q 3 out Q 2 out Q 4 out Q 5 out 353 ml/min 94 ml/min Q 1 out 86 ml/min 345 ml/min

28 FFR-CT Future Directions 90 mmhg 90 mmhg Q in 80 mmhg 61 mmhg Q 3 out Q 2 out Q 4 out Q 5 out FFR = 0.89 FFR = 0.68 Q 1 out Which FFR CT is correct?

29 FFR-CT Measuring Flow BCs from CTA In Vivo Identical Patient In Vitro

30 Transluminal Attenuation Gradient-based FFR-CT Sensitivity Prediction of Invasive FFR< ml/min FFR = 0.68 TAG-FFR-CT (ROC AUC=0.926) Murray FFR-CT (AUC=0.870) Specificity ml/min

31 Conclusion - FFR-CT is an already useful but still developing technology - The predicted dissemination of FFR-CT software by CT manufacturers is poised to enable: - Understanding of the accuracy and limitations in selected populations (prior PCI, CABG, hypertrophy) - Better lumen segmentation methods - New approaches to simulate hyperemia

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