1. Characterization of Complex Coronary Artery Stenosis Morphology by Coronary Computed Tomographic Angiography Brett M. Wertman, Victor Y. Cheng, Saibal Kar, Heidi Gransar, Ryan A. Berg, Hursh Naik, Rajendra Makkar, John D. Friedman, Jay N. Schapira, Daniel S. Berman Cedars-Sinai Medical Center, Los Angeles, CA

2. CT detection of complex stenosis morphology Disclosures Funding from the Lincy Foundation (Beverly Hills, California) Conflicts of interest: None

3. CT detection of complex stenosis morphology Background 1 Contemporary clinical trials 1-4 have adopted ≥ 70% diameter stenosis on invasive coronary angiography (ICA) as threshold to qualify for randomization to revascularization 1 RITA-2 trial participants. RITA-2. Lancet 1997;350:461-8. 2 Hueb W, et al. MASS-II. J Am Coll Cardiol 2004;43:1743-51. 3 McFalls EO, et al. N Engl J Med 2004;351:2795-804. 4 Boden, WE, et al. COURAGE. N Engl J Med 2007;356:1503-16.

4. CT detection of complex stenosis morphology Background 2 Stenosis morphology is an important determinant in PCI complication rate 1,2 1 Ellis SG, et al. Circulation 1990;82:1193–1202. 2 Ellis SG, et al. Circulation 1991;84:644–653. Published experience of CCTA performance in complex coronary lesions undergoing PCI have primarily focused on total occlusions 3-5 3 Yokoyama N, et al. Catheter Cardiovasc Interv 2006;68:1-7. 4 Soon KH, et al. J Interv Cardiol 2007;20:359-66. 5 Mollet NR, et al. Am J Cardiol 2005 Jan 15;95(2):240-3.

5. CT detection of complex stenosis morphology Aims 1Determine capability of CCTA in characterizing complex stenosis morphologies 2Determine utility of complex stenosis morphology on CCTA in predicting PCI procedure duration and contrast use

6. CT detection of complex stenosis morphology Methods 85 consecutive patients who underwent ICA within 30 days after CCTA CCTA on a Siemens DSCT scanner 1PO/IV metoprolol for HR > 70 2Sublingual NTG 3Gated, noncontrast CCS 4Gated, contrast enhanced (92 ml), helical acquired angiography

7. CT detection of complex stenosis morphology Methods: CCTA Reconstruction –0.6 mm thickness, 0.3 mm increment –End-systole: 40% of R-R –Diastole: 65%, 70%, 75%, 80% or R-R –Manual ECG editing for arrhythmic artifact –Sharp kernel if stent present or CCS > 100

8. CT detection of complex stenosis morphology Methods: CCTA CCTA Interpretation –Consensus by 2 blinded readers –Vital Images workstation –Native segments ≥ 2.0 mm in diameter –Stented and bypassed segments excluded –Oblique multiplanar reformation and oblique maximal intensity projection preferred

9. CT detection of complex stenosis morphology Methods: CCTA CCTA Interpretation Severe stenosis defined by ≥ 70% diameter stenosis on long-axis visual evaluation (see example figures) Quantification of stenosis severity performed independently Proximal LCXMid RCA

10. CT detection of complex stenosis morphology Methods: CCTA CCTA Interpretation Complex stenosis defined by any ACC/AHA Type-C morphology criteria (Ellis SG, et al.) 1) Ostial involvement 2) Major branch involvement 3) Marked vessel tortuosity proximal to lesion 4) > 90º angle at lesion site 5) > 20 mm lesion length 6) Total occlusion

11. CT detection of complex stenosis morphology Methods: ICA Acquisition –Standard technique –GE digital X-ray, AGFA Heartlab workstation Data collection –Occurrence of PCI –PCI duration (minutes) –Total contrast use (ml)

12. CT detection of complex stenosis morphology Methods: ICA ICA Interpretation –Consensus by 2 blinded readers –Severe stenosis defined by ≥ 70% diameter stenosis on visual inspection –Type-C morphology assessment similar to CCTA –Quantification of stenosis severity performed independently

13. CT detection of complex stenosis morphology Methods: Statistics Continuous variables –Means ± Standard Dev –Ranges Comparing PCI time and contrast use: –Analysis of covariance (ANCOVA) with adjustments for age and BMI –Analysis of log-transforms performed to satisfy ANCOVA assumptions

14. CT detection of complex stenosis morphology Results Population –74% men –84% referred either to follow-up on prior SPECT (44%) or for symptoms (40%) –Mean age: 67 ± 11 years –Mean BMI: 27.7 ± 4.6 kg/m2 –Mean Agatston calcium score: 734 ± 873 –Mean heart rate at CCTA: 59 (39 to 112)

15. CT detection of complex stenosis morphology Results 940 segments in 328 arteries were evaluated 93 segments had ≥ 70% stenosis on ICA by visual inspection –Median stenosis severity 73.3% 101 segments had ≥ 70% stenosis on CCTA by visual inspection –Median stenosis severity 77.3%

16. CT detection of complex stenosis morphology Results CCTA performance in ≥ 70% stenoses Detected 84 of 93 lesions (90%) Detected 49 of 52 patients (94%) False positive in 17 segments and 8 patients

17. CT detection of complex stenosis morphology Results Detection of ≥ 70% stenosis by visual CCTA and ICA evaluation ≥ 70% stenotic on ICA Correctly identified on CCTA (%) Not identified on CCTA (%) False positive on CCTA (%) Total9384 (90)9 (10)17 (17) Left main*88 (100)0 (0)1 (11) LAD territory3733 (89)4 (11)10 (23) LCX territory2319 (83)4 (17)1 (5) RCA territory2524 (96)1 (4)5 (17) * For left main, threshold was ≥ 50% stenosis

18. CT detection of complex stenosis morphology Results CCTA performance in ≥ 70% stenotic Type-C stenoses Detected 42 of 53 lesions (79%) Detected 31 of 35 patients (89%) False positive in 7 segments and 3 patients

19. CT detection of complex stenosis morphology Results CCTA detection of specific Type-C morphologies Correctly identified 46 of 62 lesions (74%) Most frequent false positive: branch involvement (12 cases) Most frequent miss: lesion length > 20 mm (7 cases)

20. CT detection of complex stenosis morphology Results Correct and incorrect characterization of Type-C lesions by CCTA n (on ICA) Correctly identified on CCTA (%) Not identified on CCTA (%) False positive on CCTA (%) Total6246 (74)16 (26)22 (32) Ostial2015 (75)5 (25)2 (12) Crosses major branch1513 (93)2 (7)12 (48) Total occlusion97 (78)2 (22)3 (30) > 20 mm in length1811 (61)7 (39)4 (26) Proximal vessel tortuosity00 (0) 1 (100) > 90° angle at lesion00 (0)

21. Ostial LAD involvement Proximal RCA total occlusion Left main plaque crossing LCX and involving ostial LAD LCX LAD Examples of Type-C Morphologies on CCTA

22. Ostial LAD involvement Proximal RCA total occlusion Left main plaque crossing LCX and involving ostial LAD LCX LAD

23. CT detection of complex stenosis morphology Results PCI, Procedure Time, and Contrast Use PCI performed in 36 patients for 46 lesion (none for total occlusion) Procedure time available in 34 patients Contrast use available in 31 patients Type-C morphology on CCTA was associated with significantly increased procedure duration and contrast use

24. CT detection of complex stenosis morphology Results Mean PCI time and contrast use in patients with and without a Type- C lesion on ICA and CCTA ICA with no Type-CICA with Type-Cp-value* Mean PCI time (min)21.6 ± 12.843.7 ± 25.2 0.005 (0.003) † Mean contrast use (ml)137.1 ± 39.2275.1 ± 152.3 0.003 (0.01) † CCTA with no Type-CCCTA with Type-CP-value* Mean PCI time (min)21.5 ± 13.342.4 ± 24.7 0.009 (0.003) † Mean contrast use (ml)139.7 ± 47.4262.6 ± 150.0 0.001 (0.02) † * Adjusted for age and body-mass index † p-values obtained after log-tranforming PCI time and contrast use.

25. CT detection of complex stenosis morphology Main Discussion Points Step-wise assessment of ≥ 70% stenosis followed by presence of Type-C morphology on CCTA emulates real-life evaluation during ICA Our data showed CCTA detects ≥ 70% stenosis with additional value of identifying Type-C features

26. CT detection of complex stenosis morphology Main Discussion Points Why did CCTA miss long lesions? –Underestimation of true lesion length by standard oblique displays of CCTA Why did CCTA overcall branch involvement? –Limitations of spatial resolution –ICA underestimated lesion complexity?

27. CT detection of complex stenosis morphology Main Discussion Points Type-C morphology on CCTA was significantly associated with longer PCI procedural time and contrast use –Alerts clinician to higher risk of contrast- induced nephropathy from PCI –Interventionalist may better plan PCI with advanced knowledge of lesion complexity

28. CT detection of complex stenosis morphology Limitations Modest sample size Referral bias –Severe stenosis on CCTA  more ICA referral –Severe noncalcified lesions  more ICA referral –Contributed to high prevalence of disease Proximal tortuosity and highly angular lesions not represented Consensual reading not community practice Visual assessment has propensity for overestimation

29. CT detection of complex stenosis morphology Conclusions Using a visual cut-off of ≥ 70% diameter stenosis in vessels segments ≥ 2 mm in diameter, CCTA can predict lesions likely to reach ≥ 70% stenosis on ICA and discern associated complex morphologies Presence of complex, severely obstructive lesions on CCTA predicts greater contrast use and longer procedure duration during PCI

30. CT detection of complex stenosis morphology Recommendation CCTA readers should routinely describe the morphology of each detected severe stenosis