1. Electron Beam Computed Tomography in the Age of 64 Slice CT Matthew J. Budoff, MD, FACC Associate Professor of Medicine Division of Cardiology Harbor-UCLA Medical Center, Torrance CA

2. 5 USES OF Coronary Artery Calcium Use a calcium score to screen patients with moderate (intermediate) Framingham risk –Positive CAC scans indicate incremental risk –Alters therapeutic goal (LDL, BP, etc) Identify patients who do not need further cardiac evaluation (scores of zero) Consider serial imaging as ongoing management tool (progression) Improve compliance Non-invasive Angiography

3. Relative Risk DMSmokeHTN<10 10-100 101-400 401-1000 >1000 EBT Coronary Calcium Score All Cause Mortality [NDR] n = 10,377 asymptomatic men and women f/u = 5.0+3.5 yrs. Shaw, Raggi et al Radiology 2003 EBT found to be independent and incremental to risk factors All Cause Mortality in Patients Without Known CAD

4. Prediction of Cardiac Events in Asymptomatic Patients by EBT The St. Francis Heart Study, JACC 2005 SFHS 3 Baseline EBT Calcium Score Annual Event Rate (%) Calcium Score >100 vs <100 Relative Risk 9.5 Any Event 10.7 Cor. Event 9.9 MI/ SCD

5. Outcome Data – St Francis Randomized Trial This study was a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha- tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. Treatment reduced low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), while reducing clinical endpoints by 30% (6.9% vs. 9.9%). Event rates were related to baseline calcium score (pre-specified analysis) and have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p=0.046 [42% reduction]). The 30% reduction in the primary end point of this study is similar to the reduction of ASCVD events seen in other large randomized clinical trials of statins, a class of drugs with unquestionable efficacy in this application Arad Y et al. Treatment of Asymptomatic Adults with Elevated Coronary Calcium Scores with Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial. J Am Coll Cardiol 2005: 46: 166-172.

6. 0.002.004.006.008.0010.0012.00 Time to Follow-up (Years) 0.75 0.80 0.85 0.90 0.95 1.00 0.001.002.003.004.005.00 Time to Follow-up (Years) 0.75 0.80 0.85 0.90 0.95 1.00 Near- and Long-Term Survival from 2 Cohorts – over 35,000 patients n=10,377 n=25,257 99.4% 97.8% 95.2% 90.4% 81.8% 99.4% 97.8% 94.5% 93.0% 76.9%  2 =1503, p<0.0001, interaction p<o.0001 CAC Score (5 Yr Mortality = 1.2%) (12-Yr Mortality = 2.1%)Difference 0-10 99.4% 99.4% 0.0% 11-100 97.8% 97.8% 0.0% 101-400 95.2% 94.5% 0.7% 401-1,000 90.4% 93.0% 0.6% >1,000 81.8% 76.9% 4.9%

7. Cooper Clinic Study - 10,782 Patients: 3.5 year follow-up Adjusted age, history of diabetes, hypertension, elevated cholesterol, over weight Ref Nonfatal MI & CHD Death 2.7 (0.8-9.3) 6.0 (2.1-17) 9.7 (3.6-26) 21.1 (7.8-57)

8. Taylor et al – PACC Study – JACC 2005 2000 patients, mean age 43 Coronary calcium was associated with an 11.8-fold increased risk for incident coronary heart disease (CHD) (p 0.002) in a Cox model controlling for the Framingham risk score. In young, asymptomatic men, the presence of coronary artery calcification provides substantial, cost-effective, independent prognostic value in predicting incident CHD that is incremental to measured coronary risk factors.

9. Anand EHJ 2006 – 510 Diabetics

10. MESA OUTCOMES CAC Score Number of hard 1 events/ Number at risk Hazard Ratio95% C.Ip-value Number of CHD events/ Number at risk Hazard Ratio95% C.Ip-value 08/34111.0 15/34111.0 1-10025/17285.27(2.37,11.73)<0.00005 39/17284.47(2.45,8.13)<0.00001 101-30024/75210.78(4.79,24.27) <0.0000141/75210.26(5.62,18.71)<0.00001 300 or greater32/83311.97(5.40,26.51)<0.0000167/83314.13(7.91,25.22)<0.00001 1 Includes only myocardial infarction and CHD death Detrano Et al. J Am Coll Cardiol 2007:49;101A.

11. MESA Study – 6,814 Patients: 3.5 year follow-up Fully adjusted – Detrano et al– ACC Abstract - JACC March 07 Ref Nonfatal MI & CHD Death 2.7 (0.8-9.3) 6.0 (2.1-17) 9.7 (3.6-26) 21.1 (7.8-57)

12. Calcium Versus Framingham n = 5 n = 27 n = 18 n = 4 n = 29 n = 17 n = 1 n = 5 n = 44 Myocardial Infarction (%)

13. “measurement of coronary calcium is an option for advanced risk assessment. High coronary calcium scores (e.g., >75 th percentile for age and sex) denotes advanced atherosclerosis and provides rationale for intensified LDL-lowering therapy.” NCEP ATP-III : Noninvasive Testing - 2001

14. European Guidelines European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (2003) which state that “Coronary calcium scanning is thus especially suited for patients at medium risk”, and use CAC to qualify conventional risk analysis.

15. AHA – Circulation 2005 This recommendation to measure atherosclerosis burden, in clinically selected intermediate–CAD risk patients (eg, those with a 10% to 20% Framingham 10-year risk estimate) to refine clinical risk prediction and to select patients for altered targets for lipid-lowering therapies.

16. MEDICARE LCD- California 10. Quantitative evaluation of coronary calcium to be used as a triage tool in patients with chest pain of suspected cardiac etiology or clear evidence of myocardial ischemia and unknown Agatston score to determine the appropriateness of coronary CTA vs. catheter coronary angiography. 11. Quantitative evaluation of coronary calcium to be used as a triage tool for lipid-lowering therapy in patients with an intermediate to high Framingham risk score. Per recommendations of the American College of Cardiology, California chapter, and California Radiological Society, two of the following diagnoses should be present: diabetes, metabolic syndrome, hypertension, family history of cardiac or vascular disease, lipid abnormalities, smoking, or obesity. Since patients are generally over age 65, this is a total of 3 Framingham risk factors. 12. Quantitative evaluation of coronary calcium in patients with an equivocal stress imaging test or in cases in which discordance exists between stress imaging testing and clinical findings.

17. Blue Shield – February 2005

19. New Guidelines From AHA

20. AHA 2006 virtually all of the prognostic and epidemiological data derived for CACP have been performed with EBCT On the basis of the substantial validation data, EBCT remains the reference standard for CACP measurement The AHA Writing Group proposes that the following minimum requirements be met in scanning for CAC: 1. Use of an electron beam scanner or a 4-level (or greater) MDCT scanner

21. AHA – CT Angiography Where MDCT is used for CT angiography, the AHA Writing Group currently recommends a minimum of 16-slice capability, submillimeter collimation, and 0.42-second gantry rotation with retrospective ECG gating. If EBCT is used, 1.5-mm slice thickness should be used.

22. Radiology 2005; 235:723–727

23. Cardiac CT Equipment Recommendations The availability of a multi–detector row helical CT or an electron-beam CT scanner is a requirement for cardiac CT applications, especially for coronary artery calcium scoring and CT angiography. For multi–detector row CT, at least four detector rows are preferred for calcium scoring and at least 16 are preferred for CT coronary angiography.

24. Presenter Disclosure Information Disclosure Information... The following relationships exist related to this presentation: Budoff MJ – speakers Bureau, GE

25. Limitations of Coronary Angiography 15-35% of all angiograms done have no significant luminal narrowing Luminogram – no wall (plaque) information Average costs high, reimbursement to physician - limited

26. Coronary artery imaging: - small diameters (~1-4 mm) - complex anatomy - rapid motion

27. Electron Beam Tomography (EBT) Robust and proven CT coronary imaging Low Radiation (0.7-1.1 mSev) e-Speed: 1.5 mm slice thickness 50 ms temporal resolution Limitations: 2 images per heart beat Heart Rates < 120 bpm High Calcium Scores/Stents

28. Electron Beam Tomography (EBT) 50 ms image acquisition time 1.5 mm slice thickness

29. Electron Beam CT CORONARY ANGIOGRAPHY 20 MINUTE PROCEDURE Intravenous access required REQUIRES 100-120 ml CONTRAST (antecubital) Iodinated Dye (same as cath lab) Breath-hold 30-40 seconds per study Images available within minutes, interpretation time 15 minutes/study

30. Non-invasive Angiography (EBA) Rasouli, AHA 2003 25 2% 92% 94%

31. Methodology for improved detection of coronary stenoses with computed tomographic angiography – AHJ 2004 86 patients evaluated with cath EBA correctly classified 49 of 53 patients (92%) as having at least 1 coronary stenosis. Overall, 103 stenoses with 50% diameter reduction were present, and 93 of these lesions were correctly detected by EBA (sensitivity 90%, specificity 93%, positive predictive value 84%, and negative predictive value 96%). Only 5% of vessels could not be assessed, predominantly due to significant calcification.

32. EBA vs. MIBI Cardiac CT Angiography (CTA) and Nuclear Myocardial Perfusion Imaging (MPI)—A Comparison in Detecting Significant Coronary Artery Disease1 Matthew J. Budoff, MD, - Acad Rad

33. EBA vs. MIBI EBA demonstrated significant higher sensitivity than MPI (95% vs. 81%, P.05). EBA demonstrated significantly higher specificity than both MPI (89% versus 78%, P.04) and CAC (56%, P.002). EBA also performed better in a per-vessel analysis (sensitivity 94%, specificity 96%) than both nuclear and CAC

34. EBT – C150 Normal dominant Right coronary artery 80% stenosis of distal LAD, after large diagonal

35. EBT E-speed Normal distal RCA AND PDA

36. Electron Beam Angiogram

37. Circumflex and OM

38. EBCT ANGIOGRAM DURING A-FIB

39. MSCT 16 slice SOFT PLAQUE WITH EBCT

40. Detection of SOFT Plaque with EBT or MDCT Potential role in risk assessment? - Accuracy / Quantification – underestimates plaque significantly (Achenbach Circ, 04) - Reproducibility? - Progression over time? - Prognostic value? - Additive Data to Calcium or level of obstruction?

43. Valves/Wall Motion

44. Coronary Veins - Pre-BiV Pacer

45. Pulmonary Veins

47. Carotids

48. Renal Angiograms

49. ALARA PRINCIPAL - Radiation EBT angiography - 1.1 mSv MSCT angiography - 9.3-11.3 mSv Cath 2.1-2.3 mSv *Dose Modulation – MSCT 5-8 mSv* Morin et al, Circulation 2003

50. When To Use EBA even with 64 available? High heart rates Younger patients (<40?, definitely <30 years old) All pediatric applications CHF – heart rates Afib patients

51. Diagnostic tool with high negative predictive value (~98%) if image quality is sufficient But accuracy is < 100% and not all vessels are visualized CONCLUSIONS