Department of Clinical Radiology, Ludwig-Maximilians University, Munich, Germany

1. Long-term predictive value of assessment of coronary atherosclerosis by contrast- enhanced coronary computed tomography angiography: meta-analysis and systematic review Fabian Bamberg MD MPH Department of Clinical Radiology, Ludwig-Maximilians University, Munich, Germany

2. Background • CT technology has progressed rapidly resulting in robustdiagnosticaccuracyforcoronayplaque / stenosis detection • Coronary CT angiography increasingly penetrates clinical practices • Beyond diagnostic value: potential prognostic value for occurrence of cardiovascular events • Todate: Small sample sizestudieswith limited evidence • Important to appropriately design future outcome studies and consideration of the public health impact

3. Examples of Cardiac CTA Findings RCA: No Plaque Proximal LAD: Presence of Plaque RCA: Significant Stenosis

4. Aim To perform a systematic review of studies that assessed the prognostic value of coronary CT angiography findings on a combined cardiovascular endpoint and pooled available evidence in a meta-analysis

5. Methods I – Study selection • PubMed, EMBASE, and the Cochrane library through January 2010 • Medical Subject Heading: “cardiac/coronary CTA" in combination with "mortality", or "survival analysis", or "outcome", or "death", or "prognosis/prognostic“ • Expert opinions • References of review articles

6. Methods II - Inclusion Criteria • Cohort studies (prospective or retrospective) of >100 subjects who were followed for >1 year • ≥16-slice CT and electron-beam CT • Studies in patients with stable presentation, i.e. stable angina • Two independent investigators abstracted information on: • Population • Technical equipment • Study quality: endpoint committee, blinded CT results and outcome assessment, exclusion of subjects after enrollment, and endpoint definition) • CT predictors studies and associated HR • Discordancy solved by consensus

7. Methods III - Statistics • Primary objective: risk associated with significant coronary stenosis (>50% luminal narrowing) and a combined CV endpoint • Secondary: Each stenosis, 3-VD, presence non-obstructive plaque • Between-study heterogeneity: Q-statistic and I2 statistic • Publication bias: funnel plots • Meta-regression: sources of heterogeneity • Age, gender, BMI, Hx CAD • CT Technique • Type of endpoint (all-cause mortality vs. combined endpoint), • Study quality

8. Results – Study selection

9. Results – Study selection • 7,335 subjects: 59.1±2.6 years, 62.8% male • FU: 20.4 months (14 to 78) • 82% single-center design • 55% Europe or 36% US • 100% suspected CAD • 18% additionally w/ known CAD • 64% 64-slice CT technology • 18% 16-slice technology 18% EBCT

10. Results – Primary endpoint – sign. stenosis • 3,670 participants, FU 21.9 months • 252 (6.8%) outcome events (62% revascularizations)

11. Results – Primary Endpoint – sign. stenosis • Q-statistic: p<0.001 • I2-test: 71.8% of the variability between-study heterogeneity • No sign of asymmetry of funnel plot (z=1.34, p=0.18)

12. Results - Meta-regression – primary endpoint No heterogeneity: proportion of males, obesity, history of CAD, CT technology used (64-slice vs. other), follow-up time, potential overfitting of the models

13. Secondary predictors n Heterogeneity due to revascularization in endpoints (both p<0.01) and higher prevalence of history of CAD (both p=0.05).

14. Summary • Coronary CT findings are strong predictors of CV events in symptomatic subjects • Independent of coronary artery calcification and cardiovascular risk factors • Choice of endpoints, classification of CT findings, and study population introduced substantial heterogeneity • Basis to homogenize reporting standards for cardiac CT, to determine appropriate design of prospective randomized trials, and to estimate the potential impact on health care systems