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

Background CT technology has progressed rapidly resulting in robust diagnostic accuracy for coronay plaque / stenosis detection Coronary CT angiography increasingly penetrates clinical practices Beyond diagnostic value: potential prognostic value for occurrence of cardiovascular events To date: Small sample size studies with limited evidence Important to appropriately design future outcome studies and consideration of the public health impact

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

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

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

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

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 I 2 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

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

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

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)

Results - Meta-regression – primary endpoint VariableStudiesN events / NHazard ratio (95% CI)P Average age >58 years* ≤58 years / / (10.04 – 39.16) 7.17 (4.23 – 12.15) 0.02 Revasc. in Endpoint Not included Included / / (3.22 – 11.74) (8.92 – 26.62) 0.03 Study Quality Higher lower / / (10.08 – 28.11) 5.86 (3.34 – 10.29) No heterogeneity: proportion of males, obesity, history of CAD, CT technology used (64-slice vs. other), follow-up time, potential overfitting of the models

Secondary predictors CT Angiography FindingEvents HR* (95%-CI) I2I2 P ZP LM Coronary Stenosis (2.6 – 17.3)71.9%0< Per Coronary Stenosis (1.1 – 1.7)95.1%< Vessel disease ( )0% Any Atherosclerotic Plaque (2.2 – 9.4)26.7% Segment with any plaque (1.17 – 1.29)7.6% Segment with NCAP (1.2 – 1.4)0% Heterogeneity due to revascularization in endpoints (both p<0.01) and higher prevalence of history of CAD (both p=0.05). n

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