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

AimTo 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 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

Results – Study selection

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 endpointVariable Studies N events / N Hazard ratio (95% CI) P

Average age

>58 years*

≤58 years

4

5

126/1657

126/2013

19.83 (10.04 – 39.16)

7.17 (4.23 – 12.15)

0.02

Revasc. in Endpoint

Not included

Included

3

6

55/1241

197/2429

6.15 (3.22 – 11.74)

15.41 (8.92 – 26.62)

0.03

Study Quality

Higher

lower

5

4

106/2157

146/1513

16.83 (10.08 – 28.11)

5.86 (3.34 – 10.29)

0.001

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 Finding Events HR* (95%-CI) I2 P Z P

LM Coronary Stenosis 142 6.64 (2.6 – 17.3) 71.9% 0<0.01 0.49 0.62

Per Coronary Stenosis 145 1.35 (1.1 – 1.7) 95.1% <0.01 0.41 0.52

3-Vessel disease 125 2.50 (1.9-3.3) 0% 0.55 0.32 0.87

Any Atherosclerotic Plaque 244 4.51 (2.2 – 9.4) 26.7% 0.33 0.96 0.32

Segment with any plaque 163 1.23 (1.17 – 1.29) 7.6% 0.35 -0.7 0.50

Segment with NCAP 124 1.29 (1.2 – 1.4) 0% 0.13 0.27 0.91

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