Editor's Note: Commentary based on Mushtaq S, De Araujo Gonçalves P, Garcia-Garcia HM, et al. Long-Term Prognostic Effect of Coronary Atherosclerotic Burden: Validation of the Computed Tomography-Leaman Score. Circ Cardiovasc Imaging 2015;8:e002332.

Study Aim

Validation of Computed tomography-adapted Leaman score (CT-LeSc) as a long-term predictor of prognosis in patients undergoing coronary CT angiography (CCTA) for suspected coronary artery disease (CAD).

Background

The presence and extent of coronary artery disease detected on coronary CT angiography (CCTA) has been demonstrated to have prognostic value in risk stratification for future cardiac events.^1,2 The Leaman score was initially developed for invasive angiography.³ The CT-adapted Leaman score (CT-LeSc) which uses plaque/lesion localization, degree of stenosis plus plaque composition, enables assessment of the total coronary atherosclerotic burden. This single center, prospective registry was designed to evaluate the long-term prognostic value of CT-LeSc in patients with suspected CAD.

Methods

This was a prospective cohort study involving 1304 patients undergoing CCTA for suspected CAD. Diamond-Forrester was used to assess pretest CAD probability. Three groups of patients were identified: normal (absence of CAD), non-obstructive CAD (< 50% diameter stenosis) and obstructive CAD (≥ 50% diameter stenosis). Patients with CT-LeSc score > 5 were grouped as high CT-LeSc, while a score ≤5 was grouped as low CT-LeSc. Two other atherosclerotic burden scores: the Segment Involvement Score (SIS) which is the total number of segments with plaque and the Segment Stenosis Score (SSS) which is the severity of stenosis of each segment were also calculated. Mean follow-up was 52 ± 22 months. Two hard cardiac events: cardiac death from acute myocardial infarction, ventricular arrhythmias or refractory heart failure; and non-fatal acute coronary syndromes were evaluated. Event free survival rates were assessed using Kaplan-Meier method, independent event predictors were identified using Cox regression models and the performance of CT-LeSc was assessed using four metrics: reclassification tables and Net Reclassification Indexes (NRI); area under the curve (AUC) for discrimination and Brier score for accuracy.

Results

For data analysis, 108 patients were excluded (70 due to uninterpretable CCTA and 38 lost to follow-up). Of the 1196 patients in the analysis, 125 patients experienced 136 hard events (18 cardiac deaths and 118 non-fatal myocardial infarction). Mean pretest CAD probability was 42.5 ± 9.9%. The majority of patients (42%, n=503) had a normal CCTA. Obstructive CAD was present in 37.8% (n=452) and non-obstructive CAD in 20.2% (n=241) patients. Statin use was sub-optimal in patients with CAD: 22% in non-obstructive CAD and low CT-LeSc, 31% in non-obstructive CAD and high CT-LeSc, 33% in obstructive CAD and low CT-LeSc and 42% in obstructive CAD and high CT-LeSc.

All three atherosclerotic scoring systems showed comparable discrimination with similar AUC for hard events: CT-LeSc 0.808 (95% CI 0.785-0.83); SIS 0.811 (95% CI 0.78-0.841); and SSS 0.82 (95% CI 0.776-0.842). CT-LeSc was better than the other two atherosclerotic scores (SSS and SIS) for identifying patients with lower risk (43% and 20% respectively). All three scores were similar in identifying patients at higher risk. The three atherosclerotic scores had similar accuracy with each having a Brier score of 0.10 All three atherosclerotic scores: CT-LeSc, SSS and SIS were independent predictors of hard cardiac events with hazard ratios of 5.39 (95% CI 3.49-8.33); 4.42 (95% CI 2.97-6.57) and 3.09 (95% CI 2.0-4.75) respectively. Interestingly, the event-free survival for patients with obstructive CAD and a high CT-LeSc (76.5%) was similar with patients with non-obstructive CAD and high CT-LeSc (78.6%; log rank p=0.627) and lower than patients with obstructive CAD and low CT-LeSc (80.7%; log rank p=810).

Conclusion

CT-LeSc is an independent long-term predictor of cardiac death and non-fatal myocardial infarction. The hard event-free survival rate in patients with non-obstructive CAD and high CT-LeSc and patients with obstructive CAD is similar.

Commentary/Perspective

This study's results are consistent with prior studies which demonstrated the prognostic implication of the presence of non-obstructive CAD for cardiac risks.⁴ In addition, this study is noteworthy for the large sample size, its use of hard cardiac events for outcome assessment and the number of cardiac event rates. However, the finding of a higher hard cardiac event rate for non-obstructive CAD with high CT-LeSc compared to obstructive CAD with low CT-LeSc is interesting. The authors partly attribute this result to the higher rates of revascularization (not included as a hard event) in patients with obstructive CAD. Lower prevalence of statin therapy in non-obstructive patients might also have played some role.This finding would need to be confirmed by randomized clinical trial. While this study validates the utility of CT-LeSc for long-term prediction of hard cardiac events, the similar performance of all three atherosclerotic scores in AUC analysis and the relative easier implementation of SSS or SIS, favor quicker adoption of these two scores in clinical practice compared to CT-LeSc. It is also important to note that unlike the low-to-intermediate CAD pretest probability for whom CCTA is recommended, the authors acknowledge that a subset of patients in the study had a high pretest CAD probability, and so do not represent the typical clinical population for whom CCTA would be used.

References

1. Bamberg, F., et al., Meta-analysis and systematic review of the long-term predictive value of assessment of coronary atherosclerosis by contrast-enhanced coronary computed tomography angiography. J Am Coll Cardiol 2011;57:2426-36.
2. Hulten, E.A., et al., Prognostic value of cardiac computed tomography angiography: a systematic review and meta-analysis. J Am Coll Cardiol 2011; 57: 1237-47.
3. Leaman, D.M., et al., Coronary artery atherosclerosis: severity of the disease, severity of angina pectoris and compromised left ventricular function. Circulation 1981; 63:285-99.
4. Mancini, G.B., et al., Predicting outcome in the COURAGE trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation): coronary anatomy versus ischemia. JACC Cardiovasc Interv 2014; 7: 195-201.

Keywords: Acute Coronary Syndrome, Area Under Curve, Arrhythmias, Cardiac, Cohort Studies, Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Coronary Disease, Cost of Illness, Disease-Free Survival, Heart Failure, Myocardial Infarction, Prevalence, Proportional Hazards Models, Prospective Studies, Registries, Tomography, Angina, Stable

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