Abstract Background Plaque progression and luminal encroachment are well-established features of atherosclerosis. However, coronary lumen size does not necessarily decrease in parallel with plaque accumulation or stenosis severity. Preservation of lumen area, both in diseased and non-diseased vessel segments, may contribute to protection against ischemia, a concept that remains insufficiently explored. Prior investigations have examined the coronary lumen volume to left ventricular mass (V/M) ratio and identified it as an independent protective factor for ischemia. However, lumen volume does not equate to lumen size and therefore may not accurately reflect the true extent of lumen preservation. Thus, we evaluated the role of lumen size, particularly defined by average lumen area (ALA) and its association with coronary ischemia. Purpose This study aimed to evaluate the relationship between ALA vessel-specific ischemia beyond diameter stenosis and percent atheroma volume (PAV). Methods We conducted a post hoc vessel-level analysis of 1,716 vessels from the CREDENCE study and 612 vessels from the PACIFIC-1 study. Both cohorts included symptomatic patients with suspected stable coronary artery disease who had prospectively undergone coronary computed tomography angiography (CTA) and invasive coronary angiography with fractional flow reserve (FFR) measurements. AI-enabled quantitative CTA (AI-QCT) was used to assess plaque volume and burden. Ischemia was defined as FFR ≤ 0.80. Each vessel (LAD, RCA, CX) included their side branches. The ALA was stratified into tertiles (small, medium, large), and three prediction models were constructed to assess the added value of ALA beyond diameter stenosis and PAV, using ROC curve analysis and net reclassification improvement (NRI). Results As illustrated in Figure 1, ischemia prevalence increased with stenosis severity and PAV, yet within each stenosis or PAV category, vessels with greater ALA showed consistently lower ischemia rates. For example, in CREDENCE vessels with 50%-70% stenosis, ischemia was observed in 60.0% of small, 43.8% of medium, and 27.8% of large vessels (all P 0.05). Similar patterns were observed within PAV strata across all plaque subtypes. In ROC analysis, Model 1 (diameter stenosis ≥ 50%) yielded an AUC of 0.82 in CREDENCE, which improved to 0.85 with the addition of PAV (Model 2), and further to 0.87 with inclusion of ALA (Model 3), along with an NRI of 0.49 (P 0.001). In PACIFIC, the AUC similarly improved from 0.84 to 0.87 with the incorporation of ALA, with an NRI of 0.51 (P 0.001) (Figure 2). Conclusion A larger lumen size relates to less coronary ischemia, irrespective of diameter stenosis and plaque burden. These findings highlight the importance of lumen preservation in response to plaque development, and its need for inclusion in coronary CTA interpretation.The impact of ALA on ischemia prevalence Incremental predictive value of average
Ding et al. (Thu,) studied this question.