Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis

Objectives: This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA). Background: Coronary CTA can noninvasively assess coronary plaques quantitatively. Methods: Patients who underwent 2 coronary CTAs at a minimum of 24 months’ interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome. Results: Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm³ [interquartile range (IQR): 0.0 to 39.6 mm³]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm³ [IQR: 0.0 to 127.4 mm³]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm³ [IQR: 96.7 to 306.4 mm³]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features. Conclusions: The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes.