Identification of vulnerable non-culprit lesions by coronary computed tomography angiography in patients with chronic coronary syndrome and diabetes mellitus

Abstract

Background: Among patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients.

Methods: Between January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression.

Results: Overall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden >70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92-6.44], a low-density non-calcified plaque (LDNCP) volume >30 mm³ (HR: 3.40, 95% CI: 2.07-5.56), a minimal luminal area (MLA) <4 mm² (HR: 2.30, 95% CI: 1.57-3.36), or a combination of three APCs (HR: 13.69, 95% CI: 9.34-20.12, p < 0.0001) than those not associated with recurrent MACEs. Sensitivity analysis regarding all indeterminate MACEs as NCL-related ones demonstrated similar results.

Conclusions: In DM patients who presented with CCS and underwent PCI, half of the MACEs occurring during the follow-up were attributable to recurrence at the site of NCLs. NCLs responsible for unanticipated MACEs were frequently characterized by a large plaque burden and LDNCP volume, a small MLA, or a combination of these APCs, as determined by CCTA.

Keywords: adverse plaque characteristic; chronic coronary syndrome; coronary computed tomography angiography; diabetes mellitus; major adverse cardiovascular event; non-culprit lesion.

Figure 1

Consort diagram.

Figure 2

Kaplan–Meier curves of patients surviving event-free from the first MACE of each classification and all.

Figure 3

Representative case of a MACE attributed to the progression of an NCL that was not treated by PCI at baseline. A 51-year-old man presented with CCS, DM (insulin therapy), hypertension, smoking, and three-vessel disease (syntax score: 19). Successful PCI of CL that had caused CCS in the proximal segment of left anterior descending was done. One angiographically mild lesion was identified in the distal segment of the right coronary artery (arrow in A), and PCI treatment of this lesion was deferred. However, the patient re-presented with MI 3 years later. ICA showed a new severe stenosis with pronounced lesion progression and thrombus at the site of the originally untreated NCL in the distal segment of the right coronary artery (arrow in B). The imaging analysis of baseline CCTA by the core laboratory showed that this NCL was a completely non-calcified plaque with positive remodeling (C). The MLA was 1.9 mm², plaque burden was 72.6%, and the volume of LDNCP was 36.7 mm³.

Figure 4

Association between the study endpoints and different combinations of APCs of NCL.