Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease

JACC Cardiovasc Imaging. 2023 Nov;16(11):1452-1464. doi: 10.1016/j.jcmg.2023.05.018. Epub 2023 Jul 19.


Background: The interplay between coronary hemodynamics and plaque characteristics remains poorly understood.

Objectives: The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics.

Methods: This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value.

Results: A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87).

Conclusions: Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688).

Keywords: calcification; coronary computed tomography angiography; lipid-rich plaque; optical coherence tomography; pullback pressure gradient; thin-cap fibroatheromas.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Angiography / methods
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / pathology
  • Fractional Flow Reserve, Myocardial*
  • Humans
  • Lipids
  • Phenotype
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests
  • Prospective Studies


  • Lipids

Associated data