Plaque Rupture in Coronary Atherosclerosis Is Associated With Increased Plaque Structural Stress

Abstract

Objectives: The aim of this study was to identify the determinants of plaque structural stress (PSS) and the relationship between PSS and plaques with rupture.

Background: Plaque rupture is the most common cause of myocardial infarction, occurring particularly in higher risk lesions such as fibroatheromas. However, prospective intravascular ultrasound-virtual histology studies indicate that <10% higher risk plaques cause clinical events over 3 years, indicating that other factors also determine plaque rupture. Plaque rupture occurs when PSS exceeds its mechanical strength; however, the determinants of PSS and its association with plaques with proven rupture are not known.

Methods: We analyzed plaque structure and composition in 4,053 virtual histology intravascular ultrasound frames from 32 fibroatheromas with rupture from the intravascular ultrasound-virtual histology in Vulnerable Atherosclerosis study and 32 fibroatheromas without rupture on optical coherence tomography from a stable angina cohort. Mechanical loading in the periluminal region was estimated by calculating maximum principal PSS by finite element analysis.

Results: PSS increased with increasing lumen area (r = 0.46; p = 0.001), lumen eccentricity (r = 0.32; p = 0.001), and necrotic core ≥10% (r = 0.12; p = 0.001), but reduced when dense calcium was ≥10% (r = -0.12; p = 0.001). Ruptured fibroatheromas showed higher PSS (133 kPa [quartiles 1 to 3: 90 to 191 kPa] vs. 104 kPa [quartiles 1 to 3: 75 to 142 kPa]; p = 0.002) and variation in PSS (55 kPa [quartiles 1 to 3: 37 to 75 kPa] vs. 43 kPa [quartiles 1 to 3: 34 to 59 kPa]; p = 0.002) than nonruptured fibroatheromas, with rupture primarily occurring either proximal or immediately adjacent to the minimal luminal area (87.5% vs. 12.5%; p = 0.001). PSS was higher in segments proximal to the rupture site (143 kPa [quartiles 1 to 3: 101 to 200 kPa] vs. 120 kPa [quartiles 1 to 3: 78 to 180 kPa]; p = 0.001) versus distal segments, associated with increased necrotic core (19.1% [quartiles 1 to 3: 11% to 29%] vs. 14.3% [quartiles 1 to 3: 8% to 23%]; p = 0.001) but reduced fibrous/fibrofatty tissue (63.6% [quartiles 1 to 3: 46% to 78%] vs. 72.7% [quartiles 1 to 3: 54% to 86%]; p = 0.001). PSS >135 kPa was a good predictor of rupture in higher risk regions.

Conclusions: PSS is determined by plaque composition, plaque architecture, and lumen geometry. PSS and PSS variability are increased in plaques with rupture, particularly at proximal segments. Incorporating PSS into plaque assessment may improve identification of rupture-prone plaques.

Keywords: atherosclerosis; coronary disease; vulnerable plaque.

Graphical abstract

Figure 1

Schematic Representation of Patient and Plaque Populations Included in the Study FEA = finite element analysis; OCT = optical coherence tomography; VH-FA = virtual histology fibroatheroma; VIVA = VH-IVUS in Vulnerable Atherosclerosis study.

Figure 2

Identification of Plaque Rupture Using Gray-Scale Intravascular Ultrasound and Optical Coherence Tomography (A and B) Gray-scale IVUS images of spontaneous plaque rupture (*). (C) OCT image showing evidence of rupture (*).(D) Thin-cap fibroatheroma (arrow) as identified by OCT with no evidence of rupture or erosion. (E) Longitudinal IVUS reconstruction of a coronary artery with evidence of plaque rupture; proximal (A′); rupture site (B′); and distal (C′) segments. IVUS = intravascular ultrasound; other abbreviation as in Figure 1.

Figure 3

Illustrative Examples for Stepwise Calculation of Plaque Structural Stress From IVUS-VH Through Finite Element Analysis (A and D) IVUS-VH images showing necrotic core (red), dense calcium (white), fibrofatty tissue (light green), and fibrous (green). (B and E) Reconstructed plaque geometry and segmented plaque components used for finite element analysis. (C and F) Plaque structural stress band plots identifying regions with high stress concentration (arrows indicate areas of high stress at the plaque/lumen boundary). IVUS-VH = intravascular ultrasound-virtual histology.

Figure 4

Indices of Vessel Geometry and Plaque Structural Stress (A to C) Regression curves illustrating best-fit relationships between PSS and (A) luminal area, (B) luminal eccentricity or (C) plaque burden. PSS = plaque structural stress.

Figure 5

Effect of Plaque Components on PSS Regression curves illustrating best-fit relationships between PSS and (A) necrotic core (%), (B) maximal arc of necrotic core (°), (C) dense calcium (%), (D) maximal arc of dense calcium (°), (E) fibrous/fibrofatty tissue (%), and (F) maximal arc of fibrous/fibrofatty tissue (°). Abbreviation as in Figure 4.

Figure 6

PSS and Variation in PSS in VH-FAs With and Without Rupture (A and B) PSS and variation in PSS in the proximal and distal segments of VH-FAs with and without plaque rupture. (C and D) PSS and variation in PSS in the proximal and distal segments of VH-TCFAs with and without PR. (E and F) PSS and variation in PSS in VH-TCFAs with PB ≥70% or MLA ≤4 mm² with and without PR. MLA = minimal luminal area; PR = plaque rupture; VH-TCFA = virtual histology thin-cap fibroatheroma; other abbreviations as in Figures 1 and 4.

Figure 7

ROC Curves Illustrating the Discriminatory Power of PSS to Identify Plaque Rupture (A) ROC curve for PSS in VH-FA. (B) ROC curve for PSS in VH-FA + MLA ≤4 mm². (C) ROC curve for PSS in VH-FA+PB ≥70%. AUC = area under the curve; CI = confidence interval; MLA = minimal lumen area; PB = plaque burden; ROC = receiver-operating characteristic; other abbreviation as in Figure 1.