Heterogeneity of Plaque Structural Stress Is Increased in Plaques Leading to MACE: Insights From the PROSPECT Study

Charis Costopoulos; Akiko Maehara; Yuan Huang; Adam J. Brown; Jonathan H. Gillard; Zhongzhao Teng; Gregg W. Stone; Martin R. Bennett

doi:10.1016/j.jcmg.2019.05.024

JACC: Cardiovascular Imaging

July 2019 DOI: 10.1016/j.jcmg.2019.05.024

Heterogeneity of Plaque Structural Stress Is Increased in Plaques Leading to MACE
Insights From the PROSPECT Study

Charis Costopoulos, Akiko Maehara, Yuan Huang, Adam J. Brown, Jonathan H. Gillard, Zhongzhao Teng, Gregg W. Stone and Martin R. Bennett

Author + information

DOI:

https://doi.org/10.1016/j.jcmg.2019.05.024

Published By:

JACC: Cardiovascular Imaging

Print ISSN:

1936-878X

Online ISSN:

1876-7591

History:

Received October 4, 2018
Revision received April 17, 2019
Accepted May 3, 2019
Published online July 17, 2019.

2019 The Authors

Author Information

Charis Costopoulos, MD, PhD^a,
Akiko Maehara, MD^b,
Yuan Huang, PhD^c,^d,^e,
Adam J. Brown, MD, PhD^a,
Jonathan H. Gillard, MD^c,
Zhongzhao Teng, PhD^d,^e,
Gregg W. Stone, MD^b and
Martin R. Bennett, MD, PhD^a,^∗ (mrb{at}mole.bio.cam.ac.uk)

^aDivision of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
^bCardiovascular Research Foundation, New York City, New York
^cDepartment of Engineering and Physical Sciences Research Council, Centre for Mathematical and Statistical Analysis of Multimodal Imaging, University of Cambridge, Cambridge, United Kingdom
^dDepartment of Radiology, University of Cambridge, Cambridge, United Kingdom
^eDepartment of Engineering, University of Cambridge, Cambridge, United Kingdom

↵∗Address for correspondence:
Prof. Martin R. Bennett, Division of Cardiovascular Medicine, University of Cambridge, Level 6, ACCI, Addenbrooke’s Hospital, Cambridge CB2 0QQ, United Kingdom.

Central Illustration

Abstract

Objectives This study sought to determine if plaque structural stress (PSS) and other plaque stress parameters are increased in plaques that cause future major adverse cardiovascular events (MACE) and if incorporating these parameters improves predictive capability of intravascular ultrasonography (IVUS).

Background Less than 10% of coronary plaques identified as high-risk by intravascular imaging result in subsequent MACE. Thus, more specific measurements of plaque vulnerability are required for effective risk stratification.

Methods Propensity score matching in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study plaque cohort resulted in 35 nonculprit lesions (NCL) associated with future MACE and 66 matched NCL that remained clinically silent. PSS was calculated by finite element analysis as the mechanical loading within the plaque structure in the periluminal region.

Results PSS was increased in the minimal luminal area (MLA) regions of NCL MACE versus no MACE plaques for all plaques (PSS: 112.1 ± 5.5 kPa vs. 90.4 ± 3.3 kPa, respectively; p = 0.001) and virtual histology thin-cap fibroatheromas (VH-TCFAs) (PSS: 119.2 ± 6.6 kPa vs. 95.8 ± 5.0 kPa, respectively; p = 0.005). However, PSS was heterogeneous over short segments, and PSS heterogeneity index (HI) was markedly greater in NCL MACE than in no-MACE VH-TCFAs (HI: 0.43 ± 0.05 vs. 0.29 ± 0.03, respectively; p = 0.01). Inclusion of PSS in plaque assessment improved the identification of NCLs that led to MACE, including in VH-TCFAs (p = 0.03) and plaques with MLA ≤4 mm² (p = 0.03). Incorporation of an HI further improved the ability of PSS to identify MACE NCLs in a variety of plaque subtypes including VH-TCFA (p = 0.001) and plaques with MLA ≤4 mm² (p = 0.002).

Conclusions PSS and variations in PSS are increased in the peri-MLA regions of plaques that lead to MACE. Moreover, longitudinal heterogeneity in PSS is markedly increased in MACE plaques, especially VH-TCFAs, potentially predisposing to plaque rupture. Incorporation of PSS and heterogeneity in PSS may improve the ability of IVUS to predict MACE.

Key Words

Footnotes

Supported by British Heart Foundation grants CH/20000003/12800, FS/13/33/30168, and FS/15/26/31441, Heart Research UK grant RG2638/14/16, Medical Research Council Confidence in Concepts award, and the National Institute of Health Research Cambridge Biomedical Research Centre. Dr. Maehara has received research grants from Abbott Vascular and Boston Scientific. Dr. Stone is a consultant for Claret, Backbeat, Sirtex, Matrizyme, Miracor, Neovasc, V-wave, Shockwave, Valfix, TherOx, Reva, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, and Ancora; has received honoraria as speaker from Amaranth and Terumo; holds equity in Ancora, Cagent, Qool Therapeutics, Aria, Caliber, MedFocus, Biostar, and Applied Therapeutics; is director and holds equity in SpectraWave; and has received royalties through Columbia University from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.