Author + information
- Received November 28, 2016
- Revision received February 21, 2017
- Accepted April 5, 2017
- Published online December 4, 2017.
- Charis Costopoulos, MDa,
- Yuan Huang, PhDb,
- Adam J. Brown, MD, PhDa,
- Patrick A. Calvert, MD, PhDc,
- Stephen P. Hoole, MDc,
- Nick E.J. West, MDc,
- Jonathan H. Gillard, MDb,
- Zhongzhao Teng, PhDb,d,∗∗ ( and )
- Martin R. Bennett, MD, PhDa,∗ ()
- aDivision of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
- bDepartment of Radiology, University of Cambridge, Cambridge, United Kingdom
- cDepartment of Interventional Cardiology, Papworth Hospital NHS Trust, United Kingdom
- dDepartment 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.
- ↵∗∗Dr. Zhongzhao Teng, Department of Radiology, University of Cambridge, Box 218 Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
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.
This work was 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 and MRC Confidence in Concepts award; and the NIHR Cambridge Biomedical Research Centre. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 28, 2016.
- Revision received February 21, 2017.
- Accepted April 5, 2017.
- 2017 The Authors