Exploring the MEchanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and computationaL Fluid Dynamic (EMERALD)

Exploring the MEchanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and computationaL Fluid Dynamics (EMERALD)

The EMERALD trial is a multinational, multicenter study. The patients presented with AMI/definite evidence of plaque rupture and had underwent coronary CT angiography from 1 month to 2 year prior to the event will be retrospectively searched. Plaques in the non-culprit vessels will be regarded as internal control to the ruptured plaque in the culprit vessel.

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction; Acute Coronary Syndrome; Plaque, Atherosclerotic; Rupture, Spontaneous

Detailed Description

The mechanisms of plaque rupture have not been fully understood. Hemodynamic forces acting on the plaque, plaque vulnerability, and the interaction between two factors might be the most important mechanism to explain various feature and location of plaque rupture.

The objectives of the study are

1. To explore the interaction between hemodynamic forces measured by computational fluid dynamics (CFD) analysis and plaque vulnerability in culprit lesion of subsequent clinical events.
2. To build rupture risk scoring system, incorporating independent predictor for plaque rupture.

The EMERALD trial is a multinational and multicenter study. The patients presented with AMI/plaque rupture and had underwent coronary CT angiography from 1 month to 2 year prior to the event will be retrospectively searched. Plaques in the non-culprit vessels will be regarded as internal control to the ruptured plaque in the culprit vessel.

The enrollment criteria will be

1. Patients who presented with acute coronary syndrome with cardiac enzyme elevation (AMI)/plaque rupture.
2. Among those patients, the patients who underwent coronary CT angiography, regardless of the reason prior to the acute event will be searched. The time limit of coronary CT angiography will be 1 month ~ 2 year prior to the event.

The Computational Fluids Dynamics (CFD) and Fluid-Structural Interaction (FSI) simulation will be performed to comprehensively evaluate the total plaque forces and their interaction with the plaque.

The comparison groups will be defined as follows; The plaque in the culprit vessel of AMI will be defined the Group A. The plaque in the non-culprit vessel of AMI will be defined as internal control, Group B.

• Study Type: Observational
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who experienced acute myocardial infarction from 2010-2014 whose diagnosis have confirmed by invasive coronary angiography with or without IVUS or OCT evaluation, and who underwent coronary CT angiography from 1 month to 2 year prior to the acute myocardial infarction event. Acute coronary syndrome without cardiac enzyme elevation (unstable angina) will be excluded. The time limit of the coronary CT angiography prior to the event is from 1 month to 2 year. Participating center will perform abovementioned search process.

Description

Inclusion Criteria:

• Patients who experienced acute myocardial infarction from 2010-2014 whose diagnosis have confirmed by invasive coronary angiography with or without IVUS or OCT evaluation, and who underwent coronary CT angiography from 1 month to 2 year prior to the acute myocardial infarction event.

Exclusion Criteria:

• Acute coronary syndrome without cardiac enzyme elevation (unstable angina)
• Patients who did not underwent coronary CT angiography, 1 month to 2 years prior to the acute myocardial infarction
• Poor CT images (unable to reconstruct 3 dimensional coronary artery model)
• The time period between coronary CT angiography and acute myocardial infarction exceed more than 2 years

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Group A (Culprit lesion); The plaque in the culprit vessel of acute myocardial infarction will be defined the Group A.
Group B (Non-culprit lesion); The plaque in the non-culprit vessel of acute myocardial infarction will be defined as internal control, Group B.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference of area under curve between prediction model with adverse plaque characteristics and model with adverse plaque characteristics and hemodynamic forces	Model 1 : percent diameter stenosis + adverse plaque characteristics defined by CT angiography Model 2 : percent diameter stenosis + adverse plaque characteristics defined by CT angiography + Hemodynamic forces defined by computational fluid dynamics	from 1 month - 2 year
The difference of net reclassification index between prediction model with adverse plaque characteristics and model with adverse plaque characteristics and hemodynamic forces	Model 1 : percent diameter stenosis + adverse plaque characteristics defined by CT angiography Model 2 : percent diameter stenosis + adverse plaque characteristics defined by CT angiography + Hemodynamic forces defined by computational fluid dynamics	from 1 month - 2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The best cut-off value of axial plaque stress to induce plaque rupture.	from 1 month - 2 year
The threshold of the plaque vulnerability (Housefiled unit of the plaque on CT) to induce rupture.	from 1 month - 2 year
The independent predictors for the plaque rupture using generalized estimating equation, and the c-index of the predicting models.	from 1 month - 2 year
The validity of rupture risk score which constructed from the predicting model.	from 1 month - 2 year
The differences in other hemodynamic parameters for example, pressure gradient, delta pressure, FFRCT, average and peak wall shear stress between Group A and Group B.	from 1 month - 2 year
The association between axial plaque stress and the parameter reflecting plaque geometry (radius gradient).	from 1 month - 2 year
The differences in axial plaque stress between Group A and Group B	from 1 month - 2 year
The differences in plaque vulnerability (Housefiled unit of the plaque on CT) between Group A and Group B	from 1 month - 2 year

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Aarhus University Hospital; Ulsan University Hospital; Inje University; Keimyung University Dongsan Medical Center; Kyoto University, Graduate School of Medicine; HeartFlow, Inc.; Wakayama Medical University
• Investigators: Study Director: Joo Myung Lee, MD, MPH, Samsung Medical Center

Publications and helpful links

General Publications

• Lee JM, Choi G, Koo BK, Hwang D, Park J, Zhang J, Kim KJ, Tong Y, Kim HJ, Grady L, Doh JH, Nam CW, Shin ES, Cho YS, Choi SY, Chun EJ, Choi JH, Norgaard BL, Christiansen EH, Niemen K, Otake H, Penicka M, de Bruyne B, Kubo T, Akasaka T, Narula J, Douglas PS, Taylor CA, Kim HS. Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics. JACC Cardiovasc Imaging. 2019 Jun;12(6):1032-1043. doi: 10.1016/j.jcmg.2018.01.023. Epub 2018 Mar 14. Erratum In: JACC Cardiovasc Imaging. 2019 Nov;12(11 Pt 1):2288-2289.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimate): March 2, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: April 2, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: pressure; acute coronary syndrome; acute myocardial infarction; coronary computed tomography angiography; computational fluid dynamics; coronary plaque; axial plaque stress; pressure gradient; plaque rupture; wall shear stress
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Wounds and Injuries; Disease; Pathological Conditions, Anatomical; Myocardial Infarction; Infarction; Syndrome; Rupture; Acute Coronary Syndrome; Plaque, Atherosclerotic; Rupture, Spontaneous
• Other Study ID Numbers: NCT02374775

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After acceptance of first manuscript, the data will be shared upon request and permission of principal investigator and participants of the study