PreDiction and Validation of Clinical CoursE of Coronary Artery DiSease With CT-Derived Non-Invasive HemodYnamic Phenotyping and Plaque Characterization (DESTINY Study) (DESTINY)

Prediction and Validation of Clinical Course of Coronary Artery Disease With CT-Derived Non-Invasive Hemodynamic Phenotyping and Plaque Characterization

Acute coronary syndrome (ACS) and sudden cardiac death can be the first manifestation of coronary artery disease and are the leading cause of death in the majority of the world's population. The main pathophysiology of ACS is well-known and fibrous cap thickness, presence of a lipid core, and the degree of inflammation have been proposed as the key determinants of plaque vulnerability. Previous studies using virtual histology intravascular ultrasound or optical coherence tomography showed that clinical application of this concept improved risk prediction of ACS. However, these approaches have not been widely adopted in daily practice due to relatively low positive predictive values, low prevalence of high-risk plaques and the invasive nature of diagnostic modalities.

Non-invasive imaging studies with coronary computed tomography angiography (CCTA) also showed the clinical value of CCTA-derived high risk plaque characteristics (HRPC). In addition, the recent progress in CCTA and computational fluid dynamics (CFD) technologies enables simultaneous assessment of anatomical lesion severity, presence of HRPC and quantification of hemodynamic forces acting on plaques in patient-specific geometric models. As plaque rupture is a complicated biomechanical process influenced by the structure and constituents of the plaque as well as the external mechanical and hemodynamic forces acting on the plaque, a comprehensive evaluation of lesion geometry, plaque characteristics and hemodynamic parameters may enhance the identification of high-risk plaque and the prediction of ACS risk.

In this regard, the current study is designed to evaluate prognostic implications of comprehensive non-invasive hemodynamic assessment using CCTA and CFD in the identification of high risk plaques that caused subsequent ACS.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Ischemic Heart Disease
• Intervention / Treatment: Diagnostic test: CCTA-derived high risk plaque characteristics; Diagnostic test: CFD-derived hemodynamic parameters

Detailed Description

The study population was collected from Samsung Medical Center. Target population is patients who suffered a clearly documented ACS (acute myocardial infarction [MI] or unstable angina with objective evidence of plaque rupture) or those who underwent significant lesion progression in angiography and treated by percutaneous coronary intervention (PCI) and had undergone CCTA from 6 months to 3 years prior to the coronary events.

CCTA images were screened for plaque characteristics and CFD analysis at core laboratories in Elucid Bioimaging, Inc, MA, USA and Shanghai Institute of Cardiovascular Diseases, Shanghai, China, respectively. Lesions with diameter stenosis (DS) > 30% based on CCTA evaluation were included analysis. The presence of conventional CCTA-HRPC (minimum lumen area<<4 mm2, plaque burden≥70%, low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification) and parameters from tissue characterization using VascuCAP software will be assessed in each lesion by an independent observer blinded to the clinical data and CFD results. The hemodynamic parameters from CFD will include 1) per-vessel FFR derived from CCTA (FFRCT); 2) change in FFRCT across the lesion (△FFRCT); 3) FFRCT pullback pressure gradient (PPG) index (FFRCT-PPG index); 4) Fractional myocardial mass (FMM) of the target stenosis.

Using the occurrence of ACS or PCI for the progressed lesion as clinical endpoint, prognostic implications of CCTA-derived HRPC or hemodynamic parameters will be analyzed.

• Study Type: Observational
• Enrollment (Actual): 356

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Institute of Cardiovascular Diseases
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The study population was collected from Samsung Medical Center. Target population is patients who suffered a clearly documented ACS (acute myocardial infarction [MI] or unstable angina with objective evidence of plaque rupture) or those who underwent significant lesion progression in angiography and treated by percutaneous coronary intervention (PCI) and had undergone CCTA from 6 months to 3 years prior to the coronary events.

Description

Inclusion Criteria:

1. Patients who presented with ACS and underwent invasive coronary angiography with identifiable culprit lesion
2. Patients who presented with stable ischemic heart disease and underwent invasive coronary angiography for the significant epicardial coronary stenosis
3. The patients who underwent coronary CT angiography, regardless of the reason (for example, routine healthcare check-up, or evaluation for stable angina or atypical chest pain) prior to the acute event.
4. Time limit of CCTA: 6 months ~ 3 years prior to the event.

5. Definition of ACS:

   • The patients with acute myocardial infarction should meet one of the following criteria;

     • Cardiac enzyme elevation "and"
     • Identified culprit lesion confirmed by invasive coronary angiography, IVUS, or OCT
   • The patients with unstable angina should be accompanied by the evidence of plaque rupture confirmed with invasive coronary angiography, IVUS, or OCT

Exclusion Criteria:

Exclusion criteria for Patient enrollment

• Patients with acute coronary syndrome without clear evidence of culprit lesion
• Patients with stents in two or more vessel territories prior to CCTA
• Poor quality of CCTA which is unsuitable for plaque and CFD analysis
• Patients with ACS culprit lesion in a stented vessel
• Patients with previous history of coronary artery bypass graft surgery
• Secondary myocardial infarction due to other general medical conditions, such as sepsis, arrhythmia, bleeding, etc.
• Poor quality CCTA images unsuitable for CFD analysis
• No available unprocessed CCTA data

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Culprit vessel of acute coronary syndrome	Diagnostic test: CCTA-derived high risk plaque characteristics; Presence of CCTA-derived high risk plaque characteristics; Diagnostic test: CFD-derived hemodynamic parameters; CFD-derived hemodynamic parameters
Non-culprit vessel of acute coronary syndrome	Diagnostic test: CCTA-derived high risk plaque characteristics; Presence of CCTA-derived high risk plaque characteristics; Diagnostic test: CFD-derived hemodynamic parameters; CFD-derived hemodynamic parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute myocardial infarction	Target vessel-related acute myocardial infarction	3 years after index CCTA
Revascularization	Target vessel-related revsacularization	3 years after index CCTA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target vessel failure	A composite of Cardiac death, Target vessel-related acute myocardial infarction, Target vessel-related revsacularization	3 years after index CCTA
All-cause death	All-cause death	3 years after index CCTA
Cardiac death	Death due to cardiac cause	3 years after index CCTA
Major adverse cardiac and cerebral events	A composite of All-cause death, Target vessel-related acute myocardial infarction, Target vessel-related revsacularization, Cerebrovascular accident	3 years after index CCTA

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Shanghai Institute of Cardiovascular Diseases; Elucid Bioimaging Inc.
• Investigators: Principal Investigator: Joo Myung Lee, MD, MPH, PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Lee SH, Hong D, Dai N, Shin D, Choi KH, Kim SM, Kim HK, Jeon KH, Ha SJ, Lee KY, Park TK, Yang JH, Song YB, Hahn JY, Choi SH, Choe YH, Gwon HC, Ge J, Lee JM. Anatomic and Hemodynamic Plaque Characteristics for Subsequent Coronary Events. Front Cardiovasc Med. 2022 May 23;9:871450. doi: 10.3389/fcvm.2022.871450. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: acute coronary syndrome; fractional flow reserve; plaque characteristics; fractional myocardial mass
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Arteriosclerosis; Arterial Occlusive Diseases; Disease Progression; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Acute Coronary Syndrome
• Other Study ID Numbers: NCT20210308-JM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Anatomized patient data can be shared upon reasonable request after decision by principal investigator

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No