Patient case: 47-year-old male with melanoma; genetic feature: APC loss of function

Clinical trial: Incident COronary EveNts Identified by Computed Tomography

Summary: The ICONIC study is a retrospective, international, multicenter, nested case-control study based on propensity scoring methods to match patients with (Cases) and without (Controls) an acute coronary syndrome (ACS). Our objective is to identify atherosclerotic plaque characteristics (APCs) that may be implicated in future ACS and compare gender-specific disparities, if any, in coronary plaques among women and men who subsequently experience a future ACS. The primary outcome is an ACS comprised of ST elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI), or unstable angina, and the secondary outcome of MI includes STEMI and NSTEMI only.

Detailed description: BACKGROUND:
  Coronary artery disease (CAD) is accountable for a substantial portion of cardiovascular morbidity and mortality worldwide. Although traditional risk prediction algorithms to determine individuals at risk of future ACS have been used, these approaches are still considered less precise for estimating individual risk, and can misclassify a large proportion of definite acute myocardial infarction (AMI) as low-risk individuals for future AMI. Moreover, current risk evaluation has focused primarily on identifying individuals with high-grade stenosis, yet, the majority of ACS tend to occur without prior high-grade coronary stenosis in the culprit event-causing plaques. Notably, in relation to gender disparity, these findings are more apparent, with prognosis appearing considerably worse for women, with greater morbidity and mortality in the post-AMI period. Although autopsy examinations and invasive modalities such as intravascular ultrasound (IVUS) have revealed characteristics of vulnerable plaque with high ACS risk, these modalities have assessed patients only after rather than before the occurrence of an ACS, which may impede on determining a cause-effect relationship.
  Coronary computed tomographic angiography (CCTA) of 64-detector rows or greater hold promise as a non-invasive modality, and has often displayed high diagnostic performance for the evaluation of CAD as compared with invasive coronary angiography. CCTA is capable of evaluating specific features of atherosclerotic plaque as well as coronary arterial wall in a similar fashion to IVUS. Consequently, APCs can be readily visualized by CCTA in culprit lesions post ACS and have demonstrated high agreement with invasive methods. Though to date, the utility of APCs by CCTA for prognostication of future risk of ACS remains unexplored either at a per-patient or per-lesion basis. Further still, no adequately sized study has examined the gender-specific disparity in APCs among individuals prior to the occurrence of an ACS.
  STUDY OVERVIEW:
  The ICONIC is a nested case-control study based similarly upon the dynamic COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, encompassing a well-characterized patient cohort that is capable of detecting a meaningful association between APCs and future ACS. ICONIC will employ CCTA to comprehensively determine whether coronary APCs beyond traditional angiographic measures of CAD will be implicated in future ACS, and further, to effectively prognosticate gender-specific risk for future ACS. To this end, ICONIC will essentially examine the primary hypothesis that APCs within coronary plaques implicated in future ACS differ from APCs not implicated in future ACS. Secondly, in order to compare the disparity in coronary plaques for women versus men who subsequently experience a future ACS, ICONIC will test gender-specific difference in plaque characteristics among men and women who will experience a future ACS.

Eligibility: Cases
  Inclusion criteria:
  -  Age ≥18 years
  -  Adjudicated STEMI / NSTEMI / Unclassified MI / UA
  Exclusion criteria:
  -  Not ACS, Possible MI, Possible UA, and Absence of cardiac enzymes
  -  Lack of CCTA
  -  Prior history of CAD (Revascularization or MI) in RedCAP/CONFIRM (Revascularization or MI date precedes CCTA)
  -  ACS in revascularized segment
  -  Prior revascularization found on CCTA during MEDIS evaluation
  -  Type 4a, 4b, or 5 MI (Interval revascularization is not an exclusion criteria)
  Controls
  Inclusion criteria:
  -  Age ≥18 years
  -  Propensity score matched within a caliper predetermined from original cohort to reduce 95% bias.
  Exclusion criteria:
  -  Prior history of CAD
  -  Death

Relevance to patient case: not relevant