The overall aim is to build an AI driven national Platform for CT cOronary angiography for clinicaL and industriaL applicatiOns (APOLLO) for automated anonymization, reporting, Agatston scoring and plaque quantification in CAD. It is a "one-stop" platform spanning diagnosis to clinical management and prognosis, and aid in predicting pharmacotherapy response.
Coronary artery disease (CAD), a blockage of the blood vessels, affects 6% of the general population and up to 20% of those over 65 years of age. CAD is a leading cause of cardiac mortality in Singapore and worldwide, with 19% of deaths in Singapore due to CAD (MOH website). Numbers of CAD cases are increasing due to ageing and the higher prevalence of contributary diseases such as diabetes. Computed Tomography Coronary Angiography (CTCA) is the first-line investigation for CAD as indicated by the National Institute for Clinical Excellence (NICE) guidelines. Recent Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) and Scottish Computed Tomography of the Heart (SCOT-HEART) trials support CTCA as the dominant means for evaluating coronary anatomy and physiology as it increases diagnostic certainty, improves efficiency of triage to invasive catheterization and reduces radiation exposure when compared to functional stress testing. Currently, CAD report generation requires 3-6 hours of a CT specialist's time to annotate scans, with inter-observer variability of 20%. In addition, there is no effective singular toolkit to analyse Agatston scores (a measure of calcified CAD), severity of stenosis, and plaque characterisation. These problems have severely constrained the effectiveness of CTCA as a diagnostic and research tool. The investigators plan to build upon Singapore's competitive advantages in artificial intelligence (AI) to provide a solution to these gaps.
Study Type
OBSERVATIONAL
Enrollment
8,000
CTCA is performed as part of routine care procedure.
National Heart Centre Singapore
Singapore, Singapore
RECRUITINGNational University Hospital
Singapore, Singapore
RECRUITINGTan Tock Seng Hospital
Singapore, Singapore
RECRUITINGAI precision toolkits: AI stenosis reporting
Stenosis reporting: Severity of stenosis and accurate anatomical localization of stenosis. The significance of a stenosis is determined by visual estimation of the maximal grade of luminal narrowing caused by the plaque. As recommended in SCCT guideline (Leipsic et al., 2014) , coronary stenosis can be graded as minimal, mild, moderate, severe and total occluded separately. Following the guideline, a stenosis will be classified as obstructive and non-obstructive. The location of the stenosis uses the SCCT model (Leipsic et al., 2014)
Time frame: baseline
AI precision toolkits: Agatston scoring
Agatston scoring: Agatston scoring of calcified plaque. As recommended in SCCT clinical practical guidelines (Leipsic et al., 2014), Agatston scoring programs generally identify pixels that exceed 130 HU as a level corresponding to calcium on a non-contrast study (Agatston et al., 1990) . The reader needs to identify each lesion discrete calcific focus) in each vessel distribution. The summed score for each vessel is generated by the scoring program based on an area-density (Agatston score) (Agatston et al., 1990) measurement of each calcified focus. The total coronary Agatston score is the sum of all calcified lesions in all coronary beds.
Time frame: baseline
AI precision toolkits: Plaque
Plaque analysis: Plaque volume, burden, type and anatomical locations. Coronary segmentation and plaque analysis is performed for segments with diameter ≥1.5 mm. Location of plaque uses the SCCT model (Leipsic et al., 2014). For each plaque, the reader marks its start-and end-points, quantifies plaque area,volume and plaque burden, and specifies its type (non-calcified, calcified, or mixed) (Achenbach et al., 2004) . Additionally, non-calcified plaque can be further divided into low attenuation plaque (LAP). A HU \<30 will signify LAP and \>30 will signify non-LAP.
Time frame: baseline
AI precision toolkits: EAT analysis
EAT analysis: Total volume and anatomical locations. EAT and pericardial adipose tissue (PAT) are metabolically active fat surrounding the coronary artery and the heart, being associated with increased risk of cardiovascular disease (Villasante et al, 2019) . EAT can be quantified on non-contrast CT scans. The annotations on the CT scans are obtained by manually drawing the pericardium first to define the region. EAT is identified using the adipose tissue attenuation references between -190 and -30 HU (Oikonomou et al., 2018) . Due to the CT scan noise and changing of attenuation, the HU value of fat can vary, so the final EAT region is verified by an experienced radiologist or cardiologist.
Time frame: baseline
AI outcome analysis
1\. Mortality (All-cause and/or cardiovascular)
Time frame: one to five years from baseline
AI outcome analysis
Major-adverse cardiovascular events (myocardial infarction, stroke, heart failure, revascularisation, arrhythmias, etc)
Time frame: one to five years from baseline
AI outcome analysis
Re-hospitalisation
Time frame: one to five years from baseline
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