Computed Tomography Coronary Angiography (CTCA) Prognostic Registry for Coronary Artery Disease
Computed Tomography Coronary Angiography (CTCA) Prognostic Registry for Coronary Artery Disease
The study aims at pooling a large population of patients with suspected coronary artery
 disease (CAD) who underwent Computed Tomography Coronary Angiography (CTCA) and who were
 adequately stratified in the first place. Then the investigators will be able to assess the
 incremental value of CTCA in the stratification of prevalence of disease (non
 obstructive/obstructive) and prognosis of patients with suspected CAD). The added information
 to current evidence is how reliable and to what extent CTCA can define the actual burden of
 disease and cardiovascular risk.
The Project aims at pooling (retrospectively) a large population of patients with suspected
 coronary artery disease (CAD) who underwent Computed Tomography Coronary Angiography (CTCA)
 and who were adequately stratified in the first place. Then the investigators will be able to
 assess the incremental value of CTCA in the stratification of prevalence of disease (non
 obstructive/obstructive) and prognosis of patients with suspected CAD. The added information
 to current evidence is how reliable and to what extent CTCA can define the actual burden of
 disease and cardiovascular risk.

 Primary objectives

 -  MACE/Major Adverse Cardiovascular Events (i.e. Cardiac Death, Unstable Angina requiring
 Hospitalization, Acute Myocardial Infarction)

 -  Prevalence of cardiovascular risk category shifting based on coronary plaque burden

 Secondary objectives

 -  Coronary Revascularizations occurred after CTCA (i.e. PCI/Percutaneous Coronary
 Revascularization and CABG/Coronary Artery Bypass Graft)

 -  Prevalence of outliers (i.e. patients lying completely outside the conventional risk
 stratification; pts with >3 risk factors and no CAD at CTCA and pts with no risk factors
 and >5 coronary segments with CAD)

 Institutional Database will be used as data supply. Data will be anonimyzed and pooled (i
 twill not be possible to detect patients' identity). For this reason the investigators will
 no task for patients' Informed Consent.

 DESIGN The investigators will retrospectively collect data from respective Institutional
 databases regarding patients who underwent CTCA for suspected CAD in the last 4 years.

 General Inclusion criteria Only patients with also Calcium Score

 ≥64-slice CT technology (or 16-slice CT technology with >4 year follow-up) Number of patients
 of at least 100 with complete clinical file and follow-up Minimum follow-up of 12 months Only
 patients with suspected Coronary Artery Disease

 METHODS Study design and patient population This is an observational retrospective study
 (consecutive patients meeting the inclusion criteria) in patients with suspected coronary
 artery disease referred to our Institutions for evaluation by Computed Tomography Coronary
 Angiography (CTCA) starting in January 2003. Participating centers will provide data from
 16-slice CTCA (minimum follow-up >4 years) or superior (i.e. 64-slice CTCA; minimum follow-up
 12 months). Each center will have to provide at least 200 patients (with complete file for
 evaluation).

 Patients are usually referred because of symptoms (chest pain, dyspnoea on exertion) and/or
 abnormal or equivocal stress test and/or high cardiovascular risk profile. Exclusion criteria
 are renal failure (creatinine clearance <60ml/min), known previous reaction to iodinated
 contrast medium and pregnancy, history of Myocardial Infarction, previous revascularization
 (PCI and/or CABG).

 All the patients will be assessed by interview and by data collection from clinical database
 of the Institution for presence of cardiovascular risk factors and symptoms. The following
 risk factors will be considered: 1) Hypertension (defined as Arterial Pressure 140/80 mmHg or
 need for antihypertensive therapy); 2) Hypercholesterolemia (LDL Cholesterol >130 mg/dl or
 current treatment with lipid-lowering therapy); 3) Diabetes Mellitus (current need for
 antidiabetic or insulin therapy); 4) Smoking habit; 5) Obesity (Body Mass Index/BMI> 30); 6)
 Family history of cardiac disease. Symptoms will be classified as no symptoms, typical chest
 pain, atypical chest pain, dyspnoea on exertion. The pre-test cardiovascular risk of the
 patients will be determined by means of the Morise risk score.

 Follow-up Follow-up data of all the patients were obtained by outpatient visit and/or phone
 contact and/or data collection from clinical database of the Institution. Minimum follow-up
 will be 6 months. Hospital/patients' records were screened for the occurrence of clinical
 events to confirm the obtained information. The clinical end-points are: 1) cardiac death, 2)
 non-fatal acute myocardial infarction, 3) unstable angina requiring hospitalization, 4)
 percutaneous or surgical revascularization. Cardiac death is defined as death caused by acute
 myocardial infarction or ventricular arrhythmias. Non-fatal myocardial infarction is defined
 based on criteria of typical chest pain, elevated cardiac enzyme levels, and typical changes
 on the electrocardiogram. Revascularization is defined as percutaneous coronary intervention
 (PCI) with stenting or coronary artery bypass surgery (CABG). The end point was the
 occurrence of one MACE at follow-up.

 Multislice computed tomography data acquisition All examinations were performed with a
 16-slice or higher CT system (Multi-vendor). First, a prospectively triggered coronary
 calcium CT data set was obtained using standardized CT parameters. Thereafter CTCA was
 performed after the administration of a bolus (60-100ml) non ionic contrast material
 (Multi-vendor) at flow rate of 4-6ml/s depending on patient status. All injections were
 performed by power injector via an antecubital vein and were followed by 50 ml of saline
 bolus chase at the same flow rate. A bolus tracking technique was used to determine the
 initiation of CT data acquisition. CTCA was performed with the best available parameters,
 depending on scanner type and generation. The reconstruction slice thickness and increment
 were 0.5-0.75mm and 0.3-0.5mm respectively. Intra-venous beta-blocker (e.g. atenolol 5-10mg)
 was administered to all patients with a heart rate >65 beats/min and without contraindication
 (known asthma or bronchospasm, systolic blood pressure <100mmHg). In addition,
 nitro-glycerine was administered sublingually to all patients, albeit contraindications
 (known significant aortic stenosis, systolic blood pressure <100mmHg). Patients with atrial
 fibrillation or frequent premature beats were included in the study. To obtain optimal image
 quality, datasets were reconstructed at least at two points of the cardiac cycle using a
 retrospective ECG gating algorithm (one diastolic cardiac phase usually at -350msec from the
 R waves and one end-systolic phase at +275msec). In the presence of motion artefacts, as in
 the case of cardiac arrhythmias, additional reconstructions were made at different time
 points of the R-R interval. At the time of the study, tube current modulation was not used.
 The estimated radiation dose would be 5-20mSv. Axial data sets are transferred to a remote
 workstation (Multi-vendor) for post-processing and subsequent evaluation.

 CTCA data analysis - Coronary Artery Calcium Score The coronary artery calcium (CACS) score
 was assessed with the application of dedicated software (Multi-vendor). Coronary artery
 calcium was identified as a dense area in the coronary artery whose attenuation exceeded the
 threshold of 130 Hounsfield units (HU). The overall calcium score was calculated according to
 Agatston score algorithm for each patient.

 CTCA data analysis - Coronary Artery Atherosclerotic plaque assessment All CTCA angiograms
 are evaluated locally by 2 experienced board certified observers. In case of disagreement, a
 joint reading was performed and a consensus was reached. Coronary arteries were divided into
 15-16 segments according to the modified American Heart Association classification and in the
 case the intermediate branch was present it was added to the classification. All coronary
 segments were considered in the analysis. First, each segment was classified as assessable or
 not assessable. All assessable segments were then evaluated for the presence of any
 atherosclerotic plaque. Axial images and curved multiplanar reconstructions of the segmental
 vasculature were utilized for the assessment. Coronary plaques were defined as described
 previously as structures of >1mm^2 within and/or adjacent to the coronary artery lumen which
 are clearly distinguishable from the vessel lumen and surrounding pericardial tissue.
 Obstructive coronary plaques were defined as plaques resulting in ≥50% luminal narrowing; non
 obstructive plaques were defined as plaques that resulted in <50% luminal narrowing. Patients
 were classified as belonging to one of three groups based on the CTCA findings: 1) patients
 with normal coronary arteries, 2) patients with non obstructive coronary artery disease, and
 3) patients with obstructive coronary artery disease (presence of at least one plaque ≥50%).

 Statistical analysis Categorical baseline characteristics, expressed as numbers and
 percentages, will be compared using the chi-square test. Continuous variables, expressed as
 mean and standard deviation (SD), will be compared using the 2-tailed t test and analysis of
 variance if normally distributed or by means of the Kruskal-Wallis method if not normally
 distributed. A composite end-point of MACE will be used (cardiac death, non-fatal infarction,
 unstable angina). Cumulative event rates as a function of time were obtained by means of the
 Kaplan-Meier method. Event curves of MACE will be compared using the log-rank test. Cox
 regression analysis will be used to identify associations between clinical characteristics
 and CTCA variables and outcome. Univariate and multivariate analyses will be performed to
 identify potential predictors. In the multivariate analysis will be included only variables
 which were significant at univariate analysis. Hazard ratios will be calculated with 95%
 confidence intervals as an estimate of the risk associated with a particular variable.
 Statistical analyses will be performed using Excel 2007 software (Microsoft, United States),
 MedCalc software (version 8.0, United States), STATA software (version 10, United States),
 SPSS software (version 12.0, United States). p values <0.05 will be considered statistically
 significant.

 Incremental value of CTCA above CACS will be analyzed. Sub-analysis for the pre-test
 cardiovascular risk stratification according to the Morise score (low-risk, intermediate
 risk, high risk) will be performed.

 Sample size Based on our experience and data from literature the investigators estimated a
 sample size of 1000 patients. Considering the retrospective nature of the study, it is
 possible that at the end the investigators will reach a population >1000 patients which will
 anyway let the study continue to the expected 2 years duration.
Inclusion Criteria:

 -  Only patients with also Calcium Score

 -  ≥64-slice CT technology (or 16-slice CT technology with >4 year follow-up)

 -  Number of patients of at least 100 with complete clinical file and follow-up

 -  Minimum follow-up of 12 months

 -  Only patients with suspected Coronary Artery Disease

 Exclusion Criteria:

 -  renal failure (creatinine clearance <60ml/min)

 -  known previous reaction to iodinated contrast medium and pregnancy

 -  history of Myocardial Infarction

 -  previous revascularization (PCI and/or CABG)