"SIMULATION MODELING OF CORONARY ARTERY DISEASE: A TOOL FOR CLINICAL DECISION SUPPORT"
"SIMULATION MODELING OF CORONARY ARTERY DISEASE: A TOOL FOR CLINICAL DECISION SUPPORT"
Coronary atherosclerosis (ATS) is a degenerative-inflammatory artery pathology underlying the
 different clinical manifestations of coronary heart disease (CHD), from stable angina due to
 constrictive plaque growth obstructing artery lumen, to acute coronary syndrome (ACS),
 secondary to abrupt lumen occlusion by atherothrombosis at the site of a ruptured or eroded
 plaque.

 Major coronary adverse events (MACE) are known to be related to local factors, the so called
 "high risk plaque" characterized by large lipid-necrotic core with a thin fibrous cap,
 intraplaque hemorrhage, rupture, erosion, and to systemic, patient-specific, factors,
 contributing to the atherogenic genotype/phenotype of the so called "high risk patient",
 presenting with an abnormally activated thrombogenic and/or inflammatory state or increased
 plasma levels of atherogenic lipid species.

 The huge social and economic impact of CHD in western and developing countries is primarily
 due to the difficulty to identify and predict, in the clinical context, which "high risk
 plaque" in which "high risk patient" will cause, independently of stenosis severity, an acute
 coronary event such as myocardial infarction or sudden coronary death, which are often the
 first manifestations of CHD in a large proportion of otherwise asymptomatic subjects. Plaque
 burden, compared to stenosis, is recognized as a better predictor of ACS and coronary CT
 angiography (CCTA) is considered as the optimal non-invasive coronary imaging modality to
 assess and quantify plaque burden and to evaluate the functional significance of a stenosis,
 by computationally estimating fractional flow reserve. Moreover, molecular studies of CHD
 patients have mostly examined associations with clinical cardiovascular outcomes:
 associations with coronary ATS assessed by quantitative CCTA may provide insight into the
 pathophysiological role of several molecular species in plaque formation and growth, and
 elucidate their potential role as discriminative biomarkers of CHD.

 Based on these considerations, aim of this study is to collect and analyze all
 patient-specific clinical and epidemiological data and patient phenotype and genotype
 blood-derived molecular information, and to combine them with local high resolution
 non-invasive CCTA imaging of actual plaque burden as well as, prospectively, of its increase
 or de novo formation over a clinically relevant timespan. The expected result, following
 local and systemic data integration and modeling, is to optimize early diagnosis and risk
 stratification of CHD beyond current clinical models and scores and to help improving primary
 and secondary prevention of MACE. The overall design of this diagnostic and prognostic
 framework has been proposed to Horizon 2020 EU Call PHC30 and approved by the European
 Commission (Grant Agreement PHC30-689068). The Consortium includes major clinical European
 University Hospitals specialized in CHD imaging and treatment and the project study has
 obtained the endorsement of the European Society of Cardiovascular Imaging.
Inclusion Criteria:

 1. male and female subjects

 2. aged 45-75 years

 3. caucasian population

 4. submitted to CCTA for suspected CHD between 2009 and 2012 (in the context of EVINCI
 and ARTreat FPVII studies) at the Hospitals reported in "SMARTool Clinical Center"
 document and satisfying the elegibility criteria reported above

 5. submitted to clinical Follow-up in the last 6 months with stable clinical conditions
 and documented CHD or persistent intermediate/high probability of CHD

 6. Signed informed consents (clinical and genetic)

 Exclusion Criteria:

 1. Multi-vessel severe disease (3 vessels and/or LM disease with >90% stenosis).

 2. Severe coronary calcification (CAC score > 600).

 3. Having undergone surgical procedures related to heart diseases (CABG, valve
 replacement, CRT or CRTD treatment, any surgery of the heart or arteries).

 4. Documented MACE at history (myocardial infarction, severe heart failure, recurrent
 angina) in the last 6 months with/without revascularization

 5. Documented severe peripheral vascular disease (carotid, femoral)

 6. Surgery of carotid and/or peripheral arteries or cerebral ischemic attack

 7. History/surgery of Abdominal Aortic Aneurysm(AAA).

 8. Severe Heart failure (NYHA Class III-IV)

 9. LV dysfunction (left ventricle EF <40%).

 10. Atrial fibrillation.

 11. Lack of written informed consent (clinical consent and/or genetic consent)

 12. Pregnancy (evaluated by urine test) and breastfeeding

 13. Active Cancer

 14. Asthma

 15. Severe untreated Hypertension (arterial blood pressure ≥ 170/110 mmHg)

 16. Cardiomyopathy or congenital heart disease

 17. Significant valvular disease (hemodynamically significant valvular stenosis or
 insufficiency by echoDoppler)

 18. Renal dysfunction (creatinine > 1.3 mg/dL)

 19. Chronic Kidney Disease (eGFR < 30 ml/min/1.73 m2)

 20. Hepatic failure (at least 3 of the following: albumin < 3.5 g/dL; prolonged
 prothrombin time-PT; jaundice; ascites)

 21. Waldenstrom disease

 22. Multiple myeloma

 23. Autoimmune/Acute inflammatory disease

 24. Previous severe adverse reaction to iodine contrast agent

 25. Positivity at blood tests for HIV, Hepatitis B and C (CRF number 1-clinical
 evaluation)

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