Main purpose of the study:

To comparatively assess the diagnostic performance of non invasive anatomical and functional imaging modalities to detect significant obstructive coronary artery disease as demonstrated at invasive coronary angiography and functional evaluation of coronary lesions (fractional flow reserve).

Objectives of the study

1. To test the accuracy of anatomical and functional non-invasive cardiac imaging in the diagnosis of IHD. To this purpose the "anatomical" information provided by CTA is obtained in every patient together with the "functional" information provided by stress radionuclide cardiac imaging (SPECT or PET), to assess myocardial perfusion, and/or by stress MRI or ECHO imaging to assess myocardial contraction. Non-invasive results are tested against invasive reference standards. The latter consists of invasive coronary angiography integrated by invasive measurement of fractional flow reserve (to assess the hemodynamic relevance of intermediate coronary stenoses).
2. To test the accuracy of integrated models, including clinical variables, risk factors and circulating biomarkers, to predict significant obstructive coronary artery disease in patients with chronic angina-like symptoms. To correlate biohumoral profiles with the coronary anatomical-functional phenotype as obtained by non invasive imaging in the same patients. To reach these goals the clinical characterization of patients (collected before non-invasive imaging) and the laboratory characterization (that includes novel biomarkers of cardiovascular risk) are compared with patient characterization derived from non invasive "anatomic-functional" imaging and with invasive diagnosis of significantly obstructive coronary disease.
3. To develop an advanced clinical and imaging reporting tool in cardiology. An informatics platform is developed to synthetically and clearly present the integrated clinical and imaging diagnostic profile of individual patients. A multimodal imaging reporting tool is developed including tools for "image fusion" of different imaging modalities (CT, SPECT, PET, MRI).
4. To define the most cost-effective work-up for the diagnosis and characterization of IHD. To this purpose the costs and the procedural risks (including radiation exposure) of non-invasive and invasive diagnostic procedures are prospectively collected. Cost-benefit and cost-effectiveness analyses is conducted alongside the EVINCI-study clinical trial.

Inclusion Criteria:

• Patients with intermediate (>20%, <90%) risk of IHD based on age,gender,symptoms and exercise stress test results

Exclusion Criteria:

• Age < 30 Yrs or > 75 yrs
• Pregnancy (suspected or ascertained)
• LV Dysfunction (LVEF < 35% by Echo or other method)
• Low (< =20%) or high (>=90%) probability of CAD
• Acute Coronary Syndrome
• Prolonged (> 20 minutes) chest pain
• De novo or accelerated angina
• Hemodynamic or electrical instability
• Recent ST-T segment or T wave changes of ischemic nature
• Acute myocardial infarction with or without ST segment elevation
• Elevated serum cardiac markers of necrosis
• Known diagnosis of CAD
• Previously known myocardial infarction
• Previous PCI
• Previous CABG
• Persistent atrial fibrillation or advanced AV Block
• Asthma or chronic treatment with aminophylline
• Recent (<6 months) cerebral ischemic attack
• Known significant carotid stenosis or vascular aneurisms
• Asthma or chronic treatment with aminophylline
• Active cancer
• Severe hypertension. Patients cannot withdraw therapy for 12 hours.
• Congenital heart disease
• Significant valvular disease
• Cardiomyopathy (e.g. DCM, HCM, ARVC, Amyloidosis)
• Inability to provide an informed consent