The SYNTAX III Revolution trial is a randomized diagnostic research study that investigates the use of CT scan and angiogram of the heart to help doctors decide which method is the best to improve blood supply to the heart in patients with complex coronary artery disease. Each patient will undergo an angiogram and CT scan per standard of care. The randomization strategy in this study is not between patients but between two teams of doctors, the so-called "Heart Teams", will be randomized: in the first round, team 1 assesses the angiogram, and team 2 assesses the CT scan. Then they make a decision about which treatment would be the best to treat complex coronary artery disease. In the second round, both teams see the imaging method that they did not see in the first round, and make the decision again. The final decision on the clinical treatment strategy is at the sole discretion of the Heart Team and there are no criteria described in SYNTAXIII Revolution protocol leading influencing this final decision.

Hypothesis: Determination of the best treatment strategy for coronary artery disease based on a CT scan will result in similar decisions as based on invasive coronary angiography.

The SYNTAX III REVOLUTION Trial is a multicenter, all-comers trial (either isolated unprotected left-main or 3-vessel disease with or without left-main disease and candidate for either CABG or PCI treatment). In SYNTAXIII REVOLUTION a diagnostic coronary angiography and a diagnostic coronary Multislice CT are performed to allow the Heart Team to assess the optimal revascularization strategy. In a normal hospital setting the angiography is considered standard of care. The multislice CT can already also be part of the diagnosis and is at the discretion of the physician. After the images of both modalities are available, the patient will no longer participate in the trial. Next step is randomization of Heart Team A and Heart B to the sequence of availability of images, i.e. randomizing whether Heart Team A will review the angiography first or the multislice CT and, automatically, Heart B the other modality. The Heart Teams need to make a decision between surgical or percutaneous treatment according to either the conventional angiography or the multislice CT angiography assessment. In addition, the incremental value of FFRCT in the decision making of the Heart Team arm allocated primarily to the assessment of the MSCT (CT first algorithm) will be a secondary endpoint. No intervention to the patient's treatment takes place

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Inclusion Criteria:

1. Patients with at least 1 stenosis (angiographic, visually determined de novo lesions with ≥50% DS) in all 3 major epicardial territories (LAD and/or side branch, CX and/or side branch, RCA and/or side branch) supplying viable myocardium with or without left main involvement;

2. Patients with hypoplastic RCA with absence of descending posterior and presence of a lesion in the LAD and CX territories may be included in the trial as a 3VD equivalent;

3. Vessel size should be at least 1.5 mm in diameter as visually assessed in diagnostic angiogram;

4. Patients with chronic stable angina or stabilized acute coronary syndrome (inclusion criteria of the SYNTAX I study):

   • stable (Canadian Cardiovascular Society Class 1, 2, 3 or 4) angina pectoris;
   • or unstable (Braunwald class IB, IC, IIB, IIC, IIIB, IIIC) angina pectoris and ischemia with normal cardiac enzyme values prior to enrollment;
   • or patients with atypical chest pain or those who are asymptomatic provided they have myocardial ischemia (e.g. treadmill exercise test, radionuclide scintigraphy, stress echocardiography);

5. All anatomical SYNTAX Scores are eligible;

6. Patient amenable to a MSCT coronary angiography (e.g. no claustrophobia, high heartrate not amenable to beta-blockers, poor renal function, etc., up to discretion of investigator);

7. Patient has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Ethical Committee of the respective clinical site;

Exclusion Criteria:

1. Under the age of 18 years;
2. Unable to give Informed Consent;
3. Known pregnancy at time of enrolment. Female of childbearing potential (and last menstruation within the last 12 months), who are not taking adequate contraceptives. Female who is breastfeeding at time of enrolment;
4. Prior PCI or CABG; history of coronary stent implantation;
5. Evidence of evolving or ongoing acute myocardial infarction (AMI) in ECG and/or elevated cardiac biomarkers (according to local standard hospital practice) have not returned within normal limits at the time of enrollment;
6. Concomitant cardiac valve disease requiring surgical therapy (reconstruction or replacement);
7. Single or two-vessel disease (at time of Heart Team consensus);
8. Atrial fibrillation or significant arrhythmias;
9. Known allergy to iodinated contrast;
10. A Body Mass Index (BMI) of 35 or greater;
11. Participation in another trial with an investigational drug or device.

Patients with complex coronary artery disease, defined as: left main (isolated, or associated with 1, 2 or 3 vessel disease) or de novo 3-vessel coronary artery disease (DS ≥50%), who are able to undergo cardiac CT with a GE high-definition RevolutionTM multi-slice CT scanner.

The research data will be entered on separate forms and stored under a code number, according to prevailing legal requirements. No names or other personal data will be stored. Only the study doctor will hold the information to link the code to the patients. The encoded data will be processed, analysed and reported by the research employees of this study, who have an obligation of secrecy.

Representatives of the sponsor or members of the Ethics Committee (EC) and regulatory authorities within Europe can have access to the medical files in order to inspect the correctness of the research data. Data may be provided to representatives and affiliates of the industries supporting the study: General Electric and HeartFlow Inc. It is possible that the results of this study are presented or published in medical journals; this will always be without mention of the identity of the patients.