Acute coronary syndromes (ACS) are frequently associated with multivessel coronary artery disease (CAD), and current guidelines recommend complete revascularization beyond the culprit lesion. Angiography-guided PCI is the standard approach, but anatomical assessment does not always reflect the functional significance of intermediate lesions, while FFR-guided strategies are limited by the need for pressure wires and hyperemia. Murray-law-based quantitative flow ratio (μFR) is a wire-free angiography-derived physiological index that may improve decision-making for revascularization in ACS patients.

The Core-μFR is an investigator-driven, multicenter, randomized, open-label and prospective trial designed to evaluate whether μFR can act as a gatekeeper for complete revascularization in patients with ACS and multivessel disease by identifying non-culprit lesions that truly require PCI.

Patients with ACS (either STEMI or NSTE-ACS) undergoing primary PCI will be considered eligible if they present multivessel CAD on visual assessment with the intention to treat the non-culprit vessel in a staged procedure within the same hospitalization. After the pPCI, eligible patients will be randomized to either group A or group B and μFR will be performed in a blinded fashion with the operator unaware of the functional result. Patients in group A will undergo a staged PCI of all NCVs guided by coronary angiography, as per standard of care. In group B, μFR will be used as a gatekeeper for staged revascularization. Operators will only be informed whether at least one non-culprit vessel is μFR-positive, without disclosure of the specific vessel involved or the μFR values. If at least one non-culprit vessel has μFR ≤0.80, patients will undergo angiography-guided PCI of all non-culprit vessels previously deemed suitable for treatment by visual assessment. If μFR is >0.80 in all non-culprit vessels, staged PCI will be deferred and the patient will be discharged without further revascularization. Finally, to test the functional reproducibility, a blinded post-hoc μFR assessment will be performed on the baseline angiograms of the staged procedures in all the patients undergoing complete revascularization. Clinical follow-up will be performed at 30 days and 1 year from randomization.

Inclusion Criteria:

1. Patients presenting with ACS within 72 hours of successful culprit PCI

2. Residual coronary artery disease, defined as at least one additional stenosis in any non-culprit vessel (NCV) with the following characteristics:

   1. at least 50% diameter stenosis by visual assessment
   2. a vessel diameter of at least 2.5 mm
   3. amenable to successful PCI

Exclusion Criteria:

1. Cardiogenic shock or severe heart failure (NYHA class ≥III)
2. Severely impaired renal function: creatinine >2 mg/dl or estimated glomerular filtration rate (eGFR) <30 ml/min/1,73 m²
3. Allergy to iodine-containing contrast agents which cannot be adequately pre-medicated
4. Pregnancy or intention to become pregnant during the trial
5. Life expectancy less than one year
6. Ambiguity in the identification of the culprit vessel/lesion
7. Clinical presentation as myocardial infarction and non-obstructive coronary artery disease (MINOCA) and/or Tako-Tsubo Syndrome
8. Any ambiguity in the diagnosis of ACS
9. Inability to provide informed consent
10. Patients with only one coronary artery lesion with diameter stenosis >90% and/or TIMI flow <3
11. Patients in whom the NCV is treated at the time of the index procedure
12. An interrogated lesion is at the site of a myocardial bridge
13. An interrogated lesion is a culprit lesion responsible for the acute myocardial infarction
14. An interrogated lesion is in a bypass graft
15. Poor angiographic image quality precluding vessel contour detection or with suboptimal contrast opacification
16. Severe vessel overlap in the stenosed segment or severe tortuosity of any interrogated vessel deemed not amenable to μFR measurement

Complete revascularization will be performed with the operators blinded to the μFR results.