Brief Summary The Purpose of the Study : The purpose of this study is to find a safe and reliable "one-stop" solution for treating heart attack patients who have multiple blocked arteries. Currently, doctors face a dilemma: Testing these other blockages during the heart attack procedure is often unreliable.

The most accurate method requires asking the patient to return 30 days later for a second invasive procedure, which is a significant burden.

The Study's Hypothesis : We are testing a new tool called UFR, which uses ultrasound images to measure blockages. Our hypothesis (or "educated guess") is that this new UFR tool is not affected by the body's stress during a heart attack and can provide a true, reliable measurement right away.

The Question the Study is Trying to Answer ： The main question this study is trying to answer is: Can the new "one-stop" UFR tool, used during the initial heart attack procedure, accurately predict which blockages are truly serious... thereby eliminating the need for patients to return for a second procedure 30 days later? Researchers will also follow 200 patients for one year, using advanced scans (like UFR, standard tests, and MRI), to better understand how the heart and arteries heal and change over time.

The ACT-EVOLVE Study: A Prospective, Longitudinal, Multi-modal Study Evaluating the Utility of Acute Phase UFR (IVUS-FFR) to Predict Functional Significance in the Stable Phase for Patients With Acute Coronary Syndrome (ACS).

Study Rationale and Background:

In patients with Acute Coronary Syndrome (ACS) and multi-vessel disease (MVD), complete revascularization (CR) is proven to improve outcomes (e.g., COMPLETE trial, Level A evidence). However, a significant "how-to paradox" exists. Physiologically-guided CR using pressure-wire FFR (pFFR) during the acute index procedure (T0) has failed to show superiority over angiography (e.g., FLOWER-MI trial).This is largely attributed to "functional drift": the acute phase is marked by significant microvascular dysfunction (CMD) and high Index of Microcirculatory Resistance (IMR), especially in STEMI. This interference renders T0 pFFR unreliable, leading to false negatives (over-estimation of FFR).While a staged procedure at a stable timepoint (T1, 30 days) provides a reliable physiological assessment, this strategy faces severe real-world challenges, including high costs, poor patient compliance, and the risk of events during the waiting period.This study hypothesizes that UFR (IVUS-FFR)-a "virtual" FFR derived from IVUS structure and computational fluid dynamics (CFD)-is immune to the acute-phase physiological disturbances (CMD). We hypothesize that T0 UFR can accurately and reliably predict the "gold standard" stable-state pFFR at T1, thus offering a "one-stop shop" solution to guide CR during the index procedure.

Study Objectives:Primary Objective: To assess the diagnostic accuracy (sensitivity, specificity, PPV, NPV, and correlation) of UFR measured in non-culprit vessels (NCV) during the acute phase (T0), compared to the gold-standard pFFR (threshold ≤ 0.80) measured in the stable phase (T1, 30 days).

Key Secondary Objectives:Functional Drift (Head-to-Head): To quantify and compare the "functional re-classification rate" of physiological indices (pFFR, RFR) from T0 to T1 in two pre-specified cohorts: STEMI vs. High-Risk NSTEMI."Structure-Function-Tissue" Coupling (1): To correlate acute culprit vessel (CV) microcirculatory damage (T0 IMR) with sub-acute myocardial tissue injury (MVO and infarct size) measured by T-CMR (3-5 days)."Structure-Function-Tissue" Coupling (2): To analyze the relationship between T0 PCI optimization quality (by post-PCI IVUS criteria) and immediate post-PCI microcirculatory damage (T0 IMR) in the culprit vessel.Longitudinal Vessel Evolution: To assess the long-term (T0 vs. T2) stability of pFFR and UFR in the stented culprit vessel, and to track the functional and structural progression of untreated NCVs (T1 to T2).Prognostic Value: To evaluate the prognostic value of T1 NCV functional status (threshold ≤ 0.80) on 1-year MACE.

Study Design:This is a prospective, longitudinal, observational registry. All key data (physiology, imaging, and CMR) will be analyzed by independent, blinded core laboratories (Physiology Core Lab, Imaging Core Lab, CMR Core Lab). A Clinical Events Committee (CEC) will adjudicate all clinical endpoints.

Study Population:Sample Size: N = 200 patients. Target Population: Patients presenting with ACS (STEMI or High-Risk NSTEMI) who have successfully undergone PCI of the culprit vessel and are found to have MVD.MVD Definition: At least one NCV with a 50-90% diameter stenosis by visual estimation. Pre-specified Stratification:Cohort A: STEMI (N ≈ 100)Cohort B: High-Risk NSTEMI (N ≈ 100)Study Procedures and Timeline:This study involves a systematic, longitudinal assessment at four key timepoints:T0 (Acute Phase - Index Procedure):Culprit Vessel (CV): After successful PCI, post-PCI IVUS, pFFR, RFR, and IMR are measured.Non-Culprit Vessel (NCV): All target NCVs (50-90%) undergo a baseline assessment with IVUS (for UFR calculation) and physiological measurements (T0 pFFR, T0 RFR, T0 IMR).

Key Action: No intervention is performed on the NCV at T0.T-CMR (Sub-Acute Phase - 3-5 Days Post-PCI):Patients (particularly the STEMI cohort) undergo a standardized Cardiac MRI (CMR) to quantify Left Ventricular Ejection Fraction (LVEF), infarct size, and Microvascular Obstruction (MVO).T1 (Stable Phase - 30 Days Post-PCI):Patients return for a planned, invasive follow-up procedure.NCV: The same NCVs assessed at T0 are re-evaluated.Gold Standard Assessment: T1 pFFR and T1 RFR are measured.Clinical Decision: The T1 pFFR result is unblinded. If T1 pFFR threshold ≤ 0.80, the patient undergoes PCI as per guidelines. If > 0.80, the patient continues on optimal medical therapy (OMT).T2 (Long-Term Follow-up - 1 Year):Clinical Follow-up: Assessment for 1-year MACE (cardiac death, target-vessel MI, clinically-driven revascularization).Invasive Follow-up: A planned (per-protocol) 1-year invasive angiographic, IVUS, and functional assessment of both the CV (for in-stent analysis) and any untreated NCV (for disease progression).

Expected Impact:The ACT-EVOLVE registry is designed to provide the first prospective, gold-standard-controlled evidence to validate UFR as a "one-stop" tool for guiding complete revascularization in the acute ACS setting. By directly comparing STEMI and NSTEMI, and building a unique T0-T1-T2 longitudinal database, this study aims to solve the "ultimate dilemma" in ACS-MVD management, potentially replacing the logistically challenging staged-procedure strategy.

Inclusion Criteria:

• Age >18 years, any sex.
• The participant is able to understand the study procedures and provides voluntary written informed consent.
• Diagnosed with Acute Coronary Syndrome (ACS) and meets the criteria for one of the two pre-specified cohorts:
• STEMI Cohort: Symptom onset < 12 hours with ECG findings of ST-segment elevation myocardial infarction.
• High-Risk NSTEMI Cohort: Meets at least one of the following: GRACE score > 140, dynamic ECG changes (ST-T), or significant Troponin elevation.
• Has undergone successful emergency PCI of the Culprit Vessel (CV), with post-PCI TIMI flow Grade 3.
• Coronary angiography confirms Multi-vessel Disease (MVD), defined as: at least one Non-Culprit Vessel (NCV) with a moderate stenosis (visual diameter stenosis 50-90%).
• The target NCV (50-90% stenosis) is deemed by the investigator to be anatomically suitable for IVUS and pressure-wire assessment.
• The participant agrees and is confirmed to be willing and able to strictly adhere to the protocol and complete all required invasive procedures, CMR scans, and follow-ups at the four timepoints (T0, T-CMR, T1, T2).

Exclusion Criteria:

• Presence of cardiogenic shock on presentation, or persistent hemodynamic instability despite successful PCI of the culprit vessel.
• Known severe allergy to iodinated contrast media or gadolinium-based contrast agents (used for CMR).
• Female participants who are pregnant, breastfeeding, or planning pregnancy within the 1-year study period.Unprotected left main coronary artery disease (stenosis <50%) requiring intervention.
• Prior history of Coronary Artery Bypass Grafting (CABG) surgery.The target NCV has received prior PCI (e.g., existing stent) or surgical revascularization.
• The target NCV is a Chronic Total Occlusion (CTO).
• Severe renal insufficiency (eGFR < 30 ml/min/1.73m²) or currently undergoing chronic dialysis.
• Standard contraindications to CMR examination (e.g., claustrophobia, non-MRI-compatible metallic implants/pacemakers).
• Known presence of a severe non-cardiac comorbidity with an expected lifespan of < 12 months (e.g., advanced malignancy).
• Known severe hematological disease (e.g., severe anemia, active bleeding, thrombocytopenia < 70 x 10⁹/L) rendering the participant unsuitable for multiple invasive procedures.
• Inability to provide informed consent or comply with the complex longitudinal follow-up protocol due to psychiatric, cognitive, or other reasons.
• Currently participating in another interventional (drug or device) clinical study.
• Any other condition which, in the investigator's opinion, makes the participant unsuitable for enrollment (e.g., severe valvular heart disease, cardiomyopathy).

The study population will be sourced from patients presenting with Acute Coronary Syndrome (STEMI or High-Risk NSTEMI) to the Emergency Department and/or cardiology services of participating multi-center hospitals.

Eligible participants will be identified and screened for enrollment in the Cardiac Catheterization Laboratory (Cath Lab) immediately following their successful index PCI procedure (T0).

The plan is to share all de-identified individual participant data (IPD) that underlie the results reported in the main publication(s) for this study. This includes all core clinical, laboratory, and follow-up outcome data, as well as all quantitative data derived from the invasive coronary physiology (pFFR/RFR/IMR), IVUS, and Cardiac MRI (IS/MVO) assessments at all timepoints (T0, T-CMR, T1, T2).

Beginning 6 months after the date of the primary manuscript publication, and remaining available for 5 years after the final publication of the main study results.

Access will be granted to qualified, non-commercial scientific researchers from accredited institutions. Requests must be submitted as a detailed research proposal to the Principal Investigator (PI) and will be reviewed by the Study Steering Committee based on scientific merit and alignment with ethical standards. Approved researchers must sign a formal Data Access Agreement that prohibits attempts at re-identification. Data will be provided via a secure, encrypted platform