Artificial Intelligence-Driven Medipixel Fractional Flow Reserve Versus Invasive Fractional Flow Reserve-Guided PCI Trial (AIM-FFR Trial)

Samsung Medical Center

Status: Begins enrollment this month

Conditions: Coronary Artery Disease; Acute Coronary Syndrome; Chronic Coronary Syndrome

Treatments: Diagnostic Test: MPFFR or Invasive FFR

Study type: Interventional

Funder types: Other

Identifiers

NCT07329699

SMC19810222

Details and patient eligibility

About

The AIM-FFR trial is a prospective, multi-center, open-label, randomized controlled, non-inferiority trial. The current trial will evaluate non-inferiority of MPFFR-guided PCI, compared with invasive FFR-guided PCI in patients with coronary artery disease.

Full description

Fractional Flow Reserve (FFR) has been established as the gold standard for determining the functional significance of coronary artery stenosis. Current guidelines have classified FFR as a Class IA recommendation for the assessment of intermediate coronary artery lesions. However, FFR remains underused in daily clinical practice, due to requirement for pressure wire use, hyperemia induction, or prolonged procedural time.

To overcome these limitations, angiography-derived computation of FFR have been widely adopted as wire-free alternatives. These technologies enable functional assessment of coronary stenosis without pressure wires, providing a less invasive and more comfortable alternative to wire-based FFR. Multiple modalities have shown reasonable diagnostic accuracy to predict FFR≤0.80. Among them, Quantitative Flow Ratio (QFR)-guided percutaneous coronary intervention (PCI) demonstrated superior clinical outcome than angiography-guided PCI. Based on these results, QFR-guided PCI is supported by class 1B recommendation from European Society of Cardiology guideline. Nevertheless, angiography-derived FFR also has limitations, primarily related to the technical and workflow demands of the process. Computation of angiography-derived FFR typically requires vessel segmentation, correspondence marking, and 3-dimensional reconstruction from angiographic images, which are time-consuming and subject to operator-dependent variability.

Indeed, recent data shows limitations of angiography-based FFR computation. Study by Ninomiya et al. evaluated five different angiography-derived FFR methods (QFR, vFFR from Pie Medical Imaging, caFFR from Rainmed Ltd, 2D-µFR, and 3D-µFR from Pulse Medical Imaging Technology). Although these angiography-derived FFR methods provided higher discrimination than angiographic stenosis severity to discriminate functionally significant stenosis defined by FFR≤0.80 or instantaneous wave-free ratio≤0.89, the AUC ranged from 0.65 to 0.75. Furthermore, recent FAVOR III Europe trial showed that QFR-guided strategy did not meet non-inferiority to FFR-guided strategy in terms of a composite of death, myocardial infarction, and unplanned revascularization at 12 months. These results support invasive FFR-guided strategy is gold standard method.

Recent advances in Artificial Intelligence (AI) have led to development of automated tools for cardiovascular diagnostics, improving both accuracy and workflow efficiency. The AI-driven angiography-based FFR (Medipixel FFR [MPFFR]) has been developed utilizing AI-based fully automated quantitative coronary angiography (AI-QCA). MPFFR utilizes automated frame selection, AI-based contouring, and real-time modeling, allowing for rapid and accurate physiological assessment without manual segmentation. In previous validation study conducted in Korea (599 vessels from 452 patients who underwent clinically indicated FFR measurement from 5 university hospitals in Korea), Mean analysis time of MPFFR was 12.5±1.7 seconds and manual correction was needed in 32 vessels (5.3%). MPFFR showed similar diagnostic performance with QFR (correlation with FFR; MPFFR vs. QFR: R=0.885 vs. R=0.860, P for comparison=0.011; area under curve to predict FFR≤0.80; 0.949 vs. 0.953, P for comparison=0.631). At a median follow-up of 2 years (interquartile range, 1.6 to 2.6 years), patients with MPFFR≤0.80 had higher risk of target vessel failure than those with MPFFR>0.80 (4.5% vs. 0.8%; adjusted HR, 5.94; 95% CI, 1.27-27.91; P=0.024). C-index to predict target vessel failure was comparable between MPFFR and QFR (0.770 vs. 0.753, P for comparison=0.469).

However, whether MPFFR-guided PCI can be used in daily practice still needs to be validated by randomized controlled trial using invasive FFR-guided PCI as reference standard. On this background, the current trial aims to compare clinical outcomes between MPFFR-guided PCI and invasive FFR-guided PCI in patients with coronary artery disease.

Enrollment: 2,100 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subject must be at least 19 years of age
2. Eligible for coronary angiography and/or percutaneous coronary intervention.
3. Chronic coronary syndrome or acute coronary syndrome (non-culprit vessels only)
4. Coronary artery disease in one or more native major epicardial vessels or their branches with reference vessel diameter of at least 2.5mm and with visually assessed coronary stenosis in which the physiological severity of the lesion is questionable (typically 40-90% diameter stenosis).
5. Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.

Exclusion criteria

1. Patients unable to provide informed consent

2. Patients with known intolerance to aspirin, P2Y12 inhibitors, or components of drug-eluting stents and drug-coated balloons

3. Patients with coronary artery bypass grafting

4. Patients who have non-cardiac co-morbid conditions with life expectancy <1 year

5. Patients with cardiogenic shock or cardiac arrest

6. Patients with severe left ventricular systolic dysfunction (ejection fraction <30%)

7. Patients with severe valvular heart disease requiring open heart surgery

8. Pregnant or lactating women

9. Angiographic exclusion criteria

   • Culprit vessel of patients with ST-elevation myocardial infarction (target lesions in non-culprit vessel can be enrolled)
   • Chronic total occlusion (target lesions in vessels without chronic total occlusion can be enrolled)
   • Ostial stenosis in left man coronary artery or right coronary artery
   • Severe tortuosity of any target vessel
   • Severe overlap in the stenosed segment
   • Poor image quality precluding identification of vessel contours

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,100 participants in 2 patient groups

MPFFR-guided PCI group

Experimental group

Description:

In patients randomized to artificial intelligence-driven angiography-based fractional flow reserve (MPFFR)-guided PCI group, MPFFR analysis will be performed using MPFFR-1000 version 2.1.0 (Medipixel Inc., Seoul, Korea). Manual correction can be applied when necessary, however, it will be strongly discouraged by the study protocols. Treatment decisions will be made based on site-measured MPFFR value. Functionally significant stenosis will be defined as MPFFR≤0.80. For lesions with MPFFR≤0.80, PCI will be recommended under current guidelines, however, final decision regarding PCI will be at the discretion of operators. In the MPFFR-guided PCI group, on-site MPFFR value will be used in decision making of revascularization. If PCI is not performed for lesions with MPFFR≤0.80, the specific reasons will be collected in electronic case report form. For lesions with MPFFR\>0.80, PCI will be deferred.

Treatment:

Diagnostic Test: MPFFR or Invasive FFR

Invasive FFR-guided PCI group

Active Comparator group

Description:

All invasive FFR measurements will be performed after diagnostic coronary angiography according to a standardized protocol as previously described. A pressure-temperature sensor guide wire (Abbott Vascular, Santa Clara, CA, USA) is positioned at the distal segment of the target lesion. To induce maximal hyperemia state, intravenous infusion of adenosine (140μg/kg/min through a peripheral vein) or intracoronary injection of nicorandil (2mg) will be used. In the presence of drift greater than 0.03 FFR unit, pressure wire will be re-equalized and FFR will be measured again. Functionally significant stenosis will be defined as FFR≤0.80. For lesions with FFR≤0.80, PCI will be recommended under current guidelines, however, final decision regarding PCI will be at the discretion of operators. If PCI is not performed for lesions with FFR≤0.80, the specific reasons will be collected in electronic case report form. For lesions with FFR\>0.80, PCI will be deferred.

Treatment:

Diagnostic Test: MPFFR or Invasive FFR