Acute Coronary Syndrome, Chronic Coronary Syndrome, Coronary Artery Disease
Conditions
Keywords
Coronary artery stenosis, Fractional flow reserve, Prognosis
Brief summary
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.
Detailed 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.
Interventions
DIAGNOSTIC_TESTMPFFR or Invasive FFR
Functionally significant stenosis will be defined as MPFFR≤0.80 or FFR≤0.80. For lesions with MPFFR≤0.80 or FFR≤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 or FFR≤0.80, the specific reasons will be collected in electronic case report form. For lesions with MPFFR\>0.80 or FFR\>0.80, PCI will be deferred.
Sponsors
Samsung Medical Center
Chonnam National University Hospital
Seoul National University Bundang Hospital
Chung-Ang University Gwangmyeong Hospital
The Catholic University of Korea
Keimyung University Dongsan Medical Center
Wonju Severance Christian Hospital
SMG-SNU Boramae Medical Center
Kangbuk Samsung Hospital, Sungkyunkwan University
Korea University Guro Hospital
Inje University Ilsan Paik Hospital
International St. Mary's Hospital
Kyungpook National University Hospital
Korea University Anam Hospital
Ajou University School of Medicine
Changwon Patima Hospital
Bundang CHA Hospital
Ulsan University Hospital
Gachon University Gil Medical Center
Inje University Haeundae Paik Hospital
Gyeongsang National University Changwon Hospital
Wonkwang University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Patients will be blinded to the assigned groups. Clinical events will be independently adjudicated by independent Clinical Events Adjudication Committee.
Intervention model description
A prospective, multi-center, open-label, randomized controlled, non-inferiority trial.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiac events (MACE) | 1 year after last patient enrollment | a composite of death from any causes, non-fatal myocardial infarction \[MI\], and clinically indicated unplanned revascularization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause death | 1 year after last patient enrollment | All-cause death (defined by Academic Research Consortium \[ARC\] II definition) |
| Cardiovascular death | 1 year after last patient enrollment | Cardiovascular death (defined by Academic Research Consortium \[ARC\] II definition) |
| Non-fatal myocardial infarction (MI) | 1 year after last patient enrollment | Non-fatal MI (according to the Fourth universal definition of MI) |
| Target vessel-related MI | 1 year after last patient enrollment | Target vessel-related MI (Target vessel denotes vessels with initially interrogated by MPFFR or invasive FFR) |
| Non-target vessel-related MI | 1 year after last patient enrollment | Non-target vessel-related MI (Target vessel denotes vessels with initially interrogated by MPFFR or invasive FFR) |
| Clinically indicated unplanned revascularization | 1 year after last patient enrollment | Clinically indicated unplanned revascularization (defined by Academic Research Consortium \[ARC\] II definition) |
| Clinically indicated target vessel revascularization | 1 year after last patient enrollment | Clinically indicated target vessel revascularization (Target vessel denotes vessels with initially interrogated by MPFFR or invasive FFR) |
| Clinically indicated non-target vessel repeat revascularization | 1 year after last patient enrollment | Clinically indicated non-target vessel repeat revascularization (Target vessel denotes vessels with initially interrogated by MPFFR or invasive FFR) |
| Vessel or Stent thrombosis | 1 year after last patient enrollment | Vessel or Stent thrombosis (definite thrombosis defined by Academic Research Consortium \[ARC\] II definition) |
| Cardiovascular death or target vessel-related MI | 1 year after last patient enrollment | A composite of Cardiovascular death or target vessel-related MI |
| Target vessel failure | 1 year after last patient enrollment | Target vessel failure (TVF, a composite of cardiovascular death, target vessel-related MI, and clinically indicated target vessel revascularization) |
| Bleeding according to BARC definition | 1 year after last patient enrollment | Bleeding according to BARC definition |
| Cerebrovascular accident (CVA) | 1 year after last patient enrollment | Cerebrovascular accident (CVA) including ischemic stroke, hemorrhagic stroke, or transient ischemic attack (TIA) |
| Contrast volume (including both diagnostic angiography and PCI) | immediately after the intervention/procedure | Contrast volume (including both diagnostic angiography and PCI) |
| Procedure time of MPFFR or invasive FFR measurement | immediately after the intervention/procedure | Procedure time of MPFFR or invasive FFR measurement |
| Procedure time including the decision-making time for PCI following coronary angiography | immediately after the intervention/procedure | Procedure time including the decision-making time for PCI following coronary angiography |
| Number of lesions interrogated | immediately after the intervention/procedure | Number of lesions interrogated by MPFFR or invasive FFR |
| Number of used stents or drug-coated balloons | immediately after the intervention/procedure | Number of used stents or drug-coated balloons |
Countries
South Korea
Contacts
CONTACTJoo Myung Lee, MD, MPH, PhD
CONTACTSeung Hun Lee, MD, PhD
PRINCIPAL_INVESTIGATORJoo Myung Lee, MD, MPH, PhD
Samsung Medical Center
Outcome results
None listed