Registry of Comprehensive Imaging and Physiological Evaluation of Deferred Lesions Based on FFR

NCT ID: NCT03030495

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 1400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-12-01
• Study Completion Date: 2025-12-31

Brief Summary

1. To compare the risk of atherosclerotic lesion progression and subsequent patient-oriented composite outcomes (all-cause mortality, any MI, or any Ischemia-driven repeat revascularization) between deferred lesions with or without over microvascular disease, defined as physiological classification

2. To explore independent predictors of atherosclerotic lesion progression in deferred lesions based on fractional flow reserve-guided strategy and treated by contemporary medical treatment

Detailed Description

The coronary artery system has 3 components with different functions: conductive epicardial coronary arteries, arterioles, and capillaries. When any one of these systems fails, myocardial ischemia can occur. Therefore, the presence of epicardial coronary artery stenosis is not necessarily a prerequisite for ischemic heart disease (IHD). Although it has not been established that microvascular disease is independent of macrovascular disease, clinical studies have consistently shown that the presence of microvascular disease is an independent predictor of poor clinical outcomes, especially in patients with acute myocardial infarction (MI).

The pressure-derived fractional flow reserve (FFR) index has become a standard invasive method to evaluate the functional significance of epicardial coronary artery stenosis, and clinical outcomes of FFR-guided percutaneous coronary intervention (PCI) have proven to be better than those of angiography-guided PCI or medical treatment. Although FFR-guided PCI has been reported to improve patient outcomes and FFR is now regarded as the gold-standard invasive method to assess the functional significance of coronary artery stenosis, there is still room for further improvement in the diagnosis and treatment of patients with high FFR. In the FAME II study, 14.6% of the registry arm (FFR > 0.80 and deferral of PCI) experienced persistent angina, and 9.0% of these patients had clinical events during a 2-year follow-up period.

Therefore, microvascular assessment using coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) can provide additional diagnostic and prognostic insights for IHD patients, especially in those with high FFR.

Recently, Lee et al. (JACC 2016) investigated clinical outcomes among patients with high-FFR and deferred revascularization, according to physiologic classification using CFR and IMR. Lee et al. firstly presented that 7.0% of patients with high FFR had high IMR and low CFR and were regarded as having overt microvascular disease. Although the proportion of patients with high FFR who had overt microvascular disease was small, Group D had the poorest clinical outcomes during follow-up. The presence of overt microvascular disease was an independent prognostic factor in patients with high FFR. In addition, the presence of overt microvascular disease had additive prognostic value aside from clinical risk factors, with significantly improved discriminant function of the prediction model. These results suggest that the invasive physiologic assessment for microvascular disease combined with CFR and IMR can help identify patients at high risk for future cardiovascular events among those with high FFR.

Previous studies have shown that the presence of microvascular disease is associated with a higher risk of cardiovascular events such as cardiac death, MI, or revascularization in patients without flow-limiting epicardial stenosis. Several mechanisms have been proposed for the association of microvascular disease and poor clinical outcomes. In addition to myocardial ischemia, microvascular disease is reported to be associated with endothelial dysfunction and inflammatory activity that precedes intimal thickening, lipid deposition in the macrovascular system, and coronary vasomotor dysfunction. In a study by Dhawan et al., coronary microvascular dysfunction in patients with non-obstructive coronary artery disease was associated with higher serum high-sensitivity C-reactive protein and a higher frequency of thin-cap fibroatheroma.

In the Lee et al.'s study, the higher clinical event rates in patients with overt microvascular disease resulted from cardiac death and revascularization rates higher than those of the other groups. These results imply that the presence of overt microvascular disease can induce accentuated atherosclerotic progression and subsequent clinical events including cardiac death and ischemia-driven repeat revascularization.

Therefore, the IMaging and Physiologic Predictors of Atherosclerotic Progression in Deferred Lesions with Contemporary Medical Treatment based on Fractional Flow Reserve-guided Strategy (IMPACT-FFR registry) was designed to compare the risk of atherosclerotic plaque progression and subsequent clinical events between deferred lesions with or without over microvascular disease, defined as physiological classification and also to explore independent predictors of atherosclerotic lesion progression in deferred lesions based on fractional flow reserve-guided strategy and treated by contemporary medical treatment.

Conditions

Ischemic Heart Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Overt microvascular disease

Fractional flow reserve\>0.80, coronary flow reserve\<2 \& Index of microvascular resistance\>25U

Comprehensive physiologic evaluation

Intervention Type: DEVICE

Comprehensive physiologic evaluation using pressure-temperature sensor wire to measure fractional flow reserve, coronary flow reserve, index of microcirculatory resistance

Intravascular imaging devices

Intervention Type: DEVICE

Intravascular ultrasound or optical coherence tomography

No Overt microvascular disease

Fractional flow reserve\>0.80, coronary flow reserve\>2 \& Index of microvascular resistance\<25U

Comprehensive physiologic evaluation

Intervention Type: DEVICE

Comprehensive physiologic evaluation using pressure-temperature sensor wire to measure fractional flow reserve, coronary flow reserve, index of microcirculatory resistance

Intravascular imaging devices

Intervention Type: DEVICE

Intravascular ultrasound or optical coherence tomography

Interventions

Comprehensive physiologic evaluation

Comprehensive physiologic evaluation using pressure-temperature sensor wire to measure fractional flow reserve, coronary flow reserve, index of microcirculatory resistance

Intervention Type: DEVICE

Intravascular imaging devices

Intravascular ultrasound or optical coherence tomography

Intervention Type: DEVICE

Other Intervention Names

Comprehensive physiologic evaluation using pressure-temperature sensor wire; Intravascular ultrasound or optical coherence tomography

Eligibility Criteria

Inclusion Criteria

• Subject must be ≥ 18 years
• Patients suspected with ischemic heart disease
• Patients with intermediate degree of stenosis (30-70% stenosis by visual estimation) with fractional flow reserve of >0.80 in major epicardial coronary artery amenable to stent implantation or vessel size≥2.5 mm
• Patients whose coronary stenosis were evaluated by invasive imaging techniques (intravascular ultrasound and optical coherence tomography) and physiologic assessment (coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve)
• Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving invasive physiologic or imaging evaluation and he/she or his/her legally authorized representative provides written informed consent to any study related procedure

Exclusion Criteria

• End-staged renal disease on peritoneal dialysis or hemodialysis (estimated GFR < 15mL/min)
• Acute hepatic injury
• Cardiogenic shock (systolic blood pressure < 90mmHg or requiring inotropics to maintain blood pressure > 90mmHg)
• The patient has a known hypersensitivity or contraindication to any of the following medications: statin, ezetimibe, heparin, aspirin, clopidogrel, prasugrel, ticagrelor
• Non-cardiac co-morbid conditions are present with life expectancy <2 year (per site investigator's medical judgment)
• Unable to perform invasive imaging study (intravascular ultrasound and optical coherence tomography) or physiologic assessment (coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: collaborator

Inje University Ilsan Paik Hospital

OTHER

Sponsor Role: collaborator

Ulsan University Hospital

OTHER

Sponsor Role: collaborator

Keimyung University Dongsan Medical Center

OTHER

Sponsor Role: collaborator

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joo-Yong Hahn

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joo-Yong Hahn, MD, PhD

Role: STUDY_CHAIR

Samsung Medical Center

Bon-Kwon Koo, MD, PhD

Role: STUDY_CHAIR

Seoul National University Hospital

Joo-Yong Hahn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Joo Myung Lee, MD, MPH, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Inje University Ilsan Paik Hospital

Goyang-si, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

IMPACT16453143

Identifier Type: -

Identifier Source: org_study_id