Multicenter Registry of Coronary Flow-Derived Indexes for Coronary Microvascular Disease (Multicenter FLOW-CMD Registry)

Prospective Registry of Coronary Flow-Derived Indexes in Patients With Coronary Artery Disease

Multicenter FLOW-CMD registry is a prospective, multi-center, registry study.

The aim of the study is to evaluate prognostic implications of coronary microvascular disease (CMD) in patients with ischemic heart disease (IHD) undergoing revascularization decision using FFR or other non-hyperemic pressure ratios.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; Ischemic Heart Disease; Coronary Microvascular Disease
• Intervention / Treatment: Diagnostic test: Invasive physiologic assessment; Diagnostic test: Intravascular imaging

Detailed Description

The diagnostic and therapeutic strategies in patients with coronary artery disease (CAD) have focused on identifying and alleviating both extent and severity of myocardial ischemia, as it is the most important prognostic fator. Thus, fractional flow reserve (FFR) has been a standard method for identifying ischemia-related epicardial coronary stenosis, accruing an abundance of clinical evidence on the benefit of FFR-guided treatment decisions. However, a high FFR value (>0.80) does not necessarily imply freedom from future events. Indeed, clinical events still occur in patients who are deferred based on high FFR. The microvasculature is one of the main components of coronary circulatory system, and the presence of microvascular disease may contribute to clinical events in patients without epicardial coronary stenosis. In the cardiac catheterization laboratory, microvascular disease can be assessed using a pressure/temperature-sensor coronary wire or a Doppler wire. Previous studies have demonstrated the incremental prognostic implications of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with high FFR, and the recent European guidelines supported the importance of invasive physiologic assessment using CFR and IMR in patients with stable coronary artery disease. Furthermore, recent Expert Consensus Documents and the European Society of Cardiology guideline of Chronic Coronary Syndrome have underlined the importance of evaluating coronary microvascular disease (CMD) in patients with ischemic heart disease (IHD) and proposed an universal definition of CMD based on: 1) functionally non-obstructive CAD defined by a fractional flow reserve (FFR)>0.80 and 2) impaired coronary microvascular function determined by abnormal CFR and/or microvascular resistance.

Another important issue in contemporary practice is how to improve patient prognosis after percutaneous coronary intervention (PCI). Although PCI can induce secondary CMD originated from multiple mechanism associated with the procedure (e.g. distal embolization or endothelial dysfunction), and although secondary CMD also affects coronary circulatory function, there has been no previous evidence evaluating the incidence and prognosis of secondary CMD after successful PCI for epicardial coronary stenosis. Furthermore, both previous and recent trials demonstrated that intravascular imaging-guided PCI optimization has significantly better clinical outcomes than angiography-only guided PCI. However, these trials could not explain the exact mechanism underlying the potential benefit of intravascular imaging-guided PCI optimization for better clinical outcome, aside from a larger final stent area following intravascular imaging-guided PCI. Although the fundamental purpose of PCI is to resolve inducible myocardial ischemia originated from epicardial coronary stenosis, several studies have demonstrated that a substantial proportion of patients who underwent angiographically successful PCI had suboptimal post-PCI FFR or non-hyperemic pressure ratios, which are independently associated with worse clinical outcomes. Previous studies demonstrated that intravascular imaging devices could identify correctable cause of suboptimal post-PCI FFR. In this regard, it can be expected that intravascular imaging-guided PCI optimization would result in better post-PCI physiologic results such as higher post-PCI FFR and CFR, compared with angiography-only guided PCI.

However, these issues have not been fully clarified. Regarding the prognostic impact of CMD, only limited data has been available on the prognostic implications of CMD defined by the universal definition among patients with IHD, especially in patients with insignificant epicardial coronary disease defined by FFR>0.80. In addition, only one prospective study evaluated optical coherence tomography (OCT)-guided PCI for post-PCI FFR in patients with non-ST segment elevation myocardial infarction. None of prospective study evaluated potential physiologic benefit of intravascular imaging-guided PCI optimization using intravascular ultrasound (IVUS) or OCT in unselected patient population.

Therefore, the primary objectives of the current multicenter prospective registry are to evaluate prognostic implications of CMD in patients with suspected IHD undergoing revascularization decision using FFR or other non-hyperemic pressure ratios and to evaluate the efficacy of intravascular imaging-guided optimization to enhance post-revascularization coronary circulatory function, compared with angiography-only guided revascularization in revascularized population.

• Study Type: Observational
• Enrollment (Actual): 1003

Contacts and Locations

Study Locations

• South Korea
  • Gwangju, South Korea
    • Chonnam National University Hospital
  • Gwangju, South Korea
    • Chosun university hospital
  • Jinju, South Korea
    • Gyeongsang National University Hospital
  • Seongnam, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Boramae Medical Center
  • Seoul, South Korea
    • Seoul St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with suspected IHD undergoing invasive coronary angiography and clinically indicated physiological assessment will be eligible. A total of 1,003 patients will be enrolled at 7 centers in South Korea.

Description

Inclusion Criteria:

1. Subject must be ≥18 years
2. Patients suspected with IHD
3. Patients undergoing physiologic assessment (CFR, IMR, and FFR) for evaluation of severity of CAD
4. 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:

1. Cardiogenic shock (systolic blood pressure <90mmHg or requiring inotropics to maintain blood pressure >90mmHg) or cardiac arrest
2. Non-cardiac co-morbid conditions are present with life expectancy <2 year (per site investigator's medical judgment).
3. Inability to undergo physiologic assessment (CFR, IMR, and FFR)
4. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Revascularized Population: Patients treated by intravascular imaging-guided PCI optimization; Among patients who received PCI, patients whose PCI was optimized through intravascular imaging device (IVUS or OCT).	Diagnostic test: Invasive physiologic assessment; All coronary physiologic parameters are measured following diagnostic angiography. Resting pd/pa, FFR, CFR and IMR will be calculated using coronary physiologic parameters. In patients treated by PCI, post-PCI physiologic assessment including CFR, IMR, and FFR will be performed.; Diagnostic test: Intravascular imaging; By the operator's discretion, stent-optimization will be performed under intravascular imaging devices (IVUS [Boston Scientific, Natick, Massachusetts, USA] or OCT [Abbott Vascular], St. Paul, MN, USA]).
Revascularized Population: Patients treated by angiography-only guided PCI; Among patients who received PCI, patients whose PCI was optimized through angiography-only.	Diagnostic test: Invasive physiologic assessment; All coronary physiologic parameters are measured following diagnostic angiography. Resting pd/pa, FFR, CFR and IMR will be calculated using coronary physiologic parameters. In patients treated by PCI, post-PCI physiologic assessment including CFR, IMR, and FFR will be performed.
Total Population: Patients with CMD (CFR<2.0 and IMR≥25); Among the enrolled patients, those who are diagnosed with CMD (CFR<2.0, IMR≥25) in physiologic assessment.	Diagnostic test: Invasive physiologic assessment; All coronary physiologic parameters are measured following diagnostic angiography. Resting pd/pa, FFR, CFR and IMR will be calculated using coronary physiologic parameters. In patients treated by PCI, post-PCI physiologic assessment including CFR, IMR, and FFR will be performed.
Total Population: Patients with preserved microvascular function (CFR≥2.0 OR IMR<25); Among the enrolled patients, those who are with preserved microvascular function (CFR≥2.0 OR IMR<25) in physiologic assessment.	Diagnostic test: Invasive physiologic assessment; All coronary physiologic parameters are measured following diagnostic angiography. Resting pd/pa, FFR, CFR and IMR will be calculated using coronary physiologic parameters. In patients treated by PCI, post-PCI physiologic assessment including CFR, IMR, and FFR will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-oriented composite outcomes (POCO)	a composite of all-cause death, MI, any repeat revascularization, or admission for heart failure	1 year after last patient enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	All-cause death	1 year after last patient enrollment
Cardiac death	Cardiac death	1 year after last patient enrollment
Target-vessel MI	Target-vessel MI	1 year after last patient enrollment
Non-target vessel MI	Non-target vessel MI	1 year after last patient enrollment
Any MI	Any MI	1 year after last patient enrollment
Admission for congestive heart failure	Admission for congestive heart failure	1 year after last patient enrollment
Stroke (ischemic and hemorrhagic)	Stroke (ischemic and hemorrhagic)	1 year after last patient enrollment
Seattle Angina Questionnaire	Physical limitation, Angina stability, Angina frequency, Treatment satisfaction, Quality of life	Baseline, 1 year, and 2 year after patient enrollment
Proportion of functionally optimized post-PCI results	Proportion of functionally optimized post-PCI results (Post-PCI FFR>0.80 and CFR>2.0) according to the use of intravascular imaging	Post-procedure
Incidence of secondary CMD after PCI	Incidence of secondary CMD (CFR<2.0 and IMR≥25) after PCI among revascularized population	Post-procedure
Target vessel revascularization (clinically-driven or all)	Target vessel revascularization (clinically-driven or all)	1 year after last patient enrollment
Non-target vessel revascularization (clinically-driven or all)	Non-target vessel revascularization (clinically-driven or all)	1 year after last patient enrollment
Any repeat revascularization (clinically-driven or all)	Any repeat revascularization (clinically-driven or all)	1 year after last patient enrollment

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Seoul St. Mary's Hospital; Chonnam National University Hospital; Seoul National University Bundang Hospital; Chosun University Hospital
• Investigators: Principal Investigator: Joo Myung Lee, MD, MPH, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2022
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 23, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Ischemic Heart Disease; Optical Coherence Tomography; Coronary Microvascular Disease; Fractional Flow Reserve; Intravascular Ultrasound; Coronary Flow Reserve; Index of Microcirculatory Resistance
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Angina Pectoris; Coronary Artery Disease; Myocardial Ischemia; Microvascular Angina
• Other Study ID Numbers: MulticenterFLOW

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked
• IPD Sharing Time Frame: After publication of first manuscript and trial results
• IPD Sharing Access Criteria: The de-identified data will be shared by permission of principle investigator, when asked
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No