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

MulticenterFlow is a prospective, multi-center, registry study.

The aim of the study is twofold:

1. To evaluate prognostic implications of coronary microvascular disease (CMD) in patients with ischemic heart disease (IHD) undergoing revascularization decision using fractional flow reserve (FFR) or other non-hyperemic pressure ratios in deferred population
2. 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 Overview

• Status: 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 prognosticator. 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.7 The microvasculature is one of the main components of coronary circulatory system, and the presence of microvascular disease can be the cause of clinical events in patients without epicardial coronary stenosis. In a cardiac catheterization laboratory, its presence can be assessed using a single pressure/temperature-sensor coronary wire or a Doppler wire. Previous studies have demonstrated the added 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 CAD. Furthermore, recent Expert Consensus Documents and the European Society of Cardiology guideline of Chronic Coronary Syndrome underlined an 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 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's prognosis after percutaneous coronary intervention (PCI). Previous trials demonstrated that intravascular imaging-guided PCI optimization has significantly better clinical outcomes than angiography-only guided PCI. However, previous trial were limited with small sample size, dealt with very selected lesion subsets such as chronic total occlusion or long lesion, or could not explain the exact mechanism that can explain the potential benefit of intravascular imaging-guided PCI optimization for better clinical outcome. Although the fundamental purpose of PCI is to resolve inducible myocardial ischemia originated from the epicardial coronary stenosis, several studies have demonstrated that a substantial proportion of patients who underwent angiographically successful PCI had suboptimal post-PCI FFR18-20 or non-hyperemic pressure ratios that was 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 have better post-PCI physiologic results such as higher post-PCI FFR and CFR, compared with angiography-only guided PCI.

However, the abovementioned 2 important issues have not been fully clarified. For the first issue 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. For the second issue regarding the potential physiologic benefit of intravascular imaging-guided PCI optimization, only 1 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 1) to evaluate prognostic implications of CMD in patients with IHD undergoing revascularization decision using FFR or other non-hyperemic pressure ratios 2) to evaluate physiologic benefit of intravascular imaging-guided PCI optimization over angiography-only guided PCI.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Joo Myung Lee, MD, MPH, PhD; Phone Number: 82-2-3410-2575; Email: drone80@hanmail.net
• Study Contact Backup: Name: David Hong, MD; Phone Number: 82-2-3410-2575; Email: hongdawi@naver.com

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Recruiting
    • Chonnam National University Hospital
    • Contact: Seung Hun Lee, MD, PhD; Email: lsh8602@naver.com
    • Principal Investigator: Seung Hun Lee, MD, PhD
  • Gwangju, Korea, Republic of
    • Recruiting
    • Chosun university hospital
    • Contact: Hyun Kuk Kim, MD, PhD; Email: sale38@hanmail.net
    • Principal Investigator: Hyun Kuk Kim, MD, PhD
  • Seongnam, Korea, Republic of
    • Not yet recruiting
    • Seoul National University Bundang Hospital
    • Contact: Ki-Hyun Jeon, MD; Email: imcardio@gmail.com
    • Principal Investigator: Ki-Hyun Jeon, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Principal Investigator: Joo Myung Lee, MD, MPH, PhD
    • Contact: Joo Myung Lee, MD, MPH, PhD; Email: drone80@hanmail.net
    • Contact: David Hong, MD; Email: hongdawi@naver.com
    • Sub-Investigator: Ki Hong Choi, MD, PhD
    • Sub-Investigator: David Hong, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul st. mary's hospital
    • Contact: Eun-Ho Chu, MD, PhD; Email: cmcchu@catholic.ac.kr
    • Principal Investigator: Eun-Ho Chu, MD, PhD

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 CAD undergoing invasive coronary angiography and clinically indicated physiological assessment will be eligible. A total of 1,000 patients will be enrolled at 5 centers in South Korea.

Description

Inclusion Criteria:

1. Subject must be ≥18 years
2. Patients suspected with IHD or CAD
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
Deferred Population: Patients with CMD (CFR<2.0 and IMR≥25); Among patients who did not undergo PCI at the discretion of the operator, patients diagnosed 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.
Deferred Population: Patients with preserved microvascular function (CFR≥2.0 OR IMR<25); Among patients who did not undergo PCI at the discretion of the operator, patients 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.
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.

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	24-month after the index procedure
The proportion of functionally optimized post-PCI results	The proportion of functionally optimized post-PCI results (post-PCI FFR>0.80 and CFR>2.0)	Immediate after the index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-oriented composite outcomes (POCO)	Patient-oriented composite outcomes (POCO)	at 60-month
All-cause death	All-cause death	24-month, and up to 60-month
Cardiac death	Cardiac death	24-month, and up to 60-month
Target-vessel MI	Target-vessel MI	24-month, and up to 60-month
Non-target vessel MI	Non-target vessel MI	24-month, and up to 60-month
MI	MI	24-month, and up to 60-month
Target vessel revascularization (ischemia-driven or all)	Target vessel revascularization (ischemia-driven or all)	24-month, and up to 60-month
Non-target vessel revascularization (ischemia-driven or all)	Non-target vessel revascularization (ischemia-driven or all)	24-month, and up to 60-month
Any repeat revascularization (ischemia-driven or all)	Any repeat revascularization (ischemia-driven or all)	24-month, and up to 60-month
Admission for congestive heart failure	Admission for congestive heart failure	24-month, and up to 60-month
Stroke (ischemic and hemorrhagic)	Stroke (ischemic and hemorrhagic)	24-month, and up to 60-month

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 (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2030

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 (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 17, 2023
• Last Verified: December 1, 2023

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: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Angina Pectoris; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; 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