Clinical trial NCT05369182: Multicenter Registry of Coronary Flow-Derived Indexes for Coronary Microvascular Disease (Multicenter FLOW-CMD Registry)
Official title: Prospective Registry of Coronary Flow-Derived Indexes in Patients With Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Coronary Microvascular Disease
Coronary Artery Disease
Ischemic Heart Disease
Keywords: Coronary Microvascular Disease
Coronary Artery Disease
Ischemic Heart Disease
Coronary Flow Reserve
Index of Microcirculatory Resistance
Fractional Flow Reserve
Intravascular Ultrasound
Optical Coherence Tomography
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Chonnam National University Hospital
name: Chosun University Hospital
name: Seoul National University Bundang Hospital
name: Seoul St. Mary's Hospital
First posted: 2022-05-11
Enrollment: 1003
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient-oriented composite outcomes (POCO)
timeFrame: 1 year after last patient enrollment
Secondary outcomes:
measure: All-cause death
timeFrame: 1 year after last patient enrollment
measure: Cardiac death
timeFrame: 1 year after last patient enrollment
measure: Target-vessel MI
timeFrame: 1 year after last patient enrollment
measure: Non-target vessel MI
timeFrame: 1 year after last patient enrollment
measure: Any MI
timeFrame: 1 year after last patient enrollment
measure: Target vessel revascularization (ischemia-driven or all)
timeFrame: 1 year after last patient enrollment
measure: Non-target vessel revascularization (ischemia-driven or all)
timeFrame: 1 year after last patient enrollment
measure: Any repeat revascularization (ischemia-driven or all)
timeFrame: 1 year after last patient enrollment
measure: Admission for congestive heart failure
timeFrame: 1 year after last patient enrollment
measure: Stroke (ischemic and hemorrhagic)
timeFrame: 1 year after last patient enrollment
measure: Seattle Angina Questionnaire
timeFrame: Baseline, 1 year, and 2 year after patient enrollment
measure: Proportion of functionally optimized post-PCI results
timeFrame: Post-procedure
measure: Incidence of secondary CMD after PCI
timeFrame: Post-procedure
Other outcomes:
Locations:
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
Study officials:
affiliation: Samsung Medical Center
name: Joo Myung Lee, MD, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References: