Relationship Between Coronary Microvascular Dysfunction and Improvement of Left Ventricular Systolic Function in Patients With Heart Failure With Reduced Ejection Fraction Caused by Non-ischemic Etiology (HFrEF-CMD)

February 5, 2024 updated by: Ki Hong Choi, Samsung Medical Center

The Role of Coronary Microvascular Dysfunction in Improving Left Ventricular Systolic Function Using Registry for Evaluation of Factors associatEd With Heart Failure With Reduced Ejection Fraction Caused by Non-ischemic Etiology (REFERENCE).

This study aims to evaluate the incidence of coronary microvascular dysfunction (CMD) and its prognostic implication for the improvement of left ventricular function in patients who have been diagnosed with heart failure with reduced ejection fraction (HFrEF) caused by non-ischemic etiology.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

HF is a clinical syndrome characterized by dyspnea or exertional limitation due to impairment of ventricular filling or ejection of blood or both. HFrEF occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling. Among them, a substantial portion of patients had non-ischemic etiology.4 The CMD, defined by impaired coronary flow reserve (CFR), is commonly observed in patients with cardiomyopathies caused by non-ischemic etiology and is well-known to be associated with poor prognosis independently of the degree of left ventricular functional abnormality. However, the presence of CMD can be more specifically evaluated by invasive physiologic assessment using both CFR and the index of microcirculatory resistance (IMR) than by non-invasive methods (doppler echocardiography, positron emission tomography, or cardiac magnetic resonance imaging [MRI]) measuring CFR alone. Considering that CMD, defined by depressed CFR with elevated IMR, reflects the impaired myocardial flow and microvascular damages, there was a possibility that it may be a predictor of irreversible myocardial damages in HFrEF patients with non-ischemic etiology. Nevertheless, there has been limited data regarding the association between the improvement of LV function and CMD for patients with HFrEF caused by non-ischemic etiology after guideline-directed medical treatment (GDMT). Therefore, the investigators sought to evaluate the incidence of CMD and its prognostic implication for the improvement of left ventricular function after GDMT in patients who have been diagnosed with HFrEF caused by non-ischemic etiology.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy)

Description

Inclusion Criteria:

  • a) Subject must be at least 19 years of age. b) Subject with symptoms or signs of HF (NYHA ≥2 dyspnea) and reduced ejection fraction (LVEF ≤ 40%) c) Subject who clinically need coronary angiography d) Subject who can voluntarily sign informed consent form

Exclusion Criteria:

  • a) Subject with significant coronary artery stenosis on coronary angiography (diameter stenosis ≥90% or 50-90% with fractional flow reserve [FFR] ≤0.80) b) Subject scheduled for cardiac replacement therapy (heart transplantation or left ventricular assisted device [LVAD] implantation) c) HF due to restrictive cardiomyopathy, active myocarditis, or constrictive pericarditis d) Significant valvular heart disease requiring surgery e) Subject who have non-cardiac co-morbid conditions with life expectancy <1 year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
HFrEF
Patients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy)
Diagnostic test: CMD test
Measured CFR and IMR
Other Names:
  • Coronary microvascular dysfunction

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of HFiEF* at 12 months
Time Frame: 1-year follow-up
HFiEF was defined as LVEF >40% measured by echocardiography at 12 months.1
1-year follow-up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Correlation between CMD and left ventricular end diastolic pressure
Time Frame: 1 year
1 year
Correlation between CMD and delta LVEF from baseline to 12 months
Time Frame: 1 year
1 year
Correlation between CMD and E/e'
Time Frame: 1 year
1 year
Correlation between CMD and delta LV systolic dimension from baseline to 12 months
Time Frame: 1 year
1 year
Correlation between CMD and delta LV diastolic dimension from baseline to 12 months
Time Frame: 1-year follow-up
1-year follow-up
Correlation between CMD and late gadolinium enhancement measured by cardiac MRI
Time Frame: 1 year
1 year
Correlation between CMD and pulmonary artery wedge pressure
Time Frame: 1 year
1 year
Correlation between CMD and mean pulmonary artery pressure
Time Frame: 1 year
1 year
Correlation between CMD and pulmonary artery pulsatility index (PAPi)
Time Frame: 1 year
1 year
Correlation between CMD and cardiac output/cardiac index
Time Frame: 1 year
1 year
Correlation between CMD and delta NT-proBNP from baseline to 12 months follow-up
Time Frame: 1-year follow-up
1-year follow-up
Proportion of CMD according to etiology
Time Frame: 1 year
1 year
Rates of All-cause death
Time Frame: 1-year follow-up
1-year follow-up
Rates of Cardiac death
Time Frame: 1-year follow-up
1-year follow-up
Rates of Readmission due to HF
Time Frame: 1-year follow-up
1-year follow-up
Rates of Readmission
Time Frame: 1-year follow-up
1-year follow-up
Rates of Implantation of implantable cardioverter defibrillator
Time Frame: 1-year follow-up
1-year follow-up
Rates of Cardiac replacement therapy (heart transplantation or LVAD)
Time Frame: 1-year follow-up
1-year follow-up
Changes of quality of life for HF (Kansas City Cardiomyopathy Questionnaire [KCCQ])
Time Frame: 1-year follow-up
1-year follow-up
Total medical cost
Time Frame: 1-year follow-up
1-year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Samsung Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ki Hong Choi, MD, Samsung Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 9, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2024

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 6, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HFrEF-CMD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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