Heart FailureHFrEF-CMDNCT06243653
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
An observational study of Heart Failure and Microvascular Angina, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Heart Failure, Microvascular Angina, Non-ischemic Cardiomyopathy
- What is being tested?
- CMD test
- How many people
- 200 participants
- Where
- 1 siteSouth Korea
- Study dates
- 9 Aug 2023to 31 Dec 2027
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy)
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Samsung Medical Center
Seoul
Ki Hong Choi, MD, 82-2-3410-3419, cardiokh@gmail.com
About this study
Official title: 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.
Read the 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.
- Being tested
- CMD test
- Keywords
- coronary microvascular dysfunction, non-ischemic cardiomyopathy
- Medical subject headings
- Heart Failure, Microvascular Angina
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMD testDiagnostic test
Also called Coronary microvascular dysfunction
Measured CFR and IMR
| Study group | Role | What they receive |
|---|---|---|
| HFrEF | Patients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy) Receives: Diagnostic Test: CMD test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of HFiEF* at 12 months
HFiEF was defined as LVEF >40% measured by echocardiography at 12 months.1
Measured: 1-year follow-up
Secondary outcomes (20)
Correlation between CMD and left ventricular end diastolic pressure
Measured: 1 year
Correlation between CMD and delta LVEF from baseline to 12 months
Measured: 1 year
Correlation between CMD and E/e'
Measured: 1 year
Correlation between CMD and delta LV systolic dimension from baseline to 12 months
Measured: 1 year
Correlation between CMD and delta LV diastolic dimension from baseline to 12 months
Measured: 1-year follow-up
Correlation between CMD and late gadolinium enhancement measured by cardiac MRI
Measured: 1 year
Correlation between CMD and pulmonary artery wedge pressure
Measured: 1 year
Correlation between CMD and mean pulmonary artery pressure
Measured: 1 year
Correlation between CMD and pulmonary artery pulsatility index (PAPi)
Measured: 1 year
Correlation between CMD and cardiac output/cardiac index
Measured: 1 year
Correlation between CMD and delta NT-proBNP from baseline to 12 months follow-up
Measured: 1-year follow-up
Proportion of CMD according to etiology
Measured: 1 year
Rates of All-cause death
Measured: 1-year follow-up
Rates of Cardiac death
Measured: 1-year follow-up
Rates of Readmission due to HF
Measured: 1-year follow-up
Rates of Readmission
Measured: 1-year follow-up
Rates of Implantation of implantable cardioverter defibrillator
Measured: 1-year follow-up
Rates of Cardiac replacement therapy (heart transplantation or LVAD)
Measured: 1-year follow-up
Changes of quality of life for HF (Kansas City Cardiomyopathy Questionnaire [KCCQ])
Measured: 1-year follow-up
Total medical cost
Measured: 1-year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2024
- Study start9 Aug 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ki Hong Choi, Samsung Medical Center
- Investigators
- Ki Hong Choi, MD, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06243653
- Sponsor's protocol ID
- HFrEF-CMD
- Acronym
- HFrEF-CMD
- Status last verified
- Feb 2024
- First submitted
- 28 Jan 2024
- Last updated
- 6 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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).
- ClinicalTrials.gov ID
- NCT06243653
- Acronym / sponsor ID
- HFrEF-CMD / HFrEF-CMD
- Keywords
- coronary microvascular dysfunction, non-ischemic cardiomyopathy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 9 Aug 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 6 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HFrEF | – | Diagnostic Test: CMD testPatients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy) |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy)
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMD testAlso: Coronary microvascular dysfunctionMeasured CFR and IMR | Diagnostic test | HFrEF |
Primary outcome
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
20 secondary outcomes
Correlation between CMD and left ventricular end diastolic pressure
Time frame: 1 year
Correlation between CMD and delta LVEF from baseline to 12 months
Time frame: 1 year
Correlation between CMD and E/e'
Time frame: 1 year
Correlation between CMD and delta LV systolic dimension from baseline to 12 months
Time frame: 1 year
Correlation between CMD and delta LV diastolic dimension from baseline to 12 months
Time frame: 1-year follow-up
Correlation between CMD and late gadolinium enhancement measured by cardiac MRI
Time frame: 1 year
Correlation between CMD and pulmonary artery wedge pressure
Time frame: 1 year
Correlation between CMD and mean pulmonary artery pressure
Time frame: 1 year
Correlation between CMD and pulmonary artery pulsatility index (PAPi)
Time frame: 1 year
Correlation between CMD and cardiac output/cardiac index
Time frame: 1 year
Correlation between CMD and delta NT-proBNP from baseline to 12 months follow-up
Time frame: 1-year follow-up
Proportion of CMD according to etiology
Time frame: 1 year
Rates of All-cause death
Time frame: 1-year follow-up
Rates of Cardiac death
Time frame: 1-year follow-up
Rates of Readmission due to HF
Time frame: 1-year follow-up
Rates of Readmission
Time frame: 1-year follow-up
Rates of Implantation of implantable cardioverter defibrillator
Time frame: 1-year follow-up
Rates of Cardiac replacement therapy (heart transplantation or LVAD)
Time frame: 1-year follow-up
Changes of quality of life for HF (Kansas City Cardiomyopathy Questionnaire [KCCQ])
Time frame: 1-year follow-up
Total medical cost
Time frame: 1-year follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
Related trials for Heart Failure
RecruitingPhase 2/3
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Heart Failure, Left Ventricular Systolic Dysfunction
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
Active, not recruiting
Heart Failure Patient Management and Interventions Using Continuous Patient Monitoring Outside Hospitals and Real-world Data
Chronic Heart Failure, Heart Transplant Recipient
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure
Not yet recruitingObservational study
Real-world Effectiveness and Safety of Savagen (Sacubitril/Valsartan) in Malaysian HFrEF Patients
Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ki Hong Choi, MD principal investigator
Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure and Microvascular Angina, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ki Hong Choi, MD (82-2-3410-3419, cardiokh@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of HFiEF* at 12 months (time frame: 1-year follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.