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NCT Number: NCT06243653

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

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.

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Key information

Age range

19 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CMD test

Diagnostic Test

Measured CFR and IMR

Other names: Coronary microvascular dysfunction

Primary outcomes

  1. 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

Secondary outcomes

  1. Correlation between CMD and left ventricular end diastolic pressure

    Time frame: 1 year

  2. Correlation between CMD and delta LVEF from baseline to 12 months

    Time frame: 1 year

  3. Correlation between CMD and E/e'

    Time frame: 1 year

  4. Correlation between CMD and delta LV systolic dimension from baseline to 12 months

    Time frame: 1 year

  5. Correlation between CMD and delta LV diastolic dimension from baseline to 12 months

    Time frame: 1-year follow-up

  6. Correlation between CMD and late gadolinium enhancement measured by cardiac MRI

    Time frame: 1 year

  7. Correlation between CMD and pulmonary artery wedge pressure

    Time frame: 1 year

  8. Correlation between CMD and mean pulmonary artery pressure

    Time frame: 1 year

  9. Correlation between CMD and pulmonary artery pulsatility index (PAPi)

    Time frame: 1 year

  10. Correlation between CMD and cardiac output/cardiac index

    Time frame: 1 year

  11. Correlation between CMD and delta NT-proBNP from baseline to 12 months follow-up

    Time frame: 1-year follow-up

  12. Proportion of CMD according to etiology

    Time frame: 1 year

  13. Rates of All-cause death

    Time frame: 1-year follow-up

  14. Rates of Cardiac death

    Time frame: 1-year follow-up

  15. Rates of Readmission due to HF

    Time frame: 1-year follow-up

  16. Rates of Readmission

    Time frame: 1-year follow-up

  17. Rates of Implantation of implantable cardioverter defibrillator

    Time frame: 1-year follow-up

  18. Rates of Cardiac replacement therapy (heart transplantation or LVAD)

    Time frame: 1-year follow-up

  19. Changes of quality of life for HF (Kansas City Cardiomyopathy Questionnaire [KCCQ])

    Time frame: 1-year follow-up

  20. Total medical cost

    Time frame: 1-year follow-up

Study contacts

Contact information is provided by the study sponsor or research team.

Ki Hong Choi, MD

CONTACT

[email protected]

82-2-3410-3419

Sponsors and collaborators

Lead sponsor

Samsung Medical Center

Other

Registry information

Official study 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).

Acronym: HFrEF-CMD

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Feb 6, 2024
Registry last updated
Feb 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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