Clinical trial 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
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).
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Microvascular Angina
Non-ischemic Cardiomyopathy
Keywords: coronary microvascular dysfunction
non-ischemic cardiomyopathy
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2024-02-06
Enrollment: 200
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with heart failure with reduced ejection fraction (HFrEF) without significant coronary artery disease (non-ischemic cardiomyopathy)

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of HFiEF* at 12 months
timeFrame: 1-year follow-up
Secondary outcomes:
measure: Correlation between CMD and left ventricular end diastolic pressure
timeFrame: 1 year
measure: Correlation between CMD and delta LVEF from baseline to 12 months
timeFrame: 1 year
measure: Correlation between CMD and E/e'
timeFrame: 1 year
measure: Correlation between CMD and delta LV systolic dimension from baseline to 12 months
timeFrame: 1 year
measure: Correlation between CMD and delta LV diastolic dimension from baseline to 12 months
timeFrame: 1-year follow-up
measure: Correlation between CMD and late gadolinium enhancement measured by cardiac MRI
timeFrame: 1 year
measure: Correlation between CMD and pulmonary artery wedge pressure
timeFrame: 1 year
measure: Correlation between CMD and mean pulmonary artery pressure
timeFrame: 1 year
measure: Correlation between CMD and pulmonary artery pulsatility index (PAPi)
timeFrame: 1 year
measure: Correlation between CMD and cardiac output/cardiac index
timeFrame: 1 year
measure: Correlation between CMD and delta NT-proBNP from baseline to 12 months follow-up
timeFrame: 1-year follow-up
measure: Proportion of CMD according to etiology
timeFrame: 1 year
measure: Rates of All-cause death
timeFrame: 1-year follow-up
measure: Rates of Cardiac death
timeFrame: 1-year follow-up
measure: Rates of Readmission due to HF
timeFrame: 1-year follow-up
measure: Rates of Readmission
timeFrame: 1-year follow-up
measure: Rates of Implantation of implantable cardioverter defibrillator
timeFrame: 1-year follow-up
measure: Rates of Cardiac replacement therapy (heart transplantation or LVAD)
timeFrame: 1-year follow-up
measure: Changes of quality of life for HF (Kansas City Cardiomyopathy Questionnaire [KCCQ])
timeFrame: 1-year follow-up
measure: Total medical cost
timeFrame: 1-year follow-up
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Ki Hong Choi, MD
role: PRINCIPAL_INVESTIGATOR
References: