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)

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: Recruiting
• Conditions: Heart Failure; Microvascular Angina; Non-ischemic Cardiomyopathy
• Intervention / Treatment: Diagnostic test: CMD test

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: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Ki Hong Choi, MD; Phone Number: 82-2-3410-3419; Email: cardiokh@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Ki Hong Choi, MD; Phone Number: 82-2-3410-3419; Email: cardiokh@gmail.com

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Proportion of HFiEF* at 12 months	HFiEF was defined as LVEF >40% measured by echocardiography at 12 months.1	1-year follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between CMD and left ventricular end diastolic pressure	1 year
Correlation between CMD and delta LVEF from baseline to 12 months	1 year
Correlation between CMD and E/e'	1 year
Correlation between CMD and delta LV systolic dimension from baseline to 12 months	1 year
Correlation between CMD and delta LV diastolic dimension from baseline to 12 months	1-year follow-up
Correlation between CMD and late gadolinium enhancement measured by cardiac MRI	1 year
Correlation between CMD and pulmonary artery wedge pressure	1 year
Correlation between CMD and mean pulmonary artery pressure	1 year
Correlation between CMD and pulmonary artery pulsatility index (PAPi)	1 year
Correlation between CMD and cardiac output/cardiac index	1 year
Correlation between CMD and delta NT-proBNP from baseline to 12 months follow-up	1-year follow-up
Proportion of CMD according to etiology	1 year
Rates of All-cause death	1-year follow-up
Rates of Cardiac death	1-year follow-up
Rates of Readmission due to HF	1-year follow-up
Rates of Readmission	1-year follow-up
Rates of Implantation of implantable cardioverter defibrillator	1-year follow-up
Rates of Cardiac replacement therapy (heart transplantation or LVAD)	1-year follow-up
Changes of quality of life for HF (Kansas City Cardiomyopathy Questionnaire [KCCQ])	1-year follow-up
Total medical cost	1-year follow-up

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Ki Hong Choi, MD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 28, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Estimated): February 6, 2024

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: non-ischemic cardiomyopathy; coronary microvascular dysfunction
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Angina Pectoris; Heart Failure; Cardiomyopathies; Microvascular Angina
• Other Study ID 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