Distribution and Clinical Implication of CMD in Patients With HFpEF Without Significant CAD

Recruiting

• Conditions: Heart Failure With Preserved Ejection Fraction; Coronary Microvascular Dysfunction
• Interventions: Diagnostic Test: Invasive physiologic evaluation (fractional flow reserve, coronary flow reserve, index of microcirculatory resistance)

• Registration Number: NCT04788576
• Lead Sponsor: Samsung Medical Center

Brief Summary

To evaluate the incidence of coronary microvascular dysfunction (CMD) and its' prognostic implication in patients who have diagnosed as heart failure with preserved ejection fraction (HFpEF) confirmed by HFA-PEFF scoring system without functionally significant coronary artery disease.

Detailed Description

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome in patients with current or prior symptoms of HF with a left ventricular ejection fraction (LVEF) ≥ 50 percent and evidence of cardiac dysfunction as a cause of symptoms (abnormal LV filling and elevated filling pressures). Previous studies have reported that HFpEF is related to various clinical risk factors such as hypertension, obesity, diabetes mellitus, chronic kidney disease, atrial fibrillation, myocardial ischemia with or without significant epicardial coronary artery stenosis, or myocardial infiltrative disease. Although its pathophysiology remains incompletely understood, findings from clinical and pre-clinical studies have suggested systemic endothelial dysfunction, oxidative stress, and coronary microvascular dysfunction (CMD) could be important pathophysiologic mechanisms for HFpEF.

In this regard, recent studies evaluated non-invasively measured coronary flow reserve (CFR) from positron emission tomography (PET), cardiac magnetic resonance imaging (MRI), or Doppler echocardiography, and presented the association of depressed global CFR with cardiac diastolic dysfunction and higher risk of clinical events. The presence of CMD can be also evaluated by invasive physiologic assessment using both CFR and index of microcirculatory resistance (IMR). Nevertheless, there has been limited study which evaluated the association between HFpEF and CMD using invasive physiologic indices and their prognostic implications, especially in patients without significant coronary artery stenosis. Therefore, we sought to evaluate the incidence of CMD and its' prognostic implication in patients who have diagnosed as heart failure with preserved ejection fraction (HFpEF) confirmed by HFA-PEFF scoring system without functionally significant coronary artery disease.

Study Timeline

• Study Start: 2021-01-25
• Study First Submitted: 2021-03-05
• Study First Submitted QC: 2021-03-05
• Study First Posted: 2021-03-09
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-28
• Last Update Posted: 2024-01-30
• Primary Completion: 2024-09-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Subject must be at least 19 years of age.
• Subject with preserved ejection fraction (ejection fraction > 50%)
• Subject presented with dyspnea on exertion (NYHA Grade 2 or more) and diagnosed as HFpEF using HFA-PEFF scoring system (HFA-PEFF ≥5 or 2-4 with abnormal stress test or invasive hemodynamic test)
• Subject who clinically need coronary angiography
• Subject who is able to voluntarily sign informed consent form

Exclusion Criteria

• Subject with reduced ejection fraction (<50%)
• Subject with significant coronary artery stenosis on coronary angiography (diameter stenosis ≥90% or 50-90% with fractional flow reserve [FFR] ≤0.80)
• Subject who has other obvious causes of dyspnea (ex, lung disease)
• Subject who have non-cardiac co-morbid conditions with life expectancy <1 year

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with heart failure with preserved ejection fraction (HFpEF)	Invasive physiologic evaluation (fractional flow reserve, coronary flow reserve, index of microcirculatory resistance)	Subject with preserved ejection fraction (ejection fraction \> 50%) and with dyspnea on exertion (NYHA Grade 2 or more) and diagnosed as HFpEF using HFA-PEFF scoring system (HFA-PEFF ≥5 or 2-4 with abnormal stress test or invasive hemodynamic test)

Primary Outcome Measures

Name	Time	Method
Proportion of CMD in patients with HFpEF	Immediate after the index procedure	Proportion of CMD confirmed by invasive physiologic evaluation

Secondary Outcome Measures

Name	Time	Method
Correlation between CMD and HFA-PEFF score	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and HFA-PEFF score
Correlation between CMD and NT-proBNP	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and NT-proBNP
Correlation between CMD and mean pulmonary artery pressure	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and mean pulmonary artery pressure
Readmission	At 2 years after the index procedure	Readmission during follow-up
Correlation between CMD and E/e'	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and E/e'
Correlation between CMD and pulmonary artery wedge pressure	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and pulmonary artery wedge pressure
Correlation between CMD and left ventricular end diastolic pressure	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and left ventricular end diastolic pressure
All-cause death	At 2 years after the index procedure	All-cause death during follow-up
Any revascularization	At 2 years after the index procedure	Any revascularization during follow-up
Proportion of heart failure with reduced ejection fraction	At 2 years after the index procedure	Proportion of progression of heart failure with reduced ejection fraction
Correlation between CMD and exercise time	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation exercise time
Cardiac death	At 2 years after the index procedure	Cardiac death during follow-up
Myocardial infarction	At 2 years after the index procedure	Myocardial infarction during follow-up
Readmission due to heart failure	At 2 years after the index procedure	Readmission due to heart failure during follow-up
Correlation between CMD and Excercise induced E/e'	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and exercise induced E/e'
Correlation between CMD and Exercise induced pulmonary artery wedge pressure	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation exercise induced and pulmonary artery wedge pressure
Correlation between CMD and mean exercise induced pulmonary artery pressure	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and exercise induced mean pulmonary artery pressure
Correlation between CMD and Gas analysis data (Peak exercise oxygen consumption, Respiratory quotient)	Immediate after the index procedure	Correlation between CMD confirmed by invasive physiologic evaluation and exercise induced peak exercise oxygen consumption, Respiratory quotient

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of