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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Distribution and Clinical Implication of Coronary Flow Reserve and Index of Microcirculatory Resistance in Patients With Heart Failure With Preserved Ejection Fraction Without Significant Coronary Artery Disease

Conditions
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Heart Failure With Preserved Ejection Fraction, Coronary Microvascular Dysfunction

Intervention / Treatment
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* Diagnostic Test: Invasive physiologic evaluation (fractional flow reserve, coronary flow reserve, index of microcirculatory resistance)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with heart failure with preserved ejection fraction (HFpEF)<br>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) | Diagnostic Test: Invasive physiologic evaluation (fractional flow reserve, coronary flow reserve, index of microcirculatory resistance)<br>* In case of heart failure with preserved ejection fraction confirmed by HFA-PEFF scoring system without functionally significant coronary artery disease, coronary angiography with invasive physiologic evaluation including fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance will be performed to evaluate the distribution and clinical implication of coronary microvascular dysfunction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of CMD in patients with HFpEF | Proportion of CMD confirmed by invasive physiologic evaluation | Immediate after the index procedure | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure with preserved ejection fraction, Coronary physiology, Coronary microvascular dysfunction, HFA-PEFF score