Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function

Study Overview
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Brief Summary
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The DIAST-CMD registry (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) is prospective registry which enrolled patients who underwent echocardiography, cnically-indicated invasive coronary angiography and comprehensive physiologic assessments including fractional flow reserve (FFR), CFR, and IMR measurements for at least 1 vessel from Samsung Medical Center. Patients with hemodynamic instability, severe LV dysfunction (left ventricular ejection fraction<40%), a culprit vessel of acute coronary syndrome, severe valvular stenosis or regurgitation were excluded.

Detailed Description
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Cardiac diastolic dysfunction refers to a condition in which abnormalities in mechanical function are present during diastole and is an independent predictor of mortality, even in patients with preserved left ventricular (LV) systolic function. Clinical manifestations of cardiac diastolic dysfunction are also variable, from asymptomatic subclinical heart failure to heart failure with preserved ejection fraction, angina or exercise intolerance without significant epicardial coronary artery disease, or end-stage heart failure. 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 cardiac diastolic dysfunction. 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). Previous studies presented CMD could be one of the major causes of angina without significant epicardial coronary artery disease and an independent predictor of adverse clinical events in patients with stable ischemic heart disease, acute myocardial infarction (MI), or myocardial disease. Nevertheless, there has been limited study which evaluated the association between cardiac diastolic dysfunction and CMD using invasive physiologic indices and their prognostic implications, especially in non-MI patients without significant coronary artery stenosis. Therefore, the current study was designed the current DIAST-CMD registry to evaluate 3 important clinical questions as to whether: (1) cardiac diastolic dysfunction is significantly associated with the presence of CMD; 2) both cardiac diastolic dysfunction and CMD are significantly associated with long-term cardiovascular death; and 3) integration of both disease entities would have incremental prognostic stratification in non-MI patients without significant epicardial coronary artery disease.

Official Title
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Prospective Registry Evaluating Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function

Conditions
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Ischemic Heart Disease, Microvascular Coronary Artery Disease, Diastolic Dysfunction, Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Diagnostic Test: Echocardiography
* Diagnostic Test: Coronary flow reserve and index of microcirculatory dysfunction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who underwent clinically-indicated invasive coronary angiography Patients who underwent comprehensive physiologic assessments Patients who were evaluated by echocardiography Exclusion Criteria: Patients with unavailable echocardiography data Patients with hemodynamic instability Patients with severe LV dysfunction (LV ejection fraction<30%) Patients with severe valvular stenosis or regurgitation Culprit vessel of acute coronary syndrome
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 cardiac diastolic dysfunction<br>Echocardiographic grades of diastolic function was defined according to 2016 ASE/EACVI recommendations for the evaluation of LV diastolic function. Cardiac diastolic dysfunction was defined as elevated E/e'≥15. | Diagnostic Test: Echocardiography<br>* Echocardiographic grades of diastolic function was defined according to 2016 ASE/EACVI recommendations for the evaluation of LV diastolic function. Cardiac diastolic dysfunction was defined as elevated E/e'≥15.<br>Diagnostic Test: Coronary flow reserve and index of microcirculatory dysfunction<br>* Coronary microcirculatory dysfunction was defined as having both depressed CFR (≤2.0) and elevated IMR (≥23U).<br>|
| Patients with coronary microcirculatory dysfunction<br>Patients with coronary microcirculatory dysfunction was defined as having both depressed CFR (≤2.0) and elevated IMR (≥23U). | Diagnostic Test: Echocardiography<br>* Echocardiographic grades of diastolic function was defined according to 2016 ASE/EACVI recommendations for the evaluation of LV diastolic function. Cardiac diastolic dysfunction was defined as elevated E/e'≥15.<br>Diagnostic Test: Coronary flow reserve and index of microcirculatory dysfunction<br>* Coronary microcirculatory dysfunction was defined as having both depressed CFR (≤2.0) and elevated IMR (≥23U).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death | Cardiovascular death | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all-cause death | all-cause death | 3 year | 
| Myocardial infarction | Myocardial infarction according to universal definition of MI | 3 year | 
| Any revascularization | Any revascularization according to ARC definition | 3 year | 
| Major adverse cardiac events | Major adverse cardiac events (MACEs, a composite of cardiovascular death, MI, and any revascularization) | 3 year | 
| Heart failure admission | Admission due to heart failure | 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary microvascular dysfunction, diastolic dysfunction, coronary flow reserve, index of microcirculatory resistance, prognosis