The DISCOVER INOCA Prospective Multi-center Registry

Recruiting

Conditions: Ischemia and No Obstructive Coronary Artery Disease
Endothelial Dysfunction
Microvascular Angina
Coronary Vasospasm
Chest Pain With Normal Coronary Angiography
Coronary Microvascular Dysfunction

Registration Number: NCT05288361

Lead Sponsor: Yale University

Brief Summary: The overall objective of this multi-center registry is to identify specific phenotypes of INOCA with both an anatomic evaluation (coronary angiography and intravascular imaging) and physiologic assessment with the Abbott Coroventis Coroflow Cardiovascular System, and to determine long-term outcomes.

Detailed Description: This is a prospective, multicenter, registry of stable patients with ischemia and no obstructive coronary artery disease (INOCA) evaluated by coronary angiography, intravascular imaging, and physiologic measurements obtained on the Coroventis Coroflow Cardiovascular System.

The Coroventis Coroflow Cardiovascular System and PressureWire™ X Guidewire (Abbott, Abbott Park, IL) are a device combination consisting of a physiology wire with wireless transmitter (Wi-Box), CoroHub Receiver, and CoroFlow Software. The PressureWire™ X guidewire is a hydrophilic-coated wire with pressure and temperature sensors that is capable of measuring physiologic indices including fractional flow reserve (FFR), resting full cycle ratio (RFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). The guidewire wirelessly transmits pressure and temperature data via the Wi-Box to the CoroHub Receiver and CoroFlow Software, which is a software interface designed to display pressure measurements, thermodilution curves, and physiologic indices. This registry will enroll 500 subjects at up to 10 sites in the United States that use the Abbott Coroventis Coroflow Cardiovascular System.

The overall objective of this multi-center registry is to identify specific phenotypes of INOCA with both an anatomic evaluation (coronary angiography and intravascular imaging) and physiologic assessment with the Abbott Coroventis Coroflow Cardiovascular System, and to determine long-term outcomes. Specific goals include:

* Describe the prevalence of the following INOCA phenotypes: coronary microvascular dysfunction (CMD), vasospastic angina, mixed CMD/vasospastic angina, other disorders of coronary physiology, and non-cardiac chest pain;

* Characterize the burden of epicardial coronary artery atherosclerosis and myocardial bridging (MB) by angiography and intracoronary imaging (intravascular ultrasound or optical coherence tomography) in patients with INOCA;

* Characterize the natural history and outcomes of patients with INOCA and determine variables associated with major adverse cardiovascular events

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 500

Inclusion Criteria

Suspected ischemic heart disease and is referred to undergo clinically indicated invasive coronary angiography
No obstructive coronary artery disease (CAD) as defined by operator visual assessment with (1) angiographically normal coronary arteries OR (2) non-obstructive CAD with angiographic stenosis < 50%, or greater than or equal to 50 but < 70% with FFR greater than or equal to 0.81 or RFR greater than or equal to 0.90
Willing to comply with specified follow-up evaluations. The participant or legally authorized representative has been informed of the nature of the study, agrees to its provisions, and has been provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

Exclusion Criteria

Pregnant or nursing
Any myocardial infarction at index presentation or within 90 days prior to enrollment, defined as any electrocardiogram diagnostic for myocardial infarction OR elevation in serum troponin greater than the upper limit of the site-defined reference range
Known left ventricular ejection fraction < 50% or cardiogenic shock requiring pressors or mechanical circulatory assistance (e.g., intra-aortic balloon pump, left ventricular assist device, other temporary cardiac support blood pump)
Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation) or dialysis at the time of screening
Prior percutaneous coronary intervention
Planned percutaneous coronary intervention (PCI)
Prior coronary artery bypass graft surgery
Prior ST-elevation myocardial infarction
History of hypertrophic cardiomyopathy
History of infiltrative heart disease (e.g., cardiac amyloidosis)
New York Heart Association Class IV congestive heart failure
Severe mitral regurgitation
Severe aortic stenosis
Severe pulmonary hypertension (Mean pulmonary artery pressure greater than or equal to 35mmHg or echocardiographic right ventricular systolic pressure greater than or equal to 60mmHg)
Known history of unrepaired or repaired congenital heart disease
Past or pending heart transplant, or on the waiting list for organ transplant
Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol, or is associated with a life expectancy of less than 1 year
Current or planned participation in a study of an investigational therapy
Angiographic stenosis in any major epicardial vessel ≥ 70% by visual estimate
Angiographic stenosis in any major epicardial vessel greater than or equal to 50% and < 70% by visual estimate with FFR less than or equal to 0.80 or RFR less than or equal to 0.89

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The proportion of subjects with each physiologic phenotypes diagnosed with the Coroflow Cardiovascular System will be reported within 24-48 hours of the procedure.	up to 48 hours after the procedure	The following phenotypes will be captured: Coronary microvascular dysfunction (CMD)- Criteria for a diagnosis of CMD include an abnormal Index of Microcirculatory Resistance (IMR) ≥ 25 and/or impaired Coronary Flow Reserve (CFR) ≤ 2.0; Vasospastic angina (VSA): Includes coronary vasospasm, microvascular spasm, and endothelial dysfunction. Criteria for coronary vasospasm include ≥ 90% narrowing of the epicardial vessel during acetylcholine testing and either or both angina and transient ischemic EKG changes. Microvascular spasm includes angina and/or ischemic EKG changes in the absence of spasm of the epicardial vessel during acetycholine infusion; Endothelial dysfunction as defined as angiographic diameter change less than or equal to 0% and but not greater than -89% in response to acetylcholine infusion; Mixed CMD/VSA; Any other disorders of coronary physiology.
The proportion of subjects that experience Major Adverse Cardiovascular Events (MACE)	Up to 5 years	The proportion of subjects that experience Major Adverse Cardiovascular Events (MACE) as reported by the clinical study sites and adjudicated by the Clinical Events Committee (CEC). Reports may come from the clinical site or self report. MACE defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes or coronary revascularization.
The proportion of subjects that exhibit mild, moderate or severe coronary artery stenosis	At the time of the procedure	The proportion of subjects that exhibit mild, moderate or severe coronary artery stenosis as measured by Optical Coherence Tomography (OCT), Intravascular Ultrasound (IVUS) or Quantitative Coronary Angiography (QCA). Mild stenosis is defined as less than or equal to 30%, Moderate stenosis is defined as 31%-69%, and severe stenosis is greater than or equal to 70%. The measurements will take place during the procedure and the analysis will be completed by a central core lab.
Lesion length during the procedure	At the time of the procedure	Lesion length during the procedure will be determined for each subject by the use of OCT, IVUS or QCA and the analysis will be completed by a central core lab. Lesion length will be defined by either less than 15mm or equal to or greater than 15mm.

Secondary Outcome Measures

Trial Locations

Locations (8): Northeast Georgia Medical Center
🇺🇸
Gainesville, Georgia, United States
NYU Langone Health
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New York, New York, United States
Columbia University Irving Medical Center
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New York, New York, United States
The Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
Stanford Hospital
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Stanford, California, United States
New York Presbyterian-Brooklyn Methodist Hospital
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Brooklyn, New York, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Yale University
🇺🇸
New Haven, Connecticut, United States

The DISCOVER INOCA Prospective Multi-center Registry

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts

Name	Time	Method
The proportion of subjects that die at any time in the study	Up to 5 years	The proportion of subjects that die at any time in the study as reported by the clinical site or the subject's family. The cause of death will be further defined as cardiovascular, and non-cardiovascular mortality as adjudicated by the CEC.
The proportion of subjects that experience a Myocardial Infarction (MI) at any time during the study.	Up to 5 Years	The proportion of subjects that experience a Myocardial Infarction (MI) at any time during the study as reported by the clinical site or self report. Fourth Universal Definition will be used to determine MI type and will be adjudicated by the CEC.
The change in the quality of life (QOL) from baseline for each subject will be assessed using the QOL EQ-5D-5L questionnaire.	At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years	QOL will be assessed by EQ-5D-5L. The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).QOL will be determined at the time of the procedure, at 30 days, 6 months, 12months and then annually up to 5 years. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
The change in depression status from baseline for each subject assessed by the Patient Health Questionnaire (PHQ)-8 questionnaire.	At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years	Depression status will be assessed by the PHQ-8 questionnaire. The PHQ-8 is a series of 8 questions will four possible answers each. The questions focus on over-all well-being as well as daily habits. The higher the score the more the patient is likely to be depressed. Depression status will be determined at the time of the procedure, at 30 days, 6 months, 12months and then annually up to 5 years.
The proportion of subjects that require revascularization of their coronary arteries at any time during the study.	Up to 5 years	Reports may come from the clinical site or self report. Revascularization will further be defined as Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG) and will be adjudicated by the CEC.
The proportion of subjects that experience Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) at any time during the study.	Up to 5 Years	The proportion of subjects that experience Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) at any time during the study as reported by the clinical site or self report. MACCE is defined as MACE and/or any stroke (NeuroARC definition) and adjudicated by the CEC.
The proportion of subjects that experience a stroke at any time during the study.	Up to 5 years	The proportion of subjects that experience a stroke at any time during the study as reported by the clinical site or self report. NeuroARC definition will be used to classify the type of stroke and will be adjudicated by the CEC.
The change in baseline of angina symptoms for each subject. The angina status will be classified at the time of the procedure, at 30 days, 6 months, 12months and then annually up to 5 years.	At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years	The change in baseline of angina symptoms for each subject as assessed by the Seattle Angina Questionaire. The Seattle Angina Questionnaire (SAQ) contains 19 questions used to measure health status in patients with coronary artery disease (CAD). The SAQ directly measure patients' current health status: Physical Limitation, Angina Frequency, and Quality of Life. The SAQ results in 3 domain scores as well as an overall summary score.
The proportion of subjects that experience a hospitalization at any time during the study.	Up to 5 years	The proportion of subjects that experience a hospitalization at any time during the study as reported by the clinical site or self report. The reason for hospitalization will be further classified as Cardiovascular related or Heart Failure and adjudicated by the CEC
Proportion of subjects that experience major bleeding at any time during the study using the Bleeding Academic Research Consortium (BARC) bleeding type	Up to 5 years	Proportion of subjects that experience major bleeding at any time during the study using the BARC bleeding type. Reports may come from the clinical site or self report. Bleeding types on a scale from 0 (no bleeding) to 5 (fatal bleeding). Major bleeding is defined as categories BARC 3-5 and will be adjudicated by the CEC.
Proportion of subjects that experience Major Vascular Complications at any time during the study.	Up to five 5 years	Proportion of subjects that experience Major Vascular Complications at any time during the study as reports by the clinical site or self report, and will be adjudicated by the CEC.
The proportion of subjects that require repeat coronary angiography at any time during the study.	Up to 5 years	The proportion of subjects that require repeat coronary angiography at any time during the study as reported by the clinical site or self report. Reported events will be adjudicated by the CEC.
The proportion of subjects with coronary lesions that experience progression to obstructive Coronary Artery Disease (CAD) at any time during the study.	Up to 5 years	The proportion of subjects with coronary lesions that experience progression to obstructive Coronary Artery Disease (CAD) at any time during the study as reported by the clinical site or self report, and will be adjudicated by the CEC.
Proportion of subjects that experience a composite of death, stroke, and MI at any time during the study.	Up to 5 years	Proportion of subjects that experience a composite of death, stroke, and MI at any time during the study as reported by the clinical site or self report, and will be adjudicated by the CEC.
Change from baseline in proportion of subjects that experience each classification of angina status during the study.	At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years	The angina status will be assessed using the Canadian Cardiovascular Society (CCS) class or Braunwald Unstable Angina classification. The angina type will be classified at the time of the procedure, at 30 days, 6 months, 1 year, and then annually up to 5 years.
The proportion of subjects that experience a series of procedural outcomes as assessed by the site and adjudicated by the CEC.	Up to 48 hours after the procedure	Procedural outcomes will be categorized into the following: Reclassification from pre-procedure diagnosis (including non-cardiac chest pain); Completion of the interventional diagnostic procedure without device-related serious adverse events or major angiographic complications; Frequency of major angiographic complications (device-related coronary artery dissection \[greater than type C\], slow or no flow, or perforation)
The change in anxiety status from baseline for each subject. will be assessed by the Generalized Anxiety Disorder (GAD)-7 questionnaire.	At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years	Anxiety status will be assessed by the GAD-7 questionnaire. The GAD-7 is a series of 7 questions will four possible answers each. The questions focus on over-all well-being as well as daily habits. The higher the score the more the patient is likely to be anxious. Anxiety status will be determined at the time of the procedure, at 30 days, 6 months, 12months and then annually up to 5 years.