PericOronary INflammaTion in Non-Obstructive Coronary Artery Disease (POINT-NOCAD)

A Single Center Study of Perivascular Coronary Inflammation in Patients With Myocardial Ischemia or Infarction With Non-Obstructive Coronary Arteries

Among patients with ischemic heart disease who are referred for coronary angiography, a substantial proportion have non-obstructive coronary artery disease (CAD). Myocardial infarction (MI) with non-obstructive coronary artery disease (MINOCA) accounts for 5-20% of patients with MI and preferentially affects women. MINOCA pathogenesis is varied and may include atherosclerotic plaque rupture, plaque erosion with thrombosis, vasospasm, embolization, dissection or a combination of mechanisms. Other patients may have clinically unrecognized myocarditis, or takotsubo syndrome masquerading as MI. Among patients referred for coronary angiography for the evaluation of stable ischemic heart disease, non-obstructive CAD is present in up to ~30% of men and ~60% of women. Stable ischemia with non-obstructive coronary arteries (INOCA) may be due to coronary microvascular dysfunction in up to 40% of these patients. Our understanding of mechanisms of MINOCA and INOCA remain incomplete. Coronary inflammation has been hypothesized as a potential mechanism contributing to coronary spasm in MINOCA and microvascular disease in INOCA.

Study Overview

• Status: Recruiting
• Conditions: Non-Obstructive Coronary Atherosclerosis
• Intervention / Treatment: Procedure: Coronary computed tomography angiography (CCTA); Drug: Isovue; Drug: Nitroglycerin; Drug: Metoprolol

Detailed Description

The PericOronary INflammaTion in Non-Obstructive Coronary Artery Disease (POINT-NOCAD) study is a single-center diagnostic, observational study enrolling men and women with MINOCA or INOCA who are planned to undergo (or underwent) clinically indicated coronary angiography. The research plan is to evaluate coronary inflammation, as measured by the perivascular coronary fat attenuation index from non-invasive coronary computed tomography angiography (CCTA), in patients with MINOCA and INOCA.

• Study Type: Observational
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathaniel Smilowitz, MD; Phone Number: 212-263-5656; Email: Nathaniel.Smilowitz@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Nathaniel Smilowitz, MD; Phone Number: 212-263-5656; Email: Nathaniel.Smilowitz@nyulangone.org
      • Principal Investigator: Nathaniel Smilowitz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 125 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults presenting to the NYU Langone Health Tisch/Kimmel Cardiac Catheterization Laboratory or the Bellevue Cardiac Catheterization laboratory will be screened and approached for consent if the patient's treating provider is amenable to their participation in the research study and if the patient is eligible for enrollment based on the eligibility criteria prior to clinically indicated cardiac catheterization.

Description

Inclusion Criteria:

• Adult age ≥18 years referred for clinically indicated coronary angiography
• Stable ischemic heart disease OR acute myocardial infarction as the indication for coronary angiography

Exclusion Criteria:

Clinical Exclusion criteria:

• Estimated glomerular filtration rate < 45 mL/min
• History of allergic reaction to iodinated contrast media
• Pregnancy

Angiographic / Post-Cath Exclusion criteria:

• Obstructive CAD (≥50% luminal obstruction in ≥1 major epicardial coronary arteries by invasive coronary angiography)
• Allergic reaction to iodinated contrast media

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Intervention group; Participants will be identified by review of the cardiac catheterization laboratory schedule each day by the principal investigator, a co-investigator, or a research coordinator. Participants with no obstructive CAD and completed microvascular testing will undergo a research CCTA.

Procedure: Coronary computed tomography angiography (CCTA); Participants will undergo CCTA. CCTA performed in this study will be technically identical to CCTA that is commonly performed in clinical practice, for which safety profiles are well defined. Guidelines implemented by the National Institutes of Health Radiation Exposure Committee will be followed. Major risks of CCTA include exposure to ionizing radiation, the requirement for intravenous catheter placement and contrast media administration, and side effects of beta-blockers and nitrates that may be used for vasodilation and heart rate control to optimize CCTA image quality.; Drug: Isovue; CCTA requires intravenous catheter placement and the administration of iodinated contrast media (Isovue).; Drug: Nitroglycerin; Medication to promote coronary vasodilation during the CCTA may be administered immediately prior to CCTA to optimize image quality; Drug: Metoprolol; Medication to promote heart rate reduction during the CCTA may be administered immediately prior to CCTA to optimize image quality

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perivascular coronary fat attenuation will be significantly greater in MINOCA patients compared with INOCA patients	Images obtained from the CCTA will be used to calculate perivascular FAI, measured around the proximal left anterior descending artery and in the right coronary artery, in the proximal 10 to 50 mm of the vessel. For each coronary vessel, will define the weighted mean attenuation of all adipose tissue-containing voxels (-190 to -30 Hounsfield units [HU]) located within a radial distance from the outer vessel wall equal to the diameter of the respective vessel.	Visit 1, Day 0
Perivascular coronary fat attenuation will be greater in INOCA patients with versus without coronary microvascular disease	Images obtained from the CCTA will be used to calculate perivascular FAI, measured around the proximal left anterior descending artery and in the right coronary artery, in the proximal 10 to 50 mm of the vessel. For each coronary vessel, will define the weighted mean attenuation of all adipose tissue-containing voxels (-190 to -30 Hounsfield units [HU]) located within a radial distance from the outer vessel wall equal to the diameter of the respective vessel.	Visit 1, Day 0
Perivascular coronary fat attenuation in patients with MINOCA will be greatest in the culprit coronary vessels with evidence of acute plaque disruption.	Images obtained from the CCTA will be used to calculate perivascular FAI, measured around the proximal left anterior descending artery and in the right coronary artery, in the proximal 10 to 50 mm of the vessel. For each coronary vessel, will define the weighted mean attenuation of all adipose tissue-containing voxels (-190 to -30 Hounsfield units [HU]) located within a radial distance from the outer vessel wall equal to the diameter of the respective vessel.	Visit 1, Day 0

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Nathaniel Smilowitz, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: August 31, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Inflammation; Atherosclerosis; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Nitroglycerin; Metoprolol
• Other Study ID Numbers: 21-00764

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data. Upon reasonable request. Requests should be directed to Nathaniel.Smilowitz@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No