Evaluation of Patients With Non-obstructive Coronary Arteries

Official title

Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease

Overview

Patients with angina and non-obstructive CAD are common within clinical practice, but remain a challenge with regard to diagnosis and treatment. When these patients undergo a comprehensive evaluation at the time of invasive coronary angiography, occult coronary abnormalities are frequently found. We hope to learn the overall prevalence and presentation of these occult coronary abnormalities and its long term outcome in this patient population.

Detailed description

This is a prospective registry of patients with chest pain, chest discomfort, breathlessness who do not have a blockage in their heart artery. This condition is known as angina/ischemia and non-obstructive coronary arteries (ANOCA/INOCA). The purpose of this registry is to help us understand the prevalence, causes of these conditions, identify effective diagnostic strategy, and long term outcome in this patient population.

Patients will undergo comprehensive invasive evaluation including coronary angiography, intravascular imaging, and physiologic measurements as a standard of care. Details regarding the participant's angiogram, endothelial function testing, microvascular testing, intravascular ultrasound, and myocardial bridge testing, if performed, will be entered into a research database.

Participants may be contacted by email or phone periodically for follow-up information, such as surveys, an update on medical history, and/or a check on their medical status or symptoms. We anticipate gathering these data at 6 months, 1 year, 3 years, 5 years, and 10 years, and every 5 years thereafter following their enrollment.

The overall objective of this registry study is to identify specific endotypes of ANOCA by invasive evaluation and study long term outcome.

Specific goals include:

1. Describe the prevalence of the following ANOCA endotypes: endothelial dysfunction, microvascular dysfunction, vasospastic angina, myocardial bridging (MB), and other disorders of coronary physiology, and non-cardiac chest pain; 2. Characterize the natural history and outcomes of patients with ANOCA and determine variables associated with major adverse cardiovascular events

Interventions

• Procedure 30 cc blood draw
• Procedure Intravascular ultrasound (IVUS)
• Procedure Coronary pressure/flow wire testing
• Procedure Coronary pressure/flow testing: Acetycholine challenge
• Procedure Procedure: Coronary pressure/flow testing: Nitroglycerin challenge
• Procedure Procedure: Procedure: Coronary pressure/flow testing: Adenosine challenge

Primary outcome measures

• Sex Differences in Endothelial Dysfunction, Microvascular Dysfunction, and Diffuse Plaque [Time frame: Day of procedure (study day one)]
• Number of participants with major adverse cardiovascular events (MACE) [Time frame: 15 years]

Secondary outcome measures (2)

• Change in Seattle angina questionnaire score [Time frame: Baseline, 6 months, 1 year, 3 year, every 5 years thereafter]
• Number of patients with cardiovascular rehospitalization [Time frame: 15 years]

Eligibility criteria

Inclusion criteria

• Patient referred for elective coronary angiography because of a reasonable clinical suspicion of coronary ischemia.
• Presence of angina or an anginal equivalent (including chest, back, shoulder, arm, neck, jaw discomfort, or shortness of breath brought on by physical exertion, emotional stress, or certain times of day/month).

Exclusion criteria

• Asymptomatic (such as a pre-op cath)
• Status-post heart transplant
• Age <18
• Renal insufficiency (creatinine >1.5)
• Presence of an acute coronary syndrome (STEMI or NSTEMI), Tako-tsubo, an abnormal ejection fraction (EF<55%), cardiogenic shock, or recent VT/VF
• Presence of another likely explanation of chest pain, such as pulmonary hypertension or aortic stenosis
• History of adverse reaction to any of the medications being used (acetylcholine, nitroglycerin, adenosine, or heparin)
• Currently taking vasoactive medication (such as nitroglycerin)
• Inability to provide an informed consent, including an inability to speak, read, or understand English, Spanish, Chinese, Farsi, Japanese, Korean, Russian, or Vietnamese
• A hearing impairment that won't allow for a typical verbal conversation or a visual impairment that won't allow for reading of the written consent
• Participation in another study (with the exception of the Stanford Gene-PAD study)
• A potentially vulnerable subject (including minors, pregnant women, economically and educationally disadvantaged, decisionally impaired, and homeless people)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

United States · 1 center

• Stanford University School of Medicine — Stanford

Publications

• Tremmel JA, Yeung AC. Ischemic heart disease in women: an appropriate time to discriminate. Rev Cardiovasc Med. 2007 Spring;8(2):61-8. PMID 17603424
• Rogers IS, Tremmel JA, Schnittger I. Myocardial bridges: Overview of diagnosis and management. Congenit Heart Dis. 2017 Sep;12(5):619-623. doi: 10.1111/chd.12499. Epub 2017 Jul 3. PMID 28675696
• Tremmel JA, Schnittger I. Myocardial bridging. J Am Coll Cardiol. 2014 Nov 18-25;64(20):2178-9. doi: 10.1016/j.jacc.2014.07.993. Epub 2014 Nov 10. No abstract available. PMID 25457408
• Tremmel JA. To Define Is to Limit: Is That Good or Bad When it Comes to Chest Pain? JACC Cardiovasc Interv. 2016 Mar 28;9(6):562-4. doi: 10.1016/j.jcin.2016.02.002. Epub 2016 Mar 2. No abstract available. PMID 26947385
• Schnittger I, Boyd JH, Tremmel JA. A Step Back in the Diagnosis and Management of Myocardial Bridging. Ann Thorac Surg. 2020 Jun;109(6):1950. doi: 10.1016/j.athoracsur.2019.09.051. Epub 2019 Nov 7. No abstract available. PMID 31706871
• Pargaonkar VS, Kobayashi Y, Kimura T, Schnittger I, Chow EKH, Froelicher VF, Rogers IS, Lee DP, Fearon WF, Yeung AC, Stefanick ML, Tremmel JA. Accuracy of non-invasive stress testing in women and men with angina in the absence of obstructive coronary artery disease. Int J Cardiol. 2019 May 1;282:7-15. doi: 10.1016/j.ijcard.2018.10.073. Epub 2018 Oct 23. PMID 30527992
• Lee BK, Lim HS, Fearon WF, Yong AS, Yamada R, Tanaka S, Lee DP, Yeung AC, Tremmel JA. Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation. 2015 Mar 24;131(12):1054-60. doi: 10.1161/CIRCULATIONAHA.114.012636. Epub 2015 Feb 20. PMID 25712205
• Parikh RV, Pargaonkar V, Ball RL, Kobayashi Y, Kimura T, Yeung AC, Cooke JP, Tremmel JA. Asymmetric dimethylarginine predicts impaired epicardial coronary vasomotion in patients with angina in the absence of obstructive coronary artery disease. Int J Cardiol. 2020 Jan 15;299:7-11. doi: 10.1016/j.ijcard.2019.07.062. Epub 2019 Jul 19. PMID 31416658

Identifiers

NCT: NCT00823563 · 51267

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗