Sex Differences in Coronary Pathophysiology

Chest Pain Clinical Trial

Official title:

Sex Differences in Symptomatic Non-Obstructive Coronary Disease: Do Women Have a Unique Coronary Pathophysiology?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00823563
• Other study ID #: SU-01092009-1542
• Status: Recruiting
• Start date: June 2007
• Est. completion date: June 2035

Study information

• Verified date: November 2023
• Source: Stanford University
• Contact: Homa Tavana
• Phone: (650) 721-5540
• Email: htavana[@]cvmed.stanford.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a research study evaluating possible causes of chest pain (or an anginal equivalent, such as fatigue resulting in a decrease in exercise tolerance, shortness of breath, or back, shoulder, neck, or jaw pain) in people with no evidence of significant coronary artery disease on their coronary angiogram (pictures of the blood vessels in the heart). The purpose of the research study is to determine if there is diffuse atherosclerosis (plaque) not appreciated by angiography, or if the coronary endothelium (lining of the blood vessels in the heart) and/or microcirculation (small vessels in the heart that are not easily seen with an angiogram) are not functioning properly in those who have chest pain (or an anginal equivalent), but normal coronary arteries on angiography. Specifically, we are interested if these findings are more common in women than men.

Description:

Women are more likely than men to have chest pain suggestive of angina but normal-appearing coronary arteries on angiography, which ultimately imparts a significant morbidity/mortality and economic burden. Recent evidence suggests that women commonly have endothelial and microcirculatory dysfunction, as well as diffusely distributed atherosclerosis--disorders that can cause chest pain, but will not be seen on angiography. This presents an intriguing basis for pathophysiologic differences between women and men, but there are no studies that actually compare the presence of such findings in women with that of men. The objective of this research project is to determine if the incidence of such pathophysiologic differences is truly higher in women than it is in men.

We hope to determine if there is a higher incidence of diffuse atherosclerotic plaque, endothelial dysfunction, and/or microcirculatory dysfunction in women compared with men. If this sex difference exists, it has significant implications for how we should be testing and treating women with chest pain but angiographically normal coronary arteries.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: June 2035
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient referred for elective coronary angiography because of a reasonable clinical suspicion of coronary ischemia.

2. 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:1) Asymptomatic (such as a pre-op cath)

2) Status-post heart transplant

3) Status-post coronary artery bypass grafting

4) Age <18

5) Renal insufficiency (creatinine >1.5)

6) Presence of an acute coronary syndrome (STEMI or NSTEMI), Tako-tsubo, an abnormal ejection fraction (EF<55%), cardiogenic shock, or recent VT/VF

7) Presence of another likely explanation of chest pain, such as pulmonary hypertension or aortic stenosis

8) History of adverse reaction to any of the medications being used (acetylcholine, nitroglycerin, adenosine, or heparin)

9) Currently taking vasoactive medication (such as nitroglycerin)

10) Inability to provide an informed consent, including an inability to speak, read, or understand English, Spanish, Chinese, Farsi, Japanese, Korean, Russian, or Vietnamese

11) 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

12) Participation in another study (with the exception of the Stanford Gene-PAD study)

13) A potentially vulnerable subject (including minors, pregnant women, economically and educationally disadvantaged, decisionally impaired, and homeless people)

Related Conditions & MeSH terms

• Chest Pain
• Ischemia

Intervention

Procedure:
• 30 cc blood draw

• Intravascular ultrasound (IVUS)

• Coronary pressure/flow wire testing

• Coronary pressure/flow testing: Acetycholine challenge

• Procedure: Coronary pressure/flow testing: Nitroglycerin challenge

• Procedure: Procedure: Coronary pressure/flow testing: Adenosine challenge

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (15)

Boyd JH, Pargaonkar VS, Scoville DH, Rogers IS, Kimura T, Tanaka S, Yamada R, Fischbein MP, Tremmel JA, Mitchell RS, Schnittger I. Surgical Unroofing of Hemodynamically Significant Left Anterior Descending Myocardial Bridges. Ann Thorac Surg. 2017 May;103 — View Citation

Forsdahl SH, Rogers IS, Schnittger I, Tanaka S, Kimura T, Pargaonkar VS, Chan FP, Fleischmann D, Tremmel JA, Becker HC. Myocardial Bridges on Coronary Computed Tomography Angiography - Correlation With Intravascular Ultrasound and Fractional Flow Reserve. — View Citation

Kobayashi Y, Fearon WF, Honda Y, Tanaka S, Pargaonkar V, Fitzgerald PJ, Lee DP, Stefanick M, Yeung AC, Tremmel JA. Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive C — View Citation

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. — View Citation

Nishikii-Tachibana M, Pargaonkar VS, Schnittger I, Haddad F, Rogers IS, Tremmel JA, Wang PJ. Myocardial bridging is associated with exercise-induced ventricular arrhythmia and increases in QT dispersion. Ann Noninvasive Electrocardiol. 2018 Mar;23(2):e124 — View Citation

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 arte — View Citation

Pargaonkar VS, Lee JH, Chow EKH, Nishi T, Ball RL, Kobayashi Y, Kimura T, Lee DP, Stefanick ML, Fearon WF, Yeung AC, Tremmel JA. Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Coronary Endothelial Function Testing of Women and Men With Angina and No Obstructive Coronary Artery Disease. Circ Cardiovasc Interv. 2020 Apr;13(4):e008587. doi: 10.1161/CIRCINTERVENTIONS.119.008587. Epub 2020 Apr 13. — View Citation

Pargaonkar VS, Tremmel JA, Schnittger I, Khandelwal A. Effect of ranolazine on symptom and quality of life in patients with angina in the absence of obstructive coronary artery disease: A case control study. Int J Cardiol. 2020 Jun 15;309:8-13. doi: 10.10 — View Citation

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 Card — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Tremmel JA, Yeung AC. Ischemic heart disease in women: an appropriate time to discriminate. Rev Cardiovasc Med. 2007 Spring;8(2):61-8. — View Citation

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. — View Citation

Yamada R, Tremmel JA, Tanaka S, Lin S, Kobayashi Y, Hollak MB, Yock PG, Fitzgerald PJ, Schnittger I, Honda Y. Functional Versus Anatomic Assessment of Myocardial Bridging by Intravascular Ultrasound: Impact of Arterial Compression on Proximal Atherosclero — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sex Differences in Endothelial Dysfunction, Microvascular Dysfunction, and Diffuse Plaque		Immediately
Secondary	Cardiovascular Outcomes		3 years and 5 years

External Links

•   Women's Heart Health at Stanford homepage