Mental Stress Reactivity in Women With CMD

NCT05401630 | Recruiting DMC

• 3 other identifiers: STUDY000031541R01HL157311-01A12025P012678
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 4

Brief Summary

Coronary Microvascular Dysfunction (CMD) occurs when there are problems in the small blood vessels/arteries of the heart, resulting in persistent chest pain that affects women. There are an estimated 3 million women in the US with CMD and about 100,000 new cases annually. This research will investigate whether the stress response physiology and autonomic function in response to mental stress are different in women with CMD compared to other groups. The autonomic nervous system (ANS) controls normally involuntary activities, such as heart rate, respiration (breathing), body temperature, blood pressure, and urinary function. This study will also examine how chronic and daily life mental stress affects the heart and blood vessels. Participants from this study will be recruited mainly from Emory Healthcare-associated hospitals, the Emory Heart Disease Center for Prevention, and Emory Healthcare outpatient cardiology clinics. Participants will have physical exams, blood tests, stress tests, exercise tests, surveys, questionnaires, and images taken of their hearts and blood vessels. They will be asked to take home devices to monitor their autonomic function, sleep, and track their mood, stress level, and symptoms for one week. Data and specimens will be saved for future research.

Conditions

Post-menopause

Keywords

Microvascular; Sympathetic activity; Mental Stress; Angina

Outcome Measures

Primary Outcomes (3)

• Planar late Heart to Mediastinal Ratio (MIBG imaging)

  The research team will compare resting sympathetic activity measured with 123I-meta-iodobenzylguanidine (MIBG) imaging between CMD women and the two control groups. The heart to the mediastinal ratio (HMR) which is an index of MIBG uptake will be calculated as per standard methods. The HMR reflects norepinephrine kinetics. Higher sympathetic activity and turnover cause less MIBG to be retained and result in a lower HMR. MIBG SPECT defect score will be determined by late (4 hours) MIBG uptake by visual blind scoring using the standard 17-segment model with 0=normal tracer uptake, 1=mildly reduced uptake, 2=moderately reduced uptake, 3=severely reduced uptake, 4=absent tracer uptake, as defined by Bax et al.

  At the end of MIBG procedure

• Changes in HRV with mental stress

  The research team will also compare autonomic reactivity during a standardized mental stress test, including heart rate variability (HRV) between CMD women and the two control groups

  Baseline (prior to stress testing) and during mental stress test

• Changes in pre-ejection period (PEP) with mental stress

  The research team will also compare autonomic reactivity during a standardized mental stress test, including the pre-ejection period (PEP) between CMD women and the two control groups. This measures systolic time interval and reflects cardiac contractility (which is under the beta-adrenergic influence). Impedance ECG measures PEP from the onset of ventricular depolarization (Q-wave on ECG) to the opening of the aortic valve for ejection of blood from the left ventricle.

  Baseline (prior to stress testing) and during mental stress test

Secondary Outcomes (3)

• Changes in flow mediated dilation (FMD test) to acute mental stress in CMD women.

  Baseline (prior to stress testing) and at the end of the mental stress test

• Changes in Peripheral arterial tonometry (PAT) test to acute mental stress in CMD women.

  Baseline (prior to stress testing) and at the end of the mental stress test

• Examine whether chronic stress burden and autonomic dysfunction during daily life is elevated in CMD women.

  At the end of 1 week of monitoring

Other Outcomes (5)

• Stressor frequency over 7 days

  At the end of 1 week of monitoring

• Assessment of quality of life and relationship to anginal symptoms

  Baseline and 12 months

• Assessment of general health status

  Baseline and 12 months

Study Arms (3)

Symptomatic women with no obstructive CAD who have CMD

EXPERIMENTAL

Symptomatic women with chest pain and no obstructive CAD who have an abnormal myocardial flow reserve (MFR \< 2.5)

Other: Study Procedures

Symptomatic women with chronic obstructive CAD (oCAD)

EXPERIMENTAL

This group will serve as one comparison group since these women represent the prevailing paradigm of ischemia from obstructive stenosis while sharing common cardiovascular risk factors with the CMD group.

Other: Study Procedures

Asymptomatic control women with no prior history of CAD or angina

ACTIVE COMPARATOR

Asymptomatic control women with no prior history of CAD or angina, who are age-matched to the CMD women; not on any cardiac medications, who will also have to pass a maximal Bruce protocol exercise treadmill test.

Other: Study Procedures

Interventions

Study Procedures OTHER

All participants will answer a series of questionnaires that address several factors such as patient medical history, family history, medication usage, health behaviors, psychological factors, etc. Questionnaires related to symptoms, psychological factors, depression, anxiety, and quality of life will be taken. All participants will undergo 123I-MIBG SPECT imaging in the morning in a fasting state. Mental Stress Testing will be conducted in the Laboratory in the morning after fasting for at least 4 hours and withdrawal of all vasoactive medications, caffeine, and tobacco 24-48 hours before testing. Participants will also undergo 1-week of Home Monitoring using a single-use, noninvasive, water-resistant, 7-day ambulatory ECG monitoring, which offers the advantage of direct access to raw data that can be downloaded from the device after use. A 3-day food recall diary, cognitive assessments via the NIH Toolbox, and a Sleep diary during home monitoring will be collected.

Asymptomatic control women with no prior history of CAD or angina; Symptomatic women with chronic obstructive CAD (oCAD); Symptomatic women with no obstructive CAD who have CMD

Eligibility Criteria

• Age: 45 Years+
• Gender Eligibility Details: Postmenopausal women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic postmenopausal women with chest pain
• age≥45 years old
• willing to undergo cardiac MIBG scan
• willing to undergo mental stress testing
• competent to give informed consent

You may not qualify if:

• Significant epicardial stenosis (defined by coronary stenosis ≥ 70% in any epicardial coronary artery or hemodynamically significant stenosis determined by fractional flow reserve)
• Left ventricular systolic dysfunction (ejection fraction ≤ 50%)
• Heart failure with a preserved ejection fraction
• Significant anemia or blood dyscrasia
• Severe uncontrolled hypertension \>180/100
• Unable to lie flat for mental stress testing
• Pre-menopausal
• Pregnant
• Pericarditis/myocarditis
• History of percutaneous coronary intervention
• Coronary artery bypass grafting
• Acute myocardial infarction/acute coronary syndrome/unstable angina within 1 month
• Significant valvular disease, including aortic or mitral stenosis
• Sinus node dysfunction/pacemaker, 2nd or 3rd-degree atrioventricular block
• Severe lung, renal, liver, or psychiatric illness

Sponsors & Collaborators

• Emory University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Emory Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30308, United States

RECRUITING

Emory Clinic

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Stress, Psychological; Angina Pectoris

Interventions

Methods

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Puja K Mehta

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Puja K Mehta, MD

CONTACT

404-712-0281; pkmehta@emory.edu

Puja K Mehta, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 10, 2022
• First Posted: June 2, 2022
• Study Start: July 19, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The research team will share the data after the study completion and after the initial data is published.
• Access Criteria: The research team will share the data via secure data transfer

Locations

US (4)