Functional myocardial ischemia as a mechanism for diastolic dysfunction in women with coronary microvascular dysfunction

Study ID
STU 022016-036

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

  • Advanced Imaging Research Center (AIRC)
  • Clements University Hospital

Contact
Michael Nelson, PhD
817/513-0383
Michael.Nelson@UTSouthwestern.edu

Principal Investigator
Michael Nelson, PhD

Summary

We anticipate enrolling a total of 70 study participants over 4 years: (1) 30 [Quote]calibration subjects[Quote], (2) 20 women with objective evidence of CMD, defined as [Quote]cases[Quote], and (3) 20 age, sex, and BMi matched health controls.

Calibration studies: We are requesting 30 [Quote]calibration subjects[Quote] to allow us to transfer our imaging protocols to the uTSW aiRC, and to optimize our experimental protocol and our magnetic resonance imaging (MRi/MRS) sequences. each subject will be allowed to repeat the MRi/MRS on two separate occasions (if needed). Subjects will meet with the research coordinator or an investigator for a discussion, with opportunity for questions, before applicable consent forms are obtained. The subject will be screened for metal in or on their body and claustrophobia using a standard MR screening form. any female of childbearing age will be screened for potential pregnancy and tested using one drop of urine in the professional aimStep PBC pregnancy test. To evaluate the effect of cardiovascular stress on left ventricular diastolic function, and to allow us to compare our MRi diastolic measures with MRi diastolic measures, subjects may be asked to complete rest/stress cardiac ultrasound outside of the MRi environment. To evaluate left ventricular diastolic function and myocardial ischemia, subjects will undergo cardiac MRi/MRS. First, subjects will remove all metal from their body and change into a gown prior to admittance to the 3T MR environment. The subject will be asked to lie still on the table of the MR machine for 5-15 minute periods during data collection. once resting baseline images/spectroscopy of the heart are obtained, the subject will perform stress MRi/MRS (i.e. isometric handgrip and lower leg exercise). at present, MRi and MRS cannot be performed on the same MRi machine (phosphorus package not available on same scanner as advanced cardiac package). MRi and MRS may therefore be performed on separate days or the same day at different times.

aim 1: once our imaging protocol is established, we will then recruit 20 women with objective evidence of CMD (defined as [Quote]cases[Quote]), and 20 age, sex, and BMi matched healthy controls. Cases with CMD will be enrolled for approximately 2 weeks, and will perform 3 study visits (aim 1 and aim 2). Healthy controls will be enrolled for approximately 1 week, and will perform 2 study visits. after screening (Visit 1), subjects will meet with the research coordinator or an investigator for a discussion, with opportunity for questions, before applicable consent forms are obtained. a small blood sample will be collected via venipuncture for basic blood chemistry assessment. Subjects will also be screened at this time for metal in or on their body and claustrophobia using a standard MR screening form. Cases and controls will then undergo a non-MRi exercise stress test (complete with stress echocardiography and blood pressure monitoring). exercise stress will include isometric handgrip, followed by incremental cycle exercise to volitional exhaustion. Subjects will then return on a separate visit (Visit 2). any female of childbearing age will be screened for potential pregnancy and tested using one drop of urine in the professional aimStep PBC pregnancy test. The subject will then remove all metal from their body and change into a gown prior to admittance to the 3T MR environment. Cases and controls will perform the same rest-stress MRi/MRS protocol established in the calibration studies (above).

aim 2: Cases with CMD will be asked to return to the aiRC on a separate visit (within 2 weeks of their initial visit, Visit 3). upon arrival, a study doctor will administer the study medication Tadalafil (20 mg). To ensure peak blood levels, imaging studies will commence 2.5 hours after drug ingestion, after which the same rest-stress MRi/MRS protocol established in aim 1 (above), will be performed.

Participant Eligibility

Calibration subjects:
1) adults, age 18-85,
2) willing to participate under the conditions described in the informed consent form (ICF)
3) able and willing to sign the ICF and applicable HIPAA forms.
4) willing to undergo screening for MR procedures.

Cases:
1) Women
2) evidence of ischemia (by stress testing),
3) no evidence of obstructive CAD, defined as 50% luminal diameter stenosis in at least 1 epicardial coronary artery.

Controls:
1) Women
2) asymptomatic, with no history or diagnosis of cardiovascular disease;
3) no evidence of ischemia during exercise stress.