Sex Differences in Myocardial Steatosis Induced Left Ventricular Dysfunction
Status:
Recruiting
Trial end date:
2023-12-01
Target enrollment:
Participant gender:
Summary
To test the specific research questions, healthy men and age-matched healthy premenopausal
females will be enrolled. Subjects will undergo cardiac magnetic resonance imaging and
spectroscopy (MRI/MRS) to evaluate cardiac morphology/function and fat metabolism. To acutely
elevate myocardial triglyceride content, subjects will be asked to abstain from eating for 2
days (reproducibly causes a significant and physiological increase in myocardial fat
deposition, transiently). Subjects will be allowed water and/or an isotonic saline solution
in order to maintain hydration status. After screening, 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. A venous blood sample will be
taken for measurement of metabolic health, circulating hormones, and systemic inflammation.
Imaging will include cine imaging for global morphology and function, tissue tagging for
regional tissue deformation, spectroscopy for fat quantification. After baseline images of
the heart are obtained, the subject will be asked to squeeze a MR-safe handgrip dynamometer
at 30% of their maximum while images of the heart are obtained. Blood pressure will also be
measured at rest and during stress. Each MRI will take approximately 90-120 minutes.
Aim 1 will test the hypothesis that cardiac steatosis induced left ventricular dysfunction is
sexually dimorphic, by comparing age-matched men and premenopausal women before and after 48
of fasting. Subjects will complete the MRI/MRS protocol described above before and after the
fasting intervention.
Aim 2 will test the hypothesis that estrogen is protective against cardiac steatosis-induced
dysfunction, by suppressing ovarian sex hormones with a GnRH antagonist and repeating the
fasting studies with and without estrogen add-back. 30 female subjects will be treated with
GnRH antagonist and repeat the 48 hour fasting intervention and cardiac MRI/MRS protocol. 15
of the subjects will receive estrogen add-back using a transdermal patch, the other 15
subjects will receive a placebo patch.
Aim 3 will test whether plasma and myocardial fatty acid composition is sexually dimorphic,
by performing comprehensive plasma and myocardial lipidomics assessment.