Imaging Histone Deacetylase in the Heart
Imaging Histone Deacetylase in the Heart
The overall goal of this PET-MR imaging trial is to evaluate 11C-Martinostat, a histone
 deacetylase targeted radioligand, in patients with aortic stenosis, individuals with
 diabetes, and healthy volunteers.
Histone deacetylases (HDACs), a class of epigenetic enzymes, play an important role in the
 pathophysiology of heart failure, including development of left ventricular hypertrophy and
 myocardial fibrosis. Preclinical data demonstrate the importance of HDAC inhibition in
 attenuating these pathological processes and maintaining the integrity of the myocardium.
 However, the role of HDACs in the human heart, and the utility of HDAC inhibition remains
 unknown. Therefore, a noninvasive method to detect HDAC activity in the human heart in
 healthy individuals and patients with heart disease may be of major medical and public health
 value to help determine prognosis, direct therapy, and guide the development of novel
 therapies for heart failure. The investigators have recently developed a novel radiotracer,
 11C-Martinostat, which binds with high affinity to class I HDACs. The objective of this
 protocol is to assess the utility of 11C-Martinostat PET-MR to detect HDAC expression in the
 hearts of healthy individuals and patients with severe aortic stenosis or diabetes.
Inclusion Criteria:

 Group 1: Healthy Volunteers (n = 30)

 -  Healthy adults with no known history of medical disease

 -  Age 18-85 years

 -  No history cardiovascular disease

 -  Ability to provide informed consent

 Group 2: Patients with Diabetes (n = 16)

 -  Age 18-85 years

 -  Diagnosis of diabetes

 -  Echocardiogram within last 12 months showing no evidence of left ventricular
 hypertrophy or hemodynamic findings consistent with heart failure with preserved
 ejection fraction

 -  Ability to provide informed consent

 Group 3: Patients with Aortic Stenosis (n = 50)

 -  Age 18-85 years

 -  Echocardiogram or cardiac MRI scan within last 12 months documenting left ventricular
 hypertrophy and degenerative calcific aortic stenosis

 -  Ability to provide informed consent

 Exclusion Criteria:

 -  Known contraindication to MRI