Imaging Histone Deacetylase in the Heart

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