Molecular Imaging of Myocardial Fibrosis in Cardiac Amyloidosis

Summary

The primary aim of our pilot study is to determine whether fibrosis in the heart can be measured with \[68Ga\]CBP8, a positron emission tomography (PET) probe, using PET/magnetic resonance imaging (MRI) imaging, in 30 individuals with documented cardiac amyloidosis. The investigators will also enroll 15 individuals with recent myocardial infarction and 15 individuals with hypertrophic cardiomyopathy as positive controls for fibrosis, and the investigators will enroll 5 individuals without cardiovascular disease to undergo \[68Ga\]CBP8 PET/MRI imaging as a healthy control group. The primary hypothesis of this study is that \[68Ga\]CBP8 will bind to interstitial collagen and quantify myocardial fibrosis in patients with cardiac amyloidosis. The investigators hypothesize that \[68Ga\]CBP8 uptake will be greater in patients with cardiac amyloidosis, myocardial fibrosis, and hypertrophic cardiomyopathy than in healthy controls. Secondly, the investigators also hypothesize that \[68Ga\]CBP8 activity more strongly correlates with standard MRI measures in patients with recent myocardial infarction and hypertrophic cardiomyopathy (where extracellular expansion is caused by myocardial fibrosis/collagen deposition) than in patients with cardiac amyloidosis (where myocardial fibrosis is combined with infiltration).

Eligibility

Inclusion Criteria for AL-amyloid subjects:

* Age \> 18 years
* Willing and able to provide consent
* AL-CA: Diagnosis of systemic light chain amyloidosis by standard criteria: Immunofixation of serum, serum free light chain (FLC) assay, a biopsy of fat pad/bone marrow, or organ biopsy, followed by typing of the light chain using immunohistochemistry or immunogold assay with confirmation by mass spectroscopy as needed AND

  * Proof of cardiac involvement by AL amyloidosis
  * Abnormal cardiac biomarkers: abnormal high sensitivity TnT 5th generation levels (\> 15 ng/L) or abnormal age-appropriate NT-proBNP (abnormal values: \< 50 years: \> 450 pg/ml; 50-75 years: \> 900 pg/ml; \> 75 years: \> 1800 pg/ml) OR
  * Abnormal echocardiogram (wall thickness \> 12 mm in the absence of other causes of increased LV wall thickness) OR
  * Abnormal CMR (wall thickness \> 12 mm, extracellular volume \> 0.40 or typical CMR appearance of cardiac amyloidosis with difficulty nulling images and non-coronary distribution late gadolinium enhancement) OR
  * Positive endomyocardial biopsy

Inclusion Criteria for ATTR-amyloid subjects:

* Age \> 18 years
* Willing and able to provide consent
* ATTR-CA: Diagnosis of either wildtype or hereditary transthyretin cardiac amyloidosis by standard criteria: Endomyocardial biopsy followed by typing of the transthyretin amyloidosis using immunohistochemistry or immunogold assay with confirmation by mass spectroscopy as needed

  * Extracardiac biopsy with typical cardiac imaging findings
  * Hereditary ATTR amyloidosis by genetic testing OR
  * Grade 2 or grade 3 myocardial uptake of 99mTc-PYP if AL amyloidosis is excluded

Inclusion Criteria for recent myocardial infarction subjects:

* Age \> 18 years
* Willing and able to provide consent
* Recent MI: Diagnosis of recent type 1 myocardial infarction by standard criteria

  * More than 6 weeks from diagnosis of MI but within 6 months
  * Imaging evidence of loss of viable myocardium or persistent regional wall motion abnormalities in a pattern consistent with an ischemic etiology in more than one segment

Inclusion Criteria for hypertrophic cardiomyopathy subjects:

* Age \> 18 years
* Willing and able to provide consent
* Hypertrophic cardiomyopathy: Diagnosis of hypertrophic cardiomyopathy by standard criteria
* MRI evidence of late gadolinium enhancement

Inclusion Criteria for recent healthy control subjects:

* Age \> 18 years
* Willing and able to provide consent
* No known cardiac amyloidosis or recent myocardial infarction

Exclusion Criteria:

* Dialysis
* NYHA (New York Heart Association) Class IV
* Acute myocardial infarction within 6 weeks
* Pregnancy or nursing
* History of adverse events from or allergy to gadolinium contrast media
* Hemodynamic instability
* Severe claustrophobia despite use of sedatives
* Decompensated heart failure (unable to lie flat for 1 hour)
* Concomitant clinically significant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
* Body weight over limit for MRI table (\>300 lbs)
* Contraindications for MRI (including non-compatible cardiac implantable electronic devices, drug infusion pumps, and metallic or electric implants)
* Any other reason determined by the investigator to be unsuitable for the study

Conditions2

Locations1 site

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