Molecular Imaging of Myocardial Fibrosis in Cardiac Amyloidosis

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. We will also enroll 15 individuals with recent myocardial infarction and 15 individuals with hypertrophic cardiomyopathy as positive controls for fibrosis, and we 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. We hypothesize that [68Ga]CBP8 uptake will be greater in patients with cardiac amyloidosis, myocardial fibrosis, and hypertrophic cardiomyopathy than in healthy controls. Secondly, we 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).

Inclusion Criteria for AL-amyloid subjects:Age > 18 yearsWilling and able to provide consentAL-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 ANDProof of cardiac involvement by AL amyloidosisAbnormal 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) ORAbnormal echocardiogram (wall thickness > 12 mm in the absence of other causes of increased LV wall thickness) ORAbnormal 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) ORPositive endomyocardial biopsyInclusion Criteria for ATTR-amyloid subjects:Age > 18 yearsWilling and able to provide consentATTR-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 neededExtracardiac biopsy with typical cardiac imaging findingsHereditary ATTR amyloidosis by genetic testing ORGrade 2 or grade 3 myocardial uptake of 99mTc-PYP if AL amyloidosis is excludedInclusion Criteria for recent myocardial infarction subjects:Age > 18 yearsWilling and able to provide consentRecent MI: Diagnosis of recent type 1 myocardial infarction by standard criteriaMore than 6 weeks from diagnosis of MI but within 6 monthsImaging evidence of loss of viable myocardium or persistent regional wall motion abnormalities in a pattern consistent with an ischemic etiology in more than one segmentInclusion Criteria for hypertrophic cardiomyopathy subjects:Age > 18 yearsWilling and able to provide consentHypertrophic cardiomyopathy: Diagnosis of hypertrophic cardiomyopathy by standard criteriaMRI evidence of late gadolinium enhancementInclusion Criteria for recent healthy control subjects:Age > 18 yearsWilling and able to provide consentNo known cardiac amyloidosis or recent myocardial infarctionExclusion Criteria:DialysisNYHA (New York Heart Association) Class IVAcute myocardial infarction within 6 weeksPregnancy or nursingHistory of adverse events from or allergy to gadolinium contrast mediaHemodynamic instabilitySevere claustrophobia despite use of sedativesDecompensated 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