Molecular Imaging of Primary Amyloid Cardiomyopathy

Summary

Cardiac amyloidosis is a major cause of early treatment-related death and poor overall survival in individuals with systemic light chain amyloidosis. This project will develop a novel approach to visualize cardiac amyloid deposits using advanced imaging methods. The long-term goal of this work is to identify the mechanisms of cardiac dysfunction, in order to guide the development of novel life-saving treatments.

Eligibility

Inclusion criteria:

* Age \> 18 years
* Diagnosis of light chain amyloidosis by standard criteria (immunofixation of serum and urine, IgG 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)

  * For subjects traveling from out of town referred for systemic AL therapy based on clinical evaluation and laboratory testing, but, pending biopsy results, study enrollment and procedures may begin before official confirmation of biopsy results. If biopsy is negative for AL amyloidosis, subject will be considered a screen failure. There will be no more than 10 subjects who fall under this screen failure for the duration of the study.
  * Subjects with localized amyloid deposition and non-systemic AL disease will be eligible for enrollment in group D.
* Willing and able to provide consent
* Additional inclusion criteria for the Remission AL-CMP: Hematological response defined as complete hematological remission or very good partial response-differential free light chain (dFLC)\<40 mg/dL for \> 1 year prior to enrollment
* Additional inclusion criteria for the Active AL-CMP - exercise: Ability to perform supine bicycle exercise. Enrollment to this arm will stop after 36 subjects complete baseline and 6 months studies.
* Additional inclusion criteria for the Active AL Pre-CMP - Normal left ventricular wall thickness (≤ 12 mm) and normal LVEF (≥55%) on echocardiography within 3 months or increased wall thickness with normal cardiac biomarker levels: not meeting above definition.
* Additional inclusion criteria for Control Multiple Myeloma subjects: diagnosis of multiple myeloma without concomitant amyloidosis by standard criteria
* Additional inclusion criteria for Control Heart Failure subjects: diagnosis of heart failure without amyloidosis by standard criteria
* Additional inclusion criteria for the active AL-CMP: Abnormal TnT 5th generation levels (\>9 ng/L: Female, \>14 ng/L: Male) or abnormal age appropriate N terminal pro-brain natriuretic peptide, NT-proBNP (abnormal values: \<50 years: \>450 pg/ml; 50-75 years:\>900 pg/ml; \>75 years: \>1800 pg/ml)

Exclusion Criteria:

* Hemodynamic instability
* Decompensated heart failure (unable to lie flat for 1 hour)
* Concomitant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
* Known obstructive epicardial coronary artery disease with stenosis \> 50% in any single territory
* Severe claustrophobia despite use of sedatives
* Presence of MRI contraindications such as metallic implants (pacemaker or ICD) at the time of study enrollment except for Control Heart Failure subjects. Control HF subjects with no devices, or, with strictly MR compatible devices will be eligible to undergo MRI.
* Significant renal dysfunction with estimated glomerular filtration rate \< 30 ml/min/m2 within 14 days of each cardiac MRI study. Subjects who develop renal dysfunction over the course of the study, meeting criteria listed above, will be excluded from the cardiac MRI scan except for control HF subjects. These subjects with eGFR \< 30 ml/min/1.73 m2 will undergo MRI without gadolinium contrast.
* Subjects on dialysis will be excluded
* Pregnant state. For women in child bearing age, a urine pregnancy test will be performed prior to the PET and the cardiac MRI studies
* Documented allergy to F-18 florbetapir, C-11 acetate or gadolinium.
* Additional exclusion criteria for the active AL-CMP subjects: Subjects unable to return to BWH for 6 and 12 month clinical evaluation
* Additional exclusion criteria for active AL-CMP-exercise subjects: Inability to exercise or return to BWH for C-11 acetate PET/CT at baseline and 6 month clinical evaluations.
* Additional exclusion criteria for active AL Pre-CMP- Inability to return to BWH 12 month clinical evaluation.

Additional exclusion criteria for microbiota study: Documented hypertrophic cardiomyopathy, HIV or chronic viral hepatitis, documented inflammatory bowel disease, systemic antibiotics, antivirals, antifungals or antiparasitic agents within 6 months, unable to mail the stool sample in a timely manner, bowel surgery, colon cancer, received chemotherapy, and pregnancy.

Conditions4

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