Light Chain Cardiac Amyloidosis
Conditions
Keywords
Light Chain Cardiac Amyloidosis, Beta-amyloid PET/CT, Therapeutic Response
Brief summary
This was a single center, prospective cohort study that is evaluating the ability of beta-amyloid dynamic PET/CT to detect potential therapeutic changes in subjects under treatment for AL-CA after one year had elapsed since their baseline beta-amyloid PET/CT. Demographic, clinical and PET imaging data were collected to characterize potential changes since their baseline scans.
Detailed description
Light chain (AL) amyloidosis is a clonal plasma cell disorder that involves the deposition of misfolded monoclonal immunoglobulin light chains in the interstitial area, resulting in amyloid fibril aggregation. Despite advances in diagnostic work-up and treatment, AL amyloidosis frequently manifests as infiltrative cardiomyopathy, a particularly lethal form of heart failure. The diagnosis of cardiac amyloidosis (CA) is often overlooked and delayed due to nonspecific clinical symptoms and comorbidities. AL-CA is highly fatal without therapy; even with state-of-the-art therapies, including daratumumab, mortality remains high in the first year. Moreover, despite successful therapy, progressive heart failure, remains a significant clinical challenge in some patients and is attributed to residual amyloid fibril infiltration degree. Early and accurate assessment of changes in amyloid burden in response to therapy remains a challenge. Currently, evaluation of response to plasma cell therapy relies on circulating AL biomarkers, which are not specific for reduction in amyloid burden. Echocardiography and CMR are used to evaluate myocardial functional and structural changes in AL amyloidosis after plasma cell-directed therapy. However, these measures lack specificity for amyloid fibrils. By contrast, beta-amyloid-binding tracers, such as 11C-PIB, 18F-Florbetapir, are emerging as quantitative and specific molecular markers of cardiac amyloid. These tracers have demonstrated high sensitivity and specificity for cardiac amyloid in preclinical and clinical studies. The investigators hypothesis that, changes in amyloid-binding tracer uptake may signal early molecular changes in myocardial amyloid.
Interventions
DRUG11C-PIB
A dosage range between 5.0-20.0 mCi of 11C-PIB will be injected by a PET-certified medical professional followed by 5ml 0.9% sodium chloride (normal saline) flush.
DRUG18F-Florbetapir
A dosage range between 6.0-12.0 mCi of 18F-Florbetapir will be injected by a PET-certified medical professional followed by 5ml 0.9% sodium chloride (normal saline) flush.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 y； 2. were proven newly diagnosed AL-CA by standard criteria; 3. subsequently received first-line therapies including anti-plasma cell therapy or targeted therapy; 4. must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
Exclusion criteria
1. received therapy with an approved treatment (e.g., Bortezomib, Daratumumab) prior to enrollment; 2. pregnancy or breastfeeding; 3. severe claustrophobia; 4. any condition deemed by the investigator to interfere with study results or increase participant risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 11C-PIB/18F-Florbetapir myocardial retention index from baseline to 12 months | Baseline and 12months | For calculation of the 11C-PIB retention index (RI), the mean tissue concentration between 10 and 20 min was divided by the integral of the blood time activity curve from 0 to 15 min after injection. For calculation of the 18F-Florbetapir RI, the mean tissue concentration between 10 and 30 min was divided by the integral of the blood time activity curve from 0 to 20 min after injection. |
| Change in 11C-PIB/18F-Florbetapir myocardial mean standardized uptake value (SUVmean) from baseline to 12 months | Baseline and 12months | Median percentage change in left ventricular SUVmean. The standardized uptake value (SUV) of the myocardium was measured by drawing the contour of the whole left ventricle at an approximate thickness of 10 mm from the base to the apex. |
| Change in 11C-PIB/18F-Florbetapir myocardial SUV ratio (SUVR) from baseline to 12 months | Baseline and 12months | For calculation of the 11C-PIB SUVR, it was defined as the SUVmean of the myocardial VOI divided by the SUVmean of the left atrium VOI between 10 and 20 minutes. For calculation of the 18F-Florbetapir SUVR, it was defined as the SUVmean of the myocardial VOI divided by the SUVmean of the left atrium VOI between 10 and 30 minutes. |
Countries
China
Contacts
CONTACTLi Huo
CONTACTXuezhu Wang
Outcome results
None listed