Cardiac Amyloidosis
Conditions
Keywords
Amyloidosis, Cardiac, Heart, Imaging, Diagnosis
Brief summary
The primary aim of this pilot study is to determine whether amyloid deposits in the heart can be measured non-invasively by F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) in 30 individuals with documented cardiac amyloidosis. We will also enroll 15 individuals without cardiac amyloidosis to undergo the F-18 florbetapir imaging as a control group. The primary hypothesis of this study is that a specific amyloid binding radiotracer will bind to the myocardial amyloid deposits and help quantify cardiac amyloid burden. A secondary aim of this study is to determine reproducibility of F-18 florbetapir imaging of the myocardium.
Detailed description
F-18 florbetapir has been studied in multiple clinical trials to image beta-amyloid deposition in the brain of subjects with Alzheimers' disease. Florbetapir F-18 has been well tolerated in studies of more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The tracer clears rapidly from the blood pool in about 20 minutes. This radiotracer has been recently approved for clinical imaging of brain amyloid in subjects with suspected Alzheimers disease. The investigators propose to test this FDA approved radiotracer for an off label indication in a pilot study to evaluate its potential utility, if any, to image cardiac amyloidosis. Amyloid related heart disease is associated with LV wall thickening due to infiltration; however, this myocardial wall thickening is not definitively distinguishable from left ventricular myocyte hypertrophy from increased afterload to the heart from hypertension or aortic stenosis. Typically myocardial or other tissue biopsy with typical echo features of amyloidosis is required for confirmation of amyloidosis. This pilot study is designed to understand whether cardiac amyloid burden can be measured using a specific radiotracer targeted against amyloid protein (F-18 Florbetapir). At this point it is unknown of F-18 Florbetapir will bind to either AL or TTR amyloid protein or to both of them or to neither of them. The investigators would like to study 15 patients with AL and 15 patients with TTR amyloidosis to understand these differences if any. The investigators also seek to understand if the signal to noise ratio of the circulating amyloid protein in the blood pool (AL amyloid disease) allows for good differentiation of myocardial amyloid uptake. 15 individuals without cardiac amyloidosis will also be enrolled as controls for this study. The purpose of the proposed research study is to examine in detail, using quantitative PET, myocardial F-18 Florbetapir uptake in cardiac amyloidosis in order to better understand mechanisms of heart damage in this disease. A secondary aim of this study is to determine reproducibility of F-18 florbetapir imaging of the myocardium in a subset of patients with amyloidosis who return for a second F-18 florbetapir scan within 30 days.
Interventions
DRUGF-18 florbetapir PET
Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for amyloid subjects: * Age \> 18 years * Biopsy proven amyloidosis outside the heart with typical echocardiographic appearance of cardiac involvement, or a positive cardiac biopsy. * Diagnosis of AL amyloidosis by standard criteria (evidence of plasma cell dyscrasia with appropriate tissue staining for AL) OR * Diagnosis of TTR amyloidosis (no evidence of plasma call dyscrasia and positive TTR staining of amyloid in tissue biopsy) * Able and willing to provide informed consent to participate in the study procedures
Exclusion criteria
* Pregnancy * Serious non-cardiac medical illness which will preclude research study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean | 1 day | Standardized uptake value (SUV) mean is defined as the mean F-18 florbetapir activity concentration \[kBq/ml\] measured within the left ventricular myocardial region of interest multiplied by the decay-corrected amount of injected F-18 florbetapir \[kBq\] normalized to patient weight \[g\]. In this study we will measure mean left ventricular global myocardial F-18 Florbetapir SUVmean on static images between 4 minutes to 30 minutes post injection of F-18 florbetapir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2 | Repeat scan was performed a median of 7 days after baseline study (range 1-46 days) | We evaluated change in F-18 florbetapir SUVmean from scan 1 to scan 2 as a percentage value \[(SUVmean1 minus SUVmean 2)/(SUVmean 1)\*100\]. In the 7 participants with cardiac amyloidosis who underwent two studies (median of 7 days apart), the percentage change in F-18 florbetapir SUVmean from scan 1 to scan 2 ranged from -38.5% to +20.8% with a median value of +2.24%. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| F-18 Florbetapir PET- Subjects With Cardiac Amyloidosis Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid) | 10 |
| F-18 Florbetapir PET- Controls Without Cardiac Amyloidosis Individuals without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid) | 6 |
| F-18 Florbetapir PET- Subjects With Cardiac Amyloidosis Reproducibility Arm Individuals with documented cardiac amyloidosis will undergo two F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) scans.
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid) | 7 |
| Total | 23 |
Baseline characteristics
| Characteristic | F-18 Florbetapir PET- Controls Without Cardiac Amyloidosis | F-18 Florbetapir PET- Subjects With Cardiac Amyloidosis | F-18 Florbetapir PET- Subjects With Cardiac Amyloidosis Reproducibility Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 12.2 | 66.8 years STANDARD_DEVIATION 13.9 | 68.1 years STANDARD_DEVIATION 5.8 | 64.8 years STANDARD_DEVIATION 12.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 5 Participants | 19 Participants |
| Region of Enrollment United States | 6 Participants | 10 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 4 Participants | 15 Participants |
| Type of amyloidosis Controls without cardiac amyloidosis | 6 Participants | 0 Participants | 0 Participants | 6 Participants |
| Type of amyloidosis Light chain cardiac amyloidosis | 0 Participants | 5 Participants | 7 Participants | 12 Participants |
| Type of amyloidosis Transthyretin cardiac amyloidosis | 0 Participants | 5 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 0 / 10 | 0 / 6 | 0 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 7 |
Outcome results
Primary
Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean
Standardized uptake value (SUV) mean is defined as the mean F-18 florbetapir activity concentration \[kBq/ml\] measured within the left ventricular myocardial region of interest multiplied by the decay-corrected amount of injected F-18 florbetapir \[kBq\] normalized to patient weight \[g\]. In this study we will measure mean left ventricular global myocardial F-18 Florbetapir SUVmean on static images between 4 minutes to 30 minutes post injection of F-18 florbetapir.
Time frame: 1 day
Population: 10 cardiac amyloidosis subjects, 6 control subjects without cardiac amyloidosis, and 7 subjects with cardiac amyloidosis were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F-18 Florbetapir PET-Cardiac Amyloidosis Subjects | Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean | 3.2 ratio | Standard Deviation 1.6 |
| F-18 Florbetapir PET- Controls Without Cardiac Amyloidosis | Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean | 1.7 ratio | Standard Deviation 0.9 |
| F-18 Florbetapir PET-Cardiac Amyloidosis Subjects in Reproducibility Arm | Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean | 5.0 ratio | Standard Deviation 1.6 |
Secondary
Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2
We evaluated change in F-18 florbetapir SUVmean from scan 1 to scan 2 as a percentage value \[(SUVmean1 minus SUVmean 2)/(SUVmean 1)\*100\]. In the 7 participants with cardiac amyloidosis who underwent two studies (median of 7 days apart), the percentage change in F-18 florbetapir SUVmean from scan 1 to scan 2 ranged from -38.5% to +20.8% with a median value of +2.24%.
Time frame: Repeat scan was performed a median of 7 days after baseline study (range 1-46 days)
Population: Subjects with cardiac amyloidosis who underwent two F-18 florbetapir PET/CT scans.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F-18 Florbetapir PET-Cardiac Amyloidosis Subjects | Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2 | 5.65 % change in SUVmean and SD | Standard Deviation 19.9 |