florbetapir-f-18 and Amyloid-Neuropathies--Familial

Cardiac amyloidosis is an important clinical entity associated with significant morbidity and mortality. Although the signs and symptoms can be apparent early in the disease course, diagnoses are often made late because of inadequate recognition. A diagnosis of cardiac amyloidosis requires careful scrutiny of a patient's symptoms, an electrocardiogram, and imaging studies, including echocardiography and magnetic resonance imaging. Further evaluation is required through the measurement of serum and urine light chains and the use of bone scintigraphy imaging to differentiate transthyretin amyloidosis from light-chain cardiac amyloidosis. The available treatments have expanded tremendously in recent years and have improved outcomes in the population with this disorder. Thus, it has become increasingly important to diagnose cardiac amyloidosis and provide timely therapies. This article will clarify the various misconceptions about cardiac amyloidosis and provide a framework for primary care providers to better identify this disease in their practice.

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Aniline Compounds; Assisted Circulation; Atrial Fibrillation; Cardiac Imaging Techniques; Cardiomyopathies; Diagnosis, Differential; Echocardiography; Electrocardiography; Ethylene Glycols; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

(18)F-florbetapir is a promising imaging biomarker for cardiac light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). Our aim, using human autopsy myocardial specimens, was to test the hypothesis that (18)F-florbetapir binds specifically to myocardial AL and ATTR amyloid deposits.. We studied myocardial sections from 30 subjects with autopsy-documented AL (n=10), ATTR (n=10), and nonamyloid controls (n=10) using (18)F-florbetapir and cold florbetapir compound and digital autoradiography. Total and nonspecific binding of (18)F-florbetapir was determined using the maximum signal intensity values. Specific binding of (18)F-florbetapir was calculated by subtracting nonspecific from total binding measurements (in decays per minute/mm(2), DPM mm(2)) and was compared with cardiac structure and function on echocardiography and the histological extent of amyloid deposits. Diffuse or focally increased (18)F-florbetapir uptake was noted in all AL and ATTR samples and in none of the control samples. Compared with control samples, mean (18)F-florbetapir-specific uptake was significantly higher in the amyloid samples (0.94±0.43 versus 2.00±0.58 DPM/mm(2); P<0.001), and in the AL compared with the ATTR samples (2.48±0.40 versus 1.52±0.22 DPM/mm(2); P<0.001). The samples from subjects with atypical echocardiographic features of amyloidosis showed quantitatively more intense (18)F-florbetapir-specific uptake compared with control samples (1.50±0.17 versus 0.94±0.43 DPM/mm(2); P=0.004), despite smaller amyloid extent than in subjects with typical echocardiograms.. (18)F-florbetapir specifically binds to myocardial AL and ATTR deposits in humans and offers the potential to screen for the 2 most common types of myocardial amyloid.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Amyloidogenic Proteins; Aniline Compounds; Autopsy; Autoradiography; Cardiomyopathies; Case-Control Studies; Cross-Sectional Studies; Ethylene Glycols; Female; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Myocardium; Positron-Emission Tomography; Prealbumin; Predictive Value of Tests; Protein Binding; Radiopharmaceuticals; Ultrasonography