Cardiac Amyloidosis Imaging, Part 1: Amyloidosis Etiology and Image Acquisition.

Cardiac amyloidosis is a systemic form of amyloidosis in which protein-based infiltrates are deposited in myocardial extracellular space. The accumulation of amyloid fibrils causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Until recently, cardiac amyloidosis was considered rare. However, the recent adoption of noninvasive diagnostic testing, including 99mTc-pyrophosphate imaging, has revealed a previously undiagnosed sizable disease prevalence. Light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), the 2 primary types, account for 95% of cardiac amyloidosis diagnoses. AL results from plasma cell dyscrasia and has a very poor prognosis. The usual treatment for cardiac AL is chemotherapy and immunotherapy. Cardiac ATTR is more chronic, usually resulting from age-related instability and misfolding of the transthyretin protein. ATTR is treated by managing heart failure and using new pharmacotherapeutic drugs. 99mTc-pyrophosphate imaging can efficiently and effectively distinguish between ATTR and cardiac AL. Although the exact mechanism of myocardial 99mTc-pyrophosphate uptake is unknown, it is believed to bind to amyloid plaque microcalcifications. 99mTc-pyrophosphate imaging has a 97% sensitivity and nearly 100% sensitivity for identifying cardiac ATTR when the AL form of the disease is ruled out through serum free light-chain and serum and urine protein electrophoresis with immunofixation testing. Although there are no published 99mTc-pyrophosphate cardiac amyloidosis imaging guidelines, the American Society of Nuclear Cardiology, Society of Nuclear Medicine and Molecular Imaging, and others have published consensus recommendations to standardize test performance and interpretation. This article, part 1 of a 3-part series in this issue of the Journal of Nuclear Medicine Technology, describes amyloidosis etiology and cardiac amyloidosis characteristics, including the types, prevalence, signs and symptoms, and disease course. It further explains the scan acquisition protocol. Part 2 of the series focuses on image/data quantification and technical considerations. Finally, part 3 describes scan interpretation, along with the diagnosis and treatment of cardiac amyloidosis.

Cardiac Amyloidosis Imaging, Part 2: Quantification and Technical Considerations.

99mTc-pyrophosphate imaging has been around for a long time. In the 1970s, it was used to image recent myocardial infarction. However, it has recently been recognized for its value in detecting cardiac amyloidosis, leading to widespread use across the United States. Increased use led to considerable procedure variability. As the evidence base to support formal guidelines was being developed, experts from several professional medical societies issued imaging and interpretation recommendations titled "ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: part 1 of 2-Evidence Base and Standardized Methods of Imaging." To reach a consensus on a protocol that would benefit the bulk of laboratories, the experts considered several parameters and radiotracer kinetics. The most critical parameters concerned injection-to-imaging delay and planar imaging versus SPECT. Accordingly, the standardized protocol recommends the injection of 370-740 MBq (10-20 mCi) of 99mTc-pyrophosphate with imaging 3 h later. Planar images of the chest are acquired in the anterior and lateral views accompanied by SPECT images. Both the planar and the SPECT images are used to semiquantitatively grade the degree of myocardial uptake compared with the amount of uptake in the ribs using a 0-3 scale. A grade of 2 or 3 on the SPECT images is considered positive for cardiac amyloidosis. The planar images are used to calculate a heart-to-contralateral-lung ratio. A ratio greater than 1.3 at 3 h helps to confirm the diagnosis of cardiac amyloid if the SPECT images have positive findings. This article is part of a 3-part series in this issue of the Journal of Nuclear Medicine Technology Part 1 details the etiology of cardiac amyloidosis and 99mTc-pyrophosphate imaging acquisition parameters. Part 2, this article, describes the procedure evolution over 50 y, image processing, and quantification. It further discusses radiotracer kinetics and 2 important technical considerations: injection-to-imaging delay and planar imaging versus SPECT. Part 3 covers study interpretation along with cardiac amyloidosis diagnosis and treatment.

Cardiac Amyloidosis Imaging, Part 3: Interpretation, Diagnosis, and Treatment.

Cardiac amyloidosis was thought to be rare, undiagnosable, and incurable. However, recently it has been discovered to be common, diagnosable, and treatable. This knowledge has led to a resurgence in nuclear imaging with 99mTc-pyrophosphate-a scan once believed to be extinct-to identify cardiac amyloidosis, particularly in patients with heart failure but preserved ejection fraction. The renewed interest in 99mTc-pyrophosphate imaging has compelled technologists and physicians to reacquaint themselves with the procedure. Although 99mTc-pyrophosphate imaging is relatively simple, interpretation and diagnostic accuracy require an in-depth knowledge of amyloidosis etiology, clinical manifestations, disease progression, and treatment. Diagnosing cardiac amyloidosis is complicated because typical signs and symptoms are nonspecific and usually attributed to other cardiac disorders. In addition, physicians must be able to differentiate between monoclonal immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). Several clinical and noninvasive diagnostic imaging (echocardiography and cardiac MRI) red flags have been identified that suggest a patient may have cardiac amyloidosis. The intent of these red flags is to raise physician suspicion of cardiac amyloidosis and guide a series of steps (a diagnostic algorithm) for narrowing down and diagnosing the specific amyloid type. One element in the diagnostic algorithm is to identify monoclonal proteins indicative of AL. Monoclonal proteins are detected by serum or urine immunofixation electrophoresis and serum free light-chain assay. Another element is identifying and grading cardiac amyloid deposition using 99mTc-pyrophosphate imaging. When monoclonal proteins are present and the 99mTc-pyrophosphate scan is positive, the patient should be further evaluated for cardiac AL. The absence of monoclonal proteins and a positive 99mTc-pyrophosphate scan is diagnostic for cardiac ATTR. Patients with cardiac ATTR need to undergo genetic testing to differentiate between wild-type ATTR and variant ATTR. This article is the third in a 3-part series in this issue of the Journal of Nuclear Medicine Technology Part 1 reviewed amyloidosis etiology and outlined 99mTc-pyrophosphate study acquisition. Part 2 described 99mTc-pyrophosphate image quantification and protocol technical considerations. This article discusses scan interpretation along with cardiac amyloidosis diagnosis and treatment.