LAUSR

Imaging techniques undergo a process of development. They are birthed from an idea or a hypothesis, and then investigators look for pre-clinical models followed by publication of clinical case reports. In the adolescence of a technique, proof-of-concept series set the stage for larger scale trials of validation. Evidence for utility builds and grows until the technique reaches maturity by demonstration of value to patients and providers. It is within this framework that Mogenstern et al report intriguing data on the early development of F-NaF imaging for the evaluation of cardiac amyloidosis. Cardiac amyloidosis (CA) is caused by deposition of insoluble proteins in the heart resulting in hypertrophy, progressing to diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF). It exists in two predominant forms: acquired monoclonal light chain (AL) vs transthyretin-related (ATTR). ATTR-CA is much more prevalent, especially in the elderly, and can be further subclassified as genetically normal (wild type or senile systemic amyloidosis, SSA) or genetically abnormal (mutant type or familial amyloid cardiomyopathy, FAC). Senile systemic amyloidosis increases in prevalence in men older than 60 years of age, and since the clinical presentation of HFpEF may be attributed to hypertension and other causes of diastolic dysfunction that are also common in the aged population, the diagnosis of ATTR-CA can be challenging and the prevalence of the disease underappreciated. The distinction between ATTR-CA and AL-CA is of paramount importance as prognosis and therapy vary significantly depending on the subtype. Despite the growing knowledge of ATTR-CA as a cause of HFpEF, there has been an unmet clinical need to provide better noninvasive methods to diagnose it. Over the last 5-10 years, there has been a dramatic increase in investigations of multimodality imaging to diagnose CA and differentiate AL-CA from ATTR-CA. In particular, nuclear cardiology techniques using boneavid SPECT tracers (technetium pyrophosphate (Tc-PYP), technetium 3, 3-diphosphono-1,2propanodicarboxylic acid (Tc-DPD), and technetium hydroxydiphosphonate (Tc-HDP)) have shown great promise. In 2013, the group responsible for the current manuscript proposed that Tc-PYP imaging may provide a means to differentiate between ATTR and AL-CA. In 2016, the use of Tc-PYP to diagnose ATTR-CA was further standardized by this group, and a multi-center consensus statement demonstrated the utility of all the bone-avid SPECT tracers to provide a highly accurate noninvasive differentiation between ATTR and AL-CA. On this background, the manuscript by Morgenstern et al in this issue of Journal of Nuclear Cardiology evaluates a potential other means of distinguishing ATTR-CA from AL-CA, using the PET tracer fluorine-labeled sodium fluoride (F-NaF). This tracer is approved by the FDA for prostate cancer screening, and has also been studied for detecting microcalcifications in coronary plaques as well as predicting progression of disease in patients with calcific aortic stenosis. In the current work, the authors present a prospective pilot study in which they enrolled 7 patients with biopsyproven CA (2 with AL-CA, 5 with ATTR-CA) who all underwent F-NaF PET imaging. The control patients (N = 5) were retrospectively assessed, and had Reprint requests: Edward J. Miller, MD PhD, Section of Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017; [email protected] J Nucl Cardiol 2018;25:1568–70. 1071-3581/$34.00 Copyright 2017 American Society of Nuclear Cardiology.