LAUSR

The diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) is now literally a million-dollar implication. With the approval of tafamidis (Vyndaqel/ Vyndamax) in 2019, ATTR-CA has become a treatable chronic disease state with potentially life prolonging therapy for those properly diagnosed and with access to this revolutionary treatment. This treatment comes at a significant expense to patients and society as the direct lifetime cost of treatment with tafamidis for ATTR-CA was recently calculated to be 1.13 million dollars per patient, and there are unanswered questions about its cost-effectiveness. As nuclear scintigraphy with bone-avid tracers (Tc-pyrophosphate (Tc-PYP) in the United State) is now central to the diagnosis of ATTR-CA eliminating the need for endomyocardial biopsy in most cases, careful consideration of ATTR-CA imaging techniques and interpretation is of foremost clinical importance to our patients and also has major economic impact for the world healthcare budget. It is crucial that Tc-PYP imaging be accurately interpreted: Mis-diagnosing ATTR-CA through Tc-PYP misinterpretation is now a ‘million-dollar mistake.’ The rapid increase in use of Tc-PYP imaging for the diagnosis ATTR-CA over the past decade developed around the concept that a refreshingly straightforward imaging scheme utilizing planar imaging provides high diagnostic yield. The visual interpretive approach to planar Tc-PYP imaging uses a 0-3 grading system of the appearance of cardiac uptake on the anterior and lateral projections adopted from Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) imaging. This was further supplemented in 2013 by the work by Bokhari et al. who developed the semiquantitative heart/contralateral chest ratio to differentiate ATTR-CA from light chain cardiac amyloidosis (ALCA) in appropriately selected patients. Additively, the seminal publication by Gilmore et al. described that the combination of visual grade 2 or 3 myocardial radiotracer uptake on planar bone scintigraphy and the absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for ATTR-CA of 100%. The patient population in this study consisted of highly selected patients evaluated at tertiary amyloid referral centers with expertise in the performance and interpretation of bone scintigraphy for many years. However, as the contemporary utilization of Tc-PYP imaging expands to the community through efforts of nuclear cardiology societies and pharmaceutical companies seeking to expand the reach of their targeted therapies, the patients undergoing Tc-PYP imaging now reflect a less selected population with a likely much lower pre-test probability of ATTR-CA. While there are little data on the rapidly evolving practice of Tc-PYP imaging, recent practice surveys indicate that at least 30% of responding hospitals perform Tc-PYP imaging to screen for cardiac amyloidosis, but often times without light chain measurement to exclude AL-CA and only 21% of institutions performed SPECT imaging in addition to planar. These data and anecdotal reports from referral centers suggest the rapid expansion of Tc-PYP imaging to non-expert centers may be leading to reduced interpretive specificity of Tc-PYP imaging for ATTR-CA both due to testing of patients that have low probability of ATTR-CA/high probability of alternative diagnoses (such as AL-CA) and imprecise acquisition/interpretation strategies. It seems reasonable to assume that this increased utilization of Tc-PYP Reprint requests: Edward J. Miller, MD, PhD, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT ; [email protected] J Nucl Cardiol 2021;28:503–6. 1071-3581/$34.00 Copyright 2021 American Society of Nuclear Cardiology.