Pursuing an underdiagnosed disease: a simple imaging test for increasing suspicion of cardiac amyloidosis

The systemic amyloidoses are a group of uncommon diseases in which the common factor is infiltration of one or more organs with a noncellular, extracellular proteinaceous material with specific light microscopic staining characteristics [1]. Significant advances in treatment have been made over the past decade, particularly in AL amyloidosis in which the precursor protein is derived from immunoglobulin light chain fragments [2]. Transthyretin (TTR)-derived amyloidosis has also been the subject of intensive investigation, and several new therapeutic approaches have completed, or are approaching, preliminary clinical testing [3–7]. Refinements in immunohistochemical and proteomic techniques have permitted precise definition of the amyloid type, a prerequisite for initiating appropriate (and avoiding inappropriate) therapies [8]. In 2005, the Bologna group published data from 25 patients with amyloidosis (17 of whom had TTR-related amyloidosis) suggesting the bone-scanning agent Tc3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) was preferentially taken up by the heart in patients with TTR amyloidosis, whereas it showed no uptake in AL amyloidosis or in controls without the disease [9]. This appeared to be isotope specific, as Tc-methylene diphosphonate (MDP) showed no uptake in 11 patients who showed distinct myocardial uptake with Tc-DPD. The authors have now expanded their original observations and, while confirming the tracer is avidly taken up in the TTR amyloid patients, they now also describe a mild to moderate uptake in one third of AL patients, thereby reducing the specificity of the test for TTR amyloidosis alone but still rendering it an interesting and informative technique [10]. Uptake of technetium-based bone imaging traces by the heart in cardiac amyloidosis is not a newly described phenomenon. As pointed out by Rapezzi and coauthors and recently reviewed in detail [11], several other nuclear imaging modalities have been proposed for imaging cardiac amyloidosis, such as Tc-aprotinin [12] and I-metaiodobenzylguanidine (MIBG) [13]. Over 25 years ago the uptake of technetium pyrophosphate (then used as a myocardial infarction imaging agent) was described in both AL and TTR amyloidosis, although the sensitivity of the imaging was subject to debate [14–16]. The type of technetium-based isotope was believed to be significant, as Tc-MDP showed little consistency for imaging amyloid cardiomyopathy, despite occasional case reports of cardiac uptake [17]. With the rapid advances in echocardiography and the echocardiographic descriptions of amyloid cardiomyopathy, technetium pyrophosphate cardiac imaging for possible amyloid cardiomyopathy became obsolete, limited to a radiologic curiosity when incidentally seen on a scan performed for other reasons such as for the evaluation of metastatic disease. Echocardiography still remains the mainstay for the initial suspicion/diagnosis of cardiac amyloidosis [1] (and was also a component of the “gold standard” used in this study), and is nowadays often complemented by cardiac MRI which R. H. Falk : S. Dorbala Cardiac Amyloidosis Program, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA