From Red Flags to Diagnosis

Diagnosing cardiac amyloidosis (CA) is challenging because of its phenotypic heterogeneity, multi-organ involvement often requiring the interaction among experts in different specialties and subspecialties, lack of a single noninvasive diagnostic tool, and still limited awareness in the medical community. Missing or delaying the diagnosis of CA may have a profound impact on patient outcome, as potentially lifesaving treatments may be omitted or delayed. The diagnostic workup of CA includes two phases: suspicion and diagnosis. The suspicion of CA should arise when “red flags” for this condition are present, particularly when increased left ventricular wall thickness has no clear explanation or is disproportionate to the possible cause. The diagnosis phase includes amyloid typing, which is critical to guide specific treatment. Different algorithms have been proposed by scientific societies; the shared elements are the importance of red flags, the need to search for bone tracer uptake, and a monoclonal protein. A tissue biopsy is needed when a monoclonal protein is found and/or cardiac bone tracer uptake is weak. When CA is suspected and a monoclonal protein is found, further exams to confirm or rule out AL-CA are crucial. Finally, all patients diagnosed with ATTR-CA should undergo genetic testing to search for TTR gene mutations.