Diagnosing cardiac amyloidosis (CA) is challenging because of its phenotypic heterogeneity, multiorgan involvement requiring 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 profoundly impact on patients' outcomes, as potentially life-saving treatments may be omitted or delayed. The suspicion of CA should arise when "red flags" for this condition are present, together with increased left ventricular wall thickness. The diagnosis of CA requires amyloid typing and differentiation between the two most common forms, light chain (AL) and either mutated or wild-type transthyretin cardiac amyloidosis (ATTR-CA), which is critical to guide a specific treatment. Scientific societies worldwide focus on the importance of red flags, and on the prompt initiation of the diagnostic process with bone tracer uptake and the search of a monoclonal protein. An extra-cardiac or endomyocardial tissue biopsy is needed when a monoclonal protein has been detected and/or cardiac bone tracer uptake is absent or weak. Finally, all patients diagnosed with ATTR-CA should undergo genetic testing to search for TTR gene mutations.
