Cardiologic Phenotypes and Natural History of FAC

Fifty years ago, the focus on the Val30Met type of the disease, in which neurologic manifestations predominate, led to the widespread notion that hereditary transthyretinrelated amyloidosis (ATTR) was essentially a neurologic disease. It is now clear that ATTR is extremely heterogeneous on both genotypic and phenotypic grounds. The clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to strictly cardiac manifestations. This heterogeneity is linked to several factors including specific transthyretin mutations, geographic distribution and endemic vs. non-endemic aggregation type. The existence of exclusively or predominantly cardiac phenotypes makes the recognition of the disease very challenging since it can mimic other more common causes of left ventricular “hypertrophy”. Assessment of such patients should include an active search for possible red flags that can indicate the correct final diagnosis. More in general the clinician must be aware that: