A phenomap of TTR amyloidosis to aid diagnostic screening.

Abstract

Cardiac amyloidosis due to transthyretin (ATTR) remains an underdiagnosed cause of cardiomyopathy. As awareness of the disease grows and referrals for ATTR increase, clinicians are likely to encounter more atypical forms of the condition in clinical practice. Therefore, physicians and treating cardiologists should be aware of the full phenotypic spectrum of ATTR. The phenotypic manifestation of ATTR varies depending on the stage of the disease, the presence and type of TTR mutation and the patient's comorbidities. ATTR findings can be grouped into four major categories: clinical profile and cardiac phenotype, extra-cardiac findings, electrocardiogram and imaging findings, which cumulatively form the full phenomap of ATTR. Results from any diagnostic test for ATTR should be interpreted in light of the pre-test probability for the disease. Findings that suggest negative markers for ATTR can point towards other forms of amyloidosis (such as AL amyloidosis) or alternate causes of left ventricular hypertrophy, including hypertrophic cardiomyopathy or Fabry disease. The rising number of referrals for ATTR cardiomyopathy presents a challenge in daily clinical practice. To prevent an increase in false-positive diagnostic test results, an ATTR phenomap can serve as a valuable tool for guiding diagnostic assessments, interpreting test outcomes and prioritizing appropriate referrals for ATTR screening.