Open AccessATTR Epidemiology, Genetics, and Prognostic Factors
Author(s) -
Andrew Chukwuemeka,
William C Mostertz,
Jan M. Griffin,
Daniel P. Judge
Publication year - 2022
Publication title -
methodist debakey cardiovascular journal
Language(s) - English
Resource type - Journals
eISSN - 1947-6094
pISSN - 1947-6108
DOI - 10.14797/mdcvj.1066
Subject(s) - medicine , transthyretin , penetrance , cardiomyopathy , disease , amyloidosis , restrictive cardiomyopathy , genetic heterogeneity , phenotype , heart failure , bioinformatics , pathology , genetics , gene , biology
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease and an underestimated cause of both heart failure and conduction abnormalities. It is characterized by pathologic accumulation of extracellular protein arising from unstable transthyretin (TTR) tetramers, which dissociate into monomers that misfold, aggregate, and form insoluble fibrils that are resistant to proteolysis. Cardiac amyloidosis appears in two distinct forms: hereditary and wild-type. There is considerable heterogeneity in the clinical presentation of ATTR, ranging from primarily cardiac, primarily neuropathic, or mixed cardiac and neuropathic disease. Pathogenic variants in the TTR gene that predominantly involve the heart include Val122Ile, Leu111Met, and Ile68Leu. The wild-type form of ATTR is also predominantly cardiac. Phenotypic heterogeneity is linked to differences among specific pathogenic TTR variants, geography, and the subtype of endemic versus nonendemic disease. Factors contributing to wild-type ATTR are largely unknown, but similar factors likely influence the penetrance of hereditary ATTR. Recognition of ATTR-CM is improving due to the increased use of cardiac scintigraphy as a noninvasive diagnostic tool, and early recognition of cardiac infiltration is crucial to optimize long-term prognosis.