ATTR Epidemiology, Genetics, and Prognostic Factors
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 in...
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| Language: | English |
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Houston Methodist DeBakey Heart & Vascular Center
2022-03-01
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| Series: | Methodist DeBakey Cardiovascular Journal |
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| Online Access: | https://account.journal.houstonmethodist.org/index.php/up-j-mdbcj/article/view/1066 |
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| author | Chukwuemeka A. Obi William C. Mostertz Jan M. Griffin Daniel P. Judge |
| author_facet | Chukwuemeka A. Obi William C. Mostertz Jan M. Griffin Daniel P. Judge |
| author_sort | Chukwuemeka A. Obi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cf50307cb3a34e7eaec74e23ec0fdc61 |
| institution | OA Journals |
| issn | 1947-6108 |
| language | English |
| publishDate | 2022-03-01 |
| publisher | Houston Methodist DeBakey Heart & Vascular Center |
| record_format | Article |
| series | Methodist DeBakey Cardiovascular Journal |
| spelling | doaj-art-cf50307cb3a34e7eaec74e23ec0fdc612025-08-20T02:22:19ZengHouston Methodist DeBakey Heart & Vascular CenterMethodist DeBakey Cardiovascular Journal1947-61082022-03-01182172610.14797/mdcvj.1066326ATTR Epidemiology, Genetics, and Prognostic FactorsChukwuemeka A. Obi0https://orcid.org/0000-0003-0637-1614William C. Mostertz1https://orcid.org/0000-0001-7001-3956Jan M. Griffin2https://orcid.org/0000-0003-1729-7464Daniel P. Judge3https://orcid.org/0000-0002-3407-0248Division of Cardiology, Medical University of South Carolina, Charleston, South CarolinaDivision of Cardiology, Medical University of South Carolina, Charleston, South CarolinaDivision of Cardiology, Medical University of South Carolina, Charleston, South Carolina; Division of Cardiology, Columbia University Irving Medical Center, New York, New YorkDivision of Cardiology, Medical University of South Carolina, Charleston, South CarolinaTransthyretin 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.https://account.journal.houstonmethodist.org/index.php/up-j-mdbcj/article/view/1066transthyretinmisfoldingattr amyloidosismutationprognosis |
| spellingShingle | Chukwuemeka A. Obi William C. Mostertz Jan M. Griffin Daniel P. Judge ATTR Epidemiology, Genetics, and Prognostic Factors Methodist DeBakey Cardiovascular Journal transthyretin misfolding attr amyloidosis mutation prognosis |
| title | ATTR Epidemiology, Genetics, and Prognostic Factors |
| title_full | ATTR Epidemiology, Genetics, and Prognostic Factors |
| title_fullStr | ATTR Epidemiology, Genetics, and Prognostic Factors |
| title_full_unstemmed | ATTR Epidemiology, Genetics, and Prognostic Factors |
| title_short | ATTR Epidemiology, Genetics, and Prognostic Factors |
| title_sort | attr epidemiology genetics and prognostic factors |
| topic | transthyretin misfolding attr amyloidosis mutation prognosis |
| url | https://account.journal.houstonmethodist.org/index.php/up-j-mdbcj/article/view/1066 |
| work_keys_str_mv | AT chukwuemekaaobi attrepidemiologygeneticsandprognosticfactors AT williamcmostertz attrepidemiologygeneticsandprognosticfactors AT janmgriffin attrepidemiologygeneticsandprognosticfactors AT danielpjudge attrepidemiologygeneticsandprognosticfactors |