{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:57:40Z","timestamp":1782352660609,"version":"3.54.5"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1647,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Pfizer Pharmaceuticals K.K."}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is caused by the deposition of wild-type transthyretin (TTR) amyloid fibrils in the heart. The age at diagnosis of ATTRwt-CM is reported to be approximately 70\u201380 years, and patients commonly present with non-disease-specific cardiac abnormalities, such as heart failure with preserved ejection fraction and diastolic dysfunction. The disease can be fatal if left untreated, with an approximate survival of 3\u20135 years from diagnosis. An oral TTR stabilizer, tafamidis, has enabled early intervention for the treatment of ATTRwt-CM. However, awareness of ATTRwt-CM remains low, and misdiagnosis and a delay in diagnosis are common. This review discusses the epidemiology, characteristics, treatment strategy, and red-flag symptoms and signs of ATTRwt-CM based on the published literature, as well as recent advances in diagnostic modalities that enable early and accurate diagnosis of the disease. We also discuss an algorithm for early and accurate diagnosis of ATTRwt-CM in daily clinical practice. In our diagnostic algorithm, a suspected diagnosis of ATTRwt-CM should be triggered by unexplained left ventricular hypertrophy (LVH), which is LVH that cannot be explained by an increased afterload due to hypertension or valvular disease. In addition, heart failure symptoms, laboratory test results (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, or high-sensitivity troponin I), electrocardiogram and imaging (echocardiogram or cardiac magnetic resonance) data, age (\u226560 years), and medical history suggestive of ATTRwt-CM (e.g. carpal tunnel syndrome) should be examined. Detailed examinations using bone scintigraphy and monoclonal protein detection tests followed by tissue biopsy, amyloid typing, and TTR genetic testing are warranted for a definite diagnosis of ATTRwt-CM.<\/jats:p>","DOI":"10.1002\/ehf2.13473","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T07:15:03Z","timestamp":1623914103000},"page":"2647-2659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Diagnosis of Wild-Type Transthyretin Amyloid Cardiomyopathy in Japan: Red-Flag Symptom Clusters and Diagnostic Algorithm"],"prefix":"10.1093","volume":"8","author":[{"given":"Takayuki","family":"Inomata","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Kitasato University Kitasato Institute Hospital , 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Tahara","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine , Kurume ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazufumi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuharu","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medical Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Ishii","sequence":"additional","affiliation":[{"name":"Pfizer Pharmaceuticals K.K. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Kitano","sequence":"additional","affiliation":[{"name":"Pfizer Pharmaceuticals K.K. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Koyama","sequence":"additional","affiliation":[{"name":"Maruko Central Hospital , Nagano ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"2026012114215561100_ehf213473-bib-0001","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000444206","article-title":"The prevalence and management of systemic amyloidosis in Western 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