Steep increase in the number of transthyretin-positive cardiac biopsy cases in Japan: evidence obtained by the nation-wide pathology consultation for the typing diagnosis of amyloidosis

Abstract

Background In 2019, 2020 and 2022, the Japanese Government approved the use of tafamidis and two technetium-scintigraphies for transthyretin amyloid (ATTR) cardiomyopathy, and announced the patient criteria for tafamidis therapy. In 2018, we had started a nation-wide pathology consultation of amyloidosis. Objective To reveal the impact of approval of tafamidis and technetium-scintigraphy on the diagnosis of ATTR cardiomyopathy. Methods Ten institutes participated in this study on the pathology consultation of amyloidosis and shared rabbit polyclonal anti-κ116-133, anti-λ118-134, and anti-transthyretin115-124 antibodies. Proteomic analysis was performed when the typing diagnosis by immunohistochemistry was unavailable. Results Out of 5400 consultation cases received from April 2018 to July 2022, the type of amyloidosis by immunohistochemistry was determined in 4119 of the 4420 Congo-red positive cases. The incidences of AA, ALκ, ALλ, ATTR, Aβ2M and others were 3.2, 11.3, 28.3, 54.9, 0.6 and 1.8%, respectively. Out of 2208 cardiac biopsy cases received, 1503 cases were ATTR positive. There were 4.0 and 4.9 times more total cases and ATTR-positive cases, respectively, in the last 12 months as compared to the first 12 months. Conclusions The approval of tafamidis and technetium-scintigraphy raised the awareness of ATTR cardiomyopathy, leading to an upsurge in ATTR-positive cardiac biopsy cases.