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-κ_116-133, anti-λ_118-134, and anti-transthyretin_115-124 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.

Keywords:

• Cardiac biopsy
• immunohistochemistry
• tafamidis
• technetium-scintigraphy
• transthyretin amyloid cardiomyopathy

Acknowledgements

The authors thank N Takimoto for excellent technical assistance and H Okada for the management of consultation.

Disclosure statement

HN has received honoraria from Alnylam, Janssen, and Pfizer. YS has received research grants and honoraria from Alnylam and Pfizer. MU has received research grants, honoraria, and non-financial support from Alnylam and Pfizer. AMH has received honoraria from Pfizer. YA has received consulting fees from Alnylam, Pfizer, and Prothena. The other authors have nothing to declare.

Additional information

Funding

This work was supported in part by the Grant for surveys and research of intractable diseases from the Ministry of Health, Labour and Welfare, Japan [H29-nanchitou(nan)-ippan-022 from 2017 to 2019; 20FC1022 from 2020 to 2022; P.I. HN].