Clinicopathological features of clinically undiagnosed sporadic transthyretin cardiac amyloidosis: a forensic autopsy-based series

Abstract

Objective

To investigate the clinicopathological features of sporadic amyloid transthyretin (ATTR) amyloidosis.

Methods

We evaluated 1698 serial Japanese forensic autopsy patients. The extent and amount of ATTR deposition in the 16 cardiac regions, including the conduction system, were semiquantitatively evaluated. Ward’s hierarchical cluster analysis was applied to classify the cases into subgroups. Also, the relationship between ATTR and amyloid atrial natriuretic factor (AANF) was evaluated.

Results

Forty-four cardiac ATTR amyloidosis patients (mean age 85.4 ± 5.7 years; 22 men) without history of hereditary polyneuropathy were identified (2.6% of all patients, 8.8% of those aged ≥80 years). All the 44 patients were not in the bedridden state and died-out-of-hospital scenarios. Of these, 10 (23%) were sudden death. Cluster analysis classified the patients into three groups (mild, atria-predominant and the severe deposition group). Amyloid deposition had already started simultaneously from each atrium and ventricle; however, the atrial septum and basilar ventricular septum were the sites that revealed the most frequent deposition. Also, a possible association between ATTR and AANF deposits was identified.

Conclusions

Sporadic ATTR amyloidosis patients might already be susceptible to a risk for sudden death even from an early-phase. Also, ATTR amyloid deposition in such cases might progress with a certain degree of regularity.

Keywords:

• Arrhythmia
• atrial natriuretic factor
• cardiac amyloidosis
• conduction system
• sudden death
• transthyretin

Acknowledgements

The authors are grateful to Ms. Tamae Sasakura, Mr. Noboru Onozuka, Ms. Syuko Matsumori, Ms. Miyuki Maekawa, and Mr. Osamu Yamamoto for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported in part by JSPS KAKENHI Grant Number JP20k18979 to SI and JP18k10119 to YH.