Role of autopsy in sudden deaths from undiagnosed cardiac amyloidosis: a systematic review with an illustrative autopsy case.

BACKGROUND/

INTRODUCTION

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy that remains underdiagnosed and may be overlooked in sudden-death investigations. We reviewed the contribution of autopsy and post-mortem methods to recognizing CA and clarifying fatal mechanisms.

METHODS

We searched PubMed/MEDLINE from database inception through 10 July 2026 using a predefined Boolean query and supplementary reference-list screening. Nineteen eligible reports were included and narratively synthesized across epidemiology, terminal mechanisms, and post-mortem diagnostic techniques.

RESULTS

Autopsy studies documented frequent ante-mortem underdiagnosis: prevalence reached 21% in unselected elderly populations, and 91.3% of cases in a cohort of 1972 autopsies had been missed during life. Sudden death was especially relevant in AL amyloidosis and commonly involved pulseless electrical activity (PEA), bradyarrhythmias, or conduction disease. In the EXCALIBUR study of 110 newly diagnosed patients, bradyarrhythmias requiring pacemaker implantation occurred in 17.3% and new-onset atrial fibrillation in 28.2%; terminal rhythms were predominantly PEA. A previously reported illustrative autopsy case of systemic AL kappa amyloidosis showed how multisystem symptoms, low-voltage ECG, renal dysfunction, and a monoclonal kappa component may remain clinically unintegrated.

CONCLUSIONS

Targeted autopsy, mapped histological sampling, Congo red staining, and reliable amyloid typing can identify otherwise unrecognized CA, improve cause-of-death attribution, and resolve medicolegal uncertainty. Correlating ante-mortem warning signs with post-mortem findings may reduce diagnostic misclassification.