Abstract

Background Cardiac amyloidosis is an increasingly recognized condition in clinical practice. Its role in sudden cardiac death (SCD), particularly as a first manifestation, remains poorly characterized. Objectives The goal of this study was to assess the clinical and pathologic characteristics of SCD decedents with histologically confirmed cardiac amyloidosis in a large autopsy-based registry. Methods This study reviewed 8,107 SCD cases referred to a specialist cardiac pathology center between 1994 and 2023. SCD was defined as cardiovascular death within 12 hours of apparent well-being. Histologic confirmation of cardiac amyloidosis was based on Congo red positivity and apple-green birefringence under polarized light. Clinical history and autopsy findings were analyzed. Results Cardiac amyloidosis was identified in 33 cases (0.4%), with 26 (79%) responsible for SCD. Most decedents were male (64%) with a mean age of 67 ± 18 years; 18% were aged <50 years. Coronary amyloid infiltration was significantly more frequent among decedents whose SCD was attributed to cardiac amyloidosis compared with those in whom cardiac amyloidosis was identified as an incidental finding (69% vs 14%; P = 0.026). Despite antemortem cardiac symptoms being present in 39%, only 1 patient (3%) had a known cardiac amyloidosis diagnosis before death. Conclusions Cardiac amyloidosis can be associated with SCD and is often undiagnosed during life. Coronary infiltration may contribute to SCD risk.