Abstract Body (Do not enter title and authors here): Background: Cardiac amyloidosis (CA) remains underdiagnosed, partly due to variability in screening recommendations. Current criteria suggest screening for CA at a left ventricular wall thickness (LVWT) ≥12 mm (ESC and ACC) or ≥14 mm (AHA), in the presence of specific clinical clues.

Research Question: Could patients with histologically confirmed CA in an autopsy cohort have been identified during life following current screening recommendations?

Methods: In this single-center retrospective study, we reviewed 104 autopsy-confirmed CA cases over 10 years (01/2014–12/2023). Twenty-three patients were included based on complete clinical records, ECGs, and echocardiograms within one year prior to death. Two pathologists applied a standardized semi-quantitative scoring system for interstitial and vascular amyloid in the left (LV) and right ventricle (RV). Patients were stratified by LVWT (<12 mm, 12–13 mm, ≥14 mm) on echocardiography, and clinical clues scored per ESC and ACC recommendations. Histopathology was correlated with antemortem data. Group comparisons used t-tests, ANOVA, or Kruskal–Wallis tests with Bonferroni-adjusted Wilcoxon tests for continuous and chi-square tests for categorical variables.

Results: Of the 23 patients (2 AL, 21 ATTR), 91% were diagnosed only at autopsy. The mean age was 80.6 ± 11.7 years and 35% were women, who were older (86.9 ± 5.3, p<0.05). The mean LVWT was 12.7 ± 2.3 mm and a ≥12 mm threshold would have missed 30% of cases and ≥14 mm 57% (Figure 1). All patients had ≥1 ACC clue and 96% ≥1 ESC clue (Table 1). Mean clinical clue scores did not differ by LVWT (Figure 2) or sex. Heart failure was present in 83%, with a reduced ejection fraction (HFrEF) more common in LVWT <12 mm (71.4%, p<0.05). LVWT ≥14 mm was associated with diagnosis before death (p<0.05) and higher interstitial amyloid (Figure 2) in the LV (p=0.04) and the RV (p=0.01).

Conclusions:
ESC and ACC red flag criteria differ but would have identified nearly all patients—had the ≥12 mm LVWT threshold been met. However, this cutoff would have missed 30% of cases, and the AHA’s ≥14 mm threshold 57%, precluding red flag assessment. Patients with LVWT <12 mm had similar red flag profiles and were more often associated with HFrEF, supporting their clinical relevance. In contrast, the ≥14 mm group showed greater interstitial burden, suggesting more advanced disease. These findings support red flag–based screening and further study in patients with normal or borderline LVWT.