Active case finding for cardiac amyloidosis in older adults with increased left ventricular wall thickness: a single-center two-phase observational study

Background Cardiac amyloidosis is increasingly treatable, making timely recognition and etiological differentiation between light-chain (AL) and transthyretin (ATTR) amyloidosis important. We assessed documented diagnostic trajectories in a historical amyloidosis cohort and the diagnostic yield of structured active case finding in older adults with increased left ventricular wall thickness. Methods This single-center observational study comprised two phases. First, 117 patients with Congo red-confirmed amyloidosis diagnosed between January 2010 and September 2026 were retrospectively reviewed; a reproducible interval between an earlier potentially related manifestation and diagnostic confirmation could be established in 27. Second, echocardiograms performed in 2023 were reviewed. Patients aged ≥ 65 years with maximum left ventricular wall thickness > 14 mm were assessed for additional amyloidosis red flags. Candidates underwent targeted etiological assessment including serum free light chains, serum and urine immunofixation, 99mTc-DPD bone scintigraphy with SPECT/CT, and tissue confirmation when required. The primary outcome was amyloidosis diagnosis among patients completing the work-up. Exploratory comparisons used the Mann-Whitney U test and Fisher's exact test. Results In the historical cohort, the median documented diagnostic interval was 1 year (IQR 0-3.75; range 0–16), and 7/27 patients (25.9%) had intervals ≥ 4 years. In the active case-finding phase, 448 patients met the initial age and wall-thickness criteria, 324 were evaluable, and 138 had at least one additional red flag. Sixty completed the diagnostic work-up. Ten cases of amyloidosis were identified (16.7%; 95% CI 9.3–28.0), including six cardiac ATTR, three AL with cardiac involvement, and one AA with renal involvement; therefore, 9/60 (15.0%) had cardiac amyloidosis. Patients with confirmed amyloidosis were older than those without amyloidosis (median 83 vs 74 years; p < 0.001). Conclusions A simple echocardiography-triggered strategy combining age, increased left ventricular wall thickness, and additional red flags achieved a clinically relevant diagnostic yield among patients completing targeted assessment and identified both ATTR and AL cardiac amyloidosis. The historical cohort also showed a subgroup with prolonged documented diagnostic trajectories. Incomplete pathway completion limits prevalence estimates but identifies an opportunity to optimize implementation and increase the clinical impact of structured active case finding.