Delayed Diagnosis of Transthyretin Cardiac Amyloidosis Is Associated With Heart Failure Hospitalizations and Mortality

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive, underdiagnosed cause of heart failure (HF). Diagnostic delays may increase cardiac injury at treatment initiation, but the relationship between delay and outcomes remains poorly defined. OBJECTIVES: The purpose of this study was to evaluate time from HF diagnosis to ATTR-CM diagnosis as a proxy for disease progression and its association with HF hospitalization (HFH) and mortality. METHODS: This retrospective cohort study used Medicare fee-for-service and Veterans Health Administration (VHA) data. We identified patients diagnosed with ATTR-CM between 2016 and 2022 using a validated algorithm based on diagnoses and medications. Time-to-diagnosis was defined as days between each patient's first HF diagnosis and first amyloid diagnosis. Using multivariable Cox models, we evaluated its association with death or HFH. RESULTS: We identified 7,770 Medicare beneficiaries and 2,557 Veterans with HF and ATTR-CM. Median age at diagnosis was 81 years in both cohorts (Medicare IQR: 76-86; VHA IQR: 74-87); women comprised 1,775 (22.8%) of Medicare and 13 (0.5%) of VHA patients. Median time-to-diagnosis was 494 days (IQR: 63-1,340) for Medicare and 490 days (IQR: 69-1,286) for VHA. After adjustment for sociodemographics, each 1-year delay was associated with a 7% increased risk of the primary outcome (Medicare HR: 1.07; 95% CI: 1.06-1.08; VHA HR: 1.07; 95% CI: 1.05-1.09). Results were similar after adjusting for comorbidities. CONCLUSIONS: Across 2 real-world populations, diagnostic delay in ATTR-CM is a clinically meaningful marker of disease progression, with longer delays associated with increased HFH and mortality.