Abstract 4349790: Association of Delayed Diagnosis of Transthyretin Cardiomyopathy with Heart Failure Hospitalizations and Mortality

Background: Timely diagnosis of transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is important for early treatment, which can improve outcomes. Aim: To characterize the clinical impact of delayed diagnosis of ATTR-CM in real-world populations. Methods: This retrospective cohort study used Medicare fee-for-service and Veterans Health Affairs (VHA) data. We identified patients with ATTR-CM diagnosed between 2016 and 2022. The time-to-diagnosis was defined as the number of days between each patient’s first heart failure (HF) diagnosis and their first ATTR-CM diagnosis. Using multivariable Cox models, we evaluated the association between the time-to-diagnosis and the composite primary outcome of all-cause mortality or heart failure hospitalization (HFH). Secondary outcomes were HFH, all- cause mortality and cardiovascular death (VHA cohort only). Results: We identified 7,770 Medicare beneficiaries and 2,557 Veterans with HF and ATTR-CM. The mean age at the time of ATTR-CM diagnosis was 81 years (interquartile range [IQR] 76, 86) for the Medicare cohort and 81 years in the VHA (IQR 74, 87). This included 1,775 (22.8%) women in the Medicare cohort and 13 (0.5%) in the VHA cohort. The median time-to-diagnosis for ATTR-CM was 494 days (IQR 63, 1340) in the Medicare cohort and 490 days in the VHA (IQR 69, 1286). After adjustment for sociodemographics, diagnostic delays of 6 months to 2 years were associated with a 41% increased risk for the primary outcome in the Medicare cohort (HR 1.41; CI 1.30-1.54) and a 66% increased risk in the VHA cohort (HR 1.66;CI 1.49-1.86) compared with a time-to-diagnosis < 6 months. The results were similar after adjusting for clinical comorbidities. After adjustment, each one-year delay in diagnosis was associated with a 7% increased risk of the composite outcome for both cohorts (Medicare HR 1.07; 95% CI 1.06-1.08 and VHA HR 1.07; 95% CI 1.05-1.09). Each one-year delay was associated with a 7-8% increase in risk of HFH (Medicare HR 1.08; CI 1.06, 1.09 and VHA HR 1.07; 1.04, 1.09) and a 7-8% increase in risk of death (Medicare HR 1.07; CI 1.06-1.09 and VHA HR 1.08; 1.06, 1.10). Conclusions: The significant delays between incident HF and diagnosis of ATTR-CM are associated with an increased risk of heart failure hospitalization and mortality. This highlights the critical need for education around ATTR-CM and novel approaches to shorten the diagnostic delay, initiate early treatment and improve outcomes for patients with ATTR-CM.