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.