Delays From Clinical Manifestations to Diagnosis of Transthyretin Amyloid Cardiomyopathy: A National Retrospective Cohort Study

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening condition. Timely and accurate diagnosis remains a challenge. We assessed time from first recorded clinical manifestation to ATTR-CM diagnosis in the United States and characterized manifestations associated with diagnostic delays. METHODS: Retrospective analysis of US claims data (Komodo Healthcare Map, July 1, 2016-June 30, 2024). Patients were required to have ≥3 years of continuous enrollment before diagnosis. RESULTS: Among 7509 patients, mean age 75.9 years, 63.2% male, 54.5% White, and 28.6% Black. Patients had a median of 8 manifestations before diagnosis; median observed time from first recorded manifestation to diagnosis was 5.2 years, shorter for variant versus wild-type ATTR-CM (4.4 versus 5.2 years). Within 3 years before diagnosis, patients had a mean of 12.04 (95% CI, 11.75-12.35) primary care physician visits and 14.45 (95% CI, 14.10-14.80) specialists of interest visits, most commonly with cardiologists and ophthalmologists. In adjusted analyses, variant ATTR-CM was associated with shorter time to diagnosis (β, -0.41 years [95% CI, -0.56 to -0.26]), whereas comorbidities, including hypertension (β, 0.46 years [95% CI, 0.27-0.64]), were associated with longer delays. CONCLUSIONS: The diagnostic trajectory for ATTR-CM can be prolonged and challenging, leading to more advanced disease at diagnosis and increased burden. Raising awareness may provide an opportunity for earlier diagnosis.