Nationwide patterns of cardiac-related mortality in amyloidosis cases: an epidemiologic study

INTRODUCTION: Cardiac amyloidosis is frequently overlooked, leading to delayed diagnosis and underestimation of its true impact on cardiac mortality. METHODS: Using CDC WONDER (1999-2020), we identified U.S. decedents aged ≥ 25 years with amyloidosis (ICD-10 E85) as the underlying cause of death and at least one cardiac-related condition as a contributing cause. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, and trends were analyzed using Joinpoint regression and autoregressive integrated moving average (ARIMA) forecasting through 2040. RESULTS: Among 16,673 deaths, the AAMR rose from 0.261 in 1999 to 0.608 in 2020, with inflection points in 2012 and 2017 and an overall annual increase of 3.96%. Mortality was higher in men (0.537 vs. 0.210) and Black individuals (0.83 vs. 0.32), with a sharp post-2017 rise, especially among Black decedents. Geographic disparities were also observed, with the highest rates in the Northeast and urban areas. Most deaths occurred in hospitals (43.2%) or at home (31.4%), and mortality rates peaked in those aged 85 and older. Forecasting models project continued increases in AAMR through 2040, reaching approximately 2.0 overall, with especially elevated rates among Black (≈ 5.9) and male (≈ 3.8) decedents. CONCLUSION: Cardiac mortality in amyloidosis has risen sharply since 2017, likely driven by improved ATTR-CM detection through non-biopsy imaging and guideline adoption. Disparities by sex, race, and geography persist, reflecting uneven diagnostic capacity concentrated in urban and Northeastern centers. Forecasts project continued increases, particularly among Black and male individuals, underscoring the need for more equitable access to diagnosis and treatment.