Tang, W. H. Wilson

Introduction: Amyloidosis complicated by heart failure (HF) poses significant mortality. We sought to identify trends in comorbid amyloidosis and HF mortality in the recent 22- year period. Methods: Mortality due to amyloid and HF as contributors of death were queried from death certificates using the CDC database from 1999 to 2020. Mortality rates and their 95% confidence intervals were adjusted for age (AAMR) through the Direct method and compared by demographic subpopulations. The Monte-Carlo permutation test was used to estimate the annual percentage change (APC). Log-linear regression models were utilized to assess temporal variation in mortality. Results: Age-adjusted mortality rates (AAMR) increased from 0.09 [0.08-0.10] in 1999 to 0.27 [0.25-0.29] in 2020. Mortality increased from 1999 to 2013 (APC +1.4, p=0.048) with an accelerating inflection point in 2013 to 2020 (APC +13.3, p<0.001). AAMR was higher among male populations (AAMR 0.20 [0.20-0.21]) compared to female populations (AAMR 0.07 [0.07- 0.07]). A significant inflection point in uprising mortality rates was observed for both male and female populations in 2013 (p<0.001). Mortality was highest among Black populations (AAMR 0.33), followed by White (AAMR 0.10), Asian/Pacific Islander (AAMR 0.06), and American Indian/Alaska Native populations (AAMR 0.04). Among Black populations, mortality remained consistent from 1999 to 2012 (APC +1.1, p=0.184), followed by an increase from 2012 to 2020 (APC +14.0, p<0.001). Among White populations, mortality remained stagnant from 1999 to 2013 (APC +0.7, p=0.302), followed by an increase starting in 2013 to 2020 (APC +13.5, p<0.001). Discussion: Our findings of a marked rise in HF-related mortality in patients with amyloidosis since 2013 highlighted the profound impact of enhanced diagnostic awareness, novel imaging techniques, and emerging therapeutics. Our analysis also showed mortality disparities between sexes, and geographic locations, races, and ethnicity that warrant targeted public health interventions. Conclusions: Amyloid and HF mortality increased in the recent 22-year period, primarily starting in 2013, emphasizing the urgent need for targeted intervention to address these disparities.