Association of Wild-Type Transthyretin Amyloidosis (ATTRwt) with Inflammatory Arthritis and Cytomegalovirus Infection

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM), particularly the wild-type form (ATTRwt), is an underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) in older adults. Despite growing recognition, its risk factors remain incompletely characterized. Methods: We analyzed 2016-2020 data from the National Inpatient Sample to identify demographic and clinical factors associated with ATTRwt, using ICD-10 code E85.82. Multivariable logistic regression assessed associations with age, sex, race, comorbidities, and inflammatory or infectious conditions. Results: Among 2,515 patients with ATTRwt, the mortality rate was 4.57%, versus 3.05% in those without ATTRwt (p=0.04). After multivariate analysis, ATTRwt was significantly associated with age (OR 1.07, p< 0.001), Black race (OR 2.79, p< 0.001), cytomegalovirus infection (OR 12.33, p< 0.001), psoriatic arthritis (OR 5.61, p=0.003), CKD (OR 3.67, p< 0.001), and gout (OR 3.39, p=0.033). Conclusion: This nationally representative study identifies several novel clinical associations with ATTRwt, including inflammatory arthritides (gout, psoriatic arthritis) and CMV infection. These findings support the hypothesis that chronic inflammation and immune dysregulation may contribute to TTR destabilization and amyloidogenesis. Future studies should explore these associations.