Abstract 4367562: Cardiac Amyloidosis Risk Across Ethnoracial and Clinical Subgroups: A 5-Year National Study

Background: Cardiac amyloidosis, a frequently underdiagnosed condition, involves amyloid fibril deposition in the heart, leading to progressive diastolic dysfunction in a nondilated ventricle. With an estimated prevalence of 1 in 2,000 for transthyretin amyloidosis (ATTR) and rising incidence of light-chain (AL) amyloidosis, early identification of risk factors is crucial for timely diagnosis and treatment to prevent advanced cardiac dysfunction. Research Question: Which demographic and clinical factors are associated with cardiac amyloidosis and its mortality risk? Methods: This retrospective cohort study analyzed hospitalized patients from the National Inpatient Sample (2016–2020) using ICD-10 codes to identify cardiac amyloidosis cases and over 50 risk factors, including hematologic, rheumatologic, and renal conditions. Inclusion criteria required a primary or secondary diagnosis of cardiac amyloidosis. Multiple logistic regression analyses, adjusted for age, sex, and comorbidities, were used to identify factors associated with cardiac amyloidosis (primary outcome) and in-hospital mortality (secondary outcome). Results: Of 23,119 patients with cardiac amyloidosis (mean age 72 years; 42% female; 60% ATTR, 35% AL), hereditary transthyretin amyloidosis (OR 215.89, 95% CI: 176.17–264.56) and familial Mediterranean fever (OR 111.99, 95% CI: 72.39–173.24) (both p < 0.001) showed the strongest associations. Other significant risk factors included hematologic conditions (multiple myeloma, OR 15.31; Waldenström’s macroglobulinemia, OR 6.99; MGUS, OR 4.45; all p< 0.001), renal conditions (CKD, OR 1.83; ESRD, OR 2.76; renal transplant, OR 2.4; all p< 0.001), and rheumatologic conditions (Sjögren’s syndrome, OR 2.04; sarcoidosis, OR 1.69; both p< 0.001). Demographically, Black race (OR 2.52, p< 0.001), Asian race (OR 1.11, p= 0.03), and older age (OR 1.05, p< 0.001) increased risk. Conditions such as asthma, diabetes, and obesity were not associated. Higher mortality was linked to ESRD (OR 2.4), multiple myeloma (OR 1.41), and older age (OR 1.015) (all p < 0.001). Conclusion: This large study identifies hereditary transthyretin amyloidosis, familial Mediterranean fever, and Black race as key risk factors for cardiac amyloidosis, with ESRD and multiple myeloma linked to higher mortality. While reliance on ICD-10 codes may limit precision, these findings support better risk stratification and screening strategies, paving the way for improved patient outcomes.