Atrial Fibrillation in Transthyretin Amyloid Cardiomyopathy: A Marker of Disease Severity but Not an Independent Predictor of Mortality

Background and objective Atrial fibrillation (AF) is the most common arrhythmia in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), although its prognostic role remains uncertain. There is substantial evidence regarding mortality when AF coexists with heart failure (HF). However, this association is not well established in patients with ATTR-CM. This study aimed to assess whether AF was an independent predictor of all-cause mortality in ATTR-CM. Methods A total of 22 patients with confirmed ATTR-CM were followed (mean follow-up: 18.2 ± 6.8 months). The association between AF and all-cause mortality was evaluated using Cox proportional hazards modeling. Results The cohort had a mean age of 72 years (AF: 75.0 ± 5.5 years vs. no AF: 69.0 ± 8.7 years), and 81.8% of patients were men. Nine (41%) patients died during follow-up; among these, six (67%) had AF. AF was present in 11 (50%) of patients. AF was associated with more advanced disease, including a higher proportion of ATTR stage III (45.5% vs. 18.2%; p = 0.14) and New York Heart Association (NYHA) class III-IV symptoms (81.8% vs. 54.5%; p = 0.13). AF was not associated with all-cause mortality in the unadjusted analysis (hazard ratio (HR) 2.12; 95% confidence interval (CI): 0.53-8.52) or after adjustment for age, ATTR stage III vs. I-II, and left ventricular global longitudinal strain (LVGLS) > -15% (HR: 0.90; 95% CI: 0.12-6.98). In contrast, ATTR stage III vs. I-II remained an independent predictor of mortality (HR: 7.05; 95% CI: 1.55-31.98). Conclusions Patients with ATTR-CM carry a high mortality burden. AF is a common rhythm disorder in this population and appears to represent a more advanced disease phenotype rather than an independent predictor of all-cause mortality. These findings suggest that AF may function as a marker of disease progression and a valuable element for clinical stratification.