Uncovering predictors of atrial fibrillation in wild-type transthyretin amyloid cardiomyopathy

Abstract Background Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by progressive myocardial infiltration with transthyretin-derived amyloid fibrils. This infiltration contributes to atrial stiffness and impaired ventricular relaxation, predisposing patients to a high incidence of atrial fibrillation (AF). Identifying predictors of AF in this population is crucial for early intervention and risk stratification. Objective To determine clinical, pharmacologic, and echocardiographic predictors of incident atrial fibrillation in patients with wtATTR-CM who are in sinus rhythm at the time of diagnosis. Methods This retrospective, single-center study included patients diagnosed with wtATTR-CM between 2014 and 2024 who were in sinus rhythm at baseline. Clinical characteristics, medication usage, laboratory data, and echocardiographic parameters were collected and compared between patients who developed AF and those who did not during follow-up. Logistic regression was performed to identify independent predictors of AF onset. Results Among 111 patients with wtATTR-CM, 59 were in sinus rhythm at diagnosis (73% male; mean age 80 ± 6 years). Over a median follow-up of 30 months (IQR 16–36), 30 patients (51%) developed atrial fibrillation. Patients who developed AF had a higher prevalence of chronic kidney disease (CKD) (50% vs. 24%, p=0.024) and were less likely to be treated with beta-blockers (21% vs. 50%, p=0.011) or spironolactone (14% vs. 37%, p=0.044). Echocardiographic evaluation revealed higher E/e′ ratios (17 ± 6.5 vs. 13 ± 6, p=0.033), reduced peak atrial longitudinal strain (PALS) (12.1 ± 4.5% vs. 15.5 ± 6.1%, p=0.034), impaired peak atrial contraction strain (PACS) (–6.3 ± 3.8% vs. –9 ± 5.5%, p=0.03), and lower left atrial total emptying fraction (LATEF) (35 ± 12.3% vs. 41.6 ± 12.2%, p=0.047). On multivariate analysis, CKD emerged as an independent predictor of AF (odds ratio [OR] 6.20; 95% confidence interval [CI] 1.28–30.14; p=0.04). Beta-blocker use was independently associated with a lower risk of AF (OR 0.10; 95% CI 0.017–0.585; p=0.019). Higher E/e′ ratio (OR 1.17; 95% CI 1.013–1.355; p=0.039) and reduced PACS (OR 1.33; 95% CI 1.005–1.755; p=0.046) were also independently predictive of AF development. Conclusion In patients with wtATTR-CM, atrial fibrillation is a common complication during follow-up. Atrial strain metrics (PALS and PACS) and diastolic function indices (E/e′) are significant echocardiographic predictors of AF. The presence of CKD increases AF risk, while beta-blocker therapy appears to exert a protective effect, non the less, it could also be a confounding factor. These findings highlight the potential role of atrial deformation imaging in risk stratification of AF in wtATTR-CM.