Clinical impact of atrial fibrillation on cardiac parameters and long-term outcomes in patients with transthyretin amyloid cardiomyopathy in the era of disease-modifying therapy
S Yamauchi, H Kondo, S Saito, K Yonezu, N TakahashiAbstract
Background
In the pre–disease-modifying therapy (DMT) era, transthyretin amyloid cardiomyopathy (ATTR-CM) was associated with poor prognosis, and atrial fibrillation (AF) was considered to have limited incremental impact on clinical outcomes. With the widespread implementation of early diagnosis and DMT initiation, outcomes have improved, and the clinical relevance of AF may have evolved. Recent reports demonstrating favorable outcomes of AF catheter ablation suggest that rhythm control strategies may be more clinically meaningful than previously recognized.
Purpose
We aimed to evaluate the clinical impact of AF and the prognostic significance of sinus rhythm maintenance achieved by catheter ablation in contemporary ATTR-CM patients receiving DMT.
Methods
This prospective multicenter study included 278 patients with ATTR-CM treated with DMT who were enrolled in the Oita ATTR-CM cohort between January 2016 and February 2026. The median follow-up was 24 months. Patients were categorized according to baseline rhythm into a maintained sinus rhythm (mSR) group (including patients with prior AF successfully treated by ablation, N=190) and a persistent AF group (N=88). Changes (Δ) in cardiac parameters were defined as the difference between values at 1 year and baseline. AF recurrence after ablation was assessed using 14-day Holter monitoring. Long-term outcomes, including all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for heart failure (HHF), were analyzed using Kaplan–Meier methods.
Results
Compared with the mSR group, patients in the persistent AF group had significantly lower left ventricular ejection fraction (LVEF), larger left atrial diameter, and reduced global longitudinal strain at baseline (P = 0.0455, P < 0.0001, P < 0.0001, respectively, Figure 1A). In addition, estimated glomerular filtration rate and serum transthyretin levels were significantly lower (P = 0.0254, P = 0.0260), whereas NT-proBNP and troponin T levels were significantly higher (P < 0.0001, P < 0.0001) in the persistent AF group (Figure 1B). In the mSR group, the decline in left ventricular ejection fraction at 1 year (ΔLVEF) was significantly attenuated (P = 0.0083), and increases in NT-proBNP and troponin T levels (ΔNT-proBNP and Δtroponin T) were significantly suppressed compared with the persistent AF group (P = 0.0454 and P = 0.0184). The mSR group had significantly lower incidences of ACM, CVD, and HHF compared with the persistent AF group (Figure 2A). Patients without recurrence after AF ablation had a lower incidence of HHF compared with those who experienced AF recurrence (Figure 2B).
Conclusion
The presence of atrial fibrillation was associated with adverse cardiac parameters in patients with ATTR-CM and may accelerate disease progression over 1 year. Rhythm control strategies aimed at maintaining sinus rhythm may reduce HHF and potentially improve prognosis in patients with ATTR-CM.