Rate vs. rhythm control in patients with transthyretin amyloid cardiomyopathy and atrial fibrillation

Background Atrial fibrillation (AF) is commonly observed in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), yet the optimal management strategies remain uncertain. AF treatment in ATTR-CM is particularly challenging, as traditional rate control medications may worsen cardiac output, while effective rhythm control is often difficult to achieve. Aim This retrospective, single-centre study compares cardiovascular outcomes of rhythm vs. rate control strategy in patients with ATTR-CM and comorbid AF, between 2014 and 2023. Methods and Results Overall, 118 patients with ATTR-CM and comorbid AF were included in the study, with a median follow up period of 747 days (IQR 357-1190). Patients in the rhythm control group (n=37, 31.5%) were compared to those in the rate control group (n=81, 68.6%). The cumulative primary endpoint was defined as the occurrence of heart failure related hospitalisation, NYHA functional class worsening and cardiovascular death. Secondary endpoint was defined as all-cause mortality. Most patients (n=97, 82.2%) had persistent AF. Median age at baseline was 79,5 (IQR 75-83) and 96 (81.4%) of patients were male. At baseline, median NAC score was 2 (IQR 1-3), median NYHA-functional classification was 2 (IQR 2-3). In the rhythm control group 18 (48.6%) were on amiodarone, 4 (10.8%) had a pulmonary vein isolation, 25 (67.6%) had at least one electrical cardioversion and 27 (73%) were on tafamidis. In the rate control group 42 (51.8%) were on beta blockers, 8 (9.9%) on calcium channel blockers, 1 (1.2%) on digoxin and 53 (65.4%) on tafamidis. The cumulative primary endpoint was observed in 20 (54%) patients in the rhythm control group vs. 59 patients (72.8%) in the rate control group (p=0.108) (Fig. 1). Heart failure-related hospitalizations occurred in 15 (40.5%) patients in the rhythm control group vs. 25 (30.8%) in the rate control group (p=0.432). Cardiovascular death was reported in 6 (16.2%) vs. 18 (22.2%) (p=0.145) cases. In the rhythm control group, 7 (18.9%) had NYHA-worsening at follow up vs. 22 (27.2%) (p=0.118). All-cause mortality was significantly lower in the rhythm control group: 2 (5.4%) vs. 25 (30.8%) (p<0.001) (Fig.2). Conclusion In our single-centre cohort of patients with ATTR-CM and comorbid AF, rhythm control was associated with significantly lower all-cause mortality. Cardiovascular death, NYHA-worsening and the cumulative endpoint, albeit trending lower in the rhythm control group, showed no statistically significant differences. Heart failure-related hospitalisations were lower in the rate control group but did not meet statistical significance.Fig. 1 Kaplan-Meier: cumulative endpoint Fig.2 Kaplan-Meier: all cause death