Atrial fibrillation in familial amyloid polyneuropathy: prevalence, clinical profile, and anticoagulation challenges

Background

With longer survival, cardiac involvement, including atrial fibrillation (AFib), is increasingly recognized in familial amyloid polyneuropathy (FAP). While AFib generally warrants anticoagulation due to thromboembolic risk, the co-occurrence of transthyretin-related cerebral amyloid angiopathy (CAA) creates a dilemma due to the risk of intracranial hemorrhage. Current guidelines are extrapolated from general ATTR studies, but no dedicated data exist specifically in FAP patients.

Methods

Retrospective study of TTR V30M mutation patients, followed at a national referral center since 2019. Clinical records were reviewed for AFib occurrence, management, anticoagulation, and thrombotic or hemorrhagic events.

Results

Among 238 patients with the TTR V30M mutation, AFib occurred in 9.2% (n=22) and was more frequent in those with cardiomyopathy (27.1% vs 4.7%, p<0.001). Patients with AFib had a mean age of 66.1±13.5 years, a median disease duration of 11(IQR 8) years, were predominantly female (54.5%), and most had pacemaker implantation (86.4%). A rhythm-control strategy was used in 45.5% of patients, mostly using amiodarone (90%), whereas beta-blocker use was rare (9.1%). In half of the patients Afib was assumed permanent.

Overall, the mean CHA₂DS₂-VA score was 2.0±1.5, with 36.4% of patients scoring 0/1 and the majority (31.8%) scoring 3. Anticoagulation was prescribed in 77.3% (n=17), predominantly with direct-acting oral anticoagulants (DOAC) (82.4%, n=14). Antiplatelet therapy was not used in any patient. Among patients not receiving anticoagulation (22.7%), the main reasons were concern for intracranial hemorrhage due to suspected/established CAA (n=3), perceived low thromboembolic risk (n=1), and fall risk (n=1). One patient was referred for left atrial appendage closure. Notably, one patient with suspected CAA did receive anticoagulation.

During a median follow-up of 47 months from anticoagulation initiation, only one minor gynecologic bleeding was reported. No thrombotic or major bleeding events, including intracranial hemorrhage, occurred.

Conclusion

AFib in TTR V30M FAP is relatively uncommon but associated with cardiomyopathy. While most AFib patients received anticoagulation, a subset was deferred over perceived bleeding risk. While management requires careful individualization, the absence of major thrombotic or hemorrhagic events suggest that anticoagulation is feasible in selected real-world FAP patients. Larger, prospective studies are needed to guide optimal strategies in this population.