Atrial fibrillation in transthyretin amyloid cardiomyopathy: marker of disease severity and implications for multidomain reassessment.

Abstract

Atrial fibrillation or flutter (AF/AFL) affects approximately 56% to 71% of patients with transthyretin amyloid cardiomyopathy (ATTR-CM), with prevalence rising in more advanced disease. AF usually arises on a background of amyloid atrial cardiomyopathy: atrial infiltration, increased stiffness, impaired reservoir and contractile mechanics, and a prothrombotic milieu present even in sinus rhythm. Whether AF contributes independently to mortality remains unsettled. Unadjusted analyses show higher mortality or event rates with AF, inconsistently significant; the association attenuates once amyloid severity is accounted for in single-center and trial datasets. The largest dataset, reported only as a conference abstract, is the exception: an association with a composite including cardiovascular hospitalization persisted after adjustment for stage. Its clinical relevance may lie less in mortality prediction than in symptoms, heart failure events, and thromboembolism. Conventional risk stratification performs poorly: CHA₂DS₂-VASc does not discriminate left atrial appendage thrombus, thrombus occurs during therapeutic anticoagulation, and in a large propensity-matched cohort stroke rates were comparable with and without AF, suggesting thromboembolic risk reflects the underlying atrial myopathy rather than rhythm status alone. Rate control is constrained by restrictive physiology; catheter ablation has been associated with favorable outcomes in observational cohorts, in selected patients and with clinically meaningful periprocedural decompensation. No disease-modifying therapy has prevented AF or reduced AF burden in a prospectively adjudicated trial. Throughout, we separate published evidence from expert practice. The data support a cross-sectional association between AF and greater ATTR-CM severity but do not establish that incident AF identifies biological progression in an individual patient.