Atrial fibrillation status and functional capacity in transthyretin cardiac amyloid cardiomyopathy

Background Atrial fibrillation is common in transthyretin cardiac amyloid cardiomyopathy (ATTR-CM), but its association with objective physical performance across atrial fibrillation status groups remains unclear. We investigated the association between atrial fibrillation status and functional capacity in ATTR-CM, using six-minute walk distance (6MWD) as the primary endpoint. Methods Consecutive adults with confirmed ATTR-CM evaluated between June 2018 and October 2025 were included and categorized as no atrial fibrillation, paroxysmal atrial fibrillation, or permanent atrial fibrillation. The primary endpoint was six-minute walk distance for submaximal functional capacity assessment. Secondary exploratory endpoints included cardiopulmonary exercise testing (CPET) parameters and NT-proBNP. Multivariable linear regression adjusted for age, sex, body mass index, and NYHA functional class; sensitivity analyses additionally considered beta-blocker use, rhythm-device status, ATTR subtype, left ventricular ejection fraction, and log-transformed NT-proBNP. Results Among 156 patients, 82 had no atrial fibrillation, 24 had paroxysmal atrial fibrillation, and 50 had permanent atrial fibrillation. Six-minute walk distance was available in 136 patients and differed across atrial fibrillation status groups: 432.9 ± 122.4 m, 309.2 ± 111.0 m, and 378.8 ± 108.7 m, respectively. After adjustment, AF status remained associated with 6MWD (overall p = 0.031), driven by lower adjusted values in paroxysmal versus no AF. Significant CPET-derived differences were present in unadjusted analyses but attenuated after adjustment for clinical parameters. Conclusions In ATTR-CM, atrial fibrillation status is associated with functional capacity, with six-minute walk distance providing the most robust parameter. Submaximal functional assessment may capture clinically relevant rhythm-related physical impairment in ATTR-CM.