Sex differences in left atrial cardiomyopathy in patients with atrial fibrillation
M Abbas, J D Dziano, J A Ariyaratnam, A E Elliott, P S SandersAbstract
Background
Although atrial fibrillation (AF) is more common in men, women with AF experience greater symptom burden, reduced quality of life, and higher risks of stroke and heart failure. The mechanisms underlying these sex-differences remain incompletely understood but may relate to disparities in the severity and expression of left atrial cardiomyopathy (LACm). This study aimed to comprehensively evaluate sex differences in the structural, mechanical, and functional features of the left atrium in patients with symptomatic AF undergoing catheter ablation.
Methods
We prospectively recruited 275 consecutive patients (27% women) with symptomatic paroxysmal or persistent AF and preserved left ventricular ejection fraction (≥50%) scheduled for catheter ablation. All participants underwent a multimodal assessment comprising echocardiography at rest and during exercise, cardiopulmonary exercise testing (CPET), and invasive hemodynamic measurements obtained during the ablation procedure. Left atrial (LA) volumes, ejection fraction (LAEF), and reservoir strain (LASr) were quantified according to ASE guidelines. Symptom burden and quality of life were assessed using the Atrial Fibrillation Symptom Severity (AFSS) and Minnesota Living with Heart Failure (MLHFQ) questionnaires. Invasive mean LA pressure and LA stiffness were measured after transseptal puncture. Propensity score matching was performed to adjust for age and AF type.
Results
Female patients were older (69.7 ± 9.2 vs. 65.6 ± 10.8 years, p = 0.04) but had comparable cardiovascular risk factors to men. Despite similar indexed LA volumes (37.4 ± 13.3 vs. 39.1 ± 11.1 mL/m², p = 0.29), women demonstrated markedly lower resting and exercise LAEF (32.2 ± 12.4 vs. 39.6 ± 13.0%, p = 0.008; 36.0 ± 11.9 vs. 46.5 ± 13.1%, p < 0.001) and higher diastolic indices (E/e′ 10.6 ± 3.5 vs. 8.3 ± 2.6, p = 0.002). Estimated pulmonary pressures were greater in women (32.1 ± 9.1 vs. 27.3 ± 6.5 mmHg, p < 0.001). Women reported more severe AF-related symptoms (AFSS 14 [7–19] vs. 9 [5–14], p < 0.001) and lower quality of life (MLHFQ 29 [14–45] vs. 17 [8–36], p = 0.006). CPET revealed significantly reduced peak VO2 in women (15.3 ± 3.9 vs. 22.7 ± 6.9 mL/kg/min, p < 0.001). Invasive mean LA pressure and stiffness index were comparable between sexes (13.9 ± 5.0 vs. 12.4 ± 4.6 mmHg, p = 0.053; 1.05 ± 0.83 vs. 0.73 ± 0.74 mmHg/mm, p = 0.16). Age- and AF-type–adjusted analyses and propensity matching confirmed these differences in functional parameters and symptom burden.
Conclusions
Despite similar LA size and invasively measured stiffness, women with AF demonstrate significantly worse LA mechanical function, higher filling pressures, and reduced exercise capacity, accompanied by greater symptom burden and poorer quality of life. These findings indicate a distinct female phenotype of atrial cardiomyopathy characterized by disproportionate mechanical impairment rather than structural enlargement.Female sex and quality of life