Biological and Social Factors Influencing Symptoms and Quality of Life in Women and Men with Atrial Fibrillation

Abstract

Purpose/Aims: The overarching purpose of this dissertation work was to explore potential biological and social factors that influence symptoms and QOL in women and men with atrial fibrillation (AF). Guided by Bronfenbrenner’s socioecological framework, this research aimed to: 1) Identify and synthesize existing evidence of sex-related differences in atrial fibrosis, epicardial adipose tissue (EAT), leptin, and adiponectin among adults with AF; 2) Compare left atrial (LA) fibrosis, LA EAT, adipokines, AF symptoms, and QOL between males and females being evaluated for AF ablation; 3) examine associations between LA fibrosis, LA EAT, adipokines, AF symptoms, and QOL in males and females being evaluated for AF ablation; and 4) explore perceptions of and gender differences in social factors—including social support, living situation, and network interactions—and their influence on AF symptoms and QOL for highly symptomatic women and men being evaluated for AF ablation. Methods: This dissertation used a multimethod design consisting of 1) a structured literature review and 2) a primary cross-sectional study with quantitative and qualitative components. The structured literature review synthesized 17 eligible studies, published through January 31, 2025, that evaluated sex-related differences in atrial fibrosis, EAT, leptin, or adiponectin among adults with AF. The primary study was a cross-sectional study including 77 adults with AF undergoing pre-ablation cardiac late gadolinium enhancement (LGE) MRI at an academic medical center in the Pacific Northwest. LA fibrosis (%), EAT volume, and EAT index were quantified using LGE-MRI, with an EAT subsample of 30 subjects. Plasma adipokines, leptin and adiponectin, were measured by enzyme immunoassay. Patient-reported AF symptom severity was measured with Atrial Fibrillation Severity Scale (AFSS); AF-related QOL with Atrial Fibrillation Effect on QualiTy of life (AFEQT), and global QOL with PROMIS Global Health v1.2 (Mental Health [MH], Physical Health [PH]). The quantitative analysis used descriptive statistics, bivariate tests, and multivariable linear regression to examine sex differences and associations among biological factors, AF symptoms, and QOL. Qualitative analysis of semi-structured telephone interviews (N=23) used inductive coding and thematic analysis in Atlas.ti to explore perceptions of social factors in symptomatic AF. Results: The structured literature review identified 17 eligible studies and found detectable sex-related differences across AF-relevant substrates and adipokines. Females more often demonstrated greater atrial fibrosis and higher adiponectin concentrations; males demonstrated greater total EAT burden; and evidence was insufficient to draw conclusions regarding leptin. In the cross-sectional study of adults with AF undergoing pre-ablation evaluation, no mean sex differences were observed in LGE-MRI measures of left atrial fibrosis, EAT, or EAT index, or in AF symptom severity and QOL measures (Table 1). However, females had higher leptin levels (27.9 ± 23.2 ng/mL vs 16.9 ± 16.3 ng/mL; p = 0.018) and adiponectin than males (8.4 ± 4.5 vs 5.0 ± 4.1 µg/mL; p = 0.001). In males, higher leptin was related to higher AF symptom severity (r = 0.37, p = 0.01) and lower global PH (r = −0.51, p < 0.001). In females, higher LA fibrosis was related to higher AF symptom severity (r = 0.48, p = 0.008), lower AF-related QOL (r = −0.42, p = 0.02) and lower global QOL (MH, r = −0.47, p = 0.009; PH, r = −0.57, p < 0.001). Also in females, higher EAT, EAT index, and leptin were related to lower AF-related QOL (r = −0.68, p = 0.007; r = −0.65, p = 0.01; r = −0.52, p = 0.004; respectively), and higher EAT index and higher leptin were related to lower global PH (r = −0.56, p = 0.047; r = −0.49, p = 0.008; respectively). In adjusted full-sample regressions, leptin was the only biomarker independently associated with higher AF symptom severity (β = 0.23, p = 0.043). The qualitative analysis identified one main theme: Support as central to well-being and AF coping; and four subthemes: 1) Support network composition and availability, 2) Reliance on emotional, informational, and instrumental support, 3) Navigating independence and receiving support, and 4) Support evaluated through network attentiveness and unmet needs. Gender differences emerged in support availability, informational and instrumental support, and identity norms shaping disclosure and help-seeking. Conclusion: Women and men with AF experience symptom burden and QOL within biological and social contexts that influence the illness experience. Sex-specific differences in AF substrate biology, adipose-derived inflammation, and social support suggest that biological and social factors may differentially influence AF symptomatology in women and men.. These findings support sex- and gender-informed AF research and clinical care focused on improving symptom burden and QOL.