Left atrial function and stiffness in HFpEF patients with and without paroxysmal atrial fibrillation: associations with PAF and clinical outcomes

Although the left atrium (LA) plays a pivotal role in the pathophysiology and progression of heart failure with preserved ejection fraction (HFpEF), the impact of atrial fibrillation (AF) on LA function and stiffness in this population remains incompletely understood. Moreover, the prognostic significance of LA functional parameters has not been fully elucidated in patients with HFpEF. In addition, exploratory analyses were performed to investigate the relationships between LA functional parameters, exercise capacity, and markers of left ventricular diastolic function. We hypothesized that impaired left atrial function is associated with an increased risk of adverse clinical outcomes in patients with HFpEF and that HFpEF patients with PAF have greater impairment in left atrial function and increased left atrial stiffness than those without AF. A total of 200 patients with HFpEF meeting the predefined inclusion and exclusion criteria were enrolled. Patients were classified according to the presence of paroxysmal atrial fibrillation. Left atrial function and stiffness were compared between groups, and the prognostic association of left atrial functional parameters was evaluated. Patients with paroxysmal atrial fibrillation (PAF) had significantly reduced left ventricular global longitudinal strain (GLS) (15.98 ± 1.41 vs. 16.72 ± 1.42, P < 0.001), higher E/e′ ratio (15.40 ± 2.95 vs. 14.42 ± 2.56, P = 0.01), larger left atrial diameter (40.19 ± 4.34 vs. 35.98 ± 2.98 mm, P < 0.001), and increased left atrial volume index (LAVI) (33.04 ± 4.27 vs. 30.99 ± 2.81 mL/m², P < 0.001). Patients without PAF exhibited better LA reservoir function, as reflected by higher peak left atrial strain (LAS-peak) (27.02 ± 1.30 vs. 24.55 ± 1.30, P < 0.001) and left atrial total emptying fraction (LAEF-total) (52.98 ± 1.15 vs. 51.81 ± 1.82, P < 0.001). In addition, LA stiffness was significantly increased in the patients with PAF, as indicated by higher ratios of E/e′ divided by LAS-peak (0.59 ± 0.14 vs. 0.54 ± 0.11, P = 0.004) and E/e′ divided by LAEF-total (0.30 ± 0.06 vs. 0.27 ± 0.05, P = 0.001). logistic regression analyses showed that impaired LA reservoir function (LAS-peak: OR 3.86, 95% CI 2.16–6.91, P < 0.001) and increased LA stiffness (E/e′ divided by LAS-peak: OR 5.78, 95% CI 1.38–22.56, P = 0.01; E/e′ divided by LAEF-total: OR 2.71, 95% CI: 1.75–4.48, P < 0.001) remained independently associated with the presence of PAF. After a mean (± SD) follow-up of 36 ± 3 months, 54 patients (27.0%) reached the composite endpoint. When LAEF-total and LAVI were simultaneously entered into the multivariable Cox model, LAEF-total remained independently associated with the composite endpoint (HR 0.59, 95% CI 0.48–0.73, P < 0.001), whereas LAVI was no longer independently associated with outcome (HR 1.05, 95% CI 0.97–1.13, P = 0.241). Patients with higher LAEF-total had significantly better overall survival compared with those with lower LAEF-total (54/54 [100%] vs. 123/146 [84.2%], P = 0.002). A similar trend was observed for stroke incidence (1/54 [1.85%] vs. 17/146 [11.64%], P = 0.029). Among patients with HFpEF without baseline AF, the incidence of new-onset AF was significantly lower in the higher LAEF-total group compared with the lower LAEF-total group (0/39 [0.0%] vs. 23/84 [27.4%], P = 0.002). In HFpEF, the presence of AF is associated with impaired LA function and increased LA stiffness. Lower LAEF-total was associated with an increased risk of adverse cardiovascular outcomes, suggesting its potential prognostic value in patients with HFpEF.