Influence of atrial fibrillation and mental health impairments on the development heart of failure with preserved ejection fraction

Abstract Introduction Psychological impairments negatively impact the onset, progression, and outcomes of cardiovascular diseases. Heart failure with preserved ejection fraction (HFpEF) has a multifaceted etiology, and its development is linked to an increased incidence of atrial fibrillation (AF) as well as mental health impairments. However, the directionality of this relationship remains unclear. This study aimed to investigate the longitudinal association between depressive and anxiety symptoms, AF, and the development of HFpEF. Methods The PREDCIT-HFpEF trial followed 202 patients with elevated cardiovascular risk but no heart failure to assess the development of HFpEF. Depressive and anxiety symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS) at baseline and follow-up. Receiver operating characteristic (ROC) analysis was conducted to evaluate the association between HADS scores and HFpEF development. Results Over a median follow-up (FU) of 5 years, 31 patients (15%) developed HFpEF. These patients were older (73±8 vs. 67±8 years, p=0.01), with no gender differences (44% female). Mean baseline HADS scores were 10.6±6.9 (total), 4.8±3.2 (depression), and 5.3±3.6 (anxiety). Clinically significant HADS total, depression, and anxiety scores were observed in 32.2%, 21.8%, and 27.7% of patients, respectively. No significant differences in baseline HADS scores were observed between those who developed HFpEF and those who did not. ROC analysis indicated that HADS scores did not predict HFpEF or AF development. However, a significantly higher proportion of patients developing HFpEF had a history of AF at baseline (1.8% vs. 9.7%; p<0.05). At FU, 22.6% of HFpEF patients experienced AF compared to 5.3% without HFpEF (p=0.004). There was a substantially higher risk of developing HFpEF in patients with a baseline history of AF (odds ratio 10.2; confidence interval 2.7–38.8, p<0.01). At FU, HFpEF patients exhibited similar total HADS (p=0.21) and anxiety (p=0.82) but significantly higher depression scores (5.1±3.5 vs. 3.5±3.3, p=0.01), with a greater percentage showing clinically significant depression (19% vs. 11%). FU HADS depression scores correlated with worse NYHA class, reduced daily activity, lower quality of life (SF-12), older age, lower blood pressure, and worse right ventricular function (p<0.05 for all). HADS scores showed no difference in patients with and without AF. Conclusion Patients at risk for HFpEF experience mental health impairments comparable to those in the general population. Baseline mental health scores did not predict future HFpEF development; however, the onset of HFpEF was associated with increased depressive symptoms, correlating with worsening heart failure symptoms, reduced functional capacity, and impaired cardiac function. In contrast, AF did not further impact mental health but was significantly associated with an increased risk of developing HFpEF.