BACKGROUND: Long-term patterns of depressive symptoms among patients with heart failure, specifically those with a preserved ejection fraction (HFpEF), and their relationship with prognoses are not well studied. METHODS: This analysis included 609 participants from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) at baseline and at 1-year, 2-year and 3-year intervals. Individual trajectory patterns based on PHQ-9 scores during the first 3 years were identified using latent class trajectory models, and their associations with clinical outcomes were evaluated using Cox regression models. RESULTS: Among the 609 participants, 316 (51.9%) were female, with a median age of 74 years (IQR: 66, 80). Four distinct depression trajectory patterns were identified: low (consistently low scores
349, 57.3%), mild (sustained mild elevation
110, 18.1%), high (sustained moderate-severe elevation
52, 8.5%) and recurrent deterioration (high baseline scores, remission, then escalation
98, 16.1%). According to the multivariate Cox model, recurrent deterioration was associated with a significantly greater risk of all-cause mortality (HR: 2.05
95% CI 1.16, 3.64) than the low trajectory pattern. No significant differences were found among the low, mild and high trajectory groups. CONCLUSIONS: Four distinct depression trajectory patterns were identified among patients with HFpEF. Notably, patients who experienced a recurrent deterioration trajectory presented a significantly increased risk of all-cause mortality. Our findings highlight the importance of monitoring patients' depressive symptoms over time rather than focusing on a single timepoint. TRIAL REGISTRATION NUMBER: NCT00094302.