RESUMO
BACKGROUND: Although anxiety and depression have been associated with adverse outcomes in chronic heart failure (HF), data on temporal evolution of these symptoms are scarce. We aimed to investigate the association between repeatedly measured depression and anxiety symptoms and clinical outcome in chronic HF patients. METHODS: In this prospective observational study, outpatients with chronic HF were included and followed-up for a maximum of 2.5 years. The hospital anxiety and depression scale (HADS) questionnaire was conducted every six months. The primary endpoint was a composite of HF hospitalization, cardiovascular death, heart transplantation and left ventricular assist device (LVAD) implantation. Cox and joint models were used to investigate the association between the HADS score and the endpoint. RESULTS: A total of 362 patients filled out a median (25th-75th percentile) of 3 [2-4] questionnaires each. Mean ± SD age was 63 ± 13 years, 72% were men. Anxiety scores remained relatively stable leading up to the endpoint, while depression scores increased. Higher baseline depression scores were significantly associated with the endpoint (hazard ratio [HR] 1.68 and 95% confidence interval [CI] 1.19-2.36 per log(score+1), p = 0.003), while higher baseline anxiety scores did not reach statistical significance (HR [95% CI] 1.34 [0.99-1.83], p = 0.061). When repeatedly measured, both higher anxiety (HR [95% CI] 1.57[1.07-2.30], p = 0.022) and depression (HR [95% CI] 2.04 [1.39-3.06], p < 0.001) scores were significantly associated with the endpoint. CONCLUSION: Serial measurements of depression and anxiety symptoms identify chronic HF patients with increased risk of adverse clinical outcomes. Screening for both disorders should be considered in clinical practice.
RESUMO
BACKGROUND: Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology. OBJECTIVE: We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms. METHODS: In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e' ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes. RESULTS: We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40. CONCLUSION: Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.
