title: Prognostic value of circulating regulatory T cells for worsening heart failure in heart failure patients with reduced ejection fraction.
abstract: Regulatory T cells (Tregs) play a crucial role in the negative regulation of immune responses. Recent studies suggest that Tregs are involved in the pathogenesis of atherosclerosis and myocarditis. Here, we investigated the involvement of Tregs on worsening heart failure (HF) in patients with reduced ejection fraction (HF-REF). The study population consisted of 32 HF-REF patients who were hospitalized for worsening HF, and 18 control subjects. Cardiac function was evaluated by echocardiography. A single venous blood sample was collected before discharge. Circulating T cells were evaluated by flow cytometry. Tregs were defined as CD4(+)CD25(+)Foxp3(+)T cells, and the correlations between the frequency of Tregs and CRP, IL-6 and several echoparameters were analysed. Furthermore, all HF-REF patients were followed up to 12 months from discharge to examine the predictors of recurrent hospitalization.In HF-REF patients, Tregs were significantly decreased (5.9 ± 1.4 versus 8.0 ± 2.2%, P < 0.01), while CD4(+)HLADR(+)T cells were increased (10.1 ± 5.4 versus 7.3 ± 3.1%, P < 0.05), compared with controls. Tregs were negatively correlated with left ventricular end-diastolic dimension, and levels of CRP and IL-6. Eleven of 32 HF-REF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that CD4/CD8 and frequency of Tregs were independent predictors for recurrent hospitalization. Furthermore, HF-REF patients expressing under 6% Treg/CD4(+)T cells showed a significantly higher incidence of recurrent hospitalization for worsening HF within 12 months.Our data suggest that Tregs might be involved in the pathogenesis of decompensated HF, and may be a novel predictor of poor prognosis in HF-REF patients.
authors.affiliation: Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University.
authors.forename: Naoko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noma
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Wataru
authors.initials: W
authors.lastname: Takabatake
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Genji
authors.initials: G
authors.lastname: Yamaoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishizawa
authors.forename: Tsunetatsu
authors.initials: T
authors.lastname: Namba
authors.forename: Kazushi
authors.initials: K
authors.lastname: Murakami
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Iwado
authors.forename: Koji
authors.initials: K
authors.lastname: Ohmori
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
mesh_terms: D000368:Aged; D004452:Echocardiography; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D011379:Prognosis; D013318:Stroke Volume / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016277:Ventricular Function, Left