Prediction of rehospitalization in patients with acute heart failure using point-of-care lung ultrasound.

BACKGROUND: More than 50% of patients admitted for acute heart failure are discharged with residual pulmonary congestion. Residual pulmonary congestion at discharge is associated with rehospitalization and death within 6 months after discharge. B-lines detected by lung ultrasound are the sonographic manifestation of pulmonary congestion, a major predictor of morbidity and mortality in patients with heart failure. The present study was performed to evaluate the prognostic value of B-lines at discharge for prediction of rehospitalization and death at 6 months in patients with acute heart failure. METHODS: This study involved a prospective cohort of 126 patients admitted to Ramathibodi Hospital for acute heart failure (mean age, 69 ± 15 years). B-lines and the size of the inferior vena cava were assessed within 24 h before discharge. The patients were followed up for 6 months after discharge. RESULTS: The mean number of B-lines at discharge was 9 ± 9, and the rate of rehospitalization within 6 months was significantly higher in patients with a significant number of B-lines (≥ 12) than in patients with a non-significant number of B-lines (< 12) (log rank χ2 = 7.74, P = 0.004). In the univariable analysis, the presence of ≥ 12 B-lines before discharge (hazard ratio = 2.15, 95% confidence interval = 1.27-3.63) was an independent predictor of events at 6 months. CONCLUSIONS: Residual pulmonary congestion before discharge as detected by point-of-care lung ultrasound predicts rehospitalization for heart failure at 6 months. The presence of non-significant B-lines identifies a subgroup at low risk of rehospitalization for heart failure.

Carbohydrate response element-binding protein (ChREBP) plays a pivotal role in beta cell glucotoxicity.

AIMS/HYPOTHESIS: This study was aimed at the elucidation of the pathogenesis of glucotoxicity, i.e. the mechanism whereby hyperglycaemia damages pancreatic beta cells. The identification of pathways in the process may help identify targets for beta cell-protective therapy. Carbohydrate response element-binding protein (ChREBP), a transcription factor that regulates the expression of multiple hyperglycaemia-induced genes, is produced in abundance in pancreatic beta cells. We hypothesise that ChREBP plays a pivotal role in mediating beta cell glucotoxicity. METHODS: We assessed the role of ChREBP in glucotoxicity in 832/13 beta cells, isolated mouse islets and human pancreas tissue sections using multiple complementary approaches under control and high-glucose-challenge conditions as well as in adeno-associated virus-induced beta cell-specific overexpression of Chrebp (also known as Mlxipl) in mice. RESULTS: Under both in vitro and in vivo conditions, ChREBP activates downstream target genes, including fatty acid synthase and thioredoxin-interacting protein, leading to lipid accumulation, increased oxidative stress, reduced insulin gene transcription/secretion and enhanced caspase activity and apoptosis, processes that collectively define glucotoxicity. Immunoreactive ChREBP is enriched in the nucleuses of beta cells in pancreatic tissue sections from diabetic individuals compared with non-diabetic individuals. Finally, we demonstrate that induced beta cell-specific Chrebp overexpression is sufficient to phenocopy the glucotoxicity manifestations of hyperglycaemia in mice in vivo. CONCLUSIONS/INTERPRETATION: These data indicate that ChREBP is a key transcription factor that mediates many of the hyperglycaemia-induced activations in a gene expression programme that underlies beta cell glucotoxicity at the molecular, cellular and whole animal levels.