Hypocapnia is an independent predictor of in-hospital mortality in acute heart failure.

AIMS: Acute heart failure (AHF) poses a major threat to hospitalized patients for its high mortality rate and serious complications. The aim of this study is to determine whether hypocapnia [defined as the partial pressure of arterial carbon dioxide (PaCO2 ) below 35 mmHg] on admission could be associated with in-hospital all-cause mortality in AHF. METHODS AND RESULTS: A total of 676 patients treated in the coronary care unit for AHF were retrospectively analysed, and the study endpoint was in-hospital all-cause mortality. The 1:1 propensity score matching (PSM) analysis, Kaplan-Meier curve, and Cox regression model were used to explore the association between hypocapnia and in-hospital all-cause mortality in AHF. Receiver operating characteristic (ROC) curve and Delong's test were used to assess the performance of hypocapnia in predicting in-hospital all-cause mortality in AHF. The study cohort included 464 (68.6%) males and 212 (31.4%) females, and the median age was 66 years (interquartile range 56-74 years). Ninety-eight (14.5%) patients died during hospitalization and presented more hypocapnia than survivors (76.5% vs. 45.5%, P < 0.001). A 1:1 PSM was performed between hypocapnic and non-hypocapnic patients, with 264 individuals in each of the two groups after matching. Compared with non-hypocapnic patients, in-hospital mortality was significantly higher in hypocapnic patients both before (22.2% vs. 6.8%, P < 0.001) and after (20.8% vs. 8.7%, P < 0.001) PSM. Kaplan-Meier curve showed a significantly higher probability of in-hospital death in patients with hypocapnia before and after PSM (both P < 0.001 for the log-rank test). Multivariate Cox regression analysis showed that hypocapnia was an independent predictor of AHF mortality both before [hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.23-3.98; P = 0.008] and after (HR 2.19; 95% CI 1.18-4.07; P = 0.013) PSM. Delong's test showed that the area under the ROC curve was improved after adding hypocapnia into the model (0.872, 95% CI 0.839-0.901 vs. 0.855, 95% CI 0.820-0.886, P = 0.028). PaCO2 was correlated with the estimated glomerular filtration rate (r = 0.20, P = 0.001), left ventricular ejection fraction (r = 0.13, P < 0.001), B-type natriuretic peptide (r = -0.28, P < 0.001), and lactate (r = -0.15, P < 0.001). Kaplan-Meier curve of PaCO2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO2 tertile was associated with increased risk of in-hospital mortality in AHF (all P < 0.05). CONCLUSIONS: Hypocapnia is an independent predictor of in-hospital mortality for AHF.

Sacubitril/Valsartan Alleviates Experimental Autoimmune Myocarditis by Inhibiting Th17 Cell Differentiation Independently of the NLRP3 Inflammasome Pathway.

Sacubitril/valsartan (Sac/Val) is a recently approved drug that is commonly used for treatment of heart failure. Several studies indicated that Sac/Val also regulated the secretion of inflammatory factors. However, the effect and mechanism of this drug modulation of inflammatory immune responses are uncertain. In this study, an experimental autoimmune myocarditis (EAM) mouse model was established by injection of α-myosin-heavy chain peptides. The effect of oral Sac/Val on EAM was evaluated by histological staining of heart tissues, measurements of cardiac troponin T and inflammatory markers (IL-6 and hsCRP). The effects of Sac/Val on NLRP3 inflammasome activation and Th1/Th17 cell differentiation were also determined. To further explore the signaling pathways, the expressions of cardiac soluble guanylyl cyclase (sGC) and NF-κB p65 were investigated. The results showed that Sac/Val downregulated the inflammatory response and attenuated the severity of EAM, but did not influence NLRP3 inflammasomes activation. Moreover, Sac/Val treatment inhibited cardiac Th17 cell differentiation, and this might be associated with sGC/NF-κB p65 signaling pathway. These findings indicate the potential use of Sac/Val for treatment of myocarditis.