Association between prehospital arterial hypercapnia and mortality in acute heart failure: a retrospective cohort study.

BACKGROUND: Acute Heart Failure (AHF) is a potentially lethal pathology and is often encountered in the prehospital setting. Although an association between prehospital arterial hypercapnia in AHF patients and admission in high-dependency and intensive care units has been previously described, there is little data to support an association between prehospital arterial hypercapnia and mortality in this population. METHODS: This was a retrospective study based on electronically recorded prehospital medical files. All adult patients with AHF were included. Records lacking arterial blood gas data were excluded. Other exclusion criteria included the presence of a potentially confounding diagnosis, prehospital cardiac arrest, and inter-hospital transfers. Hypercapnia was defined as a PaCO2 higher than 6.0 kPa. The primary outcome was in-hospital mortality, and secondary outcomes were 7-day mortality and emergency room length of stay (ER LOS). Univariable and multivariable logistic regression models were used. RESULTS: We included 225 patients in the analysis. Prehospital hypercapnia was found in 132 (58.7%) patients. In-hospital mortality was higher in patients with hypercapnia (17.4% [23/132] versus 6.5% [6/93], p = 0.016), with a crude odds-ratio of 3.06 (95%CI 1.19-7.85). After adjustment for pre-specified covariates, the adjusted OR was 3.18 (95%CI 1.22-8.26). The overall 7-day mortality was also higher in hypercapnic patients (13.6% versus 5.5%, p = 0.044), and ER LOS was shorter in this population (5.6 h versus 7.1 h, p = 0.018). CONCLUSION: Prehospital hypercapnia is associated with an increase in in-hospital and 7-day mortality in patient with AHF.

Prehospital arterial hypercapnia in acute heart failure is associated with admission to acute care units and emergency room length of stay: a retrospective cohort study.

BACKGROUND: Acute Heart Failure (AHF) is a common condition that often presents with acute respiratory distress and requires urgent medical evaluation and treatment. Arterial hypercapnia is common in AHF and has been associated with a higher rate of intubation and non-invasive ventilation in the Emergency Room (ER), but its prognostic value has never been studied in the prehospital setting. METHODS: A retrospective study was performed on the charts of all patients taken care of by a physician-staffed prehospital mobile unit between June 2016 and September 2019 in Geneva. After approval by the ethics committee, charts were screened to identify all adult patients with a diagnosis of AHF in whom a prehospital arterial blood gas (ABG) sample was drawn. The main predictor was prehospital hypercapnia. The primary outcome was the admission rate in an acute care unit (ACU, composite of intensive care and high-dependency units). Secondary outcomes were ER length of stay (LOS), orientation from ER (intensive care unit, high-dependency unit, general ward, discharge home), intubation rate at 24 h, hospital LOS and hospital mortality. RESULTS: A total of 106 patients with a diagnosis of AHF were analysed. Hypercapnia was found in 61 (58%) patients and vital signs were more severely altered in this group. The overall ACU admission rate was 48%, with a statistically significant difference between hypercapnic and non-hypercapnic patients (59% vs 33%, p = 0.009). ER LOS was shorter in hypercapnic patients (5.4 h vs 8.9 h, p = 0.016). CONCLUSIONS: There is a significant association between prehospital arterial hypercapnia, acute care unit admission, and ER LOS in AHF patients.

Statin treatment is associated with reduction in serum levels of receptor activator of NF-κB ligand and neutrophil activation in patients with severe carotid stenosis.

Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN), RANKL/osteoprotegerin (OPG) ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content) as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice.

Pharmacological treatments targeting CXC chemokines and the associated neutrophil activation and recruitment into atherosclerotic plaques hold promise for treating cardiovascular disorders. Therefore, we investigated whether FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with anti-inflammatory properties that we recently found to reduce neutrophil recruitment into the ischaemic myocardium, would exert beneficial effects in a mouse atherosclerosis model. Atherosclerotic plaque formation was induced by carotid cast implantation in ApoE-/- mice that were fed with a Western-type diet. FK866 or vehicle were administrated intraperitoneally from week 8 until week 11 of the diet. Treatment with FK866 reduced neutrophil infiltration and MMP-9 content and increased collagen levels in atherosclerotic plaques compared to vehicle. No effect on other histological parameters, including intraplaque lipids or macrophages, was observed. These findings were associated with a reduction in both systemic and intraplaque CXCL1 levels in FK866-treated mice. In vitro, FK866 did not affect MMP-9 release by neutrophils, but it strongly reduced CXCL1 production by endothelial cells which, in the in vivo model, were identified as a main CXCL1 source at the plaque level. CXCL1 synthesis inhibition by FK866 appears to reflect interference with nuclear factor-κB signalling as shown by reduced p65 nuclear levels in endothelial cells pre-treated with FK866. In conclusion, pharmacological inhibition of NAMPT activity mitigates inflammation in atherosclerotic plaques by reducing CXCL1-mediated activities on neutrophils. These results support further assessments of NAMPT inhibitors for the potential prevention of plaque vulnerability.