Predicting in-Hospital Mortality After an in-Hospital Cardiac Arrest: A Multivariate Analysis

Aim of the study: Most survivors of an in-hospital cardiac arrest do not leave the hospital alive, and there is a need for a more patient-centered, holistic approach to the assessment of prognosis after an arrest. We sought to identify pre-, peri-, and post-arrest variables associated with in-hospital mortality amongst survivors of an in-hospital cardiac arrest. Methods: This was a retrospective cohort study of patients ≥18 years of age who were resuscitated from an in-hospital arrest at our University Medical Center from January 1, 2013 to September 31, 2016. In-hospital mortality was chosen as a primary outcome and unfavorable discharge disposition (discharge disposition other than home or skilled nursing facility) as a secondary outcome. Results: 925 patients comprised the in-hospital arrest cohort with 305 patients failing to survive the arrest and a further 349 patients surviving the initial arrest but dying prior to hospital discharge, resulting in an overall survival of 29%. 620 patients with a ROSC of greater than 20 min following the in-hospital arrest were included in the final analysis. In a stepwise multivariable regression analysis, recurrent cardiac arrest, increasing age, time to ROSC, higher serum creatinine levels, and a history of cancer were predictors of in-hospital mortality. A history of hypertension was found to exert a protective effect on outcomes. In the regression model including serum lactate, increasing lactate levels were associated with lower odds of survival. Conclusion: Amongst survivors of in-hospital cardiac arrest, recurrent cardiac arrest was the strongest predictor of poor outcomes with age, time to ROSC, pre-existing malignancy, and serum creatinine levels linked with increased odds of in-hospital mortality

Neutrophil-derived S100A8/A9 amplify granulopoiesis following myocardial infarction

Myocardial infarction (MI) triggers myelopoiesis resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear. Using a mouse model of the permanent ligation of the left anterior descending (LAD) artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of acute inflammatory response and the underlying signaling pathways. Utilizing a combination of genetic and pharmacological strategies, we identified the sequalae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indices of neutrophilia with major adverse cardiovascular events (MACE) was studied in a cohort of acute MI patients. Induction of MI resulted in a rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll Like Receptor (TLR) 4 and prime the Nod Like Receptor (NLR) family Pyrin Domain-Containing 3 (Nlrp3) inflammasome in naïve neutrophils and promote interleukin 1 (IL-1β) secretion. The released IL-1β interact with its receptor (Interleukin 1 Receptor Type 1, IL1R1) on hematopoietic stem and progenitor cells in the bone marrow (BM), and stimulate granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and its downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome (ACS), higher neutrophil count on admission and post-revascularization correlates positively with major adverse cardiovascular disease (CVD) outcomes. Our study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response following myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or its downstream mediators (e.g. Nlrp3, IL-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in ACS patients