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Background: Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts., Methods: Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers., Results: Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes., Conclusions: Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation., (© 2024. The Author(s).)

Background: Stress hyperglycemia is now more common in intensive care unit (ICU) patients and is strongly associated with poor prognosis. Whether this association exists in critically ill patients with cardiogenic shock (CS) is unknown. This study investigated the prognostic relationship of stress hyperglycemia on critically ill patients with CS., Methods: We included 393 critically ill patients with CS from the MIMIC IV database in this study and categorized the patients into four groups based on quartiles of Stress hyperglycemia ratio (SHR). We assessed the correlation between SHR and mortality using restricted cubic spline analysis and Cox proportional hazards models. The primary outcomes observed were ICU mortality and hospitalization mortality., Results: The mean age of the entire study population was 68 years, of which 30% were male (118 cases). There was no significant difference between the four groups in terms of age, gender, BMI, and vital signs (P>0.05). There was an increasing trend in the levels of lactate (lac), white blood cell count (WBC), glutamic oxaloacetic transaminase (AST), glucose and Hemoglobin A1C (HbA1c) from group Q1 to group Q2, with the greatest change in patients in group Q4 (P<0.05) and the patients in group Q4 had the highest use of mechanical ventilation, the longest duration of mechanical ventilation, ICU stay and hospital stay. After adjusting for confounders, SHR was found to be strongly associated with patient ICU mortality, showing a U-shaped relationship., Conclusion: In critically ill patients with CS, stress hyperglycemia assessed by SHR was significantly associated with patient ICU mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Zhou, Liu, Dong and Xu.)

Background: Stress-induced hyperglycemia (SIH) is associated with poor outcomes in cardiogenic shock (CS), and there have been inconsistent results among patients with or without diabetes mellitus (DM). The glycemic gap (GG) is derived by subtracting A1c-derived average glucose from blood glucose levels; it is a superior indicator of SIH. We aimed to explore the role of GG in the outcomes of patients with CS., Methods: Data on patients diagnosed with CS were extracted from the MIMIC-IV v2.0 database to investigate the relationship between GG and 30-day mortality (Number of absolute GG subjects = 359; Number of relative GG subjects = 357). CS patients from the Second Affiliated Hospital of Wenzhou Medical University were enrolled to explore the correlation between GG and lactic acid (Number of absolute GG subjects = 252; Number of relative GG subjects = 251). Multivariate analysis, propensity score-matched (PSM) analysis, inverse probability treatment weighting (IPTW), and Pearson correlation analysis were applied., Results: Absolute GG was associated with 30-day all-cause mortality in CS patients (HR adjusted : 1.779 95% CI: 1.137-2.783; HR PSM : 1.954 95% CI: 1.186-3.220; HR IPTW : 1.634 95% CI: 1.213-2.202). The higher the absolute GG level, the higher the lactic acid level (β adjusted : 1.448 95% CI: 0.474-2.423). A similar trend existed in relative GG (HR adjusted : 1.562 95% CI: 1.003-2.432; HR PSM : 1.790 95% CI: 1.127-2.845; HR IPTW : 1.740 95% CI: 1.287-2.352; β adjusted :1.294 95% CI: 0.369-2.219). Subgroup analysis showed that the relationship existed irrespective of DM. The area under the curve of GG combined with the Glasgow Coma Scale (GCS) for 30-day all-cause mortality was higher than that of GCS (absolute GG: 0.689 vs. 0.637; relative GG: 0.688 vs. 0.633). GG was positively related to the triglyceride-glucose index. Kaplan-Meier curves revealed that groups of higher GG with DM had the worst outcomes. The outcomes differed among races and GG levels (all P < 0.05)., Conclusions: Among patients with CS, absolute and relative GGs were associated with increased 30-day all-cause mortality, regardless of DM. The relationship was stable after multivariate Cox regression analysis, PSM, and IPTW analysis. Furthermore, they reflect the severity of CS to some extent. Hyperlactatemia and insulin resistance may underlie the relationship between stress-induced hyperglycemia and poor outcomes in CS patients. They both improve the predictive efficacy of the GCS., (© 2024. The Author(s).)

Aims: We sought to characterize circulating protein biomarkers associated with cardiogenic shock (CS) using highly multiplex proteomic profiling., Methods and Results: This analysis employed a cross-sectional case-control study design using a biorepository of patients admitted to a cardiac intensive care unit between 2017 and 2020. Cases were patients adjudicated to have CS, and controls were those presenting for cardiac critical care without shock, including subsets of patients with isolated hypotension or heart failure (HF). The Olink platform was used to analyse 359 biomarkers with Bonferroni correction. The analysis included 239 patients presenting for cardiac critical care (69 cases with CS, 170 non-shock controls). A total of 63 biomarkers (17.7%) were significantly associated with CS after Bonferroni correction compared with all controls. Of these, nine biomarkers remained significantly associated with CS when separately cross-validated in subsets of controls presenting with isolated hypotension and HF: cathepsin D, fibroblast growth factor (FGF)-21 and -23, growth differentiation factor (GDF)-15, insulin-like growth factor-binding protein-1, N-terminal pro-B-type natriuretic peptide, osteopontin, oncostatin-M-specific receptor subunit beta (OSMR), and soluble ST2 protein (sST2). Four biomarkers were identified as providing complementary information for CS diagnosis with development of a multi-marker model: sST2, FGF-23, CTSD, and GDF-15., Conclusion: In this pilot study of targeted proteomic profiling in CS, we identified nine biomarkers significantly associated with CS when cross-validated against non-shock controls including those with HF or isolated hypotension, illustrating the potential application of a targeted proteomic approach to identify novel candidates that may support the diagnosis of CS., Competing Interests: Conflict of interest: S.M.P., D.A.M., A.B., K.K.B., E.A.B., and D.D.B. are members of the TIMI Study Group that receives institutional research grant support through Brigham and Women’s Hospital from: Abbott, Abiomed, Amgen, Anthos Therapeutics, AstraZeneca, Daiichi-Sankyo, Intarcia, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche Diagnostics, Siemens Healthcare Diagnostics, Inc., and Zora Biosciences. D.A.M. reports consulting fees from Abbott Laboratories, ARCA biopharma, InCarda, Inflammatix, Merck & Co., Novartis, and Roche Diagnostics. J.D., M.D., E.P.M., L.M., and B.O.O are employees and shareholders of Regeneron Pharmaceuticals, Inc. A.S.V. reports consulting fees from Broadview Ventures. E.A.B. reports consulting fees from Novo Nordisk, Esperion, PriMed, Medscape, Amgen, and Servier, and participation on clinical endpoint committees for studies sponsored by Kowa Pharmaceuticals. D.D.B. reports consulting fees from AstraZeneca, Mobility Bio, Inc., and Youngene Therapeutics, honoraria from the Medical Education Speakers Network (MESN) and USV Private Limited, and participation on clinical endpoint committees for studies sponsored by Beckman Coulter, Kowa Pharmaceuticals, and Tosoh Biosciences. The remaining co-authors report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients., Methods: STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes., Results: Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003)., Conclusions: Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

In-hospital mortality associated with cardiogenic shock (CS) remains high despite the use of percutaneous assist devices. We sought to determine whether support with VA-ECMO or Impella in patients with CS alters specific components of the plasma proteome. Plasma samples were collected before device implantation and 72 h after initiation of support in 11 CS patients receiving ECMO or Impella. SOMAscan was used to detect 1305 circulating proteins. Sixty-seven proteins were changed after ECMO (18 upregulated and 49 downregulated, p < 0.05), 38 after Impella (10 upregulated and 28 downregulated, p < 0.05), and only eight proteins were commonly affected. Despite minimal protein overlap, both devices were associated with markers of reduced inflammation and increased apoptosis of inflammatory cells. In summary, ECMO and Impella are associated with reduced expression of inflammatory markers and increased markers of inflammatory cell death. These circulating proteins may serve as novel targets of therapy or biomarkers to tailor AMCS use., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Acute heart failure (AHF) can result in worsening of heart failure (WHF), cardiogenic shock (CS), or death. Risk factors for these adverse outcomes are not well characterized. This study aimed to identify predictors for WHF or new-onset CS in patients hospitalized for AHF., Methods and Results: Prospective cohort study enrolling consecutive patients with AHF admitted to a large tertiary care centre with follow-up until death or discharge. WHF was defined by the RELAX-AHF-2 criteria. CS was defined as SCAI stages B-E. Potential predictors were assessed by fitting logistic regression models adjusted for age and sex. N = 233 patients were enrolled, median age was 78 years, and 80 were women (35.9%). Ischaemic cardiomyopathy was present in 82 patients (40.8%). Overall, 96 (44.2%) developed WHF and 18 (9.7%) CS. In-hospital death (8/223, 3.6%) was related to both events (WHF: OR 6.64, 95% CI 1.21-36.55, P = 0.03; CS: OR 38.27, 95% CI 6.32-231.81, P < 0.001). Chronic kidney disease (OR 2.20, 95% CI 1.25-3.93, P = 0.007), logarithmized serum creatinine (OR 2.90, 95% CI 1.51-5.82, P = 0.002), cystatin c (OR 1.86, 95% CI 1.27-2.77, P = 0.002), tricuspid valve regurgitation (OR 2.08, 95% CI 1.11-3.94, P = 0.023) and logarithmized pro-adrenomedullin (OR 3.01, 95% CI 1.75-5.38, P < 0.001) were significant predictors of WHF. Chronic kidney disease (OR 3.17, 95% CI 1.16-9.58, P = 0.03), cystatin c (OR 1.88, 95% CI 1.00-3.53, P = 0.045), logarithmized pro-adrenomedullin (OR 2.90, 95% CI 1.19-7.19, P = 0.019), and tricuspid valve regurgitation (OR 10.44, 95% CI 2.61-70.00, P = 0.003) were significantly with new-onset CS., Conclusions: Half of patients admitted with AHF experience WHF or new-onset CS. Chronic kidney disease, tricuspid valve regurgitation, and elevated pro-adrenomedullin concentrations predict these events. They could potentially serve as early warning signs for further deterioration in AHF patients., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes. In this study, we aimed to investigate the capacity of GLP-1 to predict outcome in patients with cardiogenic shock (CS) complicating myocardial infarction., Methods: Circulating GLP-1 levels were serially assessed in 172 individuals during index PCI and day 2 in a prospectively planned biomarker substudy of the IABP-SHOCK II trial. All-cause mortality at short- (30 days), intermediate- (1 year), and long-term (6 years) follow-up was used for outcome assessment., Results: Patients with fatal short-term outcome (n = 70) exhibited higher GLP-1 levels [86 (interquartile range 45-130) pM] at ICU admission in comparison to patients with 30-day survival [48 (interquartile range 33-78) pM; p < 0.001] (n = 102). Repeated measures ANOVA revealed a significant interaction of GLP-1 dynamics from baseline to day 2 between survivors and non-survivors (p = 0.04). GLP-1 levels above vs. below the median proved to be predictive for short- [hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.50-3.94; p < 0.001], intermediate- [HR 2.46; 95% CI 1.62-3.76; p < 0.001] and long-term [HR 2.12; 95% CI 1.44-3.11; p < 0.001] outcome by multivariate Cox-regression analysis., Conclusion: Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations., Trial Registration: www., Clinicaltrials: gov Identifier: NCT00491036., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Lactate and glucose are widely used biochemical parameters in current predictive risk scores for cardiogenic shock. Data regarding the relationship between lactate and glucose levels in cardiogenic shock are limited. Thus, we aimed to analyze glucose and lactate as early markers for in-hospital mortality in cardiogenic shock. In this retrospective cohort study, 312 patients presenting with cardiogenic shock to a tertiary-care hospital between 2016 and 2018 were included. Apparent cardiogenic shock was defined as hypoperfusion with hemodynamic compromise and biochemical marker increase due to diminished tissue perfusion, corresponding to SCAI shock stages. In-hospital mortality was assessed as the primary endpoint. The median age of the study population was 71 (60-79) years and the etiology of cardiogenic shock was acute myocardial infarction in 45.8%. Overall in-hospital mortality was 67.6%. In the receiver operating curve analysis, the area under the receiver-operating curve (AUC) for prediction of in-hospital mortality was higher for lactate (AUC: 0.757) than for glucose (AUC: 0.652). Both values were significantly associated with outcome (groups created with best cutoff values obtained from the Youden index). Correlation analysis showed a significant non-linear association of both values. In a multivariable stepwise Cox regression analysis, lactate remained an independent predictor for in-hospital mortality, whilst glucose, despite being implicated in energy metabolism, was not independently predictive for mortality. Together, these data suggest that lactate at admission is superior for mortality prediction in patients with apparent cardiogenic shock. Glucose was not independently predictive for mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Billig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Inflammatory processes are involved not only in coronary artery disease but also in heart failure (HF). Cardiogenic shock (CS) and septic shock are classically distinct although intricate relationships are frequent in daily practice. The impact of admission inflammation in patients with CS is largely unknown. FRENSHOCK is a prospective registry including 772 CS patients from 49 centers. One-month and one-year mortalities were analyzed according to the level of C-reactive protein (CRP) at admission, adjusted on independent predictive factors. Within 406 patients included, 72.7% were male, and the mean age was 67.4 y ± 14.7. Four groups were defined, depending on the quartiles of CRP at admission. Q1 with a CRP < 8 mg/L, Q2: CRP was 8-28 mg/L, Q3: CRP was > 28-69 mg/L, and Q4: CRP was > 69 mg/L. The four groups did not differ regarding main baseline characteristics. However, group Q4 received more often antibiotics in 47.5%, norepinephrine in 66.3%, and needed more frequently respiratory support and renal replacement therapy. Whether at 1 month (P trend  = 0.01) or 1 year (P trend  < 0.01), a strong significant trend towards increased all-cause mortality was observed across CRP quartiles. Specifically, compared to the Q1 group, Q4 patients demonstrated a 2.2-fold higher mortality rate at 1-month (95% CI 1.23-3.97, p < 0.01), which persisted at 1-year, with a 2.14-fold increase in events (95% CI 1.43-3.22, p < 0.01). Admission CRP level is a strong independent predictor of mortality at 1 month and 1-year in CS. Specific approaches need to be developed to identify accurately patients in whom inflammatory processes are excessive and harmful, paving the way for innovative approaches in patients admitted for CS.NCT02703038., (© 2024. The Author(s).)

Background: Early prognosis evaluation is crucial for decision-making in cardiogenic shock (CS) patients. Dynamic lactate assessment, for example, normalized lactate load, has been a better prognosis predictor than single lactate value in septic shock. Our objective was to investigate the correlation between normalized lactate load and in-hospital mortality in patients with CS., Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The calculation of lactate load involved the determination of the cumulative area under the lactate curve, while normalized lactate load was computed by dividing the lactate load by the corresponding period. Receiver Operating Characteristic (ROC) curves were constructed, and the evaluation of areas under the curves (AUC) for various parameters was performed using the DeLong test., Results: Our study involved a cohort of 1932 CS patients, with 687 individuals (36.1%) experiencing mortality during their hospitalization. The AUC for normalized lactate load demonstrated significant superiority compared to the first lactate (0.675 vs. 0.646, P < 0.001), maximum lactate (0.675 vs. 0.651, P < 0.001), and mean lactate (0.675 vs. 0.669, P = 0.003). Notably, the AUC for normalized lactate load showed comparability to that of the Sequential Organ Failure Assessment (SOFA) score (0.675 vs. 0.695, P = 0.175)., Conclusion: The normalized lactate load was an independently associated with the in-hospital mortality among CS patients., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the relationship between plasma soluble ST2 (sST2) levels 24 h after extracorporeal membrane oxygenation (ECMO) initiation and continuous renal replacement therapy (CRRT) in patients receiving venoarterial ECMO (V-A ECMO) support., Methods and Results: Data of patients who received ECMO support for postcardiotomy cardiogenic shock between January 2017 and July 2019 were retrospectively collected from Beijing Anzhen Hospital, Capital Medical University. Ultimately, 116 patients were included in the present study for analysis. The concentration of sST2 was determined by enzyme-linked immunosorbent assay (ELISA). The log 10 sST2 levels were higher in patients undergoing CRRT than those who did not (6.06 vs . 6.22, p = 0.019). Patients undergoing CRRT had a lower survival rate than those who did not (32.8% vs . 67.3%, p < 0.001). In the univariate logistic regression analysis, sST2, HCO 3 - , lactate, and creatinine levels 24 h after ECMO initiation were related to CRRT ( p < 0.05). In the multivariate logistic regression analysis, HCO 3 - and sST2 were identified as independent risk factors for CRRT use in patients undergoing ECMO ( p < 0.05). The area under receiver operator characteristic curve (AUC) for sST2 and HCO 3 - together was 0.72 (95% confidence interval (CI), 0.79-0.91), which was better than those of sST2 or HCO 3 - alone (0.63 vs . 0.67)., Conclusions: sST2 and HCO 3 - levels at 24 h after ECMO initiation were associated with CRRT and could predict CRRT use in postcardiotomy cardiogenic shock patients undergoing ECMO., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background:  Systemic inflammation due to cardiogenic shock is associated with vasoplegia leading to organ hypoperfusion, right heart failure, and poor clinical outcome. Extracorporeal cytokine hemoadsorption emerged to attenuate excessive levels of inflammatory cytokines, potentially improving patient outcomes. Nevertheless, its prognostic impact during high-risk left ventricular assist device (LVAD) implantation remains unknown., Methods:  In total, 40 consecutive patients with advanced heart failure underwent continuous-flow LVAD implantation at our institution between 2018 and 2020. Out of 25 high-risk patients in cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 and 2), 9 patients ( CytoSorb group ) underwent LVAD implantation with and 16 patients ( control group ) without simultaneous cytokine hemoadsorption during cardiopulmonary bypass. Besides preoperative patient characteristics, postoperative lactate clearance, vasopressor administration and mean arterial pressure, perioperative complication, and 30-day mortality rates were retrospectively analyzed., Results:  Apart from an increased rate of reoperations within the CytoSorb group, baseline characteristics including the severity of ventricular dysfunction and consecutive signs of end-organ failure were similar in both groups. Preoperative short-term mechanical circulatory support bridging was comparable (66.7 vs. 75%; p  = 0.66) prior to LVAD implantation. Procedural characteristics including intraoperative volume management and postoperative vasopressor administration were similar in both groups. There was no difference regarding postoperative lactate clearance, although postoperative mean arterial pressure was significantly higher in the control group (71.3 vs. 57.4 mm Hg; p  < 0.01). Furthermore, the 30-day mortality rate was significantly higher in the CytoSorb group (33.3 vs. 0.0%; p  = 0.01)., Conclusion:  Extracorporeal cytokine hemoadsorption during high-risk LVAD implantation was not associated with a decrease of postoperative vasopressor support, improved hemodynamics, or an accelerated lactate clearance., Competing Interests: A.M.B declared personal fees from Abbott, Abiomed, AstraZeneca, BerlinHeart, and Medtronic. H.R. declared travel grants from Abbott and Medtronic. Additionally, here are no further disclosures., (Thieme. All rights reserved.)

Background: Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI., Methods: Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis., Results: Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 × 109/L) (HR 1.815; 95%CI 1.134, 2.903; P = 0.013), low eosinophil (<0.3%) (HR 2.562; 95%CI 1.412, 4.648; P = 0.002) and low basophil (≤0.1%) (HR 1.694; 95%CI 1.106, 2.592; P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 × 109/L) (HR 1.894; 95%CI 1.285, 2.791; P = 0.001), low eosinophil (<0.3%) (HR 1.729; 95%CI 1.119, 2.670; P = 0.014) and low basophil (≤0.1%) (HR 1.560; 95%CI 1.101, 2.210; P = 0.012) were independently associated with increased risk of 30-day MACE., Conclusions: Leukocyte and its subtypes changed significantly in patients with CS complicating AMI. In addition to leukocyte, eosinophil and basophil also served as independent prognostic factors for 30-day outcomes. Moreover, as the composite of leukocyte and its subtypes increased the predictive power, thus leukocyte and its subtypes, especially eosinophil and basophil should be taken into consideration for the current risk stratification model., Competing Interests: The authors report no conflicts of interests., (Copyright © 2021 by the Shock Society.)

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53-0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35-0.59] and 0.54 [95%CI 0.42-0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13-9.76] for NLR, 1.0 [95%CI 0.998-1.002] for PLR and 1.02 [95%CI 0.99-1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose., (© 2022. The Author(s).)

Background: Acidosis and higher lactate predict worse outcomes in cardiogenic shock (CS) patients. We sought to determine whether overall acidosis severity on admission predicted in-hospital mortality in CS patients., Methods: This retrospective descriptive analysis included CS patients admitted to a single academic tertiary cardiac intensive care unit from 2007 to 2015. Admission arterial pH, base excess, and anion gap values were used to generate a Composite Acidosis Score (range 0-5, with a score ≥2 defining Severe Acidosis). Adjusted in-hospital mortality was analyzed using multivariable logistic regression., Results: We included 1,065 patients with median age of 68.9 (59.0, 77.2) years (36.4% females). Concomitant diagnoses included cardiac arrest in 38.1% and acute coronary syndrome in 59.1%. Severe Acidosis was present in 35.2%, and these patients had worse shock and more organ failure. In-hospital mortality occurred in 34.1% and was higher among patients with Severe Acidosis (54.9% vs. 22.4%, adjusted odds ratio [OR] 2.01, 95% CI 1.43-2.83, P < 0.001). Increasing Composite Acidosis Score was associated with higher in-hospital mortality (adjusted OR 1.25 per point, 95% CI 1.11-1.40, P < 0.001). Severe Acidosis was associated with higher hospital mortality at every level of shock severity and organ failure (all P < 0.05). Admission lactate level had equivalent discrimination for in-hospital mortality as the Composite Acidosis Score (0.69 vs. 0.66; P = 0.32 by De Long test)., Conclusion: Given its incremental association with higher in-hospital mortality among CS patients beyond shock severity and organ failure, we propose Severe Acidosis as a marker of hemometabolic shock. Lactate levels performed as well as a composite measure of acidosis for predicting mortality., Competing Interests: Disclosures: Dr Baran reports consulting for Getinge, Livanova, Abbott, Abiomed; serving on Steering committee for Procyrion and CareDx; and has been a speaker for Pfizer. None of the other authors has a financial disclosure or conflict of interest relevant to this research. The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: Acute myocardial infarction complicated by cardiogenic shock (AMICS) with or without out-of-hospital cardiac arrest (OHCA) have some pathophysiological differences and could potentially be considered as two individual clinical entities. Thus, there may also be differences in terms of blood borne biomarkers., Purpose: To explore potential differences in concentrations of the biomarkers lactate, mid-regional proadrenomedullin (MRproADM), Copeptin, pro-atrial natriuretic peptide (proANP), Syndecan-1, soluble thrombomodulin (sTM), soluble suppression of tumorigenicity 2 (sST2) and neutrophil gelatinase-associated lipocalin (NGAL), in patients with AMICS with or without OHCA., Method: Patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction were enrolled during a 1-year period. In the present study 86 patients with confirmed AMICS at admission were included., Results: In the adjusted analysis OHCA patients had higher levels of lactate (p = 0.008), NGAL (p = 0.03) and sTM (p = 0.011) while the level of sST2 was lower (p = 0.029). There was little difference in 30-day mortality between the OHCA and non-OHCA groups (OHCA 37% vs. non-OHCA 38%)., Conclusion: AMICS patients with or without OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels. These findings support that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities.

Background: Patients with cardiogenic shock or cardiac arrest undergoing venoarterial extracorporeal membrane oxygenation (V-A ECMO) frequently present with blood glucose levels out of normal range. The clinical relevance of such findings in the context of V-A ECMO is unknown. We therefore investigated the prognostic relevance of blood glucose at time of cannulation for V-A ECMO., Methods: We conducted a single-center retrospective registry study. All patients receiving V-A ECMO from October 2010 to January 2020 were included if blood glucose level at time of cannulation were documented. Patients were divided in five groups according to the initial blood glucose level ranging from hypoglycemic (< 80 mg/dl), normoglycemic (80-140 mg/dl), to mild (141-240 mg/dl), moderate (241-400 mg/dl), and severe (> 400 mg/dl) hyperglycemia, respectively. Clinical presentation, arterial blood gas analysis, and survival were compared between the groups., Results: 392 patients met inclusion criteria. Median age was 62 years (51.5-70.0), SAPS II at admission was 54 (43.5-63.0), and 108/392 (27.6%) were female. 131/392 were discharged alive (hospital survival 33.4%). At time of cannulation, survivors had higher pH, hemoglobin, calcium, bicarbonate but lower potassium and lactate levels compared to non-survivors (all p < 0.01). Outcome of patients diagnosed with particularly high (> 400 mg/dl) and low (< 80 mg/dl) blood glucose at time of V-A ECMO cannulation, respectively, was worse compared to patients with normoglycemic, mildly or moderately elevated values (p = 0.02). Glucose was independently associated with poor outcome after adjustment for other predictors of survival and persisted in all investigated subgroups., Conclusion: Arterial blood glucose at time of V-A ECMO cannulation predicts in-hospital survival of patients with cardiac shock or after ECPR. Whether dysglycemia represents a potential therapeutic target requires further evaluation in prospective studies., (© 2021. The Author(s).)

Abstract: In patients with ST-elevation myocardial infarction (STEMI) the immune system is activated with an inflammatory response to follow. In STEMI patients with a severe inflammatory response, risk of development of cardiogenic shock (CS) seems increased. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a glycoprotein released from mature neutrophils and plasma concentration may increase immediately after STEMI. We therefore aimed to assess whether admission NGAL plasma concentration in patients with STEMI was associated with CS development after leaving the catheterization laboratory (late CS) and 30-day all-cause mortality., Patients and Methods: From 1,892 consecutive patients with STEMI 1,626 (86%) had plasma NGAL concentration measured upon hospital admission before angiography throughout a 1-year period at two tertiary heart centers in Denmark. Patients were stratified according to NGAL quartiles (Q1-4). To assess late CS development, we adjusted for the Observatoire Régional Breton sur l'Infarctus risk score for late CS. For mortality assessment, we adjusted for gender, age, post-PCI culprit Thrombolysis in myocardial infarction flow, left ventricular ejection fraction (LVEF), kidney dysfunction, and being comatose after cardiac arrest., Results: Increasing NGAL concentration was associated with higher age, more comorbidities, and more critical patient conditions including lower blood pressure and LVEF. When adjusted for factors associated with poor outcome, NGAL remained independently associated with both late CS development (Q4 vs. Q1-3) (OR (95% CI) 3.64 (1.79-7.41) and 30-day mortality (HR (95% CI) 3.18 (1.73-5.84))., Conclusion: Admission plasma concentration of NGAL in STEMI patients is independently associated with 30-day all-cause mortality and predictive of late CS development., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: Although serum calcium has been proven to be a predictor of mortality in a wide range of diseases, its prognostic value in critically ill patients with cardiogenic shock (CS) remains unknown. This retrospective observational study is aimed at investigating the association of admission calcium with mortality among CS patients., Methods: Critically ill patients diagnosed with CS in the Medical Information Mart for Intensive Care-III (MIMIC-III) database were included in our study. The study endpoints included 30-day, 90-day, and 365-day all-cause mortalities. First, admission serum ionized calcium (iCa) and total calcium (tCa) levels were analyzed as continuous variables using restricted cubic spline Cox regression models to evaluate the possible nonlinear relationship between serum calcium and mortality. Second, patients with CS were assigned to four groups according to the quartiles (Q1-Q4) of serum iCa and tCa levels, respectively. In addition, multivariable Cox regression analyses were used to assess the independent association of the quartiles of iCa and tCa with clinical outcomes., Results: A total of 921 patients hospitalized with CS were enrolled in this study. A nonlinear relationship between serum calcium levels and 30-day mortality was observed (all P values for nonlinear trend < 0.001). Furthermore, multivariable Cox analysis showed that compared with the reference quartile (Q3: 1.11 ≤ iCa < 1.17 mmol/L), the lowest serum iCa level quartile (Q1: iCa < 1.04 mmol/L) was independently associated with an increased risk of 30-day mortality (Q1 vs. Q3: HR 1.35, 95% CI 1.00-1.83, P = 0.049), 90-day mortality (Q1 vs. Q3: HR 1.36, 95% CI 1.03-1.80, P = 0.030), and 365-day mortality (Q1 vs. Q3: HR 1.28, 95% CI 1.01-1.67, P = 0.046) in patients with CS., Conclusions: Lower serum iCa levels on admission were potential predictors of an increased risk of mortality in critically ill patients with CS., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Yue Yu et al.)

Optimal management of cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO) is still an evolving area in which assessment and optimization of the microcirculation may be critically important. We hypothesized that the venous arterial carbon dioxide gap (P(v-a)CO2 gap); the ratio of this gap to arterio-venous oxygen content (P(v-a)CO2/C(a-v)O2 ratio) and the anion gap would be early indicators of microcirculatory status and useful parameters for outcome prediction during ECMO support. We retrospectively reviewed 31 cardiogenic shock patients requiring veno-arterial ECMO, calculating P(v-a)CO2 gap and P(v-a)CO2/C(a-v)O2 ratios in the first 36 hours and the final 24 hours of ECMO support. Sixteen patients (52%) survived and 15 (48%) died. After 24 hours of ECMO support, the P(v-a)CO2 gap (4.9 ± 1.5 vs. 6.8 ± 1.9 mm Hg; p = 0.004) and anion gap (5.2 ± 1.8 vs. 8.7 ± 2.7 mmol/L; p < 0.001) were significantly higher in non-survivors. In the final 24 hours of ECMO support, the P(v-a)CO2 gap (3.5 ± 1.6 vs. 10.5 ± 3.2 mm Hg; p < 0.001), P(v-a)CO2/C(a-v)O2 ratio (1.1 ± 0.5 vs. 2.7 ± 1.0; p < 0.001), anion gap (5.1 ± 3.0 vs. 9.3 ± 5.9 mmol/L; p = 0.02), and lactate (median 1.0 [interquartile range {IQR}: 0.7-1.5] vs. 2.8 [IQR: 1.7-7.7] mmol/L; p = <0.001) were all significantly lower in survivors. Increasing P(v-a)CO2 gap and increasing anion gap were significantly associated with increased risk of mortality. Optimum cut-points for prediction of mortality were 6 mm Hg for P(v-a)CO2 gap in combination with an anion gap above 6 mmol/L in the first 24 hours of ECMO in patients with cardiogenic shock requiring ECMO., Competing Interests: Disclosure: D.B. reports relationships with ALung Technologies, Baxter, BREETHE, and Hemovent. M.S. reports having received lectures fees from Gettinge, Dräger, and Xenios. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © ASAIO 2020.)

There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID-19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID-19 patients, 10 critically ill non-COVID-19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID-19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short-term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610-616., (© 2020 American Neurological Association.)

Background: Critically ill patients with cardiogenic shock could benefit from ventricular assist device support using the Impella microaxial blood pump. However, recent studies suggested Impella not to improve outcomes. We, therefore, evaluated outcomes and predictors in a real-world scenario., Methods: In this retrospective single-center trial, 125 patients suffering from cardiac arrest/cardiogenic shock between 2008 and 2018 were analyzed. 93 Patients had a prior successful cardiopulmonary resuscitation. The primary endpoint was hospital mortality. Associations of covariates with the primary endpoint were assessed by univariable and multivariable logistic regression. Adjusted odds ratios (aOR) and optimal cut-offs (using Youden index) were obtained., Results: Hospital mortality was high (81%). Baseline lactate was 4.7mmol/L [IQR = 7.1mmol/L]. In multivariable logistic regression, only age (aOR 1.13 95%CI 1.06-1.20; p<0.001) and lactate (aOR 1.23 95%CI 1.004-1.516; p = 0.046) were associated with hospital mortality, and the respective optimal cut-offs were >3.3mmol/L and age >66 years. Patients were retrospectively stratified into three risk groups: Patients aged ≤66 years and lactate ≤3.3mmol (low-risk; n = 22); patients aged >66 years or lactate >3.3mmol/L (medium-risk; n = 52); and patients both aged >66 years and lactate >3.3mmol/L (high-risk, n = 51). Risk of death increased from 41% in the low-risk group, to 79% in the medium risk group and 100% in the high-risk group. The predictive abilities of this model were high (AUC 0.84; 95% 0.77-0.92)., Conclusion: Mortality was high in this real-world collective of severely ill cardiogenic shock patients. Better patient selection is warranted to avoid unethical use of Impella. Age and lactate might help to improve patient selection., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous studies have defined preshock as isolated hypotension or isolated hypoperfusion, whereas shock has been variably defined as hypoperfusion with or without hypotension. We aimed to evaluate the mortality risk associated with hypotension and hypoperfusion at the time of admission in a cardiac intensive care unit population., Methods: We analyzed Mayo Clinic cardiac intensive care unit patients admitted between 2007 and 2015. Hypotension was defined as systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg, and hypoperfusion as admission lactate >2 mmol/L, oliguria, or rising creatinine. Associations between hypotension and hypoperfusion with hospital mortality were estimated using multivariable logistic regression., Results: Among 10 004 patients with a median age of 69 years, 43.1% had acute coronary syndrome, and 46.1% had heart failure. Isolated hypotension was present in 16.7%, isolated hypoperfusion in 15.3%, and 8.7% had both hypotension and hypoperfusion. Stepwise increases in hospital mortality were observed with hypotension and hypoperfusion compared with neither hypotension nor hypoperfusion (3.3%; all P <0.001): isolated hypotension, 9.3% (adjusted odds ratio, 1.7 [95% CI, 1.4-2.2]); isolated hypoperfusion, 17.2% (adjusted odds ratio, 2.3 [95% CI, 1.9-3.0]); both hypotension and hypoperfusion, 33.8% (adjusted odds ratio, 2.8 [95% CI, 2.1-3.6]). Adjusted hospital mortality in patients with isolated hypoperfusion was higher than in patients with isolated hypotension ( P =0.02) and not significant different from patients with both hypotension and hypoperfusion ( P =0.18)., Conclusions: Hypotension and hypoperfusion are both associated with increased mortality in cardiac intensive care unit patients. Hospital mortality is higher with isolated hypoperfusion or concomitant hypotension and hypoperfusion (classic shock). We contend that preshock should refer to isolated hypotension without hypoperfusion, while patients with hypoperfusion can be considered to have shock, irrespective of blood pressure.

Aim: Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity, and cardiogenic shock (CS) a major cause of hospital mortality after AMI. Especially for ST elevation myocardial infarction (STEMI) patients, fast intervention is essential.Few proteins have proven clinically applicable for AMI. Most proposed biomarkers are based on a priori hypothesis-driven studies of single proteins, not enabling identification of novel candidates. For clinical use, the ability to predict AMI is important; however, studies of proteins in prediction models are surprisingly scarce.Consequently, we applied proteome data for identifying proteins associated with definitive STEMI, CS, and all-cause mortality after admission, and examined the ability of the proteins to predict these outcomes., Methods and Results: Proteome-wide data of 497 patients with suspected STEMI were investigated; 381 patients were diagnosed with STEMI, 35 with CS, and 51 died during the first year. Data analysis was conducted by logistic and Cox regression modeling for association analysis, and by multivariable LASSO regression models for prediction modeling.Association studies identified 4 and 29 proteins associated with definitive STEMI or mortality, respectively. Prediction models for CS and mortality (holding two and five proteins, respectively) improved the prediction ability as compared with protein-free prediction models; AUC of 0.92 and 0.89, respectively., Conclusion: The association analyses propose individual proteins as putative protein biomarkers for definitive STEMI and survival after suspected STEMI, while the prediction models put forward sets of proteins with putative predicting ability of CS and survival. These proteins may be verified as biomarkers of potential clinical relevance., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Takotsubo cardiomyopathy (TTC) is characterized by reversible ventricular dysfunction induced by endogenous and, occasionally, exogenous catecholamine. We present a report on a patient who developed TTC and cardiogenic shock during percutaneous coronary intervention (PCI) secondary to inadvertent norepinephrine administration. His hemodynamic status and cardiac function were totally restored within 1 week after hemodynamic support using intra-aortic balloon pump without sequela. Thus, TTC should be considered once a patient presents with symptoms mimicking acute coronary syndrome (ACS) after catecholamine administration.

Background: To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP ® ., Methods: Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality., Results: VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67-0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality., Conclusions: Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.

Introduction: Cardiogenic shock is difficult to diagnose due to diverse presentations, overlap with other shock states (i.e. sepsis), poorly understood pathophysiology, complex and multifactorial causes, and varied hemodynamic parameters. Despite advances in interventions, mortality in patients with cardiogenic shock remains high. Emergency clinicians must be ready to recognize and start appropriate therapy for cardiogenic shock early., Objective: This review will discuss the clinical evaluation and diagnosis of cardiogenic shock in the emergency department with a focus on the emergency clinician., Discussion: The most common cause of cardiogenic shock is a myocardial infarction, though many causes exist. It is classically diagnosed by invasive hemodynamic measures, but the diagnosis can be made in the emergency department by clinical evaluation, diagnostic studies, and ultrasound. Early recognition and stabilization improve morbidity and mortality. This review will focus on identification of cardiogenic shock through clinical examination, laboratory studies, and point-of-care ultrasound., Conclusions: The emergency clinician should use the clinical examination, laboratory studies, electrocardiogram, and point-of-care ultrasound to aid in the identification of cardiogenic shock. Cardiogenic shock has the potential for significant morbidity and mortality if not recognized early., Competing Interests: Declaration of Competing Interest NONE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Impella devices offer temporary mechanical circulatory support for cardiogenic shock. The manufacturer recommends systemic anticoagulation with a target activated clotting time of 160 to 180 s but provides no guidance on how to manage both the heparinized purge solution and the additional intravenous heparin needed to reach this therapeutic range. Previous publications demonstrated a lack of standardization in heparin management for Impella devices., Objective: The purpose of this study was to compare the effectiveness and safety of 2 different heparin protocols for long-term Impella support., Methods: This single-center, retrospective study included adult patients on Impella support for greater than 24 hours. The primary end point was time to therapeutic range measured in hours, from time of implantation to the first of 2 consecutive measurements within the therapeutic range. Secondary end points included percentage of time in therapeutic range, rates of major bleeding, pump thrombosis, hemolysis, and nursing satisfaction., Results: There were 19 patients identified, with 7 using the original protocol and 12 using the revised protocol. Time to therapeutic range was similar between protocols (15.5 vs 12 hours, P = NS). Another 14 patients were managed with patient-specific protocols as a result of bleeding or physician preference. In total, 42% of all patients in this study experienced major bleeding. There were no confirmed thrombosis events. This study was limited by a small sample size., Conclusion and Relevance: Despite using different heparin protocols, outcomes and bleeding events were similar between groups. Future studies are needed to determine the optimal degree of anticoagulation necessary to reduce bleeding risk.

Background: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM., Methods: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint., Results: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients., Conclusions: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer ("shuttle") of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2020 David G. Levitt et al.)

Purpose: To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal - (Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI)., Methods: A total of 137 consecutive patients admitted with STEMI and CS at two tertiary heart centres were stratified according to the IABP-SHOCK II risk score (0-2; 3/4; 5-9), and had blood sampled upon admission., Results: Plasma concentrations of Copeptin (median (pmol/L) score 0-2: 313; score 3/4: 682; score 5-9: 632 p  < 0.0001), proANP (pmol/L) (1459; 2225; 2876 p  = 0.0009) and MRproADM (nmol/L) (0.86; 1.2; 1.4 p  = 0.04) were significantly associated with the risk score, whereas ST2 (ng/mL) was not (44; 60; 45 p  = 0.23). The IABP-SHOCK II risk score predicted 30-day mortality (score 0-2: 22%; score 4/3: 51%; score 5-9: 72%, area under the curve (AUC): 0.73, p logrank < 0.0001), while the tested biomarkers did not (AUC: 0.51< p logrank < 0.57)., Conclusion: Plasma concentrations of Copeptin, MRproADM and proANP were associated with the IABP-SHOCK II risk score in STEMI patients admitted with CS. The risk score predicted 30-day mortality, with no improvement in prediction when concentrations of the assessed biomarkers were added.

Background: Cardiogenic shock complicating ST-elevation myocardial infarction is characterised by progressive left ventricular dysfunction causing inflammation and neurohormonal activation. Often, cardiogenic shock develops after hospital admission. Whether inflammation and a neurohormonal activation precede development of clinical cardiogenic shock is unknown., Methods and Results: In 93% of 2247 consecutive patients with suspected ST-elevation myocardial infarction admitted at two tertiary heart centres, admission plasma levels of pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 were measured on hospital admission. Patients were stratified according to no cardiogenic shock development and cardiogenic shock developed before (early cardiogenic shock) or after (late cardiogenic shock) leaving the catheterization laboratory. In total, 225 (10%) patients developed cardiogenic shock, amongst these patients late cardiogenic shock occurred in 64 (2.9%). All four biomarkers were independently associated with the development of late cardiogenic shock (odds ratio per two-fold increase in risk: 1.19-3.13) even when adjusted for the recently developed Observatoire Régional Breton sur l'Infarctus risk score for prediction of late cardiogenic shock development. Furthermore, pro-atrial natriuretic peptide, copeptin and mid-regional pro-adrenomedullin, but not stimulation-2, added significant predictive information, when added to the Observatoire Régional Breton sur l'Infarctus risk score (area under the receiver-operating characteristic curve, pro-atrial natriuretic peptide: 0.87, p =0.0008; copeptin: 0.86, p <0.05; mid-regional pro-adrenomedullin: 0.88, p =0.006)., Conclusions: Pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 admission plasma concentration were associated with late cardiogenic shock development in patients admitted with suspected ST-elevation myocardial infarction. Pro-atrial natriuretic peptide, mid-regional pro-adrenomedullin and copeptin had independent predictive value for late cardiogenic shock development.

There are limited data regarding the association between brain natriuretic peptide (BNP) levels obtained after weaning from extracorporeal membrane oxygenation (ECMO) and the outcomes of patients with acute coronary syndrome (ACS)-associated cardiogenic shock.We prospectively obtained data regarding patients (aged ≥ 19 years) with ACS-associated cardiogenic shock who received ECMO and were subsequently weaned off the treatment. BNP levels were collected at 5 time points: pre-ECMO implantation, post-ECMO implantation, pre-ECMO weaning, day 1 after ECMO weaning, and day 5 after ECMO weaning.Of 48 patients with ACS-related cardiogenic shock, 33 were included in this analysis. Mean patient age was 59.0 (50.0-66.5) years, and 5 patients (15.2%) were women. Eight patients had asystole/pulseless electrical activity before ECMO and 14 (42.4%) had 3-vessel disease on coronary angiography. During the 6-month follow up, 12 (36.4%) patients died. BNP levels after ECMO weaning were significantly different between 6-month survivors and non-survivors. Cox proportional hazards model revealed that BNP levels (tertiles) on days 1 and 5 after ECMO weaning were significantly associated with 6-month mortality (hazard ratio, 7.872; 95% confidence interval, 1.870-32.756; 8.658 and 1.904-39.365, respectively). According to the Kaplan-Meier curves, the first tertile had significantly longer survival compared to the third tertile for both days 1 and 5 after ECMO weaning.Post-ECMO weaning BNP levels (days 1 and 5) were significantly associated with increased 6-month mortality in patients with ACS complicated by refractory cardiogenic shock who were weaned off ECMO.

Although measurements of natriuretic peptides have a role in chronic heart failure and acute coronary syndrome, their role has not been studied in ST-elevation myocardial infarction complicated by cardiogenic shock (CS-STEMI). Sixty-four patients with CS-STEMI were prospectively recruited to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement after 24 h of the onset of angina or anginal equivalent. Patients who died within 24 h were excluded. The mean age was 56.9 ± 10.6 years and the median time to presentation was 22 h (Interquartile range 7-48 h). Thrombolysis was done in 51% and PCI in 31% of cases. The in-hospital mortality was 26.5%. The ROC analysis showed a strong relationship between elevated NT-proBNP and in-hospital mortality (AUC = 0.748; p = 0.003). An NT-proBNP value > 8582 pg/mL showed 76.5% sensitivity, 68% specificity, 46.4% positive predictive value, and 89% negative predictive value for in-hospital mortality. Acute kidney injury [Odds ratio (OR) 7.30; 95% confidence interval (CI) 1.42-37.37] and NT-proBNP (OR 1.12 per 1000 pg/mL; CI 1.012-1.25) were independent predictors of mortality in multivariate regression analysis. Although we found plasma NT-proBNP at 24 h to be an independent predictor of in-hospital mortality in CS-STEMI, additional studies with a larger sample are required to ascertain these findings and validate the appropriate cut-off values., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Cardiological Society of India. All rights reserved.)

Background: Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcomes in patients with postoperative myocardial injury-related cardiogenic shock (MIRCS). We aimed to evaluate and validate HBP as a prognostic biomarker for postoperative MIRCS., Methods: We performed a case-control study in 792 patients undergoing cardiac surgery from January 1, 2016, to August 1, 2019, including 172 patients with postoperative MIRCS and 620 age- and sex-matched controls. The association between HBP and MIRCS was determined by multivariate logistic regression analysis. Receiver operating characteristic curves (ROCs) with area under the curve (AUC) were performed to calculate the cut-off value, sensitivity and specificity. The association between HBP and cardiac troponin T (cTnT) was determined by multivariable linear regression analysis. Blood samples were drawn from the coronary sinus and arterial line of the cardiopulmonary bypass (CPB) before aortic cross-clamping (time point 1) and 5 min after aortic declamping (time point 2)., Results: Before aortic cross-clamping, coronary sinus HBP (HBP CS1 ) showed no differences between the two groups. However, after declamping, the MIRCS group had a significantly higher sinus HBP level (HBP CS2 ) than did the control group. HBP CS2 predicted MIRCS with an AUC of 0.85 (95% CI: 0.81-0.89, cut-off: 220 ng/ml, sensitivity: 92% and specificity: 70%). After adjusting for confounding factors, we found that HBP was an independent risk factor for MIRCS (OR: 7.65, 95% CI: 4.86-12.06, P < 0.01) and was positively associated with cTnT (β > 0, P < 0.01)., Conclusions: Elevated levels of coronary sinus HBP were useful biomarkers for predicting MIRCS after cardiac surgery.

Background: Thirty-day mortality in ST-elevation myocardial infarction (STEMI) patients is primarily driven by cardiogenic shock (CS). High neutrophil counts and high neutrophil/lymphocyte ratios (NLR) have previously been associated with mortality in STEMI patients; however, there is only sparse knowledge regarding their association with CS., Purpose: We sought to assess the associations between neutrophil count and NLR with the development of CS as well as 30-day mortality in STEMI patients., Methods: Patients admitted with STEMI at two tertiary Heart Centres throughout 1 year were included in the study and stratified into quartiles according to the level of leukocyte count upon admission. The primary endpoint was development of CS both before (early CS) and after leaving the catheterization laboratory (late CS). The secondary endpoint was all-cause 30-day mortality., Results: A total of 1,892 STEMI patients were included, whereof 194 (10%) developed CS while 122 (6.4%) died within 30 days. Patients in the highest quartile of neutrophils (OR: 2.54; 95% CI: 1.40-4.60; P = 0.002) and NLR (OR: 3.64; 95% CI: 2.02-6.54; P<0.0001) were at increased risk of developing late CS compared with patients in the lower quartiles, whereas there was no risk difference across quartiles regarding development of early CS. Both biomarkers correlated strongly to an increased 30-day mortality (plogrank<0.0001) and, moreover, a high level of neutrophils was independently associated with 30-day mortality (HR: 1.95; 95% CI: 1.25-3.03; P = 0.003)., Conclusion: High levels of neutrophils and a high NLR upon admission for STEMI were independently associated with an increased risk of developing late CS and, additionally, both biomarkers showed association to 30-day mortality.

Aims: Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of cardiovascular mediators. Its administration has been shown to be associated with impaired cardiac contraction and kidney haemodynamics while its inhibition restored cardiac contraction in a pre-clinical model of severe heart failure in mice. Circulating DPP3 (cDPP3) was found to be elevated in shock. The present study aims to assess the association between cDPP3 and worsening haemodynamics, namely refractory shock, in a cohort of cardiogenic shock (CS)., Methods and Results: This is an ancillary study of OptimaCC, a prospective, double-blind, multicentre, randomized study assessing efficacy and safety of catecholamines in 57 patients with CS after acute myocardial infarction. cDPP3 was measured in plasma at inclusion, 24 h, 48 h, and 72 h, and haemodynamic and biological parameters were recorded at inclusion. cDPP3 values were higher in refractory CS than non-refractory CS at inclusion (median [interquartile range]; 76.1 [37.9-238.7] ng/mL vs. 32.8 [23.9-47.6] ng/mL, P = 0.014), at 24 h (P < 0.001) and up to 48 h (P = 0.027). Furthermore, cDPP3 at inclusion discriminated CS patients who did develop refractory shock vs. non-refractory with an area under the curve of 0.73 (95% confidence interval [CI] 0.55-0.92). The high cDPP3 group (cDPP3 ≥59.1 ng/mL) at inclusion had a higher Simplified Acute Physiology Score II (SAPS II), lower cardiac index and lower estimated glomerular filtration rate. More importantly, in CS patients with high cDPP3 at inclusion, those who rapidly decreased cDPP3 at 24 h exhibited a striking reduction in the occurrence of refractory shock and death., Conclusion: In CS patients, cDPP3 gives an early prediction of outcome, including development of refractory status and/or survival., Clinical Trial Registration: clinicaltrials.gov Identifier NCT01367743., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Background: Cardiogenic shock is a very serious postoperative complication in patients undergoing heart valve surgery. Mechanical circulatory support is a recognized method of treating patients with this complication. The aim of the presented study was to assess the usefulness of selected biomarkers in predicting the occurrence of postoperative cardiogenic shock requiring mechanical circulatory support., Methods: This prospective study was conducted on a group of 712 patients undergoing heart valve surgery. The primary end-point at the intrahospital follow-up was postoperative cardiogenic shock requiring mechanical circulatory support., Results: The postoperative cardiogenic shock requiring mechanical circulatory support occurred in 20 patients. At multivariate analysis high-sensitivity Troponin T measured immediately after surgery (OR 1.006; 95% CI 1.002-1.013; P 0.009) remained independent predictor of the primary end point., Conclusions: The postoperative hs-TnT can be used to predict a postoperative cardiogenic shock requiring mechanical circulatory support.

We report a 49-year-old man, without prior medical history, consulted in the emergency department with a 5 day history of cough, fever, and dysuria. He was admitted to the intensive care unit due to septic shock. Critical care management was initiated, including mechanical ventilation and vasopressors. Endotoxic shock was suspected (endotoxin activity assay [EAA] 0.75), and 2 treatments with Polymyxin B hemoperfusion (Toraymyxin®, Toray Medical Co., Ltd., Tokyo, Japan) were performed in 48 h, alternate with high-volume hemofiltration sessions. Initial blood cultures were positive for Neisseria meningitidis (serogroup B), and a lumbar puncture was deferred because of the coagulopathy and a bleeding risk. The circulatory efficiency significantly improved after the second procedure of hemoperfusion, and the treatment resulted in a marked decrease in the serum endotoxin level (EAA <0.4). However, after 48 h, tachycardia did not improve, left ventricular ejection fraction was 20%, and circulatory insufficiency progressed. Therefore, considering the involvement of septic cardiomyopathy and cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated for circulation assistance on day 3 from admission. Continuous cytokine hemoadsorption (Cytosorb®, Cytosorbent Corporation, Monmouth Junction, NJ, USA) was incorporated into a VA-ECMO circuit for 48 h without a considerable improvement. For this reason, a 72-h continuous veno-venous hemodialysis session was started in which a high cutoff filter was used. Tachycardia and myocardial dysfunction improved by day 6, and VA-ECMO was withdrawn on the tenth day. Subsequently, nutrition management and rehabilitation were performed, and the patient was transferred to the department of respiratory medicine on day 80, he was discharged from our hospital on day 113. Sequential extracorporeal therapy may be beneficial when concomitant with circulatory assistance in uncontrollable cases of septic shock using catecholamines and blockers., (© 2019 S. Karger AG, Basel.)

Background: Reperfusion strategies in acute myocardial infarction (AMI) may result in ischemia reperfusion injury characterized by increased oxidative stress, inflammation, and ultimately death of myocardial tissue which may be of particular importance in infarct-related cardiogenic shock (CS). Many anti-oxidative and immune regulatory processes depend on selenium which in large proportions is bound to circulating selenoprotein P (SelP). Individual SelP patterns may therefore be associated with inflammatory response and possibly mortality in patients with CS post AMI., Methods: In the randomized Intra-Aortic Balloon Pump in cardiogenic Shock II (IABP-SHOCK II)-trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. In a predefined biomarker substudy of 147 patients, we analyzed SelP levels 1 and 3 days following randomization. Samples were compared with healthy controls and associations with the unspecific inflammatory marker C-reactive protein (CRP) were analyzed., Results: Compared with controls SelP levels in patients with infarct-related CS were markedly higher (2.7-fold at day 1 and 5.7-fold at day 3 following AMI, all P < 0.001). Thirty-day mortality was significantly higher in patients with SelP levels above the 75th percentile at day 3 following AMI (26% vs. 46%, P = 0.045). SelP was significantly proportionally correlated with CRP 1 (R = 0.762, P < 0.0001) and 3 days (R = 0.777 P < 0.0001) following AMI., Conclusion: SelP levels are significantly increased post AMI with CS. Higher SelP levels are associated with increased CRP levels indicative for inflammatory processes. Future studies should focus on the characterization of SelP profiles following AMI and the identification of pathomechanisms affected by SelP.

Background: Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock., Methods: We performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock., Results: In both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend., Conclusions: This pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory shock, either in the presence of infection or not. We hypothesize that these genes could be potential targets of therapeutic interventions in CS and SS., Trial Registration: ClinicalTrials.gov, NCT02141607. Registered 19 May 2014.

Purpose: In contrast to arterial lactate, previous studies have proposed central venous-to-arterial CO2 difference (P (v-a)CO2) as a more useful guide for categorizing patients at risk of developing septic shock. It is worthwhile studying P (v-a)CO2 in determining whether it could serve as a useful predictor for poor postoperative outcomes in patients undergoing cardiac surgery. We investigated the ability of P(v-a)CO2 to predict poor outcomes of patients with postoperative cardiogenic shock., Methods: In total, 1,672 patients were enrolled in this study from January 1, 2014 to June 1, 2017. Of these patients, 143 exhibited complicated and poor outcomes. To address any bias, we derived a propensity score predicting the functions of P(v-a)CO2 on poor outcomes and matched 114 cases to 114 controls with a similar risk profile. In this cohort study, poor outcomes were defined as the occurrence of any adverse complications, including sudden death, cardiac arrest, extracorporeal membrane oxygenation, oliguria, and the administration of a large amount of vasoactive-inotropic drugs., Results: In propensity-matched patients, significant differences in P(v-a)CO2 (6.11 ± 2.94 mm Hg vs. 11.21 ± 5.22 mm Hg, P < 0.001) were noted between the control group and poor outcome group. The area under the receiver operating characteristic curve of P(v-a)CO2 (AUC: 0.837, 95% CI: 0.782-0.892) for the detection of poor outcomes was significantly better compared to that of the central venous oxygen saturation and arterial lactate. Additionally, there was a negative correlation between cardiac index and P(v-a)CO2 (R= -0.68, P < 0.001)., Conclusion: We have shown a correlation between P(v-a)CO2 to cardiac output which may be used as an alternative metric to predict the poor outcomes of patients with postoperative cardiogenic shock.

Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS)., Methods and Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-15 0h level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-15 12h cutoff >7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P = .002). Adding GDF-15 12h >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality., Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

BACKGROUND There is no previously published epidemiological study exploring the association between red blood cell distribution width (RDW) and mortality in patients with cardiogenic shock (CS). The aim of this study was to examine the association between RDW and the risk of all-cause mortality in these patients. MATERIAL AND METHODS We analyzed clinical data from the MIMIC-III V1.4 database. We collected data on each patient's demographic parameters, vital signs, laboratory parameters, vital signs, comorbidities, and scoring systems on ICU admission. Cox proportional hazards models were used to assess the association between RDW levels and the 30-day, 90-day, and 365-day mortality in patients with CS. RESULTS There were 1131 patients meeting inclusion criteria in our study. In multivariate analysis, following adjustment for age, sex, and ethnicity, higher RDW in tertiles and quintiles were all associated with increased risk of 30-day, 90-day, and 365-day all-cause mortality. Furthermore, after adjusting for more relevant confounders, RDW remained a significant predictor of risk of 30-day, 90-day, and 365-day mortality (tertile 3 versus tertile 1: HR, 95% CI: 1.66, 1.19-2.31; 1.73, 1.28-2.33; 1.80, 1.38-2.34). Similarly significant robust associations were found in RDW levels stratified by quintiles. CONCLUSIONS Higher RDW is associated with increased risk of all-cause mortality in critically ill patients with CS.