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Study Objective: We evaluate the diagnostic accuracy of a high-sensitivity cardiac troponin T (hs-cTnT) level less than 5 ng/L or less than or equal to 14 ng/L at emergency department (ED) presentation, combined with the emergency physician's assessment of history and ECG, for ruling out major adverse cardiac events within 30 days., Methods: This prospective observational study enrolled consecutive ED chest pain patients. Emergency physicians' assessments of patient history and ECG were collected. The primary outcome was 30-day major adverse cardiac events, defined as acute myocardial infarction, unstable angina, cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause., Results: A total of 1,138 patients were included in the final analysis. The combination of hs-cTnT less than 5 ng/L, a nonischemic ECG result, and a nonhigh risk history was present for 29.2% of all patients and had a sensitivity of 99.2% (95% confidence interval [CI] 95.6% to 100%), negative predictive value (NPV) of 99.7% (95% CI 98.3% to 100%), and a negative likelihood ratio of 0.02 (95% CI 0 to 0.17) for 30-day major adverse cardiac events. The same combination with hs-cTnT less than or equal to 14 ng/L was present in 66.7% of the patients and had a sensitivity of 92% (95% CI 85.8% to 96.1%), NPV of 98.7% (95% CI 97.6% to 99.4%), and negative likelihood ratio of 0.11 (95% CI 0.06 to 0.20)., Conclusion: A single hs-cTnT result of less than 5 ng/L at ED presentation when combined with a nonischemic ECG result and a nonhigh risk history identified 29% of chest pain patients at a very low risk of 30-day major adverse cardiac events. A similar strategy with hs-cTnT less than or equal to 14 ng/L was associated with a higher miss rate., (Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock after acute myocardial infarction is an indication for emergent coronary artery bypass grafting in patients not amenable to percutaneous coronary intervention. Our study aimed to evaluate and identify risk factors for early and long-term outcomes in such patients., Methods: A total of 508 patients who underwent coronary artery bypass grafting for cardiogenic shock complicating acute myocardial infarction between January 2000 and June 2014 were divided into 3 time cohorts: 2000 to 2004 (n=204), 2005 to 2009 (n=166), and 2010 to 2014 (n=138). Predictors of in-hospital mortality for each time cohort and long-term mortality for all patients were identified by logistic and Cox regression analyses, respectively., Results: Mean age was 68.3±9.8 years. Of the 508 patients, 78.5% had 3-vessel and 47.1% had left main disease. Left ventricular function <30% was observed in 44.1% of patients, with 30.4%, 37.9%, 52.9%, and 3.1% requiring preoperative resuscitation, ventilation, intra-aortic balloon pump, and extracorporeal membrane oxygenation support, respectively. Overall in-hospital mortality was 33.7%; declined from 42.2% to 30.7% to 24.6%, respectively, for the 3 time cohorts (P=0.02); and was independently predicted by serum lactate >4 mmol/L (odds ratio [OR], 4.78; 95% confidence interval, 2.88-7.95; P<0.0001), ST-segment-elevation myocardial infarction (OR, 2.10; 95% confidence interval, 1.36-3.26; P=0.001), age >75 years (OR, 2.01; 95% confidence interval, 1.06-3.85; P=0.03), and left ventricular ejection fraction <30% (OR, 1.83; 95% confidence interval, 1.15-2.91; P=0.01). Cumulative survival was 42.6±2.0% and 33.4±2.0% at 5 and 10 years, respectively, and correspondingly improved to 64.3±3.0% and 49.8±3.0% in hospital survivors. Serum lactate >4 mmol/L (OR, 2.2; P<0.0001), incremental age (OR, 1.05; P<0.0001), New York Heart Association class IV (OR, 1.33; P=0.02), diabetes mellitus (OR, 1.39; P=0.005), and preoperative inotropic (OR, 2.61; P=0.001) and extracorporeal membrane oxygenation (OR, 1.68; P=0.05) support predicted late mortality., Conclusions: Emergency coronary artery bypass grafting in patients with acute myocardial infarction complicated by cardiogenic shock is associated with a high in-hospital mortality, which showed a significant decline with time. Hospital survivors have good long-term outcomes, which demonstrate the beneficial effect of surgical revascularization. Preoperative serum lactate >4 mmol/L is a strong predictor of both early and late mortality., (© 2016 American Heart Association, Inc.)

Cardiogenic shock remains a highly lethal condition. Conventional therapy including revascularization and mechanical circulatory support aims to improve cardiac output and oxygen delivery, but increasing basic and clinical observations indicate wider circulatory and cellular abnormalities, particularly at the advanced stages of shock. Progressive cardiogenic shock is associated with microcirculatory and cellular abnormalities. Cardiogenic shock is initially characterized by a failure to maintain global oxygen delivery; however, progressive cardiogenic shock is associated with the release of pro-inflammatory cytokines, derangement of the regulation of regional blood flow, microcirculatory abnormalities, and cellular dysoxia. These abnormalities are analogous to septic shock and may not be reversed by increase in oxygen delivery, even to supranormal levels. Earlier mechanical circulatory support in cardiogenic shock may limit the development of microcirculatory and cellular abnormalities., (© 2016 Wiley Periodicals, Inc.)

Background: Massive pulmonary embolism (PE) is associated with significant mortality, especially if compounded by haemodynamic instability, right ventricular (RV) dysfunction and right atrial (RA) thrombus. Thrombolysis can be lifesaving in patients with major embolism and cardiogenic shock, and accelerates the resolution of thrombus. Only three fibrinolytic agents-namely streptokinase, urokinase, and recombinant tissue plasminogen activator (alteplase) have been approved in the treatment of PE, with studies demonstrating similar safety profiles., Case Presentation: We report the case of a 33-year-old Bangladeshi Bengali female with a history of recent ankle fracture and immobilization, who presented with massive PE, leading to cardiac arrest. Upon rapid resuscitation, urgent echocardiogram revealed RV dysfunction with floating RA thrombus, and she was successfully treated with 1.5 million IU of streptokinase over 2 h as per accelerated regimen recommended by the European Society of Cardiology guidelines, resulting in successful resolution of the right heart thrombus, and significant clinical improvement. Subsequent CT pulmonary angiogram confirmed the diagnosis of PE, and she was anticoagulated to a PT/INR of 2.0-3.0 for 3 months., Conclusions: Echocardiography is a suitable alternative for rapid diagnosis of acute massive PE associated with RA thrombus and cardiovascular collapse, especially when a delay to CT pulmonary angiogram may be anticipated, and in the setting of immediate cardio-pulmonary resuscitation. Thrombolysis is a rapid and life-saving therapeutic measure in such cases.

Background: Extracellular peroxiredoxin 1 (Prdx1) has been implicated to play a pivotal role in regulating inflammation; however, its function in tissue hypoxia-induced inflammation, such as severe cardiogenic shock patients, has not yet been defined. Thus, the objective of this study was to test the hypothesis that Prdx1 possesses prognostic value and instigates systemic inflammatory response syndrome in cardiogenic shock patients undergoing extracorporeal membrane oxygenation (ECMO) support., Methods: We documented the early time course evolution of circulatory Prdx1, hypoxic marker carbonic anhydrase IX, inflammatory cytokines including IL-6, IL-8, IL-10, MCP-1, TNF-α, IL-1β, and danger signaling receptors (TLR4 and CD14) in a cohort of cardiogenic shock patients within 1 day after ECMO support. In vitro investigations employing cultured murine macrophage cell lines and human monocytes were applied to clarify the relationship between Prdx1 and inflammatory response., Results: Prdx1 not only peaked earlier than all the other cytokines we studied during the initial course, but also predicted a worse outcome in patients who had higher initial Prdx1 plasma levels. The Prdx1 levels in patients positively correlated with hypoxic markers carbonic anhydrase IX and lactate, and inflammatory cytokines. In vitro study demonstrated that hypoxia/reoxygenation induced Prdx1 release from human monocytes and enhanced the responsiveness of the monocytes in Prdx1-induced cytokine secretions. Furthermore, functional inhibition by Prdx1 antibody implicated a crucial role of Prdx1 in hypoxia/reoxygenation-induced IL-6 secretion., Conclusions: Prdx1 release during the early phase of ECMO support in cardiogenic shock patients is associated with the development of systemic inflammatory response syndrome and poor clinical outcomes. Thus, circulating Prdx1 provides not only prognostic information but may be a promising target against ischemia/reperfusion injury.

Aims: Angiopoietin-2 (Ang-2) is a mediator of capillary leakage, and increased Ang-2 levels were associated with poor in-hospital outcome in a pilot study in cardiogenic shock (CS). In this larger study, we followed this hypothesis and aimed at assessing the predictive role of Ang-2 on short- and long-term mortality, investigating the effect of intra-aortic balloon pump (IABP) treatment on Ang-2 levels, and identifying clinical and procedural predictors of increased Ang-2., Methods and Results: In the IABP-SHOCK II-trial, 600 patients with CS complicating acute myocardial infarction were assigned to therapy with or without IABP. This substudy included 189 randomized patients with serial blood sampling performed at days 1, 2, and 3. No significant differences in Ang-2 levels were found between patients with or without IABP. The Ang-2 levels above the median at day 1 were associated with 30-day [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.26-3.10, P = 0.002) and 1-year mortality (HR 2.21, 95% CI 1.49-3.27, P < 0.001). Stratification of patients according to Ang-2 levels at day 3 increased these associations (30 days HR 5.15, 95% CI 2.80-9.45, P < 0.001; 1 year HR 5.24, 95% CI 3.19-8.58, P < 0.001). The Ang-2 concentrations were independent predictors for mortality in multivariate analysis (30 days HR 4.82, 95% CI 1.52-15.23, P = 0.007; 1 year HR 2.01, 95%CI 1.24-3.24, P = 0.005). Predictors of increased Ang-2 levels at day 3 were baseline Ang-2, development of acute kidney injury, bleeding events or transfusion, and impaired reperfusion., Conclusion: In CS, high levels of Ang-2 are independently associated with poor short- and long-term outcome and associated with the reperfusion success as well as complications., Clinical Trial Registration: URL: www.clinicaltrials.gov; unique identifier: NCT00491036., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Objectives: This study sought to evaluate the influence of intraaortic balloon pump (IABP) counterpulsation on the microcirculation in patients with cardiogenic shock (CS) complicating acute myocardial infarction., Background: In patients with shock profound alterations of the microcirculation have been observed and their clinical relevance has been described. Different treatment strategies exist to improve microvascular perfusion in patients with CS; however, the role of IABP treatment is not clearly defined., Methods: A predefined substudy of the randomized Intraaortic Balloon Pump in Cardiogenic Shock II trial (IABP-SHOCK II) investigated the sublingual microcirculation using a sidestream darkfield intravital microscope on days 1, 2 and 4 after the onset of shock. Perfused capillary (<20 µm, PCD) and vessel densities (<100 µm, PVD), total capillary (TCD) and vessel (TVD) densities were determined. In addition, the proportion of perfused vessels was assessed., Results: Forty-one patients were included in this substudy (n = 24 with IABP support vs. n = 17 without IABP support). No significant differences between treatment with or without IABP regarding PCD, PVD, TCD, TVD and the proportion of perfused vessels were evident on all three timepoints (p = n.s. for all). Microvascular perfusion showed inverse correlation with subsequent serum lactate levels (-0.366; p = 0.02) without being significantly correlated with lactate levels at the timepoint of the microcirculatory investigation. In Kaplan-Meier analysis microcirculatory parameters showed significant discrimination of prediction for time to death (p < 0.05 for all)., Conclusions: In patients with CS, there is no effect of IABP treatment on microvascular perfusion. Parameters of the microcirculation might be helpful to identify high risk patients.

Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES -403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES -403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES -403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.

Background: In cardiogenic shock (CS) renal dysfunction is an important parameter of inadequate end-organ perfusion and an independent predictor of adverse outcome. Early detection of renal dysfunction is therefore important, and novel biomarkers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM1) and Cystatin C (CysC) have been suggested. However, in high-risk CS patients their role for assessing renal injury has not yet been investigated in comparison to the most widely used serum creatinine., Methods: This predefined substudy included 190 patients of the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II)-trial. Blood samples were collected directly during primary percutaneous coronary intervention, one day and two days after randomization. The primary endpoint for outcome assessment was 1 year mortality., Results: Creatinine, NGAL and KIM-1 were significantly higher in non-survivors in comparison to survivors over time in ANOVA (p<0.001; p=0.002 and p=0.04, respectively). In contrast, CysC levels were not associated with the primary endpoint (p=0.15). Receiver operator characteristics revealed that creatinine at any time point had the best predictive value for 1 year mortality. This was also true when comparing creatinine to different equations for glomerular filtration rate. In multivariable Cox-regression analysis creatinine remained the only significant independent predictor of kidney biomarkers of time to death during the first year., Conclusions: Assessment of novel biomarkers such as CysC, NGAL and KIM-1 or calculation of glomerular filtration rate provide no additional prognostic information in patients with CS complicating acute myocardial infarction in comparison to creatinine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Severe acute heart failure requires immediate intensive care unit (ICU) treatment, but prognosis and outcome of further treatment regimens largely depends on the preprocedural status of the patient. Especially, multiorgan failure including mechanical ventilation are unfavorable predictors of clinical outcome. Here, we report a strategy of immediate initiation of extracorporeal life support (ECLS) in awake and spontaneously breathing patients with acute heart failure to achieve early multiorgan recovery and gain sufficient time for further treatment planning. Twenty-three patients with severe cardiac failure refractory to standard medical management underwent ECLS treatment, after first clinical signs of cardiac failure appeared to avoid mechanical ventilation. Hemodynamic parameters and renal and liver functions were monitored. Outcome at 1 and 6 months was determined. Patients 46.1 ± 15.5 years of age were placed on ECLS due to various underlying diagnosis: ischemic heart disease (n = 6), dilatative cardiomyopathy (n = 4), myocarditis (n = 2), graft failure following heart transplantation (n = 6), or other diseases (n = 5). ECLS lasted 11.9 ± 12.9 days. Hemodynamic stabilization was achieved immediately after ECLS initiation. Vasopressors were reduced subsequently and the cardiac situation improved indicated by central venous saturation, which increased from 38.5 ± 11.3% before to 74.26 ± 8.4% (P < 0.0001) 24 h after ECLS initiation. Similarly, serum lactate levels decreased from 4.7 ± 4.6 to 1.7 ± 1.51 mmol/L (P = 0.003). Cumulative 30-day survival was 87.5%, and 6-month survival was 70.8%. In acute cardiac failure, early ECLS treatment is a safe, feasible treatment in awake patients allowing a gain of time for final decision. Moreover, this strategy avoids complications associated with sedation and mechanical ventilation and leads to recovery of secondary organ function, enabling destination therapy., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: Extracorporeal membrane oxygenation (ECMO) is used to support postcardiotomy cardiogenic shock patients. Elevated serum lactate levels might reflect hypoxia in the tissues, which is associated with mortality in critically ill patients. This study examined the association between the early dynamic behavior of lactate and mortality after ECMO support., Methods: We included 123 adult patients who had undergone cardiac surgery and received venous-arterial ECMO implantation to treat refractory postcardiotomy cardiogenic shock. The dynamic behaviors of lactate within 6 hours and 12 hours after the beginning of the ECMO support were incorporated into 2 regression models., Results: A total of 56% of the patients were successfully weaned from ECMO support. The in-hospital mortality was 65.9% overall. Univariate and multivariate analyses indicated that age (odds ratio [OR]: 1.1 in the 6-hour model; 1.1 in the 12-hour model), gender (female; OR: 5.6 in the 6-hour model; 7.7 in the 12-hour model), mean lactate concentration (OR: 1.1 in the 6-hour model; 1.2 in the 12-hour model) and lactate clearance (OR: 0.5 in the 6-hour model; 0.1 in the 12-hour model) were reliable predictors (P < .05) of in-hospital mortality. The mean lactate concentration (C statistic: 0.71) and lactate clearance (C statistic: 0.72) 12 hours after the initiation of ECMO support provided better prognostic guidance. The mean lactate concentration (OR: 1.2) and lactate clearance (OR: 0.3) were able to predict successful weaning from ECMO in the 12-hour model only., Conclusions: In addition to age and gender (female), early lactate behaviors, particularly lactate clearance, after ECMO support are highly associated with in-hospital mortality in postcardiotomy patients. Additionally, early lactate behavior is also predictive of successful weaning from ECMO., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor., Methods: We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb > 50 mg/dL was used as a marker of severe hemolysis., Results: 154 patients received ECMO for cardiac (n = 115) or pulmonary (n = 39) indications. Patients' mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p = 0.026), lower 24-hour lactic acid (p = 0.023), shorter ECMO duration (P = 0.01), fewer RBC transfusions on ECMO (p = 0.008) and lower level of PFHb 24-hours post ECMO implantation (p = 0.029). 24-hour PFHb > 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p = 0.002. A Cox proportional hazard analysis identified PFHb > 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 - 8.8, p = 0.011)., Conclusion: PFHb > 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.

Objectives: Innate immune system alterations, including dendritic cell loss, have been reproducibly observed in patients with septic shock and correlated to adverse outcomes or nosocomial infections. The goal of this study is to better understand the mechanisms behind this observation in order to better assess septic shock pathogenesis., Design: Prospective, controlled experimental study., Setting: Research laboratory at an academic medical center., Subjects: The study enrolled 71 patients, 49 with septic shock and 22 with cardiogenic shock. Seventeen healthy controls served as reference. In vitro monocyte-derived dendritic cells were generated from healthy volunteers., Interventions: Sera were assessed for their ability to promote in vitro dendritic cell death through flow cytometry detection in each group of patients. The percentage of apoptotic or necrotic dendritic cells was evaluated by annexin-V and propidium iodide staining., Measurements and Main Results: We observed that only patients with septic shock and not patients with pure cardiogenic shock were characterized by a rapid and profound loss of circulating dendritic cells. In vitro analysis revealed that sera from patients with septic shock induced higher dendritic cell death compared to normal sera or cardiogenic shock (p<0.005). Sera from surviving patients induced dendritic cell death through a caspase-dependent apoptotic pathway, whereas sera from nonsurviving patients induced dendritic cell-regulated necrosis. Dendritic cell necrosis was not due to necroptosis but was dependent of the presence of circulating histone. The toxicity of histones toward dendritic cell could be prevented by recombinant human activated protein C. Finally, we observed a direct correlation between the levels of circulating histones in patients and the ability of the sera to promote dendritic cell-regulated necrosis., Conclusions: The study demonstrates a differential mechanism of dendritic cell death in patients with septic shock that is dependent on the severity of the disease.

The purpose of this analysis is to assess the effectiveness of heparin anticoagulation in cardiogenic shock patients with TandemHeart percutaneous ventricular assist device support for which the institution's TandemHeart heparin protocol was implemented compared to those managed without protocol. This retrospective analysis included 15 patients in the protocol group and 10 patients in the nonprotocol group. Patients in the protocol group had a higher percentage of therapeutic activated partial thromboplastin time (aPTT) and lower percentage of supra-therapeutic aPTT values compared to the nonprotocol group. We conclude that TandemHeart anticoagulation may be more effectively managed through the use of a protocol than without any protocol.

Purpose: A new hemoadsorption device intended as adjunctive treatment for patients with elevated cytokine levels in the setting of SIRS and sepsis has shown promising results. We report on the beneficial application of the device in a patient with cardiogenic septic shock receiving combined extracorporeal life support with rECMO, LVAD, and CVVH despite his highly septic condition., Methods: A 39-year-old patient presented with fulminant ARDS and cardiogenic septic shock. A veno-arterial ECMO was implanted for circulatory support. During the course of illness, the patient developed acute renal failure in addition to his chronic renal insufficiency, making initiation of CVVH necessary. Due to a complete cardiac arrest in both ventricles, a left ventricular assist device (LVAD) in combination with right ECMO (rECMO) was implanted despite manifest septic conditions. In the post-operative course IL-6 levels and vasopressor dosages increased drastically. A CytoSorb hemoadsorption device was therefore installed in the CVVH circuit and 3 sessions were run during the following 4 days., Results: During CytoSorb treatment, inflammatory markers IL-6, procalcitonin, and C-reactive protein decreased concomitant with significantly reduced vasopressor support. No adverse device-related side effects were documented during or after the treatment sessions., Conclusions: This is the first clinical case report of a highly septic patient treated with the combined use of LVAD, rECMO, CVVH, and CytoSorb. The combination was practical, technically feasible, and beneficial for the patient. This combination represents a reasonable approach to improve survival in patients with multiple organ dysfunction necessitating several organ supportive techniques.

Background: RotaFlow and Levitronix CentriMag veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated as treatment for refractory cardiogenic shock (CS)., Methods: Between 2004 and 2012, 119 consecutive adult patients were supported on RotaFlow (n = 104) or CentriMag (n = 15) ECMO at our institution (79 men; age 57.3 ± 12.5 years, range:19-78 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 47) and primary graft failure (n = 26); post-acute myocardial infarction CS (n = 11); acute myocarditis (n = 3); and CS on chronic heart failure (n = 32)., Results: A central ECMO setting was established in 64 (53.7%) patients while peripherally in 55 (46.2%). Overall mean support time was 10.9 ± 8.7 days (range:1-43 days). Forty-two (35.2%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n = 77), weaning from mechanical support (n = 51; 42.8%) and bridge to heart transplantation (n = 26; 21.8%), was 64.7%. Sixty-eight (57.1%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and CK-MB relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality (p = 0.011, odds ratio [OR] = 2.48; 95% confidence interval [CI] = 1.11-3.12; p = 0.012, OR = 2.81, 95% CI = 1.02-2.53; and p = 0.012, OR = 1.94; 95% CI = 1.02-5.21; respectively). Central ECMO population had a higher rate of continuous veno-venous hemofiltration (CVVH) need and bleeding events when compared with the peripheral setting., Conclusions: Patients with a poor hemodynamic status may benefit by rapid insertion of veno-arterial ECMO. The blood lactate level, CK-MB relative index and PRBCs transfused should be strictly monitored during ECMO support., (© 2014 Wiley Periodicals, Inc.)

Background: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock., Methods/design: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs., Discussion: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015., Trial Registration: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).

Introduction: Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (AMI). Biomarkers might help in risk stratification and understanding of pathophysiology. Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 (FGF-23), which acts as a negative regulator of serum phosphate levels. The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction., Methods: In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. Our predefined biomarker substudy included 182 patients. Blood sampling was performed in a standardized procedure at three different time points (day 1 (day of admission), day 2 and day 3). Differences in outcome of patients with FGF-23 levelsmedian were compared by log-rank testing. Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year., Results: At all three time points, nonsurvivors had significantly higher FGF-23 levels compared to survivors (P<0.001 for all). Patients with FGF-23 levels above the median (395 RU/mL [interquartile range 102;2,395]) were characterized by an increased 30-day mortality and 1-year mortality. In multivariable analysis FGF-23 levels remained independent predictors for 30-day (odds ratio per 10log 1.80, 95% confidence interval (CI) 1.11 to 2.92; P=0.02) and 1-year mortality (hazard ratio 1.50, 95% CI 1.11 to 2.04, P=0.009). After stratifying the patients according to their baseline serum creatinine levels, the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median., Conclusions: In CS, high levels of FGF-23 are independently related to a poor clinical outcome. However, this prognostic association appears only to apply in patients with impaired renal function., Trial Registration: ClinicalTrials.gov NCT00491036. Registered 22 June 2007.

There is limited clinical data comparing different P2Y12-receptor inhibitors in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. The aim of the ISAR-SHOCK registry was to compare the clinical outcome of patients treated with clopidogrel vs prasugrel in this setting. Patients (n=145) with AMI complicated by cardiogenic shock and undergoing primary PCI in two centres (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009 and May 2012 were included in this registry. The use of prasugrel for patients within this registry reflected co-morbidities and platelet function testing results during the acute AMI phase. Early outcome at 30-days was reported with regard to all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding events. With regard to antiplatelet treatment in the 145 cardiogenic shock patients, 50 patients were initially treated or immediately switched to prasugrel while 95 patients were treated with clopidogrel. All-cause mortality was lower in prasugrel- vs clopidogrel-treated patients (30 % vs 50.5%, HR: 0.51, 95% CI [0.29-0.92], p=0.025). No significant differences in prasugrel- vs clopidogrel-treated patients were observed for the occurrence of MI (p=0.233), ST (p=0.306) or TIMI major bleedings (p=0.571). Results of the ISAR-SHOCK registry suggest that the use of prasugrel in AMI patients complicated by cardiogenic shock might be associated with a lower mortality risk as compared to clopidogrel therapy without increasing the risk of bleeding. These findings, however, need confirmation from specifically designed randomised studies in this high-risk cohort of patients.

Background: The RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA) veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated as treatment for refractory cardiogenic shock., Methods: Between 2004 and 2012, 119 consecutive adult patients were supported on RotaFlow (n=104) or CentriMag (n=15) ECMO at our Institution (79 men; mean age 57.3 ± 12.5 years, range 19-78 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n=47) and primary graft failure (n=26); post-acute myocardial infarction cardiogenic shock (n=11); acute myocarditis (n=3), and cardiogenic shock on chronic heart failure (n=32)., Results: A central ECMO setting was established in 64 (53.7%) patients while peripherally in 55 (46.2%). Overall mean support time was 10.9 ± 8.7 days (range 1-43 days). Forty-two (35.2%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n=77), weaning from mechanical support (n=51; 42.8%) and bridge to heart transplantation (n=26; 21.8%), was 64.7%. Sixty-eight (57.1%) patients were successfully discharged. Stepwise logistic regression identified blood lactate levels and creatine kinase-MB relative index at 72h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality. Central ECMO population had a higher rate of continuous veno-venous hemofiltration need and bleeding events compared with the peripheral setting., Conclusions: ECMO support provides encouraging results in different subsets of patients in cardiogenic shock. Blood lactate levels, creatine kinase-MB relative index and PRBCs transfused should be strictly monitored during veno-arterial ECMO running. Type of ECMO implantation, if peripheral or central, should be decided according to the specific patient subset.

Objective: Although starvation is associated with high in-hospital mortality, its related cardiac complications are not sufficiently understood. The aim of this study was to determine the clinical course and pathogenesis of cardiac complications in malnourished patients., Methods: We reviewed three cases of hypoglycemia and hypotriglyceridemia with cardiac complications in starvation., Results: This report concerns three patients, respectively suffering from anorexia nervosa, esophageal carcinoma, and Parkinson's disease. Their ages ranged from 18 to 70 y, body mass index was 11.5 ± 1.5 kg/m2 (mean ± SD), and the main symptom was coma. The average blood glucose level was 15.7 ± 7.8 mg/dL without any history of insulin use or diabetes mellitus. In all cases, hypoglycemia was refractory and repetitive so that continuous glucose administration was required to maintain euglycemia. Serum triglyceride and non-esterified fatty acid levels were also very low (7 ± 4 mg/dL and 10 ± 9.1 μEq/L, respectively). Levels of serum potassium, phosphate, and magnesium were almost normal at admission. The main cardiac complications included Takotsubo cardiomyopathy and cardiac arrest. All patients survived as a result of intensive treatment., Conclusions: Repetitive severe hypoglycemia without known background causes should be viewed as an important sign. Once this occurs, the administration of a much higher caloric input than usual accompanied by intensive monitoring will be required to maintain appropriate glucose levels. The early identification of such patients seems to be essential to reduce the high risk for cardiac complications during starvation and refeeding., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post-cardiac arrest shock, early death, and long-term outcome., Methods and Results: Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12-month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3-hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification., Conclusions: KP is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock, early death, and poor long-term outcome., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Purpose: The relationship between near-infrared spectroscopy cerebral oximetry (CrSO2), peripheral oximetry (PrSO2) and hemodynamic variables is not fully understood., Methods: The relationship between CrSO2/PrSO2 and cardiac index (CI), systemic vascular resistance index (SVRI) and mean arterial pressure (MAP) in patients experiencing cardiogenic shock and those undergoing venoarterial extracorporeal membrane oxygenation (ECMO) was retrospectively analyzed; in patients on ECMO, total circulatory index (TCI) was calculated from the sum of CI and extracorporeal blood flow index., Results: In patients experiencing cardiogenic shock (n=10), significant correlations between PrSO2 values and CI (Spearman r=0.81; P<.0001), SVRI (r=-0.45; P<.0001), and MAP (r=0.58; P<.0001) were found. Significant correlations between CrSO2 and CI (r=0.55; P<.0001) and SVRI (r=-0.47; P<.0001), but not MAP, were observed. Linear regression analysis revealed that CI could be calculated using the following equation: CI=PrSO2/24.0. In patients on VA ECMO (n=12), significant correlations were found between PrSO2 and TCI (r=0.68; P<.0001), SVRI (r=-0.47; P<.0001), and MAP (r=0.27; P=.025). Significant correlations were also found between CrSO2 and TCI (r=0.68; P<.0001) and SVRI (r=-0.51; P<.0001), but not MAP., Conclusions: Results of the present study suggest that CrSO2 and PrSO2 in particular can be used for noninvasive estimation and monitoring of global circulatory status in patients experiencing cardiogenic shock and individuals undergoing ECMO., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Circulatory assist devices such as extracorporeal membrane oxygenation are indicated in cases of cardiogenic shock refractory to optimal conventional treatment. Bleeding is a serious complication of such systems, mainly due to coagulation disorders caused by continuous administration of heparin, as well as platelet dysfunction. Serial coagulation and hemoglobin (Hb) measurements are essential. Hb measurements can be performed through repeated arterial blood gasometry, and more recently with a new spectrophotometric sensor, Masimo Rainbow Radical-7® device, which gives Hb values continuously and non-invasively. We report a case of a patient undergoing cardiac surgery who required extracorporeal membrane oxygenation for severe cardiogenic shock immediately after surgery. We compare the correlation and the level of agreement with Hb levels measured by 2 existing systems in clinical practice. Our results indicate that the Masimo® spectrophotometric monitor showed statistically comparable Hb values, in the correlation (r=.85; P<.01) and in agreement with those obtained by serial blood gas analyzer, ABL800 FLEX® (wavelength). In view of these results we consider the Masimo® device as a valid alternative for the continuous follow-up of the Hb and control of bleeding in these patients., (Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Aims: This study investigates the role of osteoprotegerin (OPG) and growth-differentiation factor 15 (GDF-15) as predictors of outcome in cardiogenic shock (CS) complicating acute myocardial infarction. The novel biomarkers OPG and GDF-15 have shown prognostic impact in various cardiovascular diseases including myocardial infarction. In acute myocardial infarction complicated by CS, the diagnostic and prognostic impact of these biomarkers has not been investigated yet. OPG and GDF-15 may have additional prognostic impact on early prognosis assessment, being potentially useful for decision-making in CS., Methods and Results: In the randomized Intra-aortic Balloon Pump in cardiogenic Shock II (IABP-SHOCK II)-trial, 600 patients with CS complicating acute myocardial infarction undergoing early revascularization were assigned to therapy with or without IABP. Within a pre-defined substudy, blood samples were collected from 190 patients during PCI. GDF-15 and OPG serum levels were measured with standard enzyme-linked immunosorbent assay kits. Patients with GDF-15 and OPG levels greater than the median showed higher rates of death at 30 days by χ(2) testing (OPG, 51% vs. 32%, P = 0.01; GDF-15, 52% vs. 31%, P = 0.005) and log rank testing [GDF-15, hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.21-2.94; P = 0.005; OPG, HR 1.74, 95% CI 1.11-2.71; P = 0.01]. Both markers were significantly predictive of 30-day mortality in univariable logistic regression analysis. In a multivariable logistic stepwise regression model, GDF-15, TIMI (Thrombolysis In Myocardial Infarction) flow grade <3 after PCI, age, LVEF, and serum lactate remained significant predictors of 30-day mortality., Conclusion: GDF-15 on admission is a significant independent predictor of short-term mortality in infarct-related CS. Trail registration: NCT00491036., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Two centrifugal pumps, the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA), used in central or peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated, in terms of double-center experience, as treatment for patients with refractory cardiogenic shock (CS). Between January 2006 and December 2012, 228 consecutive adult patients were supported on RotaFlow (n=213) or CentriMag (n=15) ECMO, at our institutions (155 men; age 58.3±10.5 years, range: 19-84 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n=118) and primary donor graft failure (n=37); postacute myocardial infarction CS (n=27); acute myocarditis (n=6); and CS on chronic heart failure (n=40). A peripheral ECMO setting was established in 126 (55.2%) patients while it was established centrally in 102 (44.7%). Overall mean support time was 10.9±9.7 days (range: 1-43 days). Eighty-four (36.8%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n=144), weaning from mechanical support (n=107; 46.9%), bridge to mid-long-term ventricular assist device (n=6; 2.6%), and bridge to heart transplantation (n=31; 13.5%), was 63.1%. One hundred twenty-two (53.5%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and MB isoenzyme of creatine kinase (CK-MB) relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality on ECMO (P=0.010, odds ratio [OR]=2.94; 95% confidence interval [CI]=1.10-3.14; P=0.010, OR=2.82, 95% CI=1.014-3.721; and P=0.011, OR=2.69; 95% CI=1.06-4.16, respectively). Central ECMO population had significantly higher rate of continuous veno-venous hemofiltration need and bleeding requiring surgery events compared with the peripheral ECMO setting population. No significant differences were seen by comparing the RotaFlow and CentriMag populations in terms of device performance. At follow-up, persistent heart failure with left ventricle ejection fraction (LVEF)≤40% was a risk factor after hospital discharge. Patients with a poor hemodynamic status may benefit from rapid central or peripheral insertion of ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support. In addition, early ventricular assist device placement or urgent listing for heart transplant should be considered in patients with persistent impaired LVEF after ECMO., (Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Purpose: This study investigated the significance of baseline cortisol levels and adrenal response to corticotropin in shocked patients after acute myocardial infarction (AMI)., Methods: A short corticotropin stimulation test was performed in 35 patients with cardiogenic shock after AMI by intravenously injecting of 250 μg of tetracosactrin (Synacthen). Blood samples were obtained at baseline (T0) before and at 30 (T30) and 60 (T60) minutes after the test to determine plasma total cortisol (TC) and free cortisol concentrations. The main outcome measure was in-hospital mortality and its association with T0 TC and maximum response to corticotropin (maximum difference [Δ max] in cortisol levels between T0 and the highest value between T30 and T60)., Results: The in-hospital mortality was 37%, and the median time to death was 4 days (interquartile range, 3-9 days). There was some evidence of an increased mortality in patients with T0 TC concentrations greater than 34 μg/dL (P=.07). Maximum difference by itself was not an independent predictor of death. Patients with a T0 TC 34 μg/dL or less and Δ max greater than 9 μg/dL appeared to have the most favorable survival (91%) when compared with the other 2 groups: T0 34 μg/dL or less and Δ max 9 μg/dL or less or T0 34 μg/dL or higher and Δ max greater than 9 μg/dL (75%; P=.8) and T0 greater than 34 μg/dL and Δ max 9 μg/dL or less (60%; P=.02). Corticosteroid therapy was associated with an increased mortality (P=.03). There was a strong correlation between plasma TC and free cortisol (r=0.85)., Conclusions: A high baseline plasma TC was associated with a trend toward increased mortality in patients with cardiogenic shock post-AMI. Patients with lower baseline TC, but with an inducible adrenal response, appeared to have a survival benefit. A prognostic system based on basal TC and Δ max similar to that described in septic shock appears feasible in this cohort. Corticosteroid therapy was associated with adverse outcomes. These findings require further validation in larger studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The purpose of this prospective study was to evaluate the effects and functional outcome of central extracorporeal life support (ECLS) with left ventricular decompression for the treatment of refractory cardiogenic shock and lung failure., Methods: Between August 2010 and August 2013, 12 consecutive patients (2 female) with a mean age of 31.6 ± 15.1 years received central ECLS with left ventricular decompression for the treatment of refractory cardiogenic shock and lung failure. Underlying disease was acute cardiac decompensation due to dilated cardiomyopathy (n = 3, 25%), coronary artery disease with acute myocardial infarction (AMI) (n = 3, 25%), and acute myocarditis (n = 6, 50%). We routinely implemented ECLS by cannulating the ascending aorta, right atrium and inserting a left ventricular decompression cannula vent via the right superior pulmonary vein., Results: All patients were successfully bridged to either recovery (n = 3, 25%), long-term biventricular support (n = 6, 50%) or cardiac transplantation (n = 3, 25%). Seven patients (58.3%) were discharged after a mean hospital stay of 42 ± 11.9 days. The overall survival from ECLS implantation to the end of the study was 58.3%. The cumulative ICU stay was 23.1 ± 9.6 days. The length of support was 8.0 ± 4.3 days (range 3-17 days)., Conclusions: We strongly recommend left ventricular decompression in refractory cardiogenic shock and lung failure to avoid pulmonary edema, left heart distension and facilitate myocardial recovery.

Objectives: Therapy refractory cardiogenic shock is associated with dismal outcome. Percutaneous implantation of an extracorporeal life support (ECLS) system achieves immediate cardiopulmonary stabilization, sufficient end-organ perfusion and reduction of subsequent multiorgan failure (MOF)., Methods: Forty-one patients undergoing percutaneous ECLS implantation for cardiogenic shock from February 2012 until August 2013 were retrospectively analysed. Mean age was 52 ± 13 years, 6 (15%) were female. Mean pH values obtained before ECLS implantation were 7.15 ± 0.24, mean lactate concentration was 11.7 ± 6.4 mmol/l. Levels obtained 6 h after ECLS implantation were 7.30 ± 0.14 and 8.7 ± 5.0 mmol/l, respectively. In 23 patients (56%) cardiogenic shock resulted from an acute coronary syndrome in 13 (32%) from cardiomyopathy, in 5 (12%) from other causes. Twenty-seven (66%) had been resuscitated, in 14 (34%) implantation was performed under ongoing cardiopulmonary resuscitation (CPR). Of note, 97% of the acute coronary syndrome patients underwent percutaneous coronary intervention (PCI) either before ECLS implantation or under ECLS support. Extracorporeal life support implantation was performed on scene (Emergency Department, Cath Lab, Intensive Care Unit) by a senior cardiac surgeon and a trained perfusionist, in 8 cases (20%) in the referring hospital., Results: Thirty-day mortality was 51% [21 patients, due to MOF (n = 14), cerebral complications (n = 6) and heart failure (n = 1)]. Logistic regression analysis identified 6-h pH values as an independent risk factor of 30-day mortality (P < 0.001, OR = 0.000, 95% CI 0.000-0.042). Neither CPR nor implantation under ongoing CPR resulted in significant differences. In 26 cases (63%), the ECLS system could be explanted, after mean support of 169 ± 67 h. Seven of these patients received cardiac surgery [ventricular assist device implantation (n = 4), heart transplantation (n = 1), other procedures (n = 2)]., Conclusions: Due to the evolution of transportable ECLS systems and percutaneous techniques implantation on scene is feasible. Extracorporeal life support may serve as a bridge-to-decision and bridge-to-treatment device. Neurological evaluation before ventricular assist device implantation and PCI under stable conditions are possible. Despite substantial mortality, ECLS implantation in selected patients by an experienced team offers additional support to conventional therapy as well as CPR and allows survival in patients that otherwise most likely would have died. This concept has to be implemented in cardiac survival networks in the future.

Introduction: Cardiogenic shock (CS) is the leading cause of mortality in patients with acute myocardial infarction (AMI). Inflammatory response seems to be common response in patients with AMI, especially those with CS. We have therefore conducted a study to determine diagnostic and prognostic utility of interleukin 6 (IL6) levels in the cohort of patients with cardiogenic and septic shock (SS) and in a control group of patients with uncomplicated AMI., Methods: In this prospective study 71 patients fulfilled the inclusion criteria: 30 patients with cardiogenic shock, 21 patients with septic shock and 20 patients with ST elevation myocardial infarction (STEMI). Plasma levels of IL6 were measured at 8 time points. The main endpoint was 3 month mortality., Results: We have shown that the highest IL6 levels during the first week were recorded in patients with septic shock with peak value at admission. The maximum level of IL6 was detected between 12 to 24 hours after the onset of MI among patients with cardiogenic shock. According to Receiver operating characteristic (ROC) statistics levels of IL6 > 357 pg/ml at admission (AUC 0.730, p = 0.031) were typical for patients with CS in comparison with control group of STEMI patients. Values of IL6 > 1 237 pg/ml at admission and > 1 071 pg/ml at 24 hours (after admission?) were typical for thouse in septic shock in comparison with CS patients. We found only a non-significant trend of IL6 for the prediction of mortality in the cohort of CS patients for levels 1 854 pg/ml (AUC 0.769, p = 0.066) sampled 12 hours after admission. There was no association of plasma levels of IL6 with mortality in septic shock patients., Conclusions: Patients with cardiogenic shock demonstrated more pronounced cytokine response as evidenced by increased levels of IL6 compared to patients with uncomplicated STEMI. Levels of IL6 peaked in SS patients at admission, in CS patients 12-24 hours after admission. In daily clinical practice routine measurement of IL6 levels for prediction of prognosis both in cardiogenic and septic shock are of little value mainly due to significant interindividual variability of IL6 values.

Background: Little evidence is available on the optimal sequence of intra-aortic balloon pump (IABP) support initiation and primary percutaneous coronary intervention (PCI) in patients who present with cardiogenic shock from ST-elevation myocardial infarction (STEMI). The aim of this study was to evaluate the order of IABP insertion and primary PCI and its association with infarct size and mortality., Methods: A series of 173 consecutive patients admitted with cardiogenic shock from STEMI and treated with primary PCI and IABP between 2000 and 2009 were included. The order of IABP insertion and primary PCI was left at the discretion of the interventional cardiologist., Results: All baseline characteristics were similar in patients who first received IABP (n=87) and patients who received IABP directly after PCI (n=86). In these two groups, cumulative 30-day mortality was 44% and 37% respectively (p=0.39). Median peak serum creatine kinase (CK) concentrations were 5692 U/l and 4034 U/l respectively (p=0.048). In multivariable analysis, IABP insertion before PCI was independently associated with higher CK levels (p=0.046). In patients who survived 30 days, IABP insertion before PCI was not associated with late mortality evaluated at five years of follow-up (HR1.5, 95% CI 0.7-3.3; p=0.34)., Conclusions: Early IABP insertion before primary PCI might be associated with higher peak CK levels, indicating a larger infarct size. A possible explanation may be the increased reperfusion delay. Our study suggests that early reperfusion could have priority over routine early IABP insertion in STEMI patients with cardiogenic shock. Randomized studies are needed to determine the optimal timing of IABP insertion relative to primary PCI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Admission blood glucose (BG) level is a predictor of mortality in patients with ST-segment elevation myocardial infarction (STEMI). However, limited data are available relating admission BG to mortality in patients with STEMI complicated by cardiogenic shock, and it is not known whether diabetic status has an independent effect on this relationship., Methods: Between November 2005 and September 2010, 816 STEMI patients with cardiogenic shock were enrolled in a nationwide, prospective, multi-center registry; 239 (29.3%) had diabetes mellitus (DM). Patients were categorized according to BG levels at admission: <7.8, 7.8-10.9, 11.0-16.5 and ≥ 16.6 mmol/L. The primary outcome was 30-day mortality. The added values of BG to the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) scores were assessed by receiver operating characteristic curves and integrated discrimination improvement analyses., Results: Thirty-day mortality was higher in patients with higher admission BG (20.4%, 23.3%, 39.8%, and 43.1% p < 0.001). Among non-diabetic patients, 30-day mortality was predicted by TIMI scores with a c-statistic of 0.615 (95% confidence interval [CI], 0.561-0.662) and GRACE scores with a c-statistic of 0.652 (95% CI, 0.604-0.695). Incorporation of admission BG increased the c-statistic for TIMI score to 0.685 (95% CI, 0.639-0.720, p < 0.001) and GRACE score to 0.708 (95% CI 0.664-0.742, p < 0.001). Additional predictive values for BG were not observed for diabetes. Integrated discrimination improvements (TIMI vs. additional BG and GRACE vs. additional BG) were 0.041 (p < 0.001) and 0.039 (p < 0.001) in non-diabetic patients., Conclusions: In a cohort of patients with STEMI complicated by cardiogenic shock, admission BG was an independent predictor of increased risk of mortality only among patients without DM.

Background: Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro- and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown., Methods: In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI)., Results: Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41;p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value., Conclusions: Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background:  Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established., Methods:  From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging., Results:  Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients., Conclusions:  Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.

Objective: Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after cardiac surgery are predictors of major complications including mortality., Patients and Methods: This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality., Results: Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L [2.8-5.1] vs 3.3 mmol/L [2.2-4.8]; P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L [3.1-8.4] vs 4 mmol/L [2.6-6.4]; P = .048); 6 hours (4 mmol/L [2.7-5.8] vs 2.6 mmol/L [2-3.6], P < .001), and 12 hours after admission (2.3 mmol/L [1.8-3.2] vs 1.7 mmol/L [1.3-2]; P < .001). In a multivariate model, higher age (odds ratio [OR], 1.048, 95% confidence interval [CI], 1.011-1.086; P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03; 95% CI, 1.200-7.510; P = .019 compared with LVEF of 40%-59%; OR, 3.571; 95% CI, 1.503-8.196; P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138; 95% CI; 1.007-1.285; P = .038), red blood cell transfusion (OR, 1.230; 95% CI, 1.086-1.393; P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI; 1.61-6.69; P = .001) are predictors of major complications., Conclusions: Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

We report on an infant presenting with acute cardiogenic shock. She was eventually diagnosed with pseudohypoparathyroidism, which is a heterogeneous group of disorders characterized by severe hypocalcemia, hyperphosphatemia, and increased parathyroid hormone. The patient responded dramatically to calcium and vitamin D supplementation; left ventricular systolic function was normalized within days of treatment. Although the diagnosis of pseudohypoparathyroidism is rare, this case is a reminder of the importance of obtaining calcium levels in patients presenting in acute cardiogenic shock.

Aims: Vascular integrity is disturbed in shock contributing to clinical appearance and serious outcomes. While angiopoietin (Ang)-1 protects from vascular inflammation and leakage, Ang-2 disrupts endothelial barrier function. The imbalance of Ang-1 and Ang-2, their association to haemodynamic deterioration, and their prognostic relevance are not known and, thus, were prospectively evaluated in patients with cardiogenic shock (CS) in this study., Methods and Results: Plasma Ang-1 and Ang-2 were determined by the enzyme immunoassay in patients with CS (n = 96), uncomplicated acute myocardial infarction (AMI, n = 20) and age-matched healthy controls (HC, n = 20). Angiopoietin-2 was three-fold elevated in CS compared with HC (P < 0.001), remained elevated in non-survivors, and decreased in survivors (P < 0.001). In contrast, Ang-1 decreased up to 35-fold in CS (P < 0.001). Angiopoietin-1 was correlated and Ang-2 was inversely related to a cardiac power index and mixed venous oxygen saturation, respectively (P < 0.001 for all). To assess the prognostic relevance, two outcome variables were considered: the 28-day mortality and the survival time (follow-up time 1 year). For Ang-2 at admission a cut-off point of 2500 pg/mL had a sensitivity of 61% and a specificity of 80% to determine 28-day mortality in CS (confirmed by receiver operating characteristic analysis, area under the curve = 0.71 ± 0.06, P < 0.001). Angiopoietin-2 levels >2500 pg/mL at admission were observed to be an independent predictor for 1-year mortality in CS confirmed by Cox proportional hazard analysis [hazard ratio (HR) 2.11; 95% confidence interval (CI) 1.03-4.36; P = 0.042]., Conclusion: Circulating Angs are closely related to outcome and severity in CS. Angiopoietin-2 emerged as an independent predictor of 28-day and 1-year mortality in CS. Larger studies are required to define the cut-off and predictive values for Ang-2. Angiopoietins may be prognostic biomarkers for survival in CS and might represent a novel therapeutic target.

Objectives: The aim of this study was to characterize levels of serum biomarkers in patients with severe refractory cardiogenic shock (SRCS) and to document temporal changes in these levels during restoration of circulation., Background: Patients with SRCS have been challenging to study because of their rapidly changing clinical condition while undergoing multiple simultaneous interventions., Methods: Twenty-one patients with SRCS received circulatory support via a percutaneously implanted ventricular assist device (PVAD). Serum samples obtained prior to PVAD support initiation, at 24 h of PVAD support, and at 7 days of PVAD support were assayed for B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor receptor-1 (sTNFR1), soluble Fas (sFas), soluble Fas ligand (sFasL), endothelin-1, and procollagen III N-terminal peptide (PIIINP). Baseline biomarker levels were qualitatively compared to reference values; levels at 24 h of PVAD support and at 7 days of PVAD support were compared to baseline using 2-tailed Wilcoxon matched pair signed rank tests with Bonferroni correction for multiple comparisons., Results: These patients with SRCS had elevated serum levels of BNP, hsCRP, sTNFR1, endothelin-1, and PIIINP. Ventricular unloading and restoration of circulation via PVAD support in patients with SRCS were associated with reductions in serum BNP, sFas, and endothelin-1 levels and increases in serum sFasL and PIIINP levels., Conclusions: This study characterizes several important baseline serum biomarker levels in patients with SRCS and introduces a novel PVAD-based protocol with the potential to "reverse"-model the pathophysiology of cardiogenic shock., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Elevated mean platelet volume (MPV) has been recently discussed as a predictor of death in patients with acute coronary syndrome (ACS), but the cut-off point of MPV in relation to poor prognosis has not been estimated so far. The aim of this study was to evaluate MPV and its prognostic value in ACS complicated by cardiogenic shock (CS). Such an analysis in patients with the most serious and fatal complication of ACS has not been performed inpreviously published research., Methods: Fifty three patients with ACS complicated by CS (age 68.9 ± 11.4, 49% women, 92% STEMI, 55% fatal CS) and 53 age- and gender-matched patients with uncomplicated ACS as a control group (age 69.1 ± 10.6, 49% women, 92% STEMI, 0% fatal) were included in our prospective study from 2010 to 2012. All the patients underwent successful primary percutaneous coronary intervention. MPV was determined on admission (MPV1) and in consecutive two days of hospitalization (MPV2, MPV3). The blood sample was analyzed immediately after collection in EDTA tubes using an automatic blood counter., Results: MPV1 was similar in both groups (8.91 ± 1.11 fl vs. 8.57 ± 0.74 fl, NS). Furthermore, there were no statistically significant differences in MPV value in fatal and nonfatal CS(8.90 ± 1.18 fl vs. 8.93 ± 1.05 fl, NS)., Conclusions: The above results suggest that MPV cannot be considered a predictor of poor in-hospital outcome in patients with ACS complicated by cardiogenic shock.

Background: No prognostic markers of myocardial recovery in patients with refractory cardiogenic shock requiring circulatory support are known, but early identification of patients who will not recover might provide an opportunity to change the treatment strategy to improve outcome. Because N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic markers in patients with cardiac failure, we hypothesized that, among patients with refractory cardiogenic shock of potentially reversible cause supported with extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might help identify patients who would recover., Methods: This was a prospective, observational, single-center study in a medical-surgical intensive care unit. Among 41 consecutive patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, 18 recovered and were successfully weaned off the machine. Blood N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and 7 post-ECMO., Results: Neither the absolute values of those biomarkers at days 1, 3, or 7 nor their kinetics during the first week differed between patients weaned or not. Areas under the receiver operating characteristic curves (95% confidence interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and 0.61 (0.43-0.78), respectively., Conclusion: In patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, early measurements of cardiac biomarkers are not useful for identifying those who would recover., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The IABP SHOCK trial was designed as a morbidity-based randomized controlled trial to determine the effect of intraaortic balloon pulsation (IABP) in patients with infarct-related cardiogenic shock (CS). The primary endpoint was the change in the APACHE II score over a 4-day period. The prospective hypothesis was that adding IABP therapy to "standard care" would reduce CS-triggered multiorgan dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with additional IABP support. In an inflammatory marker substudy, we analyzed the prognostic value of the cytokines interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β), granulocyte-colony stimulating factor (G-CSF), and monocyte chemoattractant protein-1β (MCP-1β). We also investigated the influence of IABP support, age, and gender on cytokine levels., Design: The inflammatory marker substudy of the prospective, randomized, controlled, open label IABP SHOCK Trial (ClinicalTrials.gov ID NCT00469248)., Materials and Methods: A prospective, randomized, single-center study in a 12-bed intensive care unit at a university hospital was performed. A total of 40 consecutive patients were enrolled. The observational period was 96 h., Results: The investigated cytokines showed a significant contribution in the prediction of mortality. Initial (on admission) and maximal cytokine levels during the observational period showed a similar predictive power. Patients with elevated levels of pro- and antiinflammatory cytokines had a higher risk of dying. The maximal level measured over the observation period in the hospital was also suited to identify the survivors. Close correlations between maximal cytokine levels resulted in the choice of only one independent marker (MIP-1β) into the multivariate model (OR 1.024, 95% CI 1.005-1.043). Initial cytokine levels were also suitable to predict the survivors; the risk of death significantly increases with increasing IFN-γ level (OR 1.119, 95% CI 1.005-1.246). Cytokine levels were not affected by the presence of IABP support. Age (< 75 or > 75 years) and gender did not have a clinically relevant effect on INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1 in CS patients., Conclusion: The inflammatory response in patients with myocardial infarction complicated by CS, as reflected by the inflammatory markers INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1β, have been shown to be of prognostic value in estimating clinical outcome.

Introduction: Cardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6), and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI., Methods: The present study is a prospective single-center study including 87 patients with MI complicated by CS treated with acute revascularization and intraaortic balloon counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality., Results: Significant differences between survivors (n = 59) and nonsurvivors (n = 28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, the highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis, significant values were found for Nt-proBNP at T1, and for IL-6 and PCT at all points in time. Within the multivariate analysis, age, creatinine, and IL-6 were significant determinants of 30-day mortality, in which IL-6 showed the highest level of significance., Conclusions: In patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points in time, whereas Nt-proBNP seemed to be of lower relevance.

Objective: Infants with congenital heart disease having obstruction to the left ventricular outflow and ductal-dependent systemic circulation can present critically ill with shock. Prompt disease recognition and initiation of prostaglandins are necessary to prevent excess morbidity and mortality. We assessed a large cohort of newborn infants with ductal-dependent systemic circulation to determine if B-type natriuretic peptide (BNP) is consistently elevated at presentation, potentially aiding in diagnosis and treatment., Methods: The clinical records of infants with left-sided obstructive lesions admitted from January 2005 to June 2009 were reviewed. Infants were divided into 2 groups: group 1 was diagnosed with cardiogenic/circulatory shock at presentation, and group 2 consisted of infants with ductal-dependent systemic circulation without evidence of shock. B-type natriuretic peptide levels and other variables between the groups were compared., Results: All patients with critical congenital heart disease presenting with shock had elevated BNP levels, ranging from 553 to greater than 5000 pg/mL. Infants in group 1 (shock, n = 36) had significantly higher median BNP levels of 4100 pg/mL at presentation compared with group 2 patients (no shock, n = 86), who had a median BNP of 656 pg/mL (range, 30-3930 pg/mL; P < 0.001). Every 100 U of increase in BNP at presentation increased the likelihood of shock (odds ratio, 100; P < 0.001)., Conclusions: B-type natriuretic peptide is markedly elevated in neonates presenting in shock secondary to left-sided obstructive heart disease and is an important diagnostic tool to aid in the rapid identification and treatment of these patients.

In normal circumstances central venous to arterial pCO(2) difference is approximately 1 kPa (7.5 mmHg). In shock states it is usually increased. We sought to evaluate the agreement between admission central venous to arterial pCO(2) difference and mortality in patients with acute myocardial infarction and cardiogenic shock. We hypothesized that patients with higher central venous to arterial pCO(2) difference on admission would have higher mortality. We retrospectively included 30 patients with acute myocardial infarction and cardiogenic shock (mean age 67 ± 10 years, 73 % men), of which 20 (67 %) died. Nonsignificant differences between survivors and nonsurvivors were observed in age, gender, admission mean blood pressure, heart rate, lactate, hemoglobin, peak troponin I, cardiopulmonary resuscitation, use of therapeutic hypothermia, vasopressors, inotropes, intraaortic balloon pump, and mechanical ventilation. A significant difference between survivors and nonsurvivors was observed in admission central venous to arterial pCO(2) difference (1.35 ± 0.49 kPa vs. 0.83 ± 0.36 kPa, p = 0.003). In patients with admission central venous oxygen saturation over 70 %, we observed a significant difference in central venous to arterial pCO(2) difference between survivors and nonsurvivors (1.33 ± 0.51 kPa vs. 0.7 ± 0.3 kPa, p = 0.003) and a nonsignificant difference between survivors and nonsurvivors in patients with admission central venous oxygen saturation under 70 % (1.38 ± 0.53 kPa vs. 1.25 ± 0.33 kPa, p = 0.37). Patients with decreased central venous to arterial pCO(2) difference on admission seem to be at increased risk of dying even with admission central venous oxygen saturation over 70 %.

In this prospective, observational study, we measured arterial lactate and pyruvate concentrations within the first four hours of shock and at four hour intervals during the first 24 hours in 26 patients with septic and 13 with cardiogenic shock. We also studied 10 intensive care unit patients with normal lactate levels as controls. Seven patients (18%) died during the first 24 hours of shock, 12 (31%) patients died later in the intensive care unit and 21 (54%) were discharged alive from the intensive care unit. Blood lactate values were higher at shock onset in the non-survivors than in the survivors (P=0.02) and remained significantly elevated throughout the study. The lactate/pyruvate ratio at shock onset was significantly higher in the non-survivors (24 [17 to 34] vs 15 [10 to 19], P=0.01) than in the survivors. All patients with cardiogenic shock had hyperlactataemia at the onset of shock, and 69% had a high lactate/pyruvate ratio. Only 65% of patients with septic shock had hyperlactataemia at the onset of shock and 76% of these also had a high lactate/pyruvate ratio. In conclusion, the lactate/pyruvate ratio confirms that hyperlactataemia is frequently, but not solely, due to hypoxia, especially at the onset of shock.

Background: The IABP-SHOCK-trial was a morbidity-based randomized controlled trial in patients with infarction-related cardiogenic shock (CS), which used the change of the quantified degree of multiorgan failure as determined by APACHE II score over a 4-day period as primary outcome measure. The prospective hypothesis was that adding IABP therapy to "standard care" would improve CS-triggered multi organ dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with IABP support. In an inflammatory marker substudy, we analysed the prognostic value of interleukin (IL)-1β, -6, -7, -8, and -10 in patients with acute myocardial infarction complicated by cardiogenic shock., Design: Inflammatory marker substudy of the prospective, randomized, controlled, open label IABP-SHOCK-trial (ClinicalTrials.gov ID-NCT00469248)., Setting and Methods: A single-center study was performed in a 12-bed Intensive-Care-Unit in an university hospital in which 40 consecutive patients were enrolled with an observational period of 96 h., Results: The pro- and anti-inflammatory markers IL-6, -7, -8 and -10 showed a predictive power for mortality of infarct-related CS patients, while IL-1β did not discriminate. The maximal values during the observational period, in case of IL-7 the minimal value, showed the best power to predict mortality. Both, ROC and multivariate analyses confirmed these suggestions (area under the curve: IL-8, 0.80 ± 0.08; IL-6, 0.79 ± 0.08; IL-10, 0.76 ± 0.08; IL-7, 0.69 ± 0.08). Inflammatory markers were not affected by the presence of IABP support., Conclusion: The inflammatory response in patients with myocardial infarction complicated by cardiogenic shock, as reflected by the inflammatory markers IL-6, IL-7, IL-8 and IL-10, demonstrates a clinically relevant prognostic contribution to clinical outcome.

Objectives: Activation of the receptor for advanced glycation end products by its ligands promotes inflammatory processes and tissue injury. The available evidence suggests that soluble forms of receptor for advanced glycation end products circulating in the plasma may neutralize the ligand-mediated damage by acting as a decoy. Thus, it is hypothesized that receptor for advanced glycation end products expression might be deleterious, whereas soluble receptor for advanced glycation end products might be beneficial in cardiogenic shock. However, until now, no data exist regarding the role of soluble receptor for advanced glycation end products and receptor for advanced glycation end products in humans with cardiogenic shock complicating myocardial infarction., Design: Prospective observational cohort study., Setting: Intensive critical care unit of a university hospital., Patients: Forty patients with cardiogenic shock complicating acute myocardial infarction, 20 age-matched patients with acute uncomplicated myocardial infarction and, 20 age-matched healthy volunteers., Interventions: None., Measurements and Main Results: Monocytic receptor for advanced glycation end products expression assessed by flow cytometry was significantly increased in cardiogenic shock nonsurvivors (137.02±7.48 mean fluorescence intensity; n=13) compared to survivors (67.80±8.33 mean fluorescence intensity; n=17; p<.001). Conversely, nonsurvivors had significantly decreased plasma soluble receptor for advanced glycation end products levels (79.87±10.62 arbitrary units; n=13; p=.004) compared to survivors (127.65±10.52 arbitrary units; n=17) as assessed by Western blotting. Receptor for advanced glycation end products expression and soluble receptor for advanced glycation end products levels were determined as independent predictors for 28-day mortality in cardiogenic shock confirmed by receiver-operator characteristics and multivariate analysis (receptor for advanced glycation end products: area under the curve, 0.943±0.05; p<.001; soluble receptor for advanced glycation end products: area under the curve, 0.815±0.08; p<.01). Both receptor for advanced glycation end products>103.6 mean fluorescence intensity or soluble receptor for advanced glycation end products<76.88 arbitrary units independently predicted a 27.87-fold (p<.001) and a 3.97-fold (p=.019) increase in 28-day mortality in cardiogenic shock., Conclusions: Enhanced monocytic receptor for advanced glycation end products expression and decreased plasma soluble receptor for advanced glycation end products levels play a central role in patients with cardiogenic shock associated with proinflammatory and destroying pathways, resulting in an enhanced 28-day mortality-rate. Receptor for advanced glycation end products and soluble receptor for advanced glycation end products may be prognostic biomarkers for survival in cardiogenic shock and might represent a novel therapeutic target in cardiogenic shock.

The novel Permanent Life Support (PLS; Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) as peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support system has been investigated as treatment for patients with refractory cardiogenic shock (CS). Between January 2007 and July 2011, 73 consecutive adult patients were supported on peripheral PLS ECMO system at our institution (55 men; age 60.3 ± 11.6 years, range: 23-84 years). Indications for support were failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 50) and primary donor graft failure (n = 8), post-acute myocardial infarction CS (n = 12), and CS on chronic heart failure (n = 3). Mean support time was 10.9 ± 7.6 days (range: 2-34 days). Overall, 26 (35.6%) patients died on ECMO. Among survivors on ECMO, 44 (60.2%) patients were successfully weaned from support, and three (4.1%) were switched to a mid-long-term ventricular assist device. Thirty-three (45.2%) were successfully discharged. The following variables were significantly different if survivors and nonsurvivors on ECMO were compared: age (P = 0.04), female gender (P < 0.01), cardiopulmonary resuscitation before ECMO (P < 0.01), lactate level before ECMO (P = 0.01), number of platelets, fresh frozen plasma units, and packed red blood cells (PRBCs) transfused during ECMO support (P = 0.03, P = 0.02, and P < 0.01), blood lactate level (P = 0.01), and creatine kinase isoenzyme MB (CK-MB) relative index 72 h after ECMO initiation (P < 0.001), and multiple organ failure on ECMO (P < 0.01). Stepwise logistic regression identified blood lactate level and CK-MB relative index at 72 h after ECMO initiation, and number of PRBCs transfused on ECMO as significant predictors of mortality on ECMO (P = 0.011, odds ratio [OR] = 2.48; 95% confidence interval [CI] = 1.11-3.12; P = 0.012, OR = 2.81, 95% CI = 1.026-2.531; and P = 0.012, OR = 1.94, 95% CI = 1.02-5.21; respectively). Patients with an initial poor hemodynamic status could benefit by rapid peripheral installation of PLS ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support., (© 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)