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BACKGROUND: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA.METHODS: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included.RESULTS: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point.CONCLUSIONS: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.

Aim: Myocardial dysfunction and low cardiac index are common after out-of-hospital cardiac arrest (OHCA) as part of the post-cardiac arrest syndrome. This study investigates the association of cardiac index during targeted temperature management (TTM) with mortality. Methods: In the TTM-trial, which randomly allocated patients to TTM of 33 °C or 36 °C for 24 h, we prospectively and consecutively monitored 151 patients with protocolized measurements from pulmonary artery catheters (PAC) as a single site substudy. Cardiac index, heart rate and stroke volume were measured at 3 time-points during the 24 h TTM period and averaged. Uni- and multivariate Cox regression was used to assess association with mortality. Results: Of 151 patients, 50 (33%) were deceased after 180 days. Cardiac index during TTM was not significantly associated with mortality in univariate (HR: 0.84 [0.54–1.31], p = 0.59) or multivariate analyses (HRadjusted: 1.03 [0.57–1.83], p = 0.93). Cardiac index during TTM was also not significantly associated with non-neurological death (HRadjusted: 1.25 [0.43–3.59], p = 0.68). Higher heart rate (p = 0.03) and lower stroke volume (p = 0.04) were associated with increased mortality in univariate, but not multivariate analyses. No hemodynamic variables were associated with cerebral death, however, increasing lactate during TTM (HRadjusted: 2.15 [1.19–3.85], p = 0.01) and lower mean arterial pressure during TTM (HRadjusted: 0.89 [0.81–0.97], p = 0.008) were independently associated with non-neurological death. Conclusion: Cardiac index during TTM after resuscitation from OHCA is not associated with mortality. Future studies should investigate whether certain subgroups of patients could benefit from targeting higher goals for cardiac index.

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome. Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33 °C or TTM at 36 °C for 24 h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72 h after OHCA. The primary endpoint was neurological outcome. Results: Median (quartile 1 - quartile 3) tau-A (ng/ml) values were 58 (43-71) versus 51 (43-67), 72 (57-84) versus 71 (59-82) and 76 (61-92) versus 75 (64-89) for good versus unfavourable outcome at 24, 48 and 72 h, respectively (pgroup = 0.95). Median tau C (ng/ml) values were 38 (29-50) versus 36 (29-49), 49 (38-58) versus 48 (33-59) and 48 (39-59) versus 48 (36-62) (pgroup = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48 h; tau-A: 0.51 and tau-C: 0.51). Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.

BACKGROUND: Out-of-hospital cardiac arrest is more often reported in men than in women.OBJECTIVES: We aimed to assess sex-related differences in post-resuscitation care; especially with regards to coronary angiography, percutaneous coronary intervention, mortality and functional status after out-of-hospital cardiac arrest.METHODS: We included 704 consecutive adult out-of-hospital cardiac arrest-patients with cardiac aetiology in the Copenhagen area from 2007-2011. Utstein guidelines were used for the pre-hospital data. Vital status and pre-arrest comorbidities were acquired from Danish registries and review of patient charts. Logistic regression was used to assess differences in functional status and use of post-resuscitation care. Cox regression was used to assess differences in 30-day mortality. We used 'smcfcs' and 'mice' imputation to handle missing data.RESULTS: Female sex was associated with higher 30-day mortality after adjusting for age and comorbidity (hazard ratio (HR): 1.42, confidence interval (CI): 1.13-1.79, p<0.01), this was not significant when adjusting for primary rhythm (HR: 1.12, CI: 0.88-1.42, p=0.37). Women less frequently received coronary angiography <24 h in multiple regression after out-of-hospital cardiac arrest (odds ratio (OR)CAG=0.55, CI: 0.31-0.97, p=0.041), however no difference in percutaneous coronary intervention was found (ORPCI=0.55, CI: 0.23-1.36, p=0.19). Coronary artery bypass grafting was less often performed in women (ORCABG: 0.10, CI: 0.01-0.78, p=0.03). There was no difference in functional status at discharge between men and women ( p=1).CONCLUSION: Female sex was not significantly associated with higher mortality when adjusting for confounders. Women less often underwent coronary angiography and coronary artery bypass grafting, but it is not clear whether this difference can be explained by other factors, or an actual under-treatment in women.

OBJECTIVE: Comorbidity prior to out-of-hospital cardiac arrest (OHCA) and primary rhythm in relation to survival is not well established. We aimed to assess the prognostic importance of comorbidity in relation to primary rhythm in OHCA-patients treated with Target Temperature Management (TTM).DESIGN: Consecutive comatose survivors of OHCA treated with TTM in hospitals in the Copenhagen area between 2002-2011 were included. Utstein-based pre- and in-hospital data collection was performed. Data on comorbidity was obtained from The Danish National Patient Register and patient charts, assessed by the Charlson Comorbidity Index (CCI).RESULTS: A total of 666 patients were included. A third (n = 233, 35%) presented with non-shockable rhythm, and they were less often male (64% vs. 82%, p < .001), and OHCA in public, witnessed OHCA, and bystander cardiopulmonary resuscitation (CPR) were less common compared to patients with a shockable primary rhythm (public: 27% vs. 48%, p < .001, witnessed: 79% vs. 90%, p < .001, bystander CPR: 47% vs. 63%, p < .001). 30-day mortality was 62% compared to 28% in patients with non-shockable and shockable rhythm, respectively. By Cox-regression analyses, any comorbidity (CCI ≥1) was the only factor independently associated with 30-day mortality in patients with non-shockable rhythm (HR =1.9 (95% CI: 1.2-2.9), p < .01), whereas in patients with shockable rhythm comorbidity was not associated with outcome after adjustment for prognostic factors (HR = 0.82 (0.55-1.2), p = .34). No significant interaction between primary rhythm and comorbidity in terms of mortality was present.CONCLUSION: A higher comorbidity burden was independently associated with a higher 30-day mortality rate in patients presenting with non-shockable primary rhythm but not in patients with shockable rhythm.

BACKGROUND: Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population.METHODS: This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5.RESULTS: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58-0.84 versus 0.83).CONCLUSION: NSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials.

PURPOSE: Life threatening arrhythmias are increasingly frequent with lower body temperature. While targeted temperature management (TTM) with mild hypothermia following out-of-hospital cardiac arrest (OHCA) is generally considered safe and has been suggested as a potential antiarrhythmic add-on therapy, it is unknown whether the level of TTM affects the burden of ventricular ectopic activity. We sought to assess the ventricular ectopic burden between patients treated with TTM at 33°C or 36°C for 24h.METHODS: Continuous 12-lead digital Holter electrocardiograms performed during the intervention were analyzed blinded to treatment allocation in 115 comatose OHCA-survivors from a single center of the TTM-trial. The main study showed no difference with regards to mortality.RESULTS: Fifty-eight patients were randomized to 33°C and 57 to 36°C. Cardiac arrest characteristics were similar between the groups. The number of isolated ventricular ectopic beats (VEB) per hour was similar at the beginning of the maintenance phase of TTM and decreased over time in both groups (both ptime<0.001). The reduction in VEB per hour was significantly affected by target temperature (pinteraction<0.0001), with fewer VEB in the 36°C-group. The total number of isolated, couplets and number of runs of VEB per hour showed similar results, with less ventricular ectopic activity in the 36°C-group (pinteraction<0.0001). Increasing numbers of pre-hospital defibrillations (log2) were associated with a 46% increase in ventricular ectopic activity (p<0.01), adjusted for potential confounders.CONCLUSIONS: Ventricular ectopic activity was reduced in comatose OHCA-survivors treated with TTM at 36°C compared to 33°C. Higher numbers of pre-hospital defibrillations were associated with higher incidence of ventricular ectopic activity.

Objectives: Atrial fibrillation has been associated with increased mortality in the general population and mixed populations of critical ill. Atrial fibrillation can also affect patients during post-cardiac arrest care. We sought to assess the prognostic implications of atrial fibrillation following out-of-hospital cardiac arrest, including relation to the level of targeted temperature management. Design: A post hoc analysis of a prospective randomized trial. Setting: Thirty-six ICUs. Patients: We included 897 (96%) of the 939 comatose out-of-hospital cardiac arrest survivors from the targeted temperature management trial (year, 2010-2013) with data on heart rhythm on day 2. Interventions: Targeted temperature management at 33°C or 36°C. Measurements and Main Results: Endpoints included cumulative proportion of atrial fibrillation following out-of-hospital cardiac arrest and 180-day all-cause mortality and specific death causes stratified by atrial fibrillation. Atrial fibrillation on day 2 was used as primary endpoint analyses to exclude effects of short-term atrial fibrillation related to resuscitation and initial management. The cumulative proportions of atrial fibrillation were 15% and 11% on days 1 and 2, respectively. Forty-three percent of patients with initial atrial fibrillation the first day were reported with sinus rhythm on day 2. No difference was found between the groups treated with targeted temperature management at 33°C and 36°C. Patients affected by atrial fibrillation had significantly higher 180-day mortality (atrial fibrillation: 66% vs no-atrial fibrillation: 43%; plogrank < 0.0001 and unadjusted hazard ratio, 1.75 [1.35-2.30]; p < 0.0001). The association between atrial fibrillation and higher mortality remained significant (adjusted hazard ratio, 1.34 [1.01-1.79]; p < 0.05) adjusted for potential confounders. Atrial fibrillation was independently associated with increased risk of cardiovascular death and multiple-organ

Background: Current guidelines recommend that comatose out-of-hospital cardiac arrest patients with ST-segment elevations (STEs) following return of spontaneous circulation (ROSC) should be referred for an acute coronary angiography. We sought to investigate the diagnostic value of the pre-hospital ROSC-ECG in predicting ST-elevation myocardial infarction (STEMI). Method: ROSC-ECGs of 145 comatose survivors of out-of-hospital cardiac arrest, randomly assigned in the Target Temperature Management trial, were classified according to the current STEMI ECG criteria (third universal definition of myocardial infarction). Results: STEs were present in the pre-hospital ROSC-ECG of 78 (54%) patients. A final diagnosis revealed that 69 (48%) patients had STEMI, 31 (21%) patients had non-STEMI and 45 (31%) patients had no myocardial infarction. STE in ROSC-ECGs had a sensitivity of 74% (95% confidence interval (CI) 62–84), specificity of 65% (95% CI 53–75) and a positive and negative predictive value of 65% (95% CI 54–76) and 73% (95% CI 61–83) in predicting STEMI. Time to ROSC was significantly longer (24 minutes vs. 19 minutes, P=0.02) in STE compared with no STE patients. Percutaneous coronary intervention was successful in 68% versus 36% (P<0.001) of STE compared to no STE patients. No significant difference was found in 180-day mortality rates between STE and no STE patients (36% vs. 30%, Plogrank=0.37). Conclusion: The pre-hospital ROSC-ECG is a suboptimal diagnostic tool to predict STEMI and therefore not a sensitive tool for triage to cardiac centres. This supports the incentive of referring all comatose survivors of out-of-hospital cardiac arrest of suspected cardiac origin to a tertiary heart centre with the availability of acute coronary angiography, even in the absence of STEs., BACKGROUND: Current guidelines recommend that comatose out-of-hospital cardiac arrest patients with ST-segment elevations (STEs) following return of spontaneous circulation (ROSC) should be referred for an acute coronary angiography. We sought to investigate the diagnostic value of the pre-hospital ROSC-ECG in predicting ST-elevation myocardial infarction (STEMI).METHOD: ROSC-ECGs of 145 comatose survivors of out-of-hospital cardiac arrest, randomly assigned in the Target Temperature Management trial, were classified according to the current STEMI ECG criteria (third universal definition of myocardial infarction).RESULTS: STEs were present in the pre-hospital ROSC-ECG of 78 (54%) patients. A final diagnosis revealed that 69 (48%) patients had STEMI, 31 (21%) patients had non-STEMI and 45 (31%) patients had no myocardial infarction. STE in ROSC-ECGs had a sensitivity of 74% (95% confidence interval (CI) 62-84), specificity of 65% (95% CI 53-75) and a positive and negative predictive value of 65% (95% CI 54-76) and 73% (95% CI 61-83) in predicting STEMI. Time to ROSC was significantly longer (24 minutes vs. 19 minutes, P=0.02) in STE compared with no STE patients. Percutaneous coronary intervention was successful in 68% versus 36% (P<0.001) of STE compared to no STE patients. No significant difference was found in 180-day mortality rates between STE and no STE patients (36% vs. 30%, Plogrank=0.37).CONCLUSION: The pre-hospital ROSC-ECG is a suboptimal diagnostic tool to predict STEMI and therefore not a sensitive tool for triage to cardiac centres. This supports the incentive of referring all comatose survivors of out-of-hospital cardiac arrest of suspected cardiac origin to a tertiary heart centre with the availability of acute coronary angiography, even in the absence of STEs.

INTRODUCTION: Informed consent in incapacitated adults is permitted in the form of proxy consent by both the patients' closest relative (next of kin, NOK) and general practitioner (GP). In research in acute situations not involving pharmaceuticals, Danish legislation allows for randomisation and subsequent proxy consent, as soon as possible. The aim of this study was to describe the delay associated with obtaining consent and to assess whether consent from NOK or GP/Danish Health and Medicines Authority is obtained with delays beyond the intervention.METHODS: In a prospective study, 171 comatose out-of-hospital cardiac arrest (OHCA) patients were randomised to targeted temperature management. Patients were randomised before NOK could be informed, and proxy consent was obtained as soon as possible. Written consent from NOK and GP were our study data.RESULTS: We obtained all legally required consent: 169 cases of consent were obtained from NOK, two patients gave consent before NOK, in no cases was consent denied by the proxy. Consent from NOK was obtained with a median delay of zero days (interquartile range (IQR): 0-1, max. 128 days). Delay from NOK consent to GP consent was a median of nine days (IQR: 6-23, max. 527 days).CONCLUSION: NOK fully accepted participation in a clinical trial after OHCA with short delays in consent. Consent from GPs was associated with long delays beyond the intervention, which make GPs less appropriate for proxy consent of incapacitated adults in acute situations. The Ethics Committees' approval of the trial justified by their competence and authority, combined with the NOK´s insight into the patient's wishes may be a relevant and feasible alternative to the current consent procedure.FUNDING: This work was supported by the European Regional Development Fund through the Interreg IV A OKS programme (NYPS ID: 167157) with regards to authors JHT, CH, NN and JK.TRIAL REGISTRATION: not relevant.

OBJECTIVE: To investigate the hemodynamic profile associated with different target temperatures and to assess the prognostic implication of inotropic/vasopressor support and mean arterial pressure after out-of-hospital cardiac arrest. There is a lack of information how different target temperatures may affect hemodynamics.DESIGN: Post hoc analysis of a prospective randomized study.SETTING: Thirty-six ICUs in 10 countries.PATIENTS: Nine hundred twenty patients (97%) with available vasopressor data out of 950 patients from the Target Temperature Management trial randomly assigned patients to a targeted temperature management at 33 °C or 36 °C.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, heart rate, and lactate were registered at prespecified time points. The population was stratified according to cardiovascular Sequential Organ Failure Assessment = 4 defining the high vasopressor group and cardiovascular Sequential Organ Failure Assessment less than or equal to 3 defining the low vasopressor group. The targeted temperature management 33 (TTM33) group had a hemodynamic profile with lower heart rate (-7.0 min(-1) [95% confidence limit, -8.7, -5.1]; p(group) < 0.0001), similar mean arterial pressure (-1.1 mm Hg [95% confidence limit, -2.3, 0.2]; p(group) = 0.10), and increased lactate (0.6 mmol/L [95% confidence limit, 0.3, 0.8]; p(group) < 0.0001) compared with the targeted temperature management 36 (TTM36) group. A cardiovascular Sequential Organ Failure Assessment score = 4 was recorded in 54% versus 45%, p = 0.03 in the TTM33 and the TTM36 group, respectively. The high vasopressor group carried a 53% mortality rate when compared with a 34% in the low vasopressor group, p(log-rank) less than 0.0001, with an adjusted hazard ratio of 1.38 (95% CI, 1.11-1.71; p = 0.004). There was no interaction between vasopressor group and allocated target temperature group (p = 0.40). An inverse relationship bet

BACKGROUND: Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been investigated sufficiently. The primary aim of this study was to evaluate whether a target temperature of 33°C compared with 36°C was favorable for cognitive function; the secondary aim was to describe cognitive impairment in cardiac arrest survivors in general.METHODS AND RESULTS: Study sites included 652 cardiac arrest survivors originally randomized and stratified for site to temperature control at 33°C or 36°C within the Target Temperature Management trial. Survival until 180 days after the arrest was 52% (33°C, n=178/328; 36°C, n=164/324). Survivors were invited to a face-to-face follow-up, and 287 cardiac arrest survivors (33°C, n=148/36°C, n=139) were assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed was more affected among cardiac arrest patients, but results for memory and executive functioning were similar.CONCLUSIONS: Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest survivors was also common in matched control subjects with ST-segment-elevation myocardial infarction not having had a cardiac arrest.CLINICAL

OBJECTIVE: Sympathoadrenal activation and endothelial damage are hallmarks of acute critical illness. This study investigated their association and predictive value in patients resuscitated from out-of-hospital cardiac arrest (OHCA).METHODS: Post-hoc analysis of patients included at a single site in The Targeted Temperature Management at 33 degrees versus 36 degrees after Cardiac Arrest (TTM) trial. The main study reported similar outcomes with targeting 33 versus 36 degrees. TTM main study ClinicalTrials.gov: NCT01020916. One hundred sixty three patients resuscitated from OHCA were included at a single site ICU. Blood was sampled a median 135 min (Inter Quartile Range (IQR) 103-169) after OHCA. Plasma catecholamines (adrenaline, noradrenaline) and serum endothelial biomarkers (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin) were measured at admission (immediately after randomization). We had access to data on demography, medical history, characteristics of the OHCA, patients and 180-day outcome.RESULTS: Adrenaline and noradrenaline correlated positively with syndecan-1 and thrombomodulin i.e., biomarkers reflecting endothelial damage (both p<0.05). Overall 180-day mortality was 35%. By Cox analyses, plasma adrenaline, serum sE-selectin, reflecting endothelial cell activation, and thrombomodulin levels predicted mortality. However, thrombomodulin was the only biomarker independently associated with mortality after adjusting for gender, age, rhythm (shockable vs. non-shockable), OHCA to return of spontaneous circulation (ROSC) time, shock at admission and ST elevation myocardial infarction (30-day Hazards Ratio 1.71 (IQR 1.05-2.77), p=0.031 and 180-day Hazards Ratio 1.65 (IQR 1.03-2.65), p=0.037 for 2-fold higher thrombomodulin levels).CONCLUSIONS: Circulating catecholamines and endothelial damage were intercorrelated and predicted increased mortality. Interventions aiming at protecting and/or restoring the endothelium may be benefic

Background—Studies have found higher survival rates after out-of-hospital cardiac arrest and admission to tertiary heart centers. The aim was to examine the level-of-care at tertiary centers compared with nontertiary hospitals and the association with outcome after out-of-hospital cardiac arrest. Methods and Results—Consecutive out-of-hospital cardiac arrest patients (n=1078) without ST-segment–elevation myocardial infarction admitted to tertiary centers (54%) and nontertiary hospitals (46%) were included (2002–2011). Patient charts were reviewed focusing on level-of-care and comorbidity. Survival to discharge differed significantly with 45% versus 24% of patients discharged alive (P<0.001), and after adjustment for prognostic factors admissions to tertiary centers were still associated with lower 30-day mortality (hazard ratio, 0.78 [0.64–0.96; P=0.02]), independent of comorbidity. The adjusted odds of predefined markers of level-of-care were higher in tertiary centers: admission to intensive care unit (odds ratio [OR], 1.8 [95% confidence interval, 1.2–2.5]), temporary pacemaker (OR, 6.4 [2.2–19]), vasoactive agents (OR, 1.5 [1.1–2.1]), acute (<24 hours) and late coronary angiography (OR, 10 [5.3–22] and 3.8 [2.5–5.7]), neurophysiological examination (OR, 1.8 [1.3–2.6]), and brain computed tomography (OR, 1.9 [1.4–2.6]), whereas no difference in therapeutic hypothermia was noted. Patients at tertiary centers were more often consulted by a cardiologist (OR, 8.6 [5.0–15]), had an echocardiography (OR, 2.8 [2.1–3.7]), and survivors more often had implantable cardioverter defibrillator’s implanted (OR, 2.1 [1.2–3.6]). Conclusions—Admissions to tertiary centers were associated with significantly higher survival after out-of-hospital cardiac arrest in patients without ST-segment–elevation myocardial infarction in the Copenhagen area even after adjustment for prognostic factors including comorbidity. Level-of-care seems higher in tertiary centers both in the early, BACKGROUND: Studies have found higher survival rates after out-of-hospital cardiac arrest and admission to tertiary heart centers. The aim was to examine the level-of-care at tertiary centers compared with nontertiary hospitals and the association with outcome after out-of-hospital cardiac arrest.METHODS AND RESULTS: Consecutive out-of-hospital cardiac arrest patients (n=1078) without ST-segment-elevation myocardial infarction admitted to tertiary centers (54%) and nontertiary hospitals (46%) were included (2002-2011). Patient charts were reviewed focusing on level-of-care and comorbidity. Survival to discharge differed significantly with 45% versus 24% of patients discharged alive (P<0.001), and after adjustment for prognostic factors admissions to tertiary centers were still associated with lower 30-day mortality (hazard ratio, 0.78 [0.64-0.96; P=0.02]), independent of comorbidity. The adjusted odds of predefined markers of level-of-care were higher in tertiary centers: admission to intensive care unit (odds ratio [OR], 1.8 [95% confidence interval, 1.2-2.5]), temporary pacemaker (OR, 6.4 [2.2-19]), vasoactive agents (OR, 1.5 [1.1-2.1]), acute (<24 hours) and late coronary angiography (OR, 10 [5.3-22] and 3.8 [2.5-5.7]), neurophysiological examination (OR, 1.8 [1.3-2.6]), and brain computed tomography (OR, 1.9 [1.4-2.6]), whereas no difference in therapeutic hypothermia was noted. Patients at tertiary centers were more often consulted by a cardiologist (OR, 8.6 [5.0-15]), had an echocardiography (OR, 2.8 [2.1-3.7]), and survivors more often had implantable cardioverter defibrillator's implanted (OR, 2.1 [1.2-3.6]).CONCLUSIONS: Admissions to tertiary centers were associated with significantly higher survival after out-of-hospital cardiac arrest in patients without ST-segment-elevation myocardial infarction in the Copenhagen area even after adjustment for prognostic factors including comorbidity. Level-of-care seems higher in tertiary centers

BACKGROUND: Cardiovascular dysfunction is common after out-of-hospital cardiac arrest as part of the postcardiac arrest syndrome, and hypothermia may pose additional impact on hemodynamics. The aim was to investigate systemic vascular resistance index (SVRI), cardiac index, and myocardial performance at a targeted temperature management of 33°C (TTM33) versus 36°C (TTM36).METHODS AND RESULTS: Single-center substudy of 171 patients included in the Target Temperature Management Trial (TTM Trial) randomly assigned to TTM33 or TTM36 for 24 hours after out-of-hospital cardiac arrest. Mean arterial pressure ≥65 mm Hg and central venous pressure of 10 to 15 mm Hg were hemodynamic treatment goals. Hemodynamic evaluation was performed by serial right heart catheterization and transthoracic echocardiography. Primary end point was SVRI after 24 hours of cooling and secondary end points included mean SVRI, cardiac index, systolic function, and lactate levels. The TTM33 group had a significant increase in SVRI compared with TTM36 (2595; 95% confidence interval, 2422-2767) versus 1960 (95% confidence interval, 1787-2134) dynes m(2)/s per cm(5); P<0.0001, respectively) after 24 hours of cooling with an overall difference of 556 dynes m(2)/s per cm(5) (P(group) <0.0001). TTM33 was associated with decreased cardiac index (-0.4 L/min per m(2); P(group) <0.0001), decreased heart rate (P(group)=0.01), and stroke volume index (P(group)=0.004) compared with TTM36. Left ventricular ejection fraction (P=0.39) and peak systolic myocardial velocity (P=0.62) did not differ between TTM groups. Lactate levels were significantly higher in the TTM33 group (P=0.0008).CONCLUSIONS: Targeted temperature management at 33°C with target mean arterial pressure ≥65 mm Hg is associated with increased SVRI and lower cardiac index because of lower heart rate with unaffected left ventricular systolic function compared with 36°C.CLINICAL TRIAL REGISTRATION URL: http://www.clini

AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopressor support and mortality.METHODS: In a 6-year period, 310 comatose OHCA patients treated with TH were included. Temperature, hemodynamic parameters and level of vasopressors were registered from admission to 24h after rewarming. Level of vasopressor support was assessed by the cardiovascular sub-score of Sequential Organ Failure Assessment (SOFA). The population was stratified by use of dopamine as first line intervention (D-group) or use of dopamine+norepinephrine/epinephrine (DA-group). Primary endpoint was 30-day mortality and secondary endpoint was in-hospital cause of death.RESULTS: Patients in the DA-group carried a 49% all-cause 30-day mortality rate compared to 23% in the D-group, plog-rank<0.0001, corresponding to an adjusted hazard ratio (HR) of 2.0 (95% CI: 1.3-3.0), p=0.001). The DA-group had an increased 30-day mortality due to neurological injury (HR=1.7 (95% CI: 1.1-2.7), p=0.02). Cause of death was anoxic brain injury in 78%, cardiovascular failure in 18% and multi-organ failure in 4%. The hemodynamic changes of TH reversed at normothermia, although the requirement for vasopressor support (cardiovascular SOFA≥3) persisted in 80% of patients.CONCLUSIONS: In survivors after OHCA treated with TH the induced hemodynamic changes reversed after normothermia, while the need for vasopressor support persisted. Patients requiring addition of norepinephrine/epinephrine on top of dopamine had an increased 30-day all-cause mortality, as well as death from neurological injury.

PURPOSE: We hypothesized that a targeted temperature of 33 °C as compared to that of 36 °C would increase survival and reduce the severity of circulatory shock in patients with shock on admission after out-of-hospital cardiac arrest (OHCA).METHODS: The recently published Target Temperature Management trial (TTM-trial) randomized 939 OHCA patients with no difference in outcome between groups and no difference in mortality at the end of the trial in a predefined subgroup of patients with shock at admission. Shock was defined as a systolic blood pressure of <90 mm Hg for >30 min or the need of supportive measures to maintain a blood pressure ≥90 mmHg and/or clinical signs of end-organ hypoperfusion. In this post hoc analysis reported here, we further analyzed the 139 patients with shock at admission; all had been randomized to receive intervention at 33 °C (TTM33; n = 71) or 36 °C (TTM36; n = 68). Primary outcome was 180-day mortality. Secondary outcomes were intensive care unit (ICU) and 30-day mortality, severity of circulatory shock assessed by mean arterial pressure, serum lactate, fluid balance and the extended Sequential Organ Failure assessment (SOFA) score.RESULTS: There was no significance difference between targeted temperature management at 33 °C or 36 °C on 180-day mortality [log-rank test, p = 0.17, hazard ratio 1.33, 95 % confidence interval (CI) 0.88-1.98] or ICU mortality (61 vs. 44 %, p = 0.06; relative risk 1.37, 95 % CI 0.99-1.91). Serum lactate and the extended cardiovascular SOFA score were higher in the TTM33 group (p < 0.01).CONCLUSIONS: We found no benefit in survival or severity of circulatory shock with targeted temperature management at 33 °C as compared to 36 °C in patients with shock on admission after OHCA.

Conducted electrical weapons (CEW) were invented in the 1970s and are now widely used by more than 16,000 military and law enforcement agencies worldwide. Recent studies have sug-gested that a causal relation of cardiac arrest in humans and utilization of CEW may exist and cardiac capture and fatal arrhythmia have been documented in animal studies. We believe, based on current knowledge, that CEW use may have caused human fatalities. Users should be aware of potential serious side effects and be able to provide basic life support.

BACKGROUND: Increased pulmonary capillary wedge pressure (PCWP) is an independent prognostic predictor after myocardial infarction (MI), but PCWP is difficult to assess noninvasively in subjects with preserved ejection fraction (EF). We hypothesized that biomarkers would provide information regarding PCWP at rest and during exercise in subjects with preserved EF after MI.METHODS AND RESULTS: Seventy-four subjects with EF >45% and recent MI underwent right heart catheterization at rest and during a symptom-limited semisupine cycle exercise test with simultaneous echocardiography. Plasma samples were collected at rest for assessment of midregional pro-A-type natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), copeptin, and midregional pro-adrenomedullin (MR-proADM). Plasma levels of MR-proANP and PCWP were associated at rest (r = 0.33; P = .002) and peak exercise (r = 0.35; P = .002) as well as with changes in PCWP (r = 0.26; P = .03). Plasma levels of NT-proBNP and PCWP were weakly associated at rest (r = 0.23; P = .03) and peak exercise (r = 0.28; P = .02) but not with changes in PCWP (r = 0.20; P = .09). In a multivariable analysis, plasma levels of MR-proANP remained associated with rest and exercise PCWP (P < .01), whereas NT-proBNP did not. Plasma levels of Gal-3, copeptin, and MR-proADM were not associated with PCWP at rest or peak exercise.CONCLUSIONS: In subjects recovering from an acute MI with preserved EF, plasma levels of natriuretic peptides, particularly MR-proANP, are associated with filling pressures at rest and during exercise.

Guidelines suggest that acute coronary angiography (CAG) is considered in patients resuscitated from out-of-hospital cardiac arrest with presumed cardiac aetiology. Since specialized post-resuscitation care, including therapeutic hypothermia, has proved beneficial in randomized studies, CAG should be offered to patients with a high likelihood of thrombotic coronary lesions, i.e. patients with ST-segment elevation in electrocardiogram (ECG) following resuscitation. This article suggests a triage and referral based on electronic transmission of ECG and teleconference with specialized centres in all patients.

BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.g

Left ventricular diastolic dysfunction (DD) is common after myocardial infarction (MI) despite preservation of left ventricular ejection fraction, yet it remains unclear how or whether DD affects cardiac hemodynamics with stress.