scholarly journals Circulating Levels of Brain-Enriched MicroRNAs Correlate with Neuron Specific Enolase after Cardiac Arrest—A Substudy of the Target Temperature Management Trial

2020 ◽  
Vol 21 (12) ◽  
pp. 4353
Author(s):  
Francesca Maria Stefanizzi ◽  
Niklas Nielsen ◽  
Lu Zhang ◽  
Josef Dankiewicz ◽  
Pascal Stammet ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Brain Damage ◽  
Neurological Outcome ◽  
Neuron Specific Enolase ◽  
Spontaneous Circulation ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Outcome Group ◽  
New Biomarkers ◽  
Circulating Levels

Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed (p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA.

Abstract 23: The Usefulness of Neuron-Specific Enolase in Cerebrospinal Fluid to Predict Neurological Prognosis in Cardiac Arrest Survivors Who Underwent Target Temperature Management: A Prospective Observational Study

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jung Soo Park
Keyword(s):  
Cerebrospinal Fluid ◽  
Cardiac Arrest ◽  
Observational Study ◽  
Neurological Outcome ◽  
Prospective Observational Study ◽  
Neurologic Outcome ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Target Temperature ◽  
Outcome Group

Aim: We aimed to investigate the prognostic performance between serum NSE and cerebrospinal fluid (CSF) NSE for 6-month neurologic outcome in OHCA survivors underwent target temperature management (TTM). Hypothesis: We hypothesized that the NSE levels measured in the CSF would affect the change, earlier and more sensitively than serum, according to severity of hypoxic brain damage. Methods: This single-centre prospective observational study included out-of-hospital cardiac arrest (OHCA) patients underwent TTM. NSE levels were assessed in blood and CSF samples obtained immediately (Day 0), and 24 h (Day 1), 48 h (Day 2), and 72 h (Day 3) after return of spontaneous circulation (ROSC). The primary outcome was the 6-month neurological outcome. Results: We enrolled 34 patients (males, 24; 70.6%), 16 (47.1%) had a poor neurologic outcome. CSF NSE and serum NSE values were significantly higher in the poor outcome group compared to the good outcome group at each time point, except for serum Day 0. CSF NSE and serum NSE had area under curve (AUC) of 0.819-0.972 and 0.648-0.920, respectively. CSF NSE prognostic performances were significant higher than serum NSE at Day 1 and showed excellent AUC values (0.969; 95% Confidential Interval [CI] 0.844-0.999) and high sensitivity (93.8%; 95% CI 69.8-99.8) at 100% specificity. Conclusion: We found CSF NSE values were highly predictive and sensitive markers of 6-month poor neurological outcome in OHCA survivors treated with TTM at Day 1 after ROSC. Thus, CSF NSE level at day 1 after ROSC can be a useful early prognosticator in OHCA survivors.

scholarly journals Circulating Levels of miR-574-5p Are Associated with Neurological Outcome after Cardiac Arrest in Women: A Target Temperature Management (TTM) Trial Substudy

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Adeline Boileau ◽  
Antonio Salgado Somoza ◽  
Josef Dankiewicz ◽  
Pascal Stammet ◽  
Patrik Gilje ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neurological Outcome ◽  
Cerebral Performance Category ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Target Temperature ◽  
Circulating Micrornas ◽  
Performance Category ◽  
Poor Neurological Outcome ◽  
Circulating Levels

Purpose. Postresuscitation neuroprognostication is guided by neurophysiological tests, biomarker measurement, and clinical examination. Recent investigations suggest that circulating microRNAs (miRNA) may help in outcome prediction after cardiac arrest. We assessed the ability of miR-574-5p to predict neurological outcome after cardiac arrest, in a sex-specific manner. Methods. In this substudy of the Target Temperature Management (TTM) Trial, we enrolled 590 cardiac arrest patients for which blood samples were available. Expression levels of miR-574-5p were measured by quantitative PCR in plasma samples collected 48 h after cardiac arrest. The endpoint of the study was poor neurological outcome at 6 months (cerebral performance category scores 3 to 5). Results. Eighty-one percent of patients were men, and 49% had a poor neurological outcome. Circulating levels of miR-574-5p at 48 h were higher in patients with a poor neurological outcome at 6 months (p<0.001), both in women and in men. Circulating levels of miR-574-5p were univariate predictors of neurological outcome (odds ratio (OR) [95% confidence interval (CI)]: 1.5 [1.26-1.78]). After adjustment with clinical variables and NSE, circulating levels of miR-574-5p predicted neurological outcome in women (OR [95% CI]: 1.9 [1.09-3.45]), but not in men (OR [95% CI]: 1.0 [0.74-1.28]). Conclusion. miR-574-5p is associated with neurological outcome after cardiac arrest in women.

Abstract 14644: Impact of Time to Return of Spontaneous Circulation on Neuro-protective Effect of Target Temperature Management at 33 and 36 Degrees in Comatose Survivors of Out of Hospital Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jesper Kjaergaard ◽  
Matilde Winther-Jensen ◽  
Niklas Nielsen ◽  
Anders åneman ◽  
Wise P Matt ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neurological Outcome ◽  
Spontaneous Circulation ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Significant Prognostic Factor ◽  
Target Temperature ◽  
Return Of Spontaneous Circulation ◽  
Prolonged Time ◽  
Hospital Cardiac Arrest

Introduction: Prolonged time to Return of Spontaneous Circulation (ttROSC) after Out of Hospital Cardiac Arrest (OHCA) has consistently been associated with adverse outcome by a plausible direct relation to severity of anoxic injury. Hypothesis: Target temperature management (TTM) is assumed effective against anoxic brain injury and we hypothesized that TTM at 33 degrees would be more beneficial with prolonged time to ROSC compared to 36 degrees. Methods: In a post hoc analysis of the TTM trial, which showed no overall benefit of targeting 33 °C over 36 in 939 patients (NEJM 2013), we investigated the relation of time to ROSC and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) and Modified Ranking Scale (mRS) after 180 days. Results: Prolonged ttROSC was significantly and independently associated with increased mortality, p<0.001 (figure), with Hazard Ratio (HR) of 1.02 (95% CI 1.01-1.02, p<0.001) per minute increase and level of TTM did not modify this association, p interaction =0.85. In survivors prolonged ttROSC was associated with increased odds of surviving with an unfavorable neurological outcome for CPC (p=0.008 for CPC 3-4) and a similar trend, albeit not statistically significant was observed for mRS (p=0.17, mRS 4-5). Odds for unfavorable neurological outcome (CPC>2, mRS>3) was not modified by levels of TTM overall. Conclusion: Time to ROSC remains a significant prognostic factor in comatose patients resuscitated from OHCA with regards to risk of death and risk of adverse neurological outcome in survivors. TTM at 33 degrees offers no advantage over targeting 36 degrees with regards to mortality or neurological outcome in patients with prolonged time to ROSC. Figure: Mortality rates stratified by quartiles of tome to ROSC and by TTM level. Differences tested by log rank test in between TTM in strata

Abstract 313: Neuron-specific Enolase and S-100B Protein in Crebrospinal Fluid: A Study of Sequential Analysis in Cardiac Arrest Patients Who Underwent Target Temperature Management

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Changshin Kang
Keyword(s):  
Cardiac Arrest ◽  
Sequential Analysis ◽  
Neuron Specific Enolase ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Large Sample Size ◽  
Multicenter Studies ◽  
Prognostic Performance ◽  
Neurological Outcomes ◽  
Outcome Group

Background: Neuron-specific enolase (NSE) and S-100B protein have been reported that they are associated with neurological outcome in out-of-hospital cardiac arrest (OHCA) survivors. However, comparing the prognostic performance between NSE and S-100B obtained from cerebrospinal fluid (CSF) has not been assessed yet. Therefore, this study aimed to investigate the prognostic performance of NSE and S-100B obtained from CSF for poor neurological outcomes in OHCA survivors. Methods: This was a prospective single-centre observational study, conducted from November 2018 to February 2019. The CSF samples of NSE and S-100B were serially obtained until 72 h from immediate as possible from return of spontaneous circulation (ROSC), at 24 h interval (NSE i , 24,48,72 and S-100B i , 24,48,72 ). The area under curves (AUCs) were used to identify the sensitivities of two biomarkers for predicting poor neurologic outcomes. The primary outcome was the 3-months neurological outcomes. Results: We enrolled 35 patients (males, 28), and 16 subjects had a poor neurologic outcome. NSE and S-100B levels were significantly higher in the poor outcome group compared to the good outcome group at each time point. The AUCs of NSE and S-100B for poor neurological outcomes were 0.87 versus 0.95 at immediately, 0.96 versus 0.92 at 24 h, 0.99 versus 0.97, and 0.98 versus 0.97 at 72 h after ROSC, respectively. The sensitivities with 100% specificity of NSE and S-100B for poor neurological outcomes were 62.5 versus 33.3 at immediate, 73.3 versus 71.4 at 24 h, 92.9 versus 92.3 at 48 h, and 91.7 versus 88.9 at 72 h after ROSC, respectively. Conclusions: S-100B can be useful for early predicting the neurological outcomes of comatose OHCA patients within 24 hours from ROSC in spite of low sensitivity, whereas NSE need 24 hours at least for prognostication. Further prospective with large sample size in multicenter studies are needed to confirm out results.

Abstract 161: Effectiveness of Lower Target Temperature Therapeutic Hypothermia for Post--Cardiac Arrest Victims Within 30 Minutes Resuscitation Interval

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tadashi Kaneko ◽  
Shunji Kasaoka ◽  
Ken Nagao ◽  
Naohiro Yonemoto ◽  
Hiroyuki Yokoyama ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Neurological Outcome ◽  
Propensity Score Analysis ◽  
Spontaneous Circulation ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Target Temperature ◽  
Weighting Method ◽  
Favorable Neurological Outcome

Introduction: Therapeutic hypothermia (TH) for post cardiac arrest syndrome (PCAS) patients is standard strategy to reduce brain damage. However, current randomized control study (TTM: Target temperature management study, N Engl J Med 2013) suggested that simple target temperature did not improve outcome. Furthermore, there is no evidence, whether target temperature would be changed for each status of PCAS patients. Hypothesis: Lower target temperature could improve neurological outcome in PCAS patients. Methods: Participants with J-PULSE-Hypo study database were divided into the L group (32.0-33.9°C) and the M group (34-35°C). The favorable neurological outcomes (%, CPC 1-2 on 30th day) were compared between L and M groups in all and each subgroups with propensity score analysis with IPTW (inverse probability of treatment weighting) method as multivariate analysis. The subgroups were ages and interval from collapse to ROSC (return of spontaneous circulation). Results: 477 participants were analyzed. The comparison of each groups for favorable neurological outcome were that all groups (L: 64%, n = 42, vs M: 55%, n= 424, P = 0.234, multivariate: P = 0.452), age (≤60 y.o.) (L: 70% vs M: 67%, P = 0.717, multivariate: P = 0.657), age (>60 y.o.) (L: 50% vs M: 44%, P = 0.665, multivariate: P = 0.061), interval from collapse to ROSC (≤30 min.) (L: 88% vs M: 64%, P = 0.022, multivariate: P = 0.007), and interval from collapse to ROSC (>30 min.) (L: 21% vs M: 29%, P = 0.567, multivariate: P = 0.449). Conclusions: The PCAS victims within 30 min. from collapse to ROSC, would be treated by TH with less than 34°C target temperature.

Usefulness of the Degree of Blood–brain Barrier Disruption to Predict Neurological Prognosis in Cardiac Arrest Survivors who Wnderwent Target Temperature Management: A Retrospective Study

2020 ◽  
Author(s):  
Ga Ram Jeon ◽  
Hong Joon Ahn ◽  
Jung Soo Park ◽  
Insool Yoo ◽  
Yeonho You ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Blood Brain Barrier ◽  
Neurological Outcome ◽  
Scoring System ◽  
Brain Barrier ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Target Temperature ◽  
Neurological Outcomes ◽  
Poor Neurological Outcome

Abstract Background: This study aimed to compare the day-specific association of blood–brain barrier (BBB) disruption with neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors treated with target temperature management (TTM).Methods: This retrospective single-center study included 68 OHCA survivors, who underwent TTM between April 2018 and December 2019. The albumin quotient (QA) was calculated as [albuminCSF] / [albuminserum] immediately (day 1), and at 24 h (day 2), 48 h (day 3), and 72 h (day 4) after return of spontaneous circulation (ROSC). The degree of BBB disruption was weighted using the following scoring system: 0.07 ≥ QA (normal), 0.01 ≥ QA > 0.007 (mild), 0.02 ≥ QA > 0.01 (moderate), and QA > 0.02 (severe). This system gave it 0 (normal), 1 (mild), 4 (moderate), and 9 (severe) points. Poor neurological outcome was determined at six months after ROSC and was defined as cerebral performance categories 3–5.Results: We enrolled 68 patients (males, 48; 71%); 37 (54%) of them had a poor neurological outcome. The distributions of this outcome at six months in patients with moderate and severe BBB disruption versus the other groups were 19/22 (80%) vs. 18/46 (50%) on day 1, 31/37 (79%) vs. 6/31 (32%) on day 2, 32/37 (81%) vs. 5/31 (30%) on day 3, and 32/39 (85%) vs. 5/29 (30%) on day 4 (P < 0.001). Using ROC analyses, the optimal cutoff values of QA levels for prediction of neurological outcomes were determined as: day 1, > 0.009 (sensitivity 56.8%, specificity 87.1%); day 2, > 0.012 (sensitivity 81.1%, specificity 87.1%); day 3, > 0.013 (sensitivity 83.8%, specificity 87.1%); day 4, > 0.013 (sensitivity 86.5%, specificity 87.1%); sum of all time points, > 0.039 (sensitivity 89.5%, specificity 79.4%); and scoring system, > 9 (sensitivity 91.9%, specificity 87.1%). Conclusions: Our results suggested that QA is a useful tool for predicting neurological outcomes in OHCA survivors treated with TTM. However, the prediction of poor neurological outcome using QA showed low sensitivity at 100% specificity. Thus, it could be used as part of a multimodal approach than as a single prognostic prediction tool.

Abstract 348: Impact of Low and High Partial Pressure of Carbon Dioxide on Neuron Specific Enolase Derived from Serum and Cerebrospinal Fluid in Patients Who Underwent Targeted Temperature Management After Out-of-hospital Cardiac Arrest: A Retrospective Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Changshin Kang
Keyword(s):  
Carbon Dioxide ◽  
Cerebrospinal Fluid ◽  
Cardiac Arrest ◽  
Retrospective Study ◽  
Neuron Specific Enolase ◽  
Weighted Average ◽  
Carbon Dioxide Tension ◽  
Spontaneous Circulation ◽  
Temperature Management ◽  
Multi Centre Study

Aim: In a previous study, low and high-normal arterial carbon dioxide tension (PaCO 2 ) were not associated with serum neuron specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO 2 on NSE in cerebrospinal fluid (CSF) and serum. Methods: This was a retrospective study. PaCO 2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum-maximum (Min-Max). These subgroups were divided into low (LCO 2 ) and high PaCO 2 (HCO 2 ) groups defined as PaCO 2 ≤35.3 and PaCO 2 >43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE 24,48,72 and cNSE 24,48,72 ) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO 2 and the NSE measured at 24 h after ROSC. Results: Forty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO 2 in TWA subgroup was associated with cNSE 24,48,72 , while PaCO 2 in the other subgroup were only associated with cNSE 24 . PaCO 2 and cNSE in qES subgroup showed good correlation (r= -0.61; p< 0.01), and in TWA, Median, and Min-Max subgroup showed moderate correlations (r= -0.57, r= -0.48, and r= -0.60; p< 0.01). Contrastively, sNSE was not associated and correlated with PaCO 2 in all analysis. Poor neurological outcome in LCO 2 was significantly higher than HCO 2 in qES, TWA, and Median subgroups ( p< 0.01, p< 0.01, and p= 0.02). Conclusion: Association was found between NSE and PaCO 2 using CSF, despite including normocapnic ranges; TWA of PaCO 2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.

scholarly journals Does Combining Biomarkers and Brain Images Provide Improved Prognostic Predictive Performance for Out-Of-Hospital Cardiac Arrest Survivors before Target Temperature Management?

2020 ◽  
Vol 9 (3) ◽  
pp. 744 ◽  
Author(s):  
Seung Ha Son ◽  
In Ho Lee ◽  
Jung Soo Park ◽  
In Sool Yoo ◽  
Seung Whan Kim ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neuron Specific Enolase ◽  
Area Under The Curve ◽  
Temperature Management ◽  
Target Temperature Management ◽  
High Signal ◽  
Target Temperature ◽  
Brain Images ◽  
Prognostic Performance ◽  
Hospital Cardiac Arrest

We examined whether combining biomarkers measurements and brain images early after the return of spontaneous circulation improves prognostic performance compared with the use of either biomarkers or brain images for patients with cardiac arrest following target temperature management (TTM). This retrospective observational study involved comatose out-of-hospital cardiac arrest survivors. We analyzed neuron-specific enolase levels in serum (NSE) or cerebrospinal fluid (CSF), grey-to-white matter ratio by brain computed tomography, presence of high signal intensity (HSI) in diffusion-weighted imaging (DWI), and voxel-based apparent diffusion coefficient (ADC). Of the 58 patients, 33 (56.9%) had poor neurologic outcomes. CSF NSE levels showed better prognostic performance (area under the curve (AUC) 0.873, 95% confidence interval (CI) 0.749–0.950) than serum NSE levels (AUC 0.792, 95% CI 0.644–0.888). HSI in DWI showed the best prognostic performance (AUC 0.833, 95% CI 0.711–0.919). Combining CSF NSE levels and HSI in DWI had better prognostic performance (AUC 0.925, 95% CI 0.813–0.981) than each individual method, followed by the combination of serum NSE levels and HSI on DWI and that of CSF NSE levels and the percentage of voxels of ADC (AUC 0.901, 95% CI 0.792–0.965; AUC 0.849, 95% CI 0.717–0.935, respectively). Combining CSF/serum NSE levels and HSI in DWI before TTM improved the prognostic performance compared to either each individual method or other combinations.

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