| 11. |
- Blennow Nordström, Erik, et al.
(författare)
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Neuropsychological outcome after cardiac arrest : results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2023
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
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| 12. |
- Blennow Nordström, Erik, et al.
(författare)
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Neuropsychological outcome after cardiac arrest : A prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
- 2020
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. Trial registration: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018
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| 13. |
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| 14. |
- Boileau, Adeline, et al.
(författare)
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Circulating Levels of miR-574-5p Are Associated with Neurological Outcome after Cardiac Arrest in Women : A Target Temperature Management (TTM) Trial Substudy
- 2019
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Ingår i: Disease Markers. - : Hindawi Limited. - 0278-0240 .- 1875-8630. ; 2019
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 15. |
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| 16. |
- Devaux, Yvan, et al.
(författare)
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Association of circulating MicroRNA-124-3p levels with outcomes after out-of-hospital cardiac arrest : A substudy of a randomized clinical trial
- 2016
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 2380-6583. ; 1:3, s. 305-313
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts. Initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. OBJECTIVE: To address the prognostic value of circulating miRNAs in a large cohort of comatose patients with out-of-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Target Temperature Management After Cardiac Arrest (TTM) trial, a multicenter randomized, parallel-group, assessor-blinded clinical trial, compared the 6-month neurologic outcomes and survival of patients with cardiac arrest after targeted temperature management at 33°C or 36°C. Five hundred seventy-nine patients who survived the first 24 hours after the return of spontaneous circulation and who had blood samples available for miRNA assessment were enrolled from 29 intensive care units in 9 countries from November 11, 2010, to January 10, 2013. Final follow-up was completed on July 3, 2013, and data were assessed from February 1, 2014, to February 1, 2016. INTERVENTIONS: Blood sampling at 48 hours after the return of spontaneous circulation. MAINOUTCOMES AND MEASURES: The primary end point was poor neurologic outcomeat6 months (cerebral performance category score, 3 [severe neurologic sequelae], 4 [coma], or 5 [death]). The secondary end point was survival until the end of the trial. Circulating levels of miRNAs were measured by sequencing and polymerase chain reaction. RESULTS: Of the 579 patients (265 men [80.3%]; mean [SD] age, 63 [12] years), 304 patients (52.5%) hada poor neurologic outcomeat 6months. Inthe discovery phase with short RNA sequencing in 50 patients, the brain-enriched miR-124-3p level was identified as a candidate prognostic variable for neurologic outcomes. In the validation cohort of 529 patients, mean (SD) levels of miR-124-3p were higher in patients with a poor outcome (8408 [12 465] copies/μL) compared with patients with a good outcome (1842 [3025] copies/μL; P < .001). The miR-124-3p level was significantly associated with neurologic outcomes in the univariable analysis (odds ratio, 6.72; 95% CI, 4.53-9.97). In multivariable analyses using logistic regression, miR-124-3p levels were independently associated with neurologic outcomes (odds ratio, 1.62; 95% CI, 1.13-2.32). In Cox proportional hazards models, higher levels of miR-124-3p were significantly associated with lower survival (hazard ratio, 1.63; 95% CI, 1.37-1.93). CONCLUSIONS AND RELEVANCE: Levels of miR-124-3p can be used as prognostication tools for neurologic outcome and survival after out-of-hospital cardiac arrest. Thus, miRNA levels may aid in tailoring health care for patients with cardiac arrest.
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| 17. |
- Devaux, Yvan, et al.
(författare)
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Incremental value of circulating MiR-122-5P to predict outcome after out of hospital cardiac arrest
- 2017
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 7:10, s. 2555-2564
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Tidskriftsartikel (refereegranskat)abstract
- Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial. Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p < 0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.
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| 18. |
- Dragancea, Irina, et al.
(författare)
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Protocol-driven neurological prognostication and withdrawal of life-sustaining therapy after cardiac arrest and targeted temperature management
- 2017
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 117, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- Background Brain injury is reportedly the main cause of death for patients resuscitated after out-of-hospital cardiac arrest (OHCA). However, the majority may actually die following withdrawal of life-sustaining therapy (WLST) with a presumption of poor neurological recovery. We investigated how the protocol for neurological prognostication was used and how related treatment recommendations might have affected WLST decision-making and outcome after OHCA in the targeted temperature management (TTM) trial. Methods Analyses of prospectively recorded data: details of neurological prognostication; recommended level-of-care; WLST decisions; presumed cause of death; and cerebral performance category (CPC) 6 months following randomization. Results Of 939 patients, 452 (48%) woke and 139 (15%) died, mostly for non-neurological reasons, before a scheduled time point for neurological prognostication (72 h after the end of TTM). Three hundred and thirteen (33%) unconscious patients underwent prognostication at a median 117 (IQR 93–137) hours after arrest. Thirty-three (3%) unconscious patients were not neurologically prognosticated and for 2 patients (1%) data were missing. Related care recommendations were: continue in 117 (37%); not escalate in 55 (18%); and withdraw in 141 (45%). WLST eventually occurred in 196 (63%) at median day 6 (IQR 5–8). At 6 months, only 2 patients with WLST were alive and 248 (79%) of prognosticated patients had died. There were significant differences in time to WLST and death after the different recommendations (log rank <0.001). Conclusion Delayed prognostication was relevant for a minority of patients and related to subsequent decisions on level-of-care with effects on ICU length-of-stay, survival time and outcome.
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| 19. |
- Düring, Joachim, et al.
(författare)
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Influence of temperature management at 33 °C versus normothermia on survival in patients with vasopressor support after out-of-hospital cardiac arrest : a post hoc analysis of the TTM-2 trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. Methods: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. Results: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78–1.39] in the no-, 1.22 [98.3% CI 0.97–1.53] in the moderate-, and 0.97 [98.3% CI 0.68–1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. Conclusions: In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308, registered September 20, 2016.
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| 20. |
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