Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest

Background and aims: Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. Methods: This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4–6) at 6 months after OHCA. Results: Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790–0.828), 0.835 (95% CI 0.816–0.852) for the TTM-score, 0.820 (95% CI 0.800–0.839) for the CAHP-score and 0.770 (95% CI 0.748–0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. Conclusions: The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials

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

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

Agreement between self‐reported and objectively assessed physical activity among out‐of‐hospital cardiac arrest survivors

Background: Low level of physical activity is a risk factor for new cardiac events in out‐of‐hospital cardiac arrest (OHCA) survivors. Physical activity can be assessed by self‐reporting or objectively by accelerometery.Aim: To investigate the agreement between self‐reported and objectively assessed physical activity among OHCA survivorsHypothesisSelf‐reported levels of physical activity will show moderate agreement with objectively assessed levels of physical activity.MethodCross‐sectional study including OHCA survivors in Sweden, Denmark, and the United Kingdom. Two questions about moderate and vigorous intensity physical activity during the last week were used as self‐reports. Moderate and vigorous intensity physical activity were objectively assessed with accelerometers (ActiGraph GT3X‐BT) worn upon the right hip for 7 consecutive days.Results: Forty‐nine of 106 OHCA survivors answered the two questions for self‐reporting and had 7 valid days of accelerometer assessment. More physically active days were registered by self‐report compared with accelerometery for both moderate intensity (median 5 [3:7] vs. 3 [0:5] days; p < 0.001) and vigorous intensity (1 [0:3] vs. 0 [0:0] days; p < 0.001). Correlations between self‐reported and accelerometer assessed physical activity were sufficient (moderate intensity: rs = 0.336, p = 0.018; vigorous intensity: rs = 0.375, p = 0.008), and agreements were fair and none to slight (moderate intensity: k = 0.269, p = 0.001; vigorous intensity: k = 0.148, p = 0.015). The categorization of self‐reported versus objectively assessed physical activity showed that 26% versus 65% had a low level of physical activity.Conclusion: OHCA survivors reported more physically active days compared with the results of the accelerometer assessment and correlated sufficiently and agreed fairly and none to slightly.</p

Patient inclusion.

<p>Displaying the total Targeted Temperature Management (TTM) population, Intention-To-Treat (ITT) population and outcomes by the Cerebral Performance Category (CPC) scale.</p

Predictive values of neuron-specific enolase (NSE) for poor outcome after out-of-hospital cardiac arrest.

<p>Predictive values of neuron-specific enolase (NSE) for poor outcome after out-of-hospital cardiac arrest.</p

Predictive values of neuron-specific enolase (NSE) with a low false-positive rate.

<p>Predictive values of neuron-specific enolase (NSE) with a low false-positive rate.</p

Base line characteristics stratified by neuron-specific enolase (NSE) -quartiles in 685 included patients.

<p>Base line characteristics stratified by neuron-specific enolase (NSE) -quartiles in 685 included patients.</p

Predictive ability of neuron-specific enolase (NSE) for poor outcome after out-of-hospital cardiac arrest.

<p>Receiver Operating Characteristics plots showing the predictive ability of NSE models to predict poor outcome (CPC 3–5) at 180 days after OHCA in patients remaining unconscious at day 3 with inserts showing the enlarged plots for low false-positive rates from zero to five percent (AUCs presented for identical populations).</p

Additional file 1 of Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial

Additional file 1: Fig. 1. Predicted probability of death across the 6 hypothermia groups as compared to the normothermia groups at the corresponding sites. Patients in group 1, with the lowest average temperature at 4 hours had a higher probability of death

Effects of hypothermia vs normothermia on societal participation and cognitive function at 6 months in survivors after out-of-hospital cardiac arrest

Importance: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. Objectives: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. Design, Setting, and Participants: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Interventions: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Main outcomes and measures: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes.ResultsAt 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,−0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,−0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%).ConclusionsIn this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.</p