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BACKGROUND: Prognostication of recovery in patients who are unconscious following cardiac arrest can be guided by concentrations of brain injury biomarkers in the blood. The optimal biomarker and cutoff concentrations for the prediction of outcome remain unknown. In this study, we aimed to evaluate which biomarker of brain injury is most accurate for predicting functional outcome after cardiac arrest, and to evaluate cutoff levels for the prediction of good and poor outcome.

METHODS: This study was a prospective, international, observational biomarker study within the international Targeted Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial including adults aged 18 years or older with a presumed cardiac cause or unknown cause of arrest. Patients were recruited from 24 European hospitals. Serum samples were collected at 0, 24, 48, and 72 h after admission to intensive care units. Concentrations of neuron-specific enolase, S100, neurofilament light, and glial fibrillary acidic protein were analysed with Elecsys electrochemiluminescence immunoassays. The primary outcome was 6-month good (modified Rankin Scale 0-3) or poor (modified Rankin Scale 4-6) functional outcome. Prognostic accuracy was evaluated by the area under the receiver operating characteristic curve (AUROC). The biomarker with the highest AUROC at each timepoint was compared with that of the second highest marker using DeLong's test. As pre-specified, to account for multiple comparisons using Bonferroni correction, a p value of less than 0·0125 was considered statistically significant.

FINDINGS: Between April, 2018, and January, 2020, 113 (12%) of 932 eligible patients were excluded due to death, missed sampling, or missing outcome data. 661 (81%) of 819 included patients were male and 158 (19%) were female, the mean age was 64 years (SD 13), and 418 (51%) had a poor outcome. In patients who were unconscious, neurofilament light predicted functional outcome with AUROCs at 0, 24, 48, and 72 h of 0·77 (95% CI 0·73-0·80), 0·92 (0·90-0·94), 0·93 (0·91-0·95), and 0·93 (0·91-0·95), respectively. Glial fibrillary acidic protein achieved an AUROC of 0·74 (95% CI 0·70-0·77) at 0 h, 0·87 (0·84-0·90) at 24 h, 0·87 (0·84-0·90) at 48 h, and 0·87 (0·84-0·91) at 72 h. Neuron-specific enolase predicted functional outcome with an AUROC of 0·61 (95% CI 0·56-0·65) at 0 h, 0·78 (0·75-0·82) at 24 h, 0·85 (0·81-0·88) at 48 h, and 0·86 (0·82-0·89) at 72 h. S100 achieved an AUROC of 0·74 (95% CI 0·71-0·78) at 0 h, 0·84 (0·81-0·87) at 24 h, 0·79 (0·75-0·82) at 48 h, and 0·78 (0·74-0·82) at 72 h. Neurofilament light had a statistically significantly higher AUROC than the second highest marker, glial fibrillary acidic protein, at 24, 48, and 72 h (p<0·0001), but not at 0 h (p=0·27).

INTERPRETATION: Neurofilament light is a highly accurate predictor of long-term outcome after cardiac arrest and superior to other relevant biomarkers evaluated in this study.

FUNDING: The Swedish Research Council (Vetenskapsrådet), the Swedish Heart-Lung Foundation, the Stig and Ragna Gorthon Foundation, the Knutsson Foundation, the Laerdal Foundation, the Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, the Bundy Academy at Lund University, Regional Research Support in Skåne, the Swedish Government, and Roche Diagnostics International.

Background

The reported prevalence of pulmonary embolism (PE) detected during intensive care varies substantially. Computed tomography pulmonary angiography (CTPA) is the diagnostic reference method, but assessing pre-test probability and finding distinct indications for CTPA from clinical observations is difficult in mechanically ventilated critically ill patients.

Aims

To describe the rate of positive diagnostic outcome (yield) from CTPA exams performed on PE suspicion and to identify predictors in the free text motivational reasons from the referring clinician and among selected patient variables during intensive care for other conditions.

Methods

CTPA exams and reports in adult, mechanically ventilated patients referred from two intensive care units during a 5-year period were compared to the radiology order content and to data collected from medical records. The association between a positive exam and five arbitrarily defined reasons for ordering the exam as well as selected patient variables was assessed using multivariable logistic regression.

Results

Among 1113 thoracic computed tomography exams, 243 were CTPA ordered on clinical PE suspicion, yielding 52 (21% [95% CI: 17–26]) positives. Reasons “Elevated D-dimer” and “Undefined clinical suspicion” were significantly associated with a positive exam. However, none of the selected patient variables was significantly associated with a CTPA finding of PE.

Conclusion

The diagnostic yield of clinical CTPA exams for suspected PE in mechanically ventilated patients fell within a range commonly cited for suspected acute PE in emergency department populations, but its association with clinical signs described in the CTPA order and with selected patient variables was low.

Background: Cardiac arrest (CA) is a major cause of mortality and morbidity. Accurate prediction of neurological outcome and survival remains challenging. In this context, our study aimed to explore novel molecular biomarkers that could provide additional insights into the pathophysiology of brain injury after CA and potentially distinguish patients with no brain injury (CPC 1) from those with any degree of neurological damage from moderate injury up to death (CPC 2-5), and complement existing prognostic tools.

Methods: Whole blood samples collected 48 h after return of spontaneous circulation were analyzed by RNA sequencing in a subgroup of 50 CA patients from the monocenter North Pole cohort, and by quantitative PCR in 233 patients from the same cohort as well as in 511 patients from the multicenter TTM trial. The association of gene expression changes with 6-month neurological outcome (assessed by the Cerebral Performance Category (CPC) score) and survival was studied.

Results: In a discovery phase with a subset of 50 patients from the North Pole cohort (25 CPC 1 and 25 CPC 5), direct RNA sequencing identified the solute carrier family 2 member 1 (SLC2A1), a gene encoding a major glucose transporter at the blood-brain barrier (GLUT1), as significantly upregulated in CPC 5 patients (dead with severe neurological impairment) compared to survivors without neurological sequelae (CPC 1). This upregulation was confirmed by quantitative PCR and extended to the entire North Pole cohort (p < 0.001). SLC2A1 was an independent predictor of neurological sequelae or death in this cohort. In the TTM trial, SLC2A1 was also upregulated in patients with neurological sequelae or death (p < 0.001) and was an independent predictor of neurological sequelae or death, providing an incremental predictive value to a baseline clinical model (odds ratio = 2.06, 95% confidence interval 1.31-3.4, p = 2.82E-03, and likelihood ratio test p < 0.001).

Conclusion: Blood level of SLC2A1 is a tentative blood biomarker that may aid in neurological outcome prediction after CA and also provide new insights into post-CA injury mechanisms.

Importance: Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer.

Objectives: To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest.

Design, Setting, and Participants: The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively.

Intervention: Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 degrees C).

Main Outcomes and Measures: The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT).

Results: Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, -0.02 [95% CI, -0.67 to 0.63]; SDMT: mean difference, -0.09 [95% CI, -0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, -2.00 to -1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, -0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months.

Conclusions and Relevance: Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery.

BACKGROUND: Reperfusion by mechanical thrombectomy (MT) is an alternative for reperfusion in acute pulmonary embolism (PE) when systemic thrombolysis (ST) is contraindicated or has failed.

OBJECTIVES: To evaluate the early experience from MT in Sweden with comparison to ST.

METHODS: We included all adult patients treated with large-bore MT in Sweden from January the year the technique was introduced until December 2023 as well as patients concurrently treated with ST in the respective hospitals. The primary outcome was a composite of early death or severe bleeding.

RESULTS: During the study period, MT was performed exclusively with the FlowTriever system (FT). Among 132 patients included in 7 hospitals, 61 patients aged 67±15 years (mean ± SD) were treated with FT only and 61 aged 68±14 years with ST only. High-risk PE was present in 32 patients in the FT group and 38 in the ST group. The other patients all had intermediate-high risk PE. There were 6 primary outcome events in the FT group and 17 in the ST group (adjusted OR 0.19; 95% CI 0.05-0.69). Five (8%) patients in the FT group and 13 (21%) in the ST group died within 30 days (OR 0.33; 95% CI 0.11-0.99). One severe bleeding occurred after FT and 7 after ST (OR 0.18; 95% CI 0.03-1.10).

CONCLUSION: Mechanical thrombectomy, using the FlowTriever system, in high and intermediate-high risk pulmonary embolism was effective and possibly safer than reperfusion with systemic thrombolysis.

Background: Patients discharged alive after in-hospital cardiac arrest (IHCA) have an increased mortality up to a year after hospital discharge. Improving our ability to identify patients at high risk of death one year after IHCA may improve survival through secondary prevention. We aimed to evaluate the possibility to predict recurrent cardiac arrestor death among in-hospital cardiac arrest survivors with support from a machine learning model. Method: All patients (>18 year) discharged alive after IHCA in the Swedish registry for cardiopulmonary resuscitation (SRCR) from 2010 to 2021 were included. Potential predictors included in the model were data related to the index IHCA, comorbidities, socioeconomic data and prescription medication obtained from national Swedish registries. Extreme gradient boosting (XGBoost) model was trained to predict the outcome. Receiver operating characteristics and area under the curve (ROC-AUC) was used to evaluate model performance. Results: Of the 7302 included patients, 22% had developed the outcome. The best performing model with 1241 variables had ROC-AUC 0.72 (95% CI 0.70-0.75). Features of greatest importance were highest serum creatinine measured before IHCA, age and unknown civil status. Comorbidity and cardiac arrest circumstances were important classes of features for this model. Conclusion: In this dataset, an XGBoost model could predict recurrent cardiac arrest or death within one year after IHCA with a modest performance and good accuracy. If these results can be validated, this model could potentially be used clinically to assess the risk of another cardiac arrest in survivors of IHCA.

Objective: 30-day survival after cardiac arrest is low, 12.4% and 36% for out-of-hospital and in-hospital cardiac arrest, respectively. Heart failure is a known risk condition for cardiac arrest. Improving our ability to identify patients at high risk of cardiac arrest would enable prevention. We aimed to develop a prediction model for cardiac arrest to be used in patients newly diagnosed with heart failure.

Design: A nationwide registry-based observational study.Setting Data were sourced from the Swedish Heart Failure Registry (1 January 2005 to 31 December 2021).Participants This cohort included 45 068 patients discharged from hospital after first hospitalisation for newly diagnosed heart failure. Patients discharged from hospital with palliative care and/or implantable defibrillators were excluded.Outcome measure and analysis The primary outcome was defined as cardiac arrest registered in the Swedish Registry for Cardiopulmonary Resuscitation until final follow-up (15 November 2022). Patients who died without resuscitation were treated as competing events. A Random Survival Forest model for competing risk was developed using predictors from the heart failure registry. The model was evaluated with Brier score, observed versus predicted cumulative incidence, Concordance-index (C-index) and time-dependent area under the curve of a receiver operating characteristics graph (AUC-ROC).

Results: In this cohort, 2399 (5%) patients had received cardiopulmonary resuscitation (CPR) (5%), and 31 989 (71%) patients died without resuscitation. Our model with 82 predictors had a low Brier score indicating a capacity to accurately predict cumulative incidence of cardiac arrest on a group level. However, the model also had a low C-index 0.52 and low AUC-ROC 0.63-0.65.

Conclusion: Our Random Survival Forest model for competing risk could not accurately predict cardiac arrest in individual patients newly diagnosed with heart failure, because the event death without attempted resuscitation was treated as a competing event. The lack of information on transitions to palliative care and Do-Not-Attempt-CPR-orders limits the clinical relevance of any cardiac arrest prediction model.

Background: Guidelines recommend systemic thrombolysis (ST) as first-line reperfusion therapy for highrisk pulmonary embolism (PE), however, clinical concerns regarding bleeding risk frequently limit its use in clinical practice. Catheter-directed therapy (CDT) should be considered when ST is contraindicated or has failed but is increasingly used outside these recommendations despite limited guideline support. Prospective data on short-and long-term outcomes after CDT, particularly in relation to a concurrent ST-treated population, remain scarce. PE-NORDIC aims to evaluate short-and long-term outcomes after CDT and ST for PE in the Nordic countries.

Methods: In this multicenter prospective observational study conducted in the Nordics, 244 adult patients with confirmed acute PE treated with CDT or ST will be enrolled and followed for up to 1 year. The primary outcome is a composite of all-cause mortality or severe bleeding within 30 days. Secondary outcomes include the individual components of the primary composite, need for rescue treatment, recurrent PE, length of stay in intensive care unit and hospital, right ventricular function, functional capacity, dyspnea, health-related quality of life, health economics, and PE complications. Analyses will be performed using multivariable regression models adjusted for relevant clinical confounders, with complementary propensity score-based methods. Strengths and limitations of this study: center dot Multicenter prospective real-world study with comprehensive short-and long-term data collection in a rare patient population. center dot Broad inclusion criteria enhancing generalizability. center dot Pragmatic inclusion reflecting routine clinical practice, combined with structured and active follow-up. center dot Non-randomized design with risk of confounding by indication and residual confounding, despite statistical adjustment.

Background

Unit-to-unit transfer of critically ill patients infers hazards that may cause adverse events. Circumstantial factors associated with mortality after intensive care include days in the ICU, night-time or weekend discharge and capacity transfer as compared to other reasons for transfer. Distance travelled may also constitute an indirect risk. The aim of this study was to assess potential associations between these circumstantial factors and the risk of death 30 days after transfer.

Methods

Data from 2015 to 2019 was retrieved from the Swedish Intensive Care Registry. Logistic regression was used for risk analysis.

Results

Among 4,327 patients, 965 (22%) were deceased 30 days after transfer. 1351 patients undergoing capacity transfer had a higher morbidity than patients transferred for other reasons. Using univariable logistic regression, days spent in the referring ICU before transfer, capacity transfer as compared to clinical transfer and repatriation as well as SAPS3 in the receiving ICU were associated with a higher risk of death at 30 days. However, after multivariable regression with adjustment for ICD-10 diagnosis and Standardised Mortality Rate in the receiving ICU, these associations were lost.

Conclusion

Our results suggest that inter-hospital transfer is safe to carry out at any time of day and over shorter as well as longer distances.

Aims: To investigate whether out-of-hospital cardiac arrest (OHCA) survivors had lower levels of self-reported physical activity compared to a non-cardiac arrest control group with myocardial infarction (MI), and to explore if symptoms of anxiety, depression, kinesiophobia (fear of movement), and fatigue were associated with a low level of physical activity.Methods and results: Pre-defined case-control sub-study within the international Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Out-of-hospital cardiac arrest survivors at 8 of 61 TTM2 sites in Sweden, Denmark, and the UK were invited. Participants were matched 1:1 to MI controls. Both OHCA survivors and MI controls answered two questions on self-reported physical activity, categorized as a low, moderate, or high level of physical activity, and questionnaires on anxiety and depression symptoms, kinesiophobia, and fatigue 7 months after the cardiac event. Overall, 106 of 184 (58%) eligible OHCA survivors were included and matched to 91 MI controls. In total, 25% of OHCA survivors and 20% of MI controls reported a low level of physical activity, with no significant difference (P = 0.13). Symptoms of kinesiophobia and fatigue were significantly associated with a low level of physical activity in both groups. Out-of-hospital cardiac arrest survivors had significantly more kinesiophobia compared to MI controls (18% vs. 9%, P = 0.04), while levels of anxiety and depression symptoms and fatigue were similar.Conclusion: Out-of-hospital cardiac arrest survivors had similar levels of physical activity compared to matched MI controls. High level of kinesiophobia and fatigue were associated with a low level of physical activity in both groups.Registration ClinicalTrials.gov: NCT03543332