Combined effects of targeted blood pressure, oxygenation, and duration of device-based fever prevention after out-of-hospital cardiac arrest on 1-year survival: post hoc analysis of a randomized controlled trial.

BACKGROUND: The "Blood Pressure and Oxygenation Targets in Post Resuscitation Care" (BOX) trial investigated whether a low versus high blood pressure target, a restrictive versus liberal oxygenation target, and a shorter versus longer duration of device-based fever prevention in comatose patients could improve outcomes. No differences in rates of discharge from hospital with severe disability or 90-day mortality were found. However, long-term effects and potential interaction of the interventions are unknown. Accordingly, the objective of this study is to investigate both individual and combined effects of the interventions on 1-year mortality rates. METHODS: The BOX trial was a randomized controlled two-center trial that assigned comatose resuscitated out-of-hospital cardiac arrest patients to the following three interventions at admission: A blood pressure target of either 63 mmHg or 77 mmHg; An arterial oxygenation target of 9-10 kPa or 13-14 kPa; Device-based fever prevention administered as an initial 24 h at 36 °C and then either 12 or 48 h at 37 °C; totaling 36 or 72 h of temperature control. Randomization occurred in parallel and simultaneously to all interventions. Patients were followed for the occurrence of death from all causes for 1 year. Analyzes were performed by Cox proportional models, and assessment of interactions was performed with the interventions stated as an interaction term. RESULTS: Analysis for all three interventions included 789 patients. For the intervention of low compared to high blood pressure targets, 1-year mortality rates were 35% (138 of 396) and 36% (143 of 393), respectively, hazard ratio (HR) 0.92 (0.73-1.16) p = 0.47. For the restrictive compared to liberal oxygenation targets, 1-year mortality rates were 34% (135 of 394) and 37% (146 of 395), respectively, HR 0.92 (0.73-1.16) p = 0.46. For device-based fever prevention for a total of 36 compared to 72 h, 1-year mortality rates were 35% (139 of 393) and 36% (142 of 396), respectively, HR 0.98 (0.78-1.24) p = 0.89. There was no sign of interaction between the interventions, and accordingly, no combination of randomizations indicated differentiated treatment effects. CONCLUSIONS: There was no difference in 1-year mortality rates for a low compared to high blood pressure target, a liberal compared to restrictive oxygenation target, or a longer compared to shorter duration of device-based fever prevention after cardiac arrest. No combination of the interventions affected these findings. Trial registration ClinicalTrials.gov NCT03141099, Registered 30 April 2017.

Psychometric Properties of the Kansas City Cardiomyopathy Questionnaire in a Surgical Population of Patients With Aortic Valve Stenosis.

The 12-item version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was originally developed for patients with heart failure but has been used and tested among patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation. Whether the instrument is suitable for patients with AS who underwent surgical aortic valve replacement (SAVR) is currently unknown. Thus, we aimed to investigate the psychometric properties of the KCCQ-12 before and after SAVR among patients with severe AS. We conducted a prospective cohort of 184 patients with AS who completed the KCCQ-12 and the EuroQol 5 Dimension 5 Levels before and 4 weeks after surgery. Construct validity was investigated with hypothesis testing and an analysis of Spearman's correlation between the two instruments. Structural validity was investigated with explorative and confirmatory factor analyses and reliability with Cronbach's α. All analyses were conducted on data from the two time points (preoperatively and four weeks after surgery). The hypothesis testing revealed how the New York Heart Association class was significantly correlated with the preoperative KCCQ-12 total score (higher New York Heart Association class, worse score). A longer length of hospital stay and living alone were significantly associated with poorer postoperative KCCQ-12 total score. KCCQ-12 and EuroQol 5 Dimension 5 Levels were moderately correlated in most domains/the total score/Visual Analogue Scale score. Principal component analyses revealed two 3-factor structures. The confirmatory factor analyses did not support the original model at any time point. Cronbach's α ranged from 0.22 to 0.84 in three preoperative factors and from 0.39 to 0.76 in the postoperative factors. The total Cronbach's α was 0.83 for the suggested preoperative 3-factor model and 0.83 for the postoperative model. In conclusion, the Danish version of the KCCQ-12 tested in a population of patients with AS who underwent SAVR appears to have acceptable construct validity, whereas structural validity cannot be confirmed for the original four-factor model. Overall reliability is good.

Sex differences in symptoms of anxiety, depression, post-traumatic stress disorder, and cognitive function among survivors of out-of-hospital cardiac arrest.

AIMS: Anxiety, depression, and post-traumatic stress disorder (PTSD) among out-of-hospital cardiac arrest (OHCA) survivors may impact long-term recovery. Coping and perception of symptoms may vary between sexes. The aim was to explore sex differences in psychological consequences following OHCA. METHODS AND RESULTS: This was a prospective observational study of OHCA survivors who attended a structured 3-month follow-up. Symptoms of anxiety/depression were measured using the Hospital Anxiety and Depression Scale, range 0-21, with a cut-off score of ≥8 for significant symptoms; PTSD was measured with the PTSD Checklist for DSM-5 (PCL-5), range 0-80. A score of ≥33 indicated PTSD symptoms. Cognitive function was assessed by the Montreal Cognitive Assessment. From 2016 to 2021, 381 consecutive comatose OHCA survivors were invited. Of these, 288 patients (76%) participated in the follow-up visit [53 (18%) females out of 80 survivors and 235 (82%) males out of 300 alive at follow-up (78%)]. Significant symptoms of anxiety were present in 47 (20%) males and 19 (36%) females (P = 0.01). Significant symptoms of PTSD were present in 30% of males and 55% of females (P = 0.01). Adjusting for pre-specified covariates using multivariable logistic regression, female sex was significantly associated with anxiety [odds ratio (OR): 2.18, confidence interval (CI): 1.09-4.38, P = 0.03]. This difference was especially pronounced among young females (below median age, ORadjusted: 3.31, CI: 1.32-8.29, P = 0.01) compared with young males. No significant sex difference was observed for depression or cognitive function. CONCLUSION: Symptoms of anxiety and PTSD are frequent in OHCA survivors, and female survivors report significantly more symptoms of anxiety and PTSD compared with males. In particular, young females were significantly more symptomatic than young males.

Duration of Device-Based Fever Prevention after Cardiac Arrest.

BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking. METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months. RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).