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ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.

Aims: Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low‐dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP). Methods: From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. Results: We included 29 patients (age 52 [46–64] years, 69% female). NOR median time to peak effect on MAP was 74 [53–94] s. After bolus administration, MAP increased by 24% (15–31%). A 2‐comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. Conclusion: We have developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target‐controlled infusion. [ABSTRACT FROM AUTHOR]

Objective: Mean arterial pressure is widely used as the variable to monitor during anesthesia. But there are many other variables proposed to define intraoperative arterial hypotension. The goal of the present study was to search arterial pressure variables linked with prolonged postoperative length of stay (pLOS). Design: Retrospective cohort study of adult patients having received general anesthesia for a scheduled non-cardiac surgical procedure between 15th July 2017 and 31st December 2019. Methods: pLOS was defined as a stay longer than the median (main outcome), adjusted for surgery type and duration. 330 arterial pressure variables were analyzed and organized through a clustering approach. An unsupervised hierarchical aggregation method for optimal cluster determination, employing Kendall's tau coefficients and a penalized Bayes information criterion was used. Variables were ranked using the absolute standardized mean distance (aSMD) to measure their effect on pLOS. Finally, after multivariate independence analysis, the number of variables was reduced to three. Results: Our study examined 9,516 patients. When LOS is defined as strictly greater than the median, 34% of patients experienced pLOS. Key arterial pressure variables linked with this definition of pLOS included the difference between the highest and lowest pulse pressure values computed throughout the surgery (aSMD[95%CI] = 0.39[0.31–0.40], p<0.001), the accumulated time pulse pressure above 61mmHg (aSMD = 0.21[0.17–0.25], p<0.001), and the lowest MAP during surgery (aSMD = 0.20[0.16–0.24], p<0.001). Conclusions: By applying a clustering approach, three arterial pressure variables were associated with pLOS. This scalable method can be applied to various dichotomized outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Awake surgery is now a common approach for the resection of glioma. One of the surgical complications is mini-stroke which take the form of periresectional small areas of brain ischemic lesions. The main objective of this study is to evaluate the association between factors related to anesthetic management and the risk of mini-stroke, in awake surgery for glioma resection. Methods: In this single-center retrospective study, all patients who were operated on, between 2011 and 2022, in awake conditions for a glioma resection, were retrospectively included. The studied anesthetic parameters included hemodynamic variables, fluid intake and urinary output. The primary endpoint was the presence of mini-stroke on a magnetic resonance imaging performed within the first 48 h postoperatively. Results: A total of 176 surgeries were included. Mini-stroke was present in 120/171 surgeries (70%), with a median volume of 1.2 interquartile range [0.4–2.2] cubic centimeters (cc). In a multivariable analysis, only the per operative urinary output was significantly associated with the incidence of postoperative mini-strokes (adjusted odd-ratio 0.65, 95% confidence interval 0.45–0.94, p = 0.02). No variables related to the anesthetic management were associated with the volume of postoperative mini-strokes. In particular, the time spent below 90% of the baseline systolic blood pressure was not associated with either the risk or the volume of mini-strokes. Conclusion: During awake surgery for glioma resection, among several anesthesia related factors, only the per operative urinary output was associated with the incidence of postoperative mini-stroke. [ABSTRACT FROM AUTHOR]

Aims: An elevated risk of adverse events persists for years in cardiogenic shock (CS) survivors with high mortality rate and physical/mental disability. This study aims to link clinical CS‐survivor phenotypes with distinct late host‐response patterns at intensive care unit (ICU) discharge and long‐term outcomes using model‐based clustering. Methods and results: In the original prospective, observational, international French and European Outcome Registry in Intensive Care Units (FROG‐ICU) study, ICU patients with CS on admission were identified (N = 228). Among them, 173 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct CS‐survivor phenotypes at ICU discharge using 15 readily available clinical and laboratory variables. The primary endpoint was 1 year of mortality after ICU discharge. Secondary endpoints were readmission and physical/mental disability [short form‐36 questionnaire (SF‐36) score] within 1 year after ICU discharge. Two distinct phenotypes at ICU discharge were identified (A and B). Patients in Phenotype B (38%) were more anaemic and had higher circulating levels of lactate, sustained kidney injury, and persistent elevation in plasma markers of inflammation, myocardial fibrosis, and endothelial dysfunction compared with Phenotype A. They had also a higher rate of non‐ischaemic origin of CS and right ventricular dysfunction on admission. CS survivors in Phenotype B had higher 1 year of mortality compared with Phenotype A (P = 0.045, Kaplan–Meier analysis). When adjusted for traditional risk factors (i.e. age, severity of illness, and duration of ICU stay), Phenotype B was independently associated with 1 year of mortality [adjusted hazard ratio = 2.83 (95% confidence interval 1.21–6.60); P = 0.016]. There was a significantly lower physical quality of life in Phenotype B patients at 3 months (i.e. SF‐36 physical component score). Conclusions: A phenotype with sustained inflammation, myocardial fibrosis, and endothelial dysfunction at ICU discharge was identified from readily available data and was independently associated with poor long‐term outcomes in CS survivors. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common condition in severely ill patients associated with poor outcomes. We assessed the associations between urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary liver-type fatty acid-binding protein (uLFABP), and urinary cystatin C (uCysC) concentrations and patient outcomes. Methods: We assessed the predictive performances of uNGAL, uLFABP, and uCysC measured in the early phase of intensive care unit (ICU) management and at discharge from the ICU in severely ill patients for short- and long-term outcomes. The primary outcome was the occurrence of AKI during ICU stay; secondary outcomes were 28-day and 1-yr allcause mortality. Results: In total, 1,759 patients were admitted to the ICU, and 728 (41.4%) developed AKI. Median (interquartile range, IQR) uNGAL, uLFABP, and uCysC concentrations on admission were 147.6 (39.9-827.7) ng/mL, 32.4 (10.5-96.0) ng/mL, and 0.33 (0.12-2.05) mg/L, respectively. Biomarker concentrations on admission were higher in patients who developed AKI and associated with AKI severity. Three hundred fifty-six (20.3%) and 647 (37.9%) patients had died by 28 days and 1-yr, respectively. Urinary biomarker concentrations at ICU discharge were higher in non-survivors than in survivors. The areas under the ROC curve (95% confidence interval) of uLFABP for the prediction of AKI, 28-day mortality, and 1-yr mortality (0.70 [0.67-0.72], 0.63 [0.59-0.66], and 0.57 [0.51-0.63], respectively) were inferior to those of the other biomarkers. Conclusions: uNGAL, uLFABP, and uCysC concentrations on admission were associated with poor outcomes. However, their predictive performance, individually and in combination, was limited. Further studies are required to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Comprehensive uptitration of neurohormonal blockade targets fundamental mechanisms underlying development of congestion and may be an additional approach for decongestion after acute heart failure (AHF)., Objectives: This hypothesis was tested in the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies) trial., Methods: In STRONG-HF, patients with AHF were randomized to the high-intensity care (HIC) arm with fast up-titration of neurohormonal blockade or to usual care (UC). Successful decongestion was defined as an absence of peripheral edema, pulmonary rales, and jugular venous pressure <6 cm., Results: At baseline, the same proportion of patients in both arms had successful decongestion (HIC 48% vs UC 46%; P = 0.52). At day 90, higher proportion of patients in the HIC arm (75%) experienced successful decongestion vs the UC arm (68%) (P = 0.0001). Each separate component of the congestion score was significantly better in the HIC arm (all, P < 0.05). Additional markers of decongestion also favored the HIC: weight reduction (adjusted mean difference: -1.36 kg; 95% CI: -1.92 to -0.79 kg), N-terminal pro-B-type natriuretic peptide level, and lower orthopnea severity (all, P < 0.001). More effective decongestion was achieved despite a lower mean daily dose of loop diuretics at day 90 in the HIC arm. Among patients with successful decongestion at baseline, those in the HIC arm had a significantly better chance of sustaining decongestion at day 90. Successful decongestion in all subjects was associated with a lower risk of 180-day HF readmission or all-cause death (HR: 0.40; 95% CI: 0.27-0.59; P < 0.0001)., Conclusions: In STRONG-HF, intensive uptitration of neurohormonal blockade was associated with more efficient and sustained decongestion at day 90 and a lower risk of the primary endpoint., Competing Interests: Funding Support and Author Disclosures The study was funded through a grant provided to Heart Initiative by Roche Diagnostics International. Dr Mebazaa has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; has received honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnea. Drs Cotter and Davison are directors of Heart Initiative, a nonprofit organization, and employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Cohen-Solal has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. Dr Metra has received personal fees from Amgen, LivaNova, and Vifor Pharma as a member of executive committees of sponsored clinical trials; and from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics for participation to advisory boards or for speaking at sponsored meetings. Mr Edwards, Drs Barros, Novosadova, and Takagi are employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Chioncel has received grants from Servier. Dr Diaz has received supporting fees for coordination of STRONG-HF trial activities. Dr Filippatos has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier, and Amgen. Dr Sliwa has received grants from Medtronic and Servier; and has received honoraria from MSD, Novartis, and Sanofi. Dr Voors has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. Dr Damasceno works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. Dr Pang has received grants or research contracts from the American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; has received consulting fees from Roche; has received honoraria from WebMD; and has financial interest in The Heart Course. Dr Čelutkienė has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as a consultant for or on the Advisory Board/Steering Committee/Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Redcardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as co-founder and nonexecutive director of Us2.ai. Dr Pagnesi has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, and Vifor Pharma. Dr Arrigo has received speaker fees from Abbott Vascular and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated., Methods and Results: We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care., Conclusions: Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Acute kidney injury (AKI) is a common condition in severely ill patients associated with poor outcomes. We assessed the associations between urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary liver-type fatty acid-binding protein (uLFABP), and urinary cystatin C (uCysC) concentrations and patient outcomes., Methods: We assessed the predictive performances of uNGAL, uLFABP, and uCysC measured in the early phase of intensive care unit (ICU) management and at discharge from the ICU in severely ill patients for short- and long-term outcomes. The primary outcome was the occurrence of AKI during ICU stay; secondary outcomes were 28-day and 1-yr allcause mortality., Results: In total, 1,759 patients were admitted to the ICU, and 728 (41.4%) developed AKI. Median (interquartile range, IQR) uNGAL, uLFABP, and uCysC concentrations on admission were 147.6 (39.9-827.7) ng/mL, 32.4 (10.5-96.0) ng/mL, and 0.33 (0.12-2.05) mg/L, respectively. Biomarker concentrations on admission were higher in patients who developed AKI and associated with AKI severity. Three hundred fifty-six (20.3%) and 647 (37.9%) patients had died by 28 days and 1-yr, respectively. Urinary biomarker concentrations at ICU discharge were higher in non-survivors than in survivors. The areas under the ROC curve (95% confidence interval) of uLFABP for the prediction of AKI, 28-day mortality, and 1-yr mortality (0.70 [0.67-0.72], 0.63 [0.59-0.66], and 0.57 [0.51-0.63], respectively) were inferior to those of the other biomarkers., Conclusions: uNGAL, uLFABP, and uCysC concentrations on admission were associated with poor outcomes. However, their predictive performance, individually and in combination, was limited. Further studies are required to confirm our results.