Pulmonary Artery Catheter Use and In-hospital Outcomes in Cardiac Surgery: A Systematic Review and Meta-analysis.

OBJECTIVES: To determine the association of intraoperative pulmonary artery catheter (PAC) use with in-hospital outcomes in cardiac surgical patients. METHODS: MEDLINE, Embase, and Cochrane Library (Wiley) databases were screened for studies that compared cardiac surgical patients receiving intraoperative PAC with controls and reporting in-hospital mortality. Secondary outcomes included intensive care unit (ICU) length of stay, cost of hospitalization, fluid volume administered, intubation time, inotropes use, acute kidney injury (AKI), stroke, myocardial infarction (MI), and infections. RESULTS: Seven studies (25,853 patients, 88.6% undergoing coronary artery bypass graft surgery) were included. In-hospital mortality was significantly increased with PAC use (OR 1.57; 95% CI 1.12-2.20, p = 0.04); PAC use was also associated with greater intraoperative inotrope use (OR 2.61; 95% CI 1.54-4.41) and costs (SMD = 0.20; 95% CI 0.16-0.23), longer ICU stay (SMD = 0.29; 95% CI 0.25-0.33), and longer intubation time (SMD = 0.44; 95% CI 0.12-0.76). CONCLUSIONS: PAC use is associated with significantly increased odds of in-hospital mortality, but the amount and quality of the available evidence is limited. Prospective randomized trials testing the effect of PAC on the outcomes of cardiac surgical patients are urgently needed.

Association of Cerebral Oximetry With Brain Ischemic Lesions and Functional Outcomes in Arch Repair.

BACKGROUND: This exploratory analysis of the randomized controlled Aortic Surgery Cerebral Protection Evaluation CardioLink-3 trial sought to determine if cerebral oximetry desaturation during elective proximal arch repair is associated with detrimental postoperative neuroradiologic and neurofunctional outcomes. METHODS: Cerebral oximetry and pre- and postoperative brain magnetic resonance imaging data from 101 participants were analyzed. Oximetry data from the trial allocation groups were compared; the relationships between cerebral oximetry indices and new ischemic cerebral lesions on magnetic resonance imaging and neurologic outcomes were also evaluated. RESULTS: Total cerebral desaturation events (>20% decrease from baseline) on the left (median [interquartile range], 1 [1-3] vs 1.5 [0.5-3] with innominate and axillary cannulation; P = .80) were comparable to those on the right (1 [1-3] vs 1 [0-3]; P = .75) as were the total area under the curve of desaturation (left, P = .61; right, P = .84). Seventy patients had new ischemic lesions, among whom 36 had new severe lesions. Total desaturation events and area under the curve of desaturation were similar in patients with and without new ischemic lesions or severe lesions. The nadir regional cerebral saturation was lower on the left (49% [41-56]) than the right (53% [44-59]); left desaturation episodes were associated with lower postoperative cognitive test scores (P = .004). CONCLUSIONS: The innominate and axillary cannulation techniques for elective proximal arch repair with unilateral antegrade cerebral perfusion were associated with similar occurrences of cerebral oximetry desaturation and neither were associated with new ischemic lesions.

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

BACKGROUND: Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment. METHODS: Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity. RESULTS: Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes. CONCLUSIONS: The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery. Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

L'état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L'administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l'état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L'administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L'essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l'anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l'état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l'administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l'état confusionnel, comparativement à une politique d'administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d'équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l'essai si leurs équipes d'anesthésie cardiaque acceptent d'appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l'état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d'administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l'ensemble des périodes a lieu avant le début de l'essai à l'hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l'essai. Le critère d'évaluation principal est l'incidence de l'état confusionnel dans les 72 heures suivant l'intervention chirurgicale. L'étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l'Amérique du Nord. L'état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l'état confusionnel. L'essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l'administration de benzodiazépines durant une chirurgie cardiaque réduit l'incidence de l'état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

Methemoglobin as a marker of acute anemic stress in cardiac surgery.

Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.

Wearable Cardiac Rhythm Monitoring Device for Detection of Postoperative Atrial Fibrillation.

PURPOSE: This study evaluated the use of a wearable, patch-based cardiac rhythm monitoring device in detecting postoperative atrial fibrillation (POAF) among cardiac surgical patients within 30 days after hospital discharge. DESCRIPTION: From the SEARCH-AF (The Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation) CardioLink-1 trial, this study examined rates of POAF according to surgery type and the incremental value of continuous cardiac rhythm monitoring among patients who underwent valve surgery. The primary outcome was cumulative atrial fibrillation or atrial flutter lasting for ≥6 minutes detected by continuous monitoring or atrial fibrillation or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization. EVALUATION: The primary outcome occurred in 8.2%, 13.5%, and 21.2% of patients who underwent isolated coronary artery bypass grafting (CABG), isolated valve surgery, and combined CABG and valve surgery. Relative to patients who underwent isolated CABG, those patients who had valve surgery were more likely to experience POAF. A higher diagnostic yield was obtained when the patch-based cardiac rhythm monitor was applied in patients who underwent valve surgery. CONCLUSIONS: Use of a wearable, patch-based cardiac monitoring device was an effective detection strategy among patients undergoing valve surgery, given their higher risk of developing POAF.

The Impact of Statins on Postdischarge Atrial Fibrillation After Cardiac Surgery: Secondary Analysis from a Randomized Trial.

Background: Whether statins reliably reduce the risk of postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery remains controversial. We sought to determine the impact of statin use on new-onset postdischarge POAF in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized controlled trial. Methods: We randomized 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥ 2) and no history of preoperative atrial fibrillation (AF) to 30-day continuous cardiac rhythm monitoring after discharge from cardiac surgery with a wearable, patched-based device or to usual care. The primary endpoint was the occurrence of cumulative AF and/or atrial flutter lasting for ≥ 6 minutes detected by continuous monitoring, or AF and/or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization. Results: The 260 patients (77.4%) discharged on statins were more likely to be male (P = 0.018) and to have lower CHA2DS2-VASc scores (P = 0.011). Patients treated with statins at discharge had a 2-fold lower rate of POAF than those who were not treated with statins in the entire cohort (18.4% vs 8.1%, log-rank P = 0.0076). On multivariable Cox regression including the CHA2DS2-VASc score adjustment, statin use was associated with a lower risk of POAF (hazard ratio 0.43, 95% confidence interval: 0.25-0.98, P = 0.043). Use of statins at a higher intensity was associated with lower risk of POAF, suggestive of a dose-response effect (log-rank P trend = 0.0082). Conclusions: The use of statins was associated with a reduction in postdischarge POAF risk among patients undergoing cardiac surgery. The routine use of high-intensity statin to prevent subacute POAF after discharge deserves further study.

Contexte: L'efficacité des statines dans la réduction du risque de fibrillation auriculaire postopératoire (FAPO) chez les patients ayant subi une chirurgie cardiaque ne fait pas l'unanimité. Nous avons tenté de déterminer l'effet de l'utilisation des statines sur la survenue d'une FAPO inaugurale consécutive au congé de l'hôpital dans l'essai SEARCH-AF CardioLink-1, un essai contrôlé à répartition aléatoire sur le suivi étroit en postopératoire des arythmies cardiaques et de la fibrillation auriculaire. Méthodologie: Nous avons réparti aléatoirement 336 patients présentant des facteurs de risque d'AVC (score CHA2DS2-VASc ≥ 2) sans antécédents de fibrillation auriculaire (FA) préopératoire dans deux groupes : les patients du premier groupe étaient équipés d'un dispositif portable sous forme de timbre pour la surveillance continue du rythme cardiaque pendant 30 jours après la sortie de l'hôpital suivant une chirurgie cardiaque; les patients du second groupe étaient suivis de façon conventionnelle. Le critère d'évaluation principal était la survenue cumulative de FA et/ou de flutter auriculaire durant ≥ 6 minutes détecté par la surveillance continue, ou la FA et/ou le flutter auriculaire confirmé par un électrocardiogramme à 12 dérivations dans les 30 jours suivant la répartition aléatoire. Résultats: Les 260 patients (77,4 %) prenant des statines à leur congé de l'hôpital étaient plus susceptibles d'être des hommes (p = 0,018) et d'avoir un score CHA2DS2-VASc plus faible (p = 0,011). Les patients traités par des statines à leur congé de l'hôpital avaient deux fois moins de risques de présenter une FAPO que les patients ne recevant pas de statines dans l'ensemble de la cohorte (18,4 % contre 8,1 %, valeur de p calculée selon le test de Mantel-Haenszel = 0,0076). Dans une régression de Cox multivariable incluant l'ajustement du score CHA2DS2-VASc, l'utilisation des statines a été associée à un risque moindre de FAPO (rapport des risques instantanés : 0,43, intervalle de confiance à 95 % de 0,25 à 0,98; p = 0,043). L'utilisation de statines à plus fortes doses a été associée à un risque moindre de FAPO, ce qui laisse croire à un effet dose-réponse (valeur de p de tendance selon le test de Mantel-Haenszel = 0,0082). Conclusions: L'utilisation de statines est associée à une réduction du risque de FAPO après le congé de l'hôpital chez les patients ayant subi une chirurgie cardiaque. L'utilisation systématique de statines à fortes doses pour prévenir la FAPO subaiguë après le congé d'hôpital mérite une étude plus approfondie.

Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial).

INTRODUCTION: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies. METHODS AND ANALYSIS: This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites. ETHICS AND DISSEMINATION: The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT05126303.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits. METHODS: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality. RESULTS: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I2=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I2=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I2=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I2=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality). CONCLUSIONS: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42019128144.

Mitral repair with leaflet preservation versus leaflet resection and ventricular reverse remodeling from a randomized trial.

OBJECTIVES: In the Canadian Mitral Research Alliance (CAMRA) Trial CardioLink-2 leaflet resection versus preservation techniques for posterior leaflet prolapse was investigated and no difference was shown in their effect on mean mitral gradient at peak exercise at 12 months postoperatively. The purpose of this subanalysis was to evaluate the effect of the 2 strategies on left ventricular (LV) reverse remodeling after repair. METHODS: A total of 104 patients were randomized to either a leaflet resection or leaflet preservation strategy. Echocardiograms, performed at baseline (preoperative), predischarge, and 12 months postoperatively, were analyzed in a blinded fashion at a core laboratory. RESULTS: All patients underwent successful mitral repair. At discharge, 3 patients showed moderate mitral regurgitation, whereas the remainder showed mild or less regurgitation. Compared with the baseline echocardiogram, the indexed end diastolic volume was reduced at the discharge echocardiogram (P < .0001) and was further reduced at the 12-month echocardiogram (P = .01). In contrast, the indexed end systolic volume did not significantly change from baseline assessed at the predischarge echocardiogram (P = .32) but improved at 12 months postoperatively (P < .0001), resulting in a corresponding improvement in ejection fraction at 12 months (P < .0001). The type of mitral repair strategy had no significant effect on LV reverse remodeling trends. CONCLUSIONS: The mitral repair strategies used did not influence postoperative LV reverse remodeling, which occurred in stages. Although LV end diastolic dimensions recovered before discharge, improvements in LV end systolic dimension were evident 12 months after repair.

Risk Factors for Postrepair Elevated Mitral Gradient: A Post-hoc Analysis of a Randomized Trial.

BACKGROUND: Predischarge elevated mean mitral gradients (>5 mm Hg) may occur after repair for degenerative mitral regurgitation. We sought to identify risk factors associated with elevated gradients and to evaluate its impact on functional outcomes at 12 months in this subanalysis of the Canadian Mitral Research Alliance CardioLink-2 trial. METHODS: One hundred four patients with degenerative mitral regurgitation undergoing mitral repair were randomized to either a leaflet resection or preservation strategy. Logistic regression was used to identify risk factors associated with an elevated gradient. Functional outcomes at 12 months were compared between participants with and without elevated gradients. RESULTS: Elevated gradients was identified in 15 participants (14.4%), which was not significantly different based on allocation to each repair strategy (P = .10). Patients with elevated gradients were more likely to be women (odds ratio [OR], 4.28; 95% confidence interval [CI], 1.29-14.19; P = .02) and to have a lower preoperative hemoglobin level (OR, 0.93; 95% CI, 0.89-0.98; P = .01) and smaller intercommissural diameter (OR, 0.86; 95% CI, 0.76-0.97; P = .02) and mitral annuloplasty size (OR, 0.71; 95% CI, 0.57-0.87; P = .001). The ratio of intercommissural diameter-to-annuloplasty size was similar between those with and without elevated gradients (both 0.8 ± 0.1, P = .69). At 12 months those with elevated gradients had a worse New York Heart Association functional status (P = .0001), lower peak oxygen saturation in exercise test (P = .01), smaller body weight-walk distance product (P = .02), and higher Borg scale (P = .01) in the 6-minute walk test. CONCLUSIONS: Female gender, smaller mitral anatomy sizes, and lower preoperative hemoglobin levels were associated with postoperative elevated mitral gradients, which was in turn were associated with reduced functional status. Further research is warranted to investigate these potential risk factors.

Acute Infarcts on Brain MRI Following Aortic Arch Repair With Circulatory Arrest: Insights From the ACE CardioLink-3 Randomized Trial.

BACKGROUND: to investigate the frequency and distribution of new ischemic brain lesions detected by diffusion-weighted imaging on brain magnetic resonance imaging after aortic arch surgery. METHODS: This preplanned secondary analysis of the randomized, controlled ACE (Aortic Surgery Cerebral Protection Evaluation) CardioLink-3 trial compared the safety and efficacy of innominate versus axillary artery cannulation during elective proximal aortic arch surgery. Participants underwent pre and postoperative magnetic resonance imaging. New ischemic lesions were defined as lesions visible on postoperative, but not preoperative diffusion weighted imaging. RESULTS: Of the 111 trial participants, 102 had complete magnetic resonance imaging data. A total of 391 new ischemic lesions were observed on diffusion-weighted imaging in 71 (70%) patients. The average number of lesions in patients with ischemic lesion were 5.5±4.9 with comparable numbers in the right (2.9±2.0) and left (3.0±2.3) hemispheres (P=0.49). Half the new lesions were in the middle cerebral artery territory; 63% of the cohort had ischemic lesions in the anterior circulation, 49% in the posterior circulation, 42% in both, and 20% in watershed areas. A probability mask of all diffusion-weighted imaging lesions revealed that the cerebellum was commonly involved. More severe white matter hyperintensity on preoperative magnetic resonance imaging (odds ratio, 1.80 [95% CI, 1.10-2.95]; P=0.02) and lower nadir nasopharyngeal temperature during surgery (odds ratio per 1°C decrease, 1.15 [95% CI, 1.00-1.32]; P=0.05) were associated with the presentation of new ischemic lesion; older age (risk ratio per 1-year increase, 1.02 [95% CI, 1.00-1.04]; P=0.03) and lower nadir temperature (risk ratio per 1°C decrease, 1.06 [95% CI, 1.00-1.14]; P=0.06) were associated with greater number of lesions. CONCLUSIONS: In patients who underwent elective proximal aortic arch surgery, new ischemic brain lesions were common, and predominantly involved the middle cerebral artery territory or cerebellum. Underlying small vessel disease, lower temperature nadir during surgery, and advanced age were risk factors for perioperative ischemic lesions. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02554032.

Prolonged mechanical ventilation after cardiac surgery: substudy of the Transfusion Requirements in Cardiac Surgery III trial.

PURPOSE: Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications. METHODS: Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored. RESULTS: Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications. CONCLUSION: In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.

RéSUMé: OBJET: La ventilation mécanique (VM) prolongée est une complication majeure après chirurgie cardiaque. Nous avons effectué une analyze secondaire de l'étude TRICS III sur les besoins de transfusion au cours de la chirurgie cardiaque pour décrire la durée de la VM, identifier les facteurs associés à une VM prolongée et examiner les associations de la VM prolongée avec la mortalité et les complications. MéTHODES: Quatre mille huit cent neuf participants subissant une chirurgie cardiaque dans 71 hôpitaux à travers le monde ont été inclus. La VM prolongée a été définie à partir de la définition de la Society of Thoracic Surgeons comme un événement durant 24 heures ou plus. Des associations ajustées de facteurs liés aux patients et à la chirurgie avec la VM prolongée ont été examinées en utilisant une régression logistique multifactorielle. Des associations de la VM prolongée avec des complications ont été évaluées en utilisant des rapports de cotes; les associations ajustées entre VM prolongée et mortalité ont été évaluées au moyen d'une régression multinominale. Les associations d'une VM de plus courte durée avec la survie et des complications ont été explorées. RéSULTATS: La VM prolongée est survenue chez 15 % (725/4 809) des participants. Une VM prolongée a été associée à des facteurs chirurgicaux indicateurs de complexité (comme une chirurgie cardiaque antérieure, la durée de la circulation extracorporelle et les tentatives de débranchement) et à des facteurs liés au patient (comme un état préopératoire critique, une défaillance ventriculaire gauche, une insuffisance rénale et une hypertension pulmonaire). La VM prolongée a été associée à des complications périopératoires, mais pas à des complications à long terme. Après ajustement pour le risque, la VM prolongée a été associée à la mortalité périopératoire; son association avec la mortalité à long terme des survivants a été plus faible. Les durées plus courtes de VM n'ont pas été associées à une augmentation du risque de mortalité ou à des complications. CONCLUSION: Dans cette étude auxiliaire de l'essai TRICS III, la VM prolongée a été fréquente après chirurgie cardiaque et a été associée à des facteurs de risque liés au patient et à la chirurgie. Bien que la VM prolongée ait présenté de fortes associations avec les complications périopératoires et la mortalité, elle n'a pas été associée avec des complications à long terme et était plus faiblement associée à la mortalité à long terme parmi les survivants. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT02042898); enregistrée le 23 janvier 2014. Il s'agit d'une étude auxiliaire de l'étude TRICS III sur les besoins de transfusion en chirurgie cardiaque.

ONTraC: A 20-Year History of a Successfully Coordinated Provincewide Patient Blood Management Program: Lessons Learned and Goals Achieved.

Our understanding of the risks associated with perioperative anemia and transfusion, in terms of increased morbidity and mortality, has evolved over the past 2 decades. By contrast, our understanding of the potential mechanisms of injury and optimal treatment strategies remains incomplete. As such, the important role of effective patient blood management (PBM) programs, which address both the effective treatment of anemia and minimizes the need for red blood cell (RBC) transfusion, is of central importance to optimizing patient care and improving patient outcomes. We report on important clinical outcomes of the Ontario Transfusion Coordinator (ONTraC Program), a network of 25 hospital sites, working in coordination over the past 20 years. Transfusion nurse coordinators were assigned to apply multimodal best practice in PBM (including recommended changes in surgical approach; diagnosis, assessment, and treatment of anemia; and adherence to more restrictive RBC transfusion thresholds). Data were collected on various clinical parameters. We further described lessons learned and difficulties encountered in this multisite PBM initiative. A significant reduction in RBC transfusions was observed for numerous indexed surgeries. For example, RBC transfusion rates for knee arthroplasty decreased from 25% in 2002 to 0.4% in 2020. For coronary artery bypass graft (CABG) surgery, transfusion rates decreased from 60% in 2002 to 27% in 2020. We also observed a decrease in RBC units utilized per transfused patient for knee (2.1 ± 0.5 [2002] vs 1.0 ± 0.6 [2020] units per patient) and CABG surgery (3.3 ± 0.6 [2002] vs 2.3 ± 1.9 [2020] units per patient). These reductions were associated with favorable clinical outcomes, including reduced length of hospital stay (P = .00003) and a reduced rate of perioperative infections (P < .001) for nontransfused versus transfused patients. These advances have been achieved with estimated savings in the tens of millions of dollars annually. Our experience and data support the hypothesis that instituting an integrated network of transfusion nurse coordinators can provide an effective provincewide PBM program, reduce RBC transfusions, improve some patient outcomes, and reduce health care costs, as an example of a "win-win-win" medical program.

Update on Applications and Limitations of Perioperative Tranexamic Acid.

Tranexamic acid (TXA) is a potent antifibrinolytic with documented efficacy in reducing blood loss and allogeneic red blood cell transfusion in several clinical settings. With a growing emphasis on patient blood management, TXA has become an integral aspect of perioperative blood conservation strategies. While clinical applications of TXA in the perioperative period are expanding, routine use in select clinical scenarios should be supported by evidence for efficacy. Furthermore, questions regarding optimal dosing without increased risk of adverse events such as thrombosis or seizures should be answered. Therefore, ongoing investigations into TXA utilization in cardiac surgery, obstetrics, acute trauma, orthopedic surgery, neurosurgery, pediatric surgery, and other perioperative settings continue. The aim of this review is to provide an update on the current applications and limitations of TXA use in the perioperative period.

Low-dose aspirin and rivaroxaban combination therapy to overcome aspirin non-sensitivity in patients with vascular disease.

Approximately 20% of vascular patients treated with acetyl salicylic acid (i.e., aspirin) demonstrate less than expected platelet inhibition - putting them at a four-fold increased risk of adverse cardiovascular events. Low-dose rivaroxaban (2.5 mg twice daily) in combination with low-dose aspirin has been shown to reduce adverse cardiovascular and limb events when compared to aspirin alone. In this study, light transmission aggregometry was used to measure arachidonic acid-induced platelet aggregation to evaluate the potential of combining low-dose rivaroxaban and aspirin in attenuating or overcoming aspirin non-sensitivity. In the discovery phase, 83 patients with peripheral arterial disease (PAD) taking 81 mg aspirin daily were recruited from the outpatient vascular surgery clinic at St Michael's Hospital between January to September 2021. 19 (23%) were determined to be non-sensitive to aspirin. After ex-vivo addition of 2.5 mg dosage equivalent of rivaroxaban, aspirin non-sensitivity was overcome in 11 (58%) of these 19 patients. In the validation phase, 58 patients with cardiovascular risk factors who were not previously prescribed aspirin were recruited. In this group, ex-vivo addition of 2.5 mg dosage equivalent of rivaroxaban significantly reduced arachidonic acid-induced platelet aggregation in the presence of aspirin. These results demonstrate the potential for low-dose rivaroxaban to overcome aspirin non-sensitivity in patients with PAD. Further studies are needed to evaluate and confirm these findings.

Stage-based approach to predict left ventricular reverse remodeling after mitral repair.

BACKGROUND: Although predictors of reverse left ventricular (LV) remodeling postmitral valve repair are critical for guiding perioperative decision-making, there remains a paucity of randomized, prospective data to support the criteria that potential predictor variables must meet. METHODS AND RESULTS: The CAMRA CardioLink-2 randomized trial allocated 104 patients to either leaflet resection or preservation strategies for mitral repair. The correlation of indexed left ventricular end-systolic volume (LVESVI), indexed left ventricular end-diastolic volume (LVEDVI), and left ventricular ejection fraction (LVEF) were tested with univariate analysis and subsequently with multivariate analysis to determine independent predictors of reverse remodeling at discharge and at 12 months postoperatively. At discharge, both LVESVI and LVEDVI were independently associated with their preoperative values (p < .001 for both) and LVEF by preoperative LVESVI (p < .001). Mitral ring size was favorably associated with the change in LVESVI (p < .05) and LVEF (p < .01) from predischarge to 12 months, while the mean mitral valve gradient after repair was adversely associated with the change in LVESVI (p < .05) and LVEDVI (p < .05). No significant associations were found between reverse remodeling and coaptation height nor mitral repair technique. CONCLUSIONS: Beyond confirming the lack of impact of mitral repair technique on reverse remodeling, this investigation suggests that recommending surgery before significant LV dilatation or dysfunction, as well as higher postoperative mitral valve hemodynamic performance, may enhance remodeling capacity following mitral repair.