Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. OBJECTIVES: This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. METHODS: This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. RESULTS: Among 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. CONCLUSIONS: There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

Five-Year Hospital Readmission After Coronary Artery Bypass Surgery and the Association With Off-Pump Surgery and Sex.

Background Limited data exist on long-term readmission and its association with patient and procedural characteristics after coronary artery bypass grafting. We aimed to investigate 5-year readmission after coronary artery bypass grafting and specifically focus on the role of sex and off-pump surgery. Methods and Results We performed a post hoc analysis of the CORONARY (Coronary Artery Bypass Grafting [CABG] Off or On Pump Revascularization) trial, involving 4623 patients. The primary outcome was all-cause readmission, and the secondary outcome was cardiac readmission. Cox models were used to investigate the association of outcomes with sex and off-pump surgery. Hazard function for sex was studied over time using a flexible, fully parametric model, and time-segmented analyses were performed accordingly. Rho coefficient was calculated for the correlation between readmission and long-term mortality. Median follow-up was 4.4 years (interquartile range, 2.9-5.4 years). The cumulative incidence rates of all-cause and cardiac readmission were 29.4% and 8.2% at 5 years, respectively. Off-pump surgery was not associated with either all-cause or cardiac readmission. The hazard for all-cause readmission in women over time was constantly higher than the hazard for men (hazard ratio [HR], 1.21 [95% CI, 1.04-1.40]; P=0.011). Time-segmented analyses confirmed the higher risk for all-cause (HR, 1.21 [95% CI, 1.05-1.40]; P<0.001) and cardiac (HR, 1.26 [95% CI, 1.03-1.69]; P=0.033) readmission in women after the first 3 years of follow-up. All-cause readmission was strongly correlated with long-term all-cause mortality (Rho, 0.60 [95% CI, 0.48-0.66]), whereas cardiac readmission was strongly correlated with long-term cardiovascular mortality (Rho, 0.60 [95% CI, 0.13-0.86]). Conclusions Readmission rates are substantial at 5 years after coronary artery bypass grafting and are higher in women but not with off-pump surgery. Registration URL: http://www.clinicaltrials.gov/; Unique identifier: NCT00463294.

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.

Anterolateral territory coronary artery bypass grafting strategies: a non-inferiority randomized clinical trial: the AMI-PONT trial.

OBJECTIVES: The main objective was to assess whether a composite coronary artery bypass grafting strategy including a saphenous vein graft bridge to distribute left internal mammary artery outflow provides non-inferior patency rates compared to conventional grafting surgery with separated left internal mammary artery to left anterior descending coronary graft and aorto-coronary saphenous vein grafts to other anterolateral targets. METHODS: All patients underwent isolated grafting surgery with cardiopulmonary bypass and received ≥2 grafts/patients on the anterolateral territory. The graft patency (i.e. non-occluded) was assessed using multislice spiral computed tomography at 1 year. RESULTS: From 2012 to 2021, 208 patients were randomized to a bridge (n = 105) or conventional grafting strategy (n = 103). Patient characteristics were comparable between groups. The anterolateral graft patency was non-inferior in the composite bridge compared to conventional grafting strategy at 1 year [risk difference 0.7% (90% confidence interval -4.8 to 6.2%)]. The graft patency to the left anterior descending coronary was no different between groups (P = 0.175). Intraoperatively, the bridge group required shorter vein length for anterolateral targets (P < 0.001) and exhibited greater Doppler flow in the mammary artery pedicle (P = 0.004). The composite outcome of death, myocardial infarction or target vessel reintervention at 30 days was no different (P = 0.164). CONCLUSIONS: Anterolateral graft patency of the composite bridge grafting strategy is non-inferior to the conventional grafting strategy at 1 year. This novel grafting strategy is safe, efficient, associated with several advantages including better mammary artery flow and shorter vein requirement, and could be a valuable alternative to conventional grafting strategies. Ten-year clinical follow-up is underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585285.

What Is the Fate of Total Joint Arthroplasty Patients Who Are Asked to Quit Smoking Prior to Surgery?

Background: Smoking is a known risk factor for complications following primary total joint arthroplasty (TJA). Little is known regarding the fate of patients who are asked to quit smoking before surgery. The purpose of this study was to evaluate the success of smoking cessation prior to primary TJA and the impact of smoking cessation on perioperative outcomes. Methods: This is a retrospective review of patients who presented between 2008 and 2020 to a single academic medical center with a documented smoking history and were asked to quit smoking prior to receiving a date for primary TJA. The cohort was surveyed about smoking cessation, smoking history, use of quit aids, seeking surgery elsewhere due to the cessation policy, and postoperative complications. Descriptive statistics evaluated the relationship between demographics, smoking cessation, and postoperative complications. Results: A total of 101 patients completed the survey with an overall response rate of 48%. Sixty-two percent of patients quit smoking before surgery, and 51% of these patients reported remaining smoke-free at 6 months postoperatively. The average time to quit before TJA was 45 days (range: 1-365 days), and 62% quit without quit aids. The wound complication/infection rate was significantly higher for patients who did not stop smoking prior to TJA (4 of 16; 27%) than for those who did quit prior to surgery (3 of 63; 5%; P = .02). Conclusions: This study demonstrates that most patients (62%) will stop smoking, if required, prior to primary TJA. Furthermore, 51% of patients reported abstinence from smoking at 6 months following TJA. TJA appears to be an effective motivator for smoking cessation. Level of Evidence: III (retrospective cohort study).

Conduit selection and early graft failure in coronary artery bypass surgery: A post hoc analysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) coronary artery bypass grafting study.

OBJECTIVES: Relative rates of early graft failure and conduit selection in coronary artery bypass grafting (CABG) surgery remain controversial. Therefore, we sought to determine the incidence and determinants of graft failure of the left internal mammary artery (LIMA), radial artery, saphenous vein, and right internal mammary artery (RIMA) 1 year after CABG surgery. METHODS: A post hoc analysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) CABG study, involving patients from 83 centers in 22 countries. We completed an analysis of 3480 grafts from 1068 patients who underwent CABG surgery with complete computed tomography angiography data. The primary outcome was graft failure as diagnosed by computed tomography angiography 1 year after surgery. RESULTS: Graft failure occurred in 6.4% (68/1068) for LIMA, 9.9% (9/91) for radial artery, 10.4% (232/2239) for saphenous vein, and 26.8% (22/82) for RIMA grafts. The RIMA had a greater rate of graft failure (26.8%) than radial artery (9.9%) and veins (10.4%) (adjusted odds ratio, 2.69; 95% confidence interval, 1.30-5.57; P = .008 and adjusted odds ratio, 2.07; 95% confidence interval, 1.33-3.21; P = .001, respectively). CONCLUSIONS: In this international trial dataset, LIMA and radial artery performed as expected, whereas vein grafts performed better. However, high rates of RIMA failure are worrisome and highlight the need for a thorough evaluation of the patency and safety of the RIMA in CABG surgery.

Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation.

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs' release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies.

Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.

OBJECTIVE: Organ donation after circulatory death (DCD) is a potential solution for the shortage of suitable organs for transplant. Heart transplantation using DCD donors is not frequently performed due to the potential myocardial damage following warm ischemia. Heat shock protein (HSP) 90 has recently been investigated as a novel target to reduce ischemia/reperfusion injury. The objective of this study is to evaluate an innovative HSP90 inhibitor (HSP90i) as a cardioprotective agent in a model of DCD heart. METHODS: A DCD protocol was initiated in anesthetized Lewis rats by discontinuation of ventilation and confirmation of circulatory death by invasive monitoring. Following 15 minutes of warm ischemia, cardioplegia was perfused for 5 minutes at physiological pressure. DCD hearts were mounted on a Langendorff ex vivo heart perfusion system for reconditioning and functional assessment (60 minutes). HSP90i (0.01 µmol/L) or vehicle was perfused in the cardioplegia and during the first 10 minutes of ex vivo heart perfusion reperfusion. Following assessment, pro-survival pathway signaling was evaluated by western blot or polymerase chain reaction. RESULTS: Treatment with HSP90i preserved left ventricular contractility (maximum + dP/dt, 2385 ± 249 vs 1745 ± 150 mm Hg/s), relaxation (minimum -dP/dt, -1437 ± 97 vs 1125 ± 85 mm Hg/s), and developed pressure (60.7 ± 5.6 vs 43.9 ± 4.0 mm Hg), when compared with control DCD hearts (All P = .001). Treatment abrogates ischemic injury as demonstrated by a significant reduction of infarct size (2,3,5-triphenyl-tetrazolium chloride staining) of 7 ± 3% versus 19 ± 4% (P = .03), troponin T release, and mRNA expression of Bax/Bcl-2 (P < .05). CONCLUSIONS: The cardioprotective effects of HSP90i when used following circulatory death might improve transplant organ availability by expanding the use of DCD hearts.

Patient Resilience Influences Opioid Consumption in Primary Total Joint Arthroplasty Patients.

Background: Resilience and depression may influence opioid consumption in patients undergoing primary hip and knee arthroplasty (TJA); however, data evaluating these relationships are limited. Methods: We retrospectively identified 119 patients undergoing TJA who completed preoperative questionnaires to measure resilience (Brief Resilience Scale) and depression (PHQ-9) from 2017 to 2018 at a single institution. Patients were stratified into high, normal, and low resilience groups as well as no, mild, and major depression groups. Opioid use was recorded in morphine milligram equivalents (MMEs). Nonparametric statistical testing was performed with significance level at P < 0.05. Results: Higher levels of resilience correlated with less postoperative inpatient opioid use (P = 0.003). Patients with high resilience were less likely to use preoperative opioids compared to those with low resilience (OR = 6.08, 95% CI [1.230.5]). There was no difference in postoperative outpatient opioid prescriptions between resilience groups. Lower levels of depression correlated with less postoperative inpatient opioid use, though this did not reach statistical significance (P = 0.058). Additionally, there was no significant difference in preoperative opioid use or postoperative outpatient opioid prescriptions between depression groups. Conclusion: Patients with higher levels of resilience are less likely to use opioids before TJA and utilize lower amounts of opioids while inpatient following surgery. Depression correlated with higher postoperative inpatient opioid use; however, the present findings regarding this relationship are inconclusive. Resilience is a psychological trait that may impact opioid use in patients undergoing TJA and should be viewed as a modifiable risk factor. Level of Evidence: III.

White blood cell count and clinical outcomes after left main coronary artery revascularization: insights from the EXCEL trial.

BACKGROUND: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD). METHODS: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L). RESULTS: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually. CONCLUSION: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.

Impact of early quantitative morbidity on 1-year outcomes in coronary artery bypass graft surgery.

OBJECTIVES: We applied the Clavien-Dindo Complications Classification (CDCC) and the Comprehensive Complication Index (CCI) to the CORONARY trial to assess whether quantitative early morbidity affects outcomes at 1 year. METHODS: All postoperative hospitalization and 30-day follow-up complications were assigned a CDCC grade. CCI were calculated for all patients (n = 4752). Kaplan-Meier analysis examined 1-year mortality and 1-year co-primary outcome (i.e. death, non-fatal stroke, non-fatal myocardial infarction, new-onset renal failure requiring dialysis or repeat coronary revascularization) by CDCC grade. Multivariable logistic regression evaluated the predictive value of CCI for both outcomes. RESULTS: For off-pump and on-pump coronary artery bypass graft surgery, median CDCC were 1 [interquartile range: 0, 2] and 2 [1, 2] (P < 0.001), while median CCI were 8.7 [0, 22.6] and 20.9 [8.7, 29.6], respectively (P < 0.001). In on-pump, there were more grade I and grade II complications, particularly grade I and II transfusions (P < 0.001) and grade I acute kidney injury (P = 0.039), and more grade IVa respiratory failures (P = 0.047). Patients with ≥IIIa complications had greater cumulative 1-year mortality (P < 0.001). The median CCI was 8.7 [0, 22.6] in patients who survived and 22.6 [8.7, 44.3] in patients who died at 1 year (P < 0.001). The CCI remained an independent risk factor for 1-year mortality and 1-year co-primary outcome after multivariable adjustment (P < 0.001). CONCLUSIONS: On-pump coronary artery bypass graft surgery had a greater number of complications in the early postoperative period, likely driven by transfusions, respiratory outcomes and acute kidney injury. This affects 1-year outcomes. Similar analyses have not yet been used to compare both techniques and could prove useful to quantify procedural morbidity. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT00463294; Unique Identifier: NCT00463294.

Are Morbidly Obese Patients Equally Benefitting From Care Improvements in Total Hip Arthroplasty?

BACKGROUND: Morbidly obese patients have increased rates of complications following primary total hip arthroplasty (THA) and it is not clear whether improvements in THA care pathways are equally benefitting these patients. The purpose of this study is to assess if reductions in complications have similarly improved for both morbidly obese and non-morbidly obese patients after THA. METHODS: Patients undergoing primary THA between 2011 and 2019 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified by body mass index (BMI) <40 and ≥40 kg/m2. Thirty-day rates of infectious complications, readmissions, reoperation, and any complication were assessed. Trends in complications were compared utilizing odds ratios and multivariate analyses. RESULTS: In total, 234,334 patients underwent THA and 16,979 (7.8%) had BMI ≥40 kg/m2. Patients with BMI ≥40 kg/m2 were at significantly higher odds for readmission, reoperation, and infectious complications. Odds for any complication were lower for morbidly obese patients in 2011, not different from 2012 to 2014, and higher from 2015 to 2019 compared to lower BMI patients. Odds for any non-transfusion complication were higher for morbidly obese patients and there was no improvement for either group over the study period. There were improvements in rates of readmission and reoperation for patients with BMI <40 kg/m2 and readmission for BMI >40 kg/m2. CONCLUSION: Odds for readmission and reoperation for non-morbidly obese patients and readmission for morbidly obese patients improved from 2011 to 2019. Reductions in transfusions are largely responsible for improvements in overall complication rates. Although morbidly obese patients remain at higher risk for complications, there does not appear to be a growing disparity in outcomes between morbidly obese and non-morbidly obese patients.

Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study.

BACKGROUND: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. METHODS: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. RESULTS: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. CONCLUSIONS: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02610283.

Skeletonized vs Pedicled Internal Mammary Artery Graft Harvesting in Coronary Artery Bypass Surgery: A Post Hoc Analysis From the COMPASS Trial.

Importance: The relative safety and patency of skeletonized vs pedicled internal mammary artery grafts in patients undergoing coronary artery bypass graft (CABG) surgery are unknown. Objective: To investigate the association of skeletonized vs pedicled harvesting with internal mammary artery graft patency and clinical outcomes 1 year after CABG surgery. Design, Setting, and Participants: This study was a post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) clinical trial, which enrolled 27 395 patients from 602 centers in 33 countries from March 2013 through May 2016. Eligibility criteria for the trial included CABG surgery for coronary artery disease with at least 2 grafts implanted and an estimated glomerular filtration rate of at least 30 mL/min. A total of 1002 of 1448 patients were randomized to the CABG arm of the COMPASS trial and underwent skeletonized (282 [28.1%]) or pedicled (720 [71.9%]) internal mammary artery harvesting. The patients had evaluable angiography results 1 year after surgery. Data were analyzed from October 11, 2019, to May 14, 2020. Interventions: Patients underwent graft harvesting with either the pedicled technique or skeletonized technique. Main Outcomes and Measures: The primary outcome was graft occlusion 1 year after CABG surgery, as assessed by computed tomography angiography. Results: A total of 1002 patients underwent skeletonized (282 [28.1%]; mean [SD] age, 65.9 [8.1] years; 229 men [81.2%]; 194 White patients [68.8%]) or pedicled (720 [71.9%]; mean [SD] age, 64.8 [7.6] years; 603 men [83.8%]; 455 White patients [63.2%]) internal mammary artery harvesting. Rates of internal mammary artery graft occlusion 1 year after CABG surgery were higher in the skeletonized group than in the pedicled group (33 of 344 [9.6%] vs 30 of 764 [3.9%]; graft-level adjusted odds ratio, 2.41; 95% CI, 1.39-4.20; P = .002), including the left internal mammary artery to left anterior descending artery (21 of 289 [7.3%] vs 25 of 725 [3.4%]; graft-level adjusted odds ratio, 2.10; 95% CI, 1.14-3.88, P = .02). After a mean follow-up of 23 months, skeletonized graft harvesting was also associated with a higher rate of major adverse cardiovascular events (20 [7.1%] vs 15 [2.1%]; adjusted hazard ratio, 3.19; 95% CI, 1.53-6.67; P = .002) and repeated revascularization (14 [5.0%] vs 10 [1.4%]; adjusted hazard ratio, 2.75; 95% CI, 1.10-6.88; P = .03). Conclusions and Relevance: This post hoc analysis of the COMPASS randomized clinical trial found that harvesting of the internal mammary artery during CABG surgery using a skeletonized technique was associated with a higher rate of graft occlusion and worse clinical outcomes than the traditional pedicled technique. Future randomized clinical trials are needed to establish the safety and patency of the skeletonized technique. Trial Registration: ClinicalTrials.gov Identifier: NCT01776424.

Daytime Variation of Clinical Outcome in Cardiac Surgery: A Propensity-Matched Cohort Study.

OBJECTIVE: The purpose of the present study was to investigate the hypothesis of a nychthemeral variation in the tolerance to ischemia and reperfusion injury in adult cardiac surgeries. DESIGN: Retrospective cohort study. SETTING: A single academic center. PARTICIPANTS: All patients undergoing nonemergent aortic valve replacement (AVR) ± coronary artery bypass graft between January 2012 and May 2018 were included. They were divided into two groups (morning and afternoon) according to the time of the day at the beginning of surgery. Propensity score matching estimated by multivariate logistic regression with a 1:1 matching ratio was performed to ensure that the two groups were comparable. This allowed obtaining 269 pairs, for a total of 538 patients. INTERVENTION: The objective of the study was to assess whether there were differences in perioperative and postoperative outcomes between the morning and the afternoon groups. RESULTS: There was no between-group difference in the primary composite endpoints, namely the occurrence of death, myocardial infarction, low cardiac output, and stroke during the 30 days following the surgery. Regarding cardiac biomarkers, there were no between-group differences for both postoperative evolution of troponin T plasma levels and the maximum postoperative troponin T plasma level. CONCLUSION: These results did not support the hypothesis that the timing of the surgery could influence the tolerance to ischemia and reperfusion injury, at least in patients undergoing nonemergent AVR or a combined AVR with coronary artery bypass graft.

What is the Clinical Utility of Synovial Alpha Defensin Testing of Antibiotic Spacers Before Reimplantation?

BACKGROUND: The purpose of this study was to evaluate the diagnostic performance of standalone alpha defensin (AD) testing of antibiotic spacers during two stage exchange and to determine if the addition of AD testing to other commonly used laboratory tests improves the ability to detect persistent infection in an antibiotic spacer. METHODS: Cases of two-stage exchange for periprosthetic joint infection from 2016 to 2019 at a single institution were retrospectively reviewed. Cases were classified as persistently infected or not infected in accordance with 2014 and 2018 Musculoskeletal Infection Society criteria to determine if AD provided any clinical utility beyond the other commonly used tests that make up both criteria. Delphi Consensus criteria at 1 year were used as the gold standard for determining recurrent periprosthetic joint infection. RESULTS: Fifty-two spacers (25 hips and 27 knees) in 51 patients were included for analysis. Five spacers were persistently infected based on Musculoskeletal Infection Society criteria. One spacer underwent reresection and the remaining 4 underwent reimplantation with no subsequent infectious complications. All 48 patients who were categorized as not infected underwent reimplantation; at 1 year postoperatively, 7 (13%) had failed due to infection. Three spacers (6%) had a positive AD test. Two spacers with positive AD tests underwent reimplantation, neither had failed at 1 year postoperatively. Sensitivity of standalone AD testing was 0%, and specificity was 96%. CONCLUSION: Standalone AD testing for the purpose of predicting repeat infection after two-stage exchange arthroplasty exhibits sensitivity of 0% and low predictive value. Addition of synovial AD testing did not increase the diagnostic performance of commonly used synovial and serologic markers of infection. LEVEL OF EVIDENCE: IV-retrospective cohort study.