Transcriptome analysis of Burkitt lymphoma cells treated with anti-convulsant drugs that are inhibitors of Epstein-Barr virus lytic reactivation.

Herpesviruses have two distinct life cycle stages, latency and lytic replication. Epstein-Barr virus (EBV), a gamma-herpesvirus, establishes latency in vivo and in cultured cells. Cell lines harboring latent EBV can be induced into the lytic cycle by treatment with chemical inducing agents. In the Burkitt lymphoma cell line HH514-16 the viral lytic cycle is triggered by butyrate, a histone deacetylase (HDAC) inhibitor. Butyrate also alters expression of thousands of cellular genes. However, valproic acid (VPA), another HDAC inhibitor with global effects on cellular gene expression blocks EBV lytic gene expression in Burkitt lymphoma cell lines. Valpromide (VPM), an amide derivative of VPA, is not an HDAC inhibitor, but like VPA blocks induction of the EBV lytic cycle. VPA and VPM are the first examples of inhibitors of initial stages of lytic reactivation. We compared the effects of VPA and VPM, alone and in combination with butyrate, on host cellular gene expression using whole transcriptome analysis (RNA-seq). Gene expression was analyzed 6 h after addition of the compounds, a time before the first EBV lytic transcripts are detected. The results address two alternative, yet possibly complementary, mechanisms for regulation of EBV lytic reactivation. First, cellular genes that were up- or down-regulated by butyrate, but no longer altered in the presence of VPA or VPM, represent genes that correlated with EBV lytic reactivation. Second, genes regulated similarly by VPA and VPM in the absence and presence of butyrate are candidates for suppressors of EBV reactivation. Two genes upregulated by the lytic cycle inhibitors, CHAC1 and SLC7A11, are related to redox status and the iron-dependent cell death pathway ferroptosis. This study generates new hypotheses for control of the latency to lytic cycle switch of EBV and provides the first description of effects of the anti-convulsant drug VPM on global human cellular gene expression.

Outcomes After Transcatheter Mitral Valve Replacement According to Regurgitation Etiology.

BACKGROUND: Whether transcatheter mitral valve replacement (TMVR) devices perform similarly with respect to the underlying mitral regurgitation (MR) etiology remains unknown. The aim of the present analysis was to assess outcomes of TMVR according to the MR underlying etiology among the CHoice of OptImal transCatheter trEatment for Mitral Insufficiency (CHOICE-MI) registry. METHODS: Of 746 patients, 229 patients (30.7%) underwent TMVR. The study population was subdivided according to primary, secondary, or mixed MR. Patients with mitral annular calcification were excluded. The primary study endpoint was a composite endpoint of all-cause mortality or hospitalization for heart failure at 1 year. Secondary study endpoints were all-cause and cardiovascular mortality at 1 year, New York Heart Association functional class, and residual MR, both at discharge and 1 year. RESULTS: The predominant MR etiology was secondary MR (58.4%), followed by primary MR (28.7%) and mixed MR (12.9%). Technical success and procedural mortality were similar according to MR etiology. Discharge echocardiography revealed residual MR 2+ in 11.3%, 3.7%, and 5.3% of patients with primary, secondary, and mixed MR, respectively (P = .1). MR elimination was similar in all groups up to the 1-year follow-up. There was no difference in terms of primary combined outcome occurrence according to MR etiology. One-year all-cause mortality was reported in 28.8%, 24.2%, and 32.1% of patients with primary, secondary, and mixed MR, respectively (P = .07). CONCLUSIONS: In our study we did not find differences in short-term and 1-year outcomes after TMVR according to MR etiology.

Amyloid Transthyretin Cardiomyopathy in Elderly Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR-CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR-CM undergoing transcatheter aortic valve implantation. Methods and Results Prospective screening for ATTR-CM with Technetium99-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium99-3,3-diphosphono-1,2-propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR-CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5; P=0.001), male sex (82.4% versus 57.7%; P=0.005), and prior carpal tunnel surgery (17.6% versus 4.3%; P=0.007) were associated with coexisting ATTR-CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%; P<0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8; P<0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m2; P<0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6; P<0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5; P=0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04-12.53]; stroke: HR, 0.46 [95% CI, 0.03-7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69-3.43]) and 1-year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37-2.96]; stroke: HR, 0.34 [95% CI, 0.02-5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67-3.34]) were similar between groups. Conclusions Coexisting ATTR-CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri-interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT04061213.

Association of atrial fibrillation with survival in patients with low-flow low-gradient aortic stenosis with preserved ejection fraction undergoing TAVI.

AIMS: There is limited evidence on the prognostic significance of atrial fibrillation (AF) in patients with low flow, low gradient aortic stenosis with preserved ejection fraction (LFLG-pEF AS). We aimed to evaluate the recovery of stroke volume after transcatheter aortic valve implantation (TAVI) and clinical outcomes in patients with LFLG-pEF AS stratified by presence or absence of AF. METHODS AND RESULTS: In a prospective TAVI registry, patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) were stratified according to flow-gradient status and presence of AF. Among 2 259 TAVI patients with preserved LVEF between August 2007 and June 2021, 765 had high-gradient AS (HG AS) and 444 had LFLG-pEF AS. AF was observed in 199 patients with HG AS (26.0%) and 190 patients with LFLG-pEF AS (42.8%). At 1 year, SVi was significantly improved in LFLG-pEF AS patients without AF, while SVi remained low in patients with AF (from 25.9 ± 8.5 mL/m2 to 37.2 ± 9.9 mL/m2 and from 26.8 ± 5.1 mL/m2 to 26.1 ± 9.1 mL/m2, respectively). LFLG-pEF AS patients with AF had an increased risk of 1-year all-cause mortality compared with those without AF (HRadjusted 2.57; 95% CI 1.44-4.59). LFLG-pEF AS patients without AF had similar mortality compared with HG AS patients without AF (HRadjusted 0.85; 95% CI 0.49-1.46). CONCLUSIONS: Patients with LFLG-pEF AS and AF experienced no relevant recovery of stroke volume after TAVI, but a more than two-fold increased risk of death compared to patients with HG AS or LFLG-pEF AS without AF. Clinical Trial Registration: https://www.clinicaltrials.gov. NCT01368250.

Efficacy of levosimendan infusion in patients undergoing a left ventricular assist device implant in a propensity score matched analysis of the EUROMACS registry-the Euro LEVO-LVAD study.

OBJECTIVES: Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS: The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS: In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. CONCLUSIONS: In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.

Treatment of infected hybrid arch prosthesis with self-assembled bovine elephant trunk grafts.

Graft infections are associated with severe morbidity and mortality. The widespread use of the frozen elephant technique increases the incidence of complex aortic patients to suffer from graft infections. Surgery of these patients is challenging. Removal of the stent graft portion of the frozen elephant technique prosthesis via sternotomy carries the risk of irreparable damage to the descending aorta. There is currently no single-stage surgical strategy that allows for the removal of all infected material apart from a hemi-clamshell approach. This approach is technically demanding and associated with significant morbidity and mortality. This results in conservative treatment in a substantial number of patients. Pericardial tube grafts have shown to be an excellent option in treating graft infections in various aortic segments with promising results concerning freedom of re-infection and survival. We report a single-stage, trans-sternal approach to remove all infected materials and simultaneously treat the descending aorta to prevent aortic catastrophe in 2 consecutive cases.

Surgical versus transcatheter repair for secondary mitral regurgitation: A propensity score-matched cohorts comparison.

OBJECTIVES: To compare the efficacy and clinical outcomes of transcatheter edge-to-edge mitral valve repair (TMVr) and surgical mitral valve repair (SMVr) among patients with secondary mitral regurgitation (SMR). METHODS: Consecutive patients with SMR treated using either TMVr (n = 199) or SMVr (n = 222) at 2 centers were included and retrospectively analyzed. To account for differences in patient demographic characteristics, 1:1 propensity score matching was performed. The primary endpoint was all-cause death within 2 years after the procedure. RESULTS: The study population consisted of 202 matched patients. At 2 years, all-cause mortality was 24.3% for TMVr and 23.0% for SMVr (hazard ratio, 0.97; 95% confidence interval, 0.55-1.71; P = .909). Severe heart failure symptoms at 2 years were less prevalent after SMVr (New York Heart Association functional class III or IV: 13.5% vs 29.5%; P = .032) than after TMVr. A higher proportion of the SMVr patients had SMR reduction to none or mild at discharge (90.8% vs 72.0%; P < .001) and 2 years (86.5% vs 59.6%; P < .001). Among patients who achieved none or mild MR at discharge, 7 patients (10.1%) in the SMVr group and 15 (34.9%) in the TMVr group had progression to moderate or greater MR at 2 years (P = .003). Left ventricular ejection fraction (LVEF) significantly improved (+10.1% ± 11.1%; P < .001) after SMVr (LVEF at 2 years: 45.7% ± 12.8%), whereas it remained unchanged (-1.3% ± 8.9%; P = .260) after TMVr (LVEF at 2 years: 34.0% ± 13.2%). CONCLUSIONS: In this propensity score-matched analysis, there was no significant difference in 2-year survival between TMVr and SMVr, despite greater and more durable SMR reduction, as well as LVEF improvement in the surgical group.

Concomitant tricuspid valve repair in left ventricular assist device implantation may increase the risk for temporary right ventricular support but does not impact overall outcomes.

OBJECTIVES: Tricuspid valve repair in left ventricular assist device implantation continues to pose a challenge and may impact the occurrence of early and late right heart failure. We investigated the effects of concomitant tricuspid repair on clinical outcomes. METHODS: A retrospective, multicentre study enrolled adult patients who received continuous-flow left ventricular assist devices between 2005 and 2017 and compared those who received concomitant tricuspid valve repair to those who did not. Primary outcomes were early right heart failure necessitating temporary ventricular assist devices and right heart failure-related rehospitalizations requiring inotropic or diuretic treatment. RESULTS: Out of 526 patients who underwent left ventricular assist device implantation, 110 (21%) received a concomitant tricuspid valve repair. Those patients were sicker, and most had moderate or severe tricuspid regurgitation. A significantly higher incidence of temporary right ventricular assist devices was observed in the group with concomitant tricupid valve repair (18% vs. 11%, P = 0.049), with a significantly elevated risk for temporary right heart assist device (sHR 1.68, 95% CI 1.04-2.72; P = 0.037). After adjusting for confounders, no significant differences were found in the incidence of and risk for most clinical outcomes, including right heart failure-related rehospitalizations (P = 0.891) and death (P = 0.563). CONCLUSIONS: Concomitant tricuspid valve repair, when deemed necessary in left ventricular assist device implantation, may increase the risk of early right heart failure requiring a temporary right ventricular assist device but does not impact the incidence or risk of death or rehospitalizations due to late right heart failure.

Risk and Timing of Noncardiac Surgery After Transcatheter Aortic Valve Implantation.

Importance: Noncardiac surgery after transcatheter aortic valve implantation (TAVI) is a clinical challenge with concerns about safety and optimal management. Objectives: To evaluate perioperative risk of adverse events associated with noncardiac surgery after TAVI by timing of surgery, type of surgery, and TAVI valve performance. Design, Setting, and Participants: This cohort study was conducted using data from a prospective TAVI registry of patients at the tertiary care University Hospital in Bern, Switzerland. All patients undergoing noncardiac surgery after TAVI were identified. Data were analyzed from November through December 2021. Exposures: Timing, clinical urgency, and risk category of noncardiac surgery were assessed among patients who had undergone TAVI and subsequent noncardiac surgery. Main Outcomes and Measures: A composite of death, stroke, myocardial infarction, and major or life-threatening bleeding within 30 days after noncardiac surgery. Results: Among 2238 patients undergoing TAVI between 2013 and 2020, 300 patients (mean [SD] age, 81.8 [6.6] years; 144 [48.0%] women) underwent elective (160 patients) or urgent (140 patients) noncardiac surgery after TAVI and were included in the analysis. Of these individuals, 63 patients (21.0%) had noncardiac surgery within 30 days of TAVI. Procedures were categorized into low-risk (21 patients), intermediate-risk (190 patients), and high-risk (89 patients) surgery. Composite end points occurred within 30 days of surgery among 58 patients (Kaplan-Meier estimate, 19.7%; 95% CI, 15.6%-24.7%). There were no significant differences in baseline demographics between patients with the 30-day composite end point and 242 patients without this end point, including mean (SD) age (81.3 [7.1] years vs 81.9 [6.5] years; P = .28) and sex (25 [43.1%] women vs 119 [49.2%] women; P = .37). Timing (ie, ≤30 days from TAVI to noncardiac surgery), urgency, and risk category of surgery were not associated with increased risk of the end point. Moderate or severe prosthesis-patient mismatch (adjusted hazard ratio [aHR], 2.33; 95% CI, 1.37-3.95; P = .002) and moderate or severe paravalvular regurgitation (aHR, 3.61; 95% CI 1.25-10.41; P = .02) were independently associated with increased risk of the end point. Conclusions and Relevance: These findings suggest that noncardiac surgery may be performed early after successful TAVI. Suboptimal device performance, such as prosthesis-patient mismatch and paravalvular regurgitation, was associated with increased risk of adverse outcomes after noncardiac surgery.

The European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery: third report.

OBJECTIVES: In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. METHODS: Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011-2013, 2014-2017 and 2018-2020). Adverse event rates (AERs) were calculated and stratified into early phase (<3 months) and late phase (>3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (<3 vs >3 months). RESULTS: In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4-7: 23, 25 and 33%; P < 0.001) and in-hospital deaths (18.5, 17.2 and 11.2; P < 0.001) decreased significantly between eras. Overall, mortality, transplants and the probability of weaning were 55, 25 and 2% at 5 years after the implant, respectively. Major infections were mainly noted early after the implant occurred (AER<3 months: 1.44 vs AER>3 months: 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant. CONCLUSIONS: In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent.

Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multicentre experience.

AIMS: Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS: All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41). CONCLUSION: In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement.

Natural history and mid-term prognosis of severe tricuspid regurgitation: A cohort study.

Objectives: The objective of this study was to characterize a population of patients with severe tricuspid regurgitation (TR) evaluated at a tertiary care center, assess mid-term clinical outcomes, and identify prognostic factors. Background: The impact of TR on morbidity and mortality is increasingly recognized. Clinical characteristics and long-term outcomes of patients suffering from TR remain unclear. Methods: This is a retrospective observational single-center study from a tertiary care hospital including patients with echocardiographic diagnosis of severe TR between January 2017 and December 2018. We used the Kaplan-Meier method to estimate survival for up to 4 years. After excluding patients with tricuspid valve (TV) intervention and surgery during follow-up, a multivariate analysis was performed to assess predictors of 2-year mortality using the Cox regression model. Results: A total of 278 patients (mean age 74.9 ± 13.7 years, 47.8% female) with severe TR were included in the study. The majority (83.1%; n = 231) had secondary TR. Comorbidities such as atrial fibrillation (AFib) (68.0%; n = 189), severe renal failure (44.2%; n = 123), pulmonary hypertension (PHT) (80.9%; n = 225), and right ventricular (RV) dysfunction (59.7%; n = 166) were highly prevalent. More than half of patients with a cardiac implantable electronic device (CIED) (54.3%; n = 44) showed echocardiographic signs of lead-leaflet interaction causing or contributing to TR. The estimated 2- and 4-year all-cause mortality was 50 and 69%, respectively. Using multivariate analysis, age, severe renal failure, heart failure with reduced ejection fraction (HFrEF), and vena contracta width ≥14 mm were identified as predictors of 2-year mortality. Nine percent (n = 25) of the study cohort underwent transcatheter or surgical treatment for TR during follow-up. Conclusion: Our study shows the high burden of morbidity and the dismal survival of patients with severe TR. It also highlights the extent of the therapeutic need, since the vast majority of patients were left untreated. Additionally, CIED RV lead-associated TR was prevalent suggesting a need for more attention in clinical routine and research.

Providing safe perioperative care in cardiac surgery during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has potentiated the need for implementation of strict safety measures in the medical care of surgical patients - and especially in cardiac surgery patients, who are at a higher risk of COVID-19-associated morbidity and mortality. Such measures not only require minimization of patients' exposure to COVID-19 but also careful balancing of the risks of postponing nonemergent surgical procedures and providing appropriate and timely surgical care. We provide an overview of current evidence for preoperative strategies used in cardiac surgery patients, including risk stratification, telemedicine, logistical challenges during inpatient care, appropriate screening capacity, and decision-making on when to safely operate on COVID-19 patients. Further, we focus on perioperative measures such as safe operating room management and address the dilemma over when to perform cardiovascular surgical procedures in patients at risk.

Comorbidity-dependent changes in alpha and broadband electroencephalogram power during general anaesthesia for cardiac surgery.

BACKGROUND: Age and comorbidities are reported to induce neurobiological transformations in the brain. Whilst the influence of ageing on anaesthesia-induced electroencephalogram (EEG) changes has been investigated, the effect of comorbidities has not yet been explored. We hypothesised that certain diseases significantly affect frontal EEG alpha and broadband power in cardiac surgical patients. METHODS: We analysed the frontal EEGs of 589 patients undergoing isoflurane general anaesthesia from a prospective observational study. We used multi- and uni-variable regression to analyse the relationships between comorbidities and age as independent with peak and oscillatory alpha, and broadband power as dependent variables. A score of comorbidities and minimum alveolar concentration (MAC) was built to interrogate the combined effect of age and score on alpha and broadband power. RESULTS: At the univariable level, many comorbidities were associated with lower EEG alpha or broadband power. Multivariable regression indicated the independent association of numerous comorbidities and MAC with peak alpha (R2=0.19) and broadband power (R2=0.31). The association with peak alpha power is markedly reduced when the underlying broadband effect is subtracted (R2=0.09). Broadband measures themselves are more strongly correlated with comorbidities and MAC (R2=0.31) than age (R2=0.15). CONCLUSIONS: Comorbidities and age are independently associated with decreasing frontal EEG alpha and broadband power during general anaesthesia. For alpha power, the association is highly dependent on the underlying broadband effect. These findings might have significant clinical consequences for automated computation for depth of anaesthesia in comorbid patients, because misclassification might pose the risk of under- or over-dosing of anaesthetics. CLINICAL TRIAL REGISTRATION: NCT02976584.

Frontal electroencephalogram reveals emergence-like brain activity occurring during transition periods in cardiac surgery.

BACKGROUND: Cardiac surgery has one of the highest incidences of intraoperative awareness. The periods of initiation and discontinuation of cardiopulmonary bypass could be high-risk periods. Certain frontal EEG patterns might plausibly occur with unintended intraoperative awareness. This study sought to quantify the incidence of these pre-specified patterns during cardiac surgery. METHODS: Two-channel bihemispheric frontal EEG was recorded in 1072 patients undergoing cardiac surgery as part of a prospective observational study. Spectrograms were created, and mean theta (4-7 Hz) power and peak alpha (7-17 Hz) frequency were measured in patients under general anaesthesia with isoflurane. Emergence-like EEG activity in the spectrogram during surgery was classified as an alpha peak frequency increase by 2 Hz or more, and a theta power decrease by 5 dB or more in comparison with the median pre-bypass values. RESULTS: Data from 1002 patients were available for analysis. Fifty-five of those patients (5.5%) showed emergence-like EEG activity at least once during surgery with a median duration of 13.2 min. These patients were younger (median age, 59 vs 67 yr; P<0.001) and the median end-tidal isoflurane concentration before cardiopulmonary bypass was higher (0.82 vs 0.75 minimum alveolar concentration [MAC]; P=0.013). There was no significant difference between those with or without emergence-like EEG activity in sex, lowest core temperature, or duration of surgery. Forty-six of these EEG changes (84%) occurred within a 1 h time window centred on separation from cardiopulmonary bypass. CONCLUSION: The findings of this study suggest that approximately one in 20 patients undergoing cardiac surgery with a volatile anaesthetic agent have a sustained EEG pattern while surgery is ongoing that is often seen with emergence from general anaesthesia. Monitoring the frontal EEG during cardiopulmonary bypass may identify these events and potentially reduce the incidence of unintended awareness. CLINICAL TRIAL REGISTRATION: NCT02976584.