Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: a statistical analysis plan for the ProMPT-2 randomised controlled trial.

BACKGROUND: The ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low- and high-dose propofol supplementation of the cardioplegia solution during adult cardiac surgery versus sham supplementation. This update presents the statistical analysis plan, detailing how the trial data will be analysed and presented. Outlined analyses are in line with the Consolidated Standards of Reporting Trials and the statistical analysis plan has been written prior to database lock and the final analysis of trial data to avoid reporting bias (following recommendations from the International Conference on Harmonisation of Good Clinical Practice). METHODS/DESIGN: ProMPT-2 is a multi-centre, blinded, parallel three-group randomised controlled trial aiming to recruit 240 participants from UK cardiac surgery centres to either sham cardioplegia supplementation, low dose (6 µg/ml) or high dose (12 µg/ml) propofol cardioplegia supplementation. The primary outcome is cardiac-specific troponin T levels (a biomarker of cardiac injury) measured during the first 48 h following surgery. The statistical analysis plan describes the planned analyses of the trial primary and secondary outcomes in detail, including approaches to deal with missing data, multiple testing, violation of model assumptions, withdrawals from the trial, non-adherence with the treatment and other protocol deviations. It also outlines the planned sensitivity analyses and exploratory analyses to be performed. DISCUSSION: This manuscript prospectively describes, prior to the completion of data collection and database lock, the analyses to be undertaken for the ProMPT-2 trial to reduce risk of reporting and data-driven analyses. TRIAL REGISTRATION: ISRCTN ISRCTN15255199. Registered on 26 March 2019.

Hypobaric type oxygenators - physics and physiology.

Brain injury is still a serious complication after cardiac surgery. Gaseous microemboli (GME) are known to contribute to both short and longer-term brain injury after cardiac surgery. Hypobaric and novel dual-chamber oxygenators use the physical behaviors and properties of gases to reduce GME. The aim of this review was to present the basic physics of the gases, the mechanism in which the hypobaric and dual-chamber oxygenators reduce GME, their technical performance, the preclinical studies, and future directions. The gas laws are reviewed as an aid to understanding the mechanisms of action of oxygenators. Hypobaric-type oxygenators employ a high oxygen, no nitrogen environment creating a steep concentration gradient of nitrogen out of the blood and into the oxygenator, reducing the risk of GMEs forming. Adequately powered clinical studies have never been carried out with a hypobaric or dual-chamber oxygenator. These are required before such technology can be recommended for widespread clinical use.

Effect of on-pump vs. off-pump coronary artery bypass grafting in patients with non-dialysis-dependent severe renal impairment: propensity-matched analysis from the UK registry dataset.

Introduction: On-pump coronary artery bypass (ONCABG) grafting in patients with a pre-existing poor renal reserve is known to carry significant morbidity and mortality. There is limited controversial evidence on the benefit of off-pump coronary artery bypass (OPCABG) grafting in these high-risk groups of patients. We compared early clinical outcomes in propensity-matched cohorts of patients with non-dialysis-dependent pre-operative severe renal impairment undergoing OPCABG vs. ONCABG, captured in a large national registry dataset. Methods: All data for patients with a pre-operative creatinine clearance of less than 50 mL/min who underwent elective or urgent isolated OPCABG or ONCABG from 1996 to 2019 were extracted from the UK National Adult Cardiac Surgery Audit (NACSA) database. Propensity score matching was performed using 1:1 nearest neighbor matching without replacement using several baseline characteristics. We investigated the effect of ONCABG vs. OPCABG in the matched cohort using cluster-robust standard error regression. Results: We identified 8,628 patients with severe renal impairment undergoing isolated CABG, of whom 1,142 (13.23%) underwent OPCABG during the study period. We compared 1,141 propensity-matched pairs of patients undergoing OPCABG vs. ONCABG. The median age of the matched population was 78 years in both groups, with no significant imbalance post-matching in the rest of the variables. There was no difference between OPCABG and ONCABG in in-hospital mortality rates, post-operative dialysis, and stroke rates. However, the return to theatre for bleeding or tamponade was higher in ONCABG vs. OPCABG (P > 0.02); however, OPCABG reduced the total length of stay in the hospital by 1 day (P = 0.008). After double adjustment in the matched population using cluster-robust standard regression, ONCABG did not increase mortality compared to OPCABG (OR, 1.05, P = 0.78), postoperative stroke (OR, 1.7, P = 0.12), and dialysis (OR, 0.7, P = 0.09); however, ONCABG was associated with an increased risk of bleeding (OR, 1.53, P = 0.03). Discussion: In this propensity analysis of a large national registry dataset, we found no difference in early mortality and stroke in patients with pre-operative severe renal impairment undergoing OPCABG or ONCABG surgery; however, ONCABG was associated with an increased risk of return to theatre for bleeding and an increased length of hospital stay.

Stroke after Cardiac Surgery: A Risk Factor Analysis of 580,117 Patients from UK National Adult Cardiac Surgical Audit Cohort.

Cerebrovascular accident is the most ominous complication observed after cardiac surgery, carrying an increased risk of morbidity and mortality. Analysis of the problem shows its multidimensional nature. In this study, we aimed to identify major determinants among classic variables, either demographic, clinical or type of surgical procedure, based on the analysis of a large dataset of 580,117 patients from the UK National Adult Cardiac Surgical Audit (NACSA). For this purpose, univariate and multivariate logistic regression models were utilized to determine associations between predictors and dependent variable (Stroke after cardiac surgery). Odds ratios (ORs) and 95% confidence intervals (CIs) were constructed for each independent variable. Statistical analysis allows us to confirm with greater certainty the predictive value of some variables such as age, gender, diabetes mellitus (diabetes treated with insulin OR = 1.37, 95%CI = 1.23-1.53), and systemic arterial hypertension (OR = 1.11, 95%CI = 1.05-1.16);, to emphasize the role of preoperative atrial fibrillation (OR = 1.10, 95%CI = 1.03-1.16) extracardiac arteriopathy (OR = 1.70, 95%CI = 1.58-1.82), and previous cerebral vascular accident (OR 1.71, 95%CI = 1.6-1.9), and to reappraise others like smoking status (crude OR = 1.00, 95%CI = 0.93-1.07 for current smokers) or BMI (OR = 0.98, 95%CI = 0.97-0.98). This could allow for better preoperative risk stratification. In addition, identifying those surgical procedures (for example thoracic aortic surgery associated with a crude OR of 3.72 and 95%CI = 3.53-3.93) burdened by a high risk of neurological complications may help broaden the field of preventive and protective techniques.

Impact of explanted valve type on aortic valve reoperations: nationwide UK experience.

OBJECTIVES: This nationwide retrospective cohort study assessed the impact of the explanted valve type on reoperative outcomes in aortic valve surgery within the UK over a 23-year period. METHODS: Data were sourced from the National Institute for Cardiovascular Outcomes Research (NICOR) database. All patients undergoing first-time isolated reoperative aortic valve replacement between 1996 and 2019 in the UK were included. Concomitant procedures, homograft implantation or aortic root enlargement were excluded. Propensity score matching was utilized to compare outcomes and risk factors for in-hospital mortality was evaluated through multivariable logistic regression. Final model selection was conducted using Akaike Information Criterion through bootstrapping. The primary end point was in-hospital mortality, and secondary end points included postoperative morbidities. RESULTS: Out of 2371 patients, 24.9% had mechanical and 75% had bioprosthetic valves implanted during the primary procedure. Propensity matched groups of 324 patients each, were compared. In-hospital mortality for mechanical and bioprosthetic valve explants was 7.1% and 5.9%, respectively (P = 0.632). On multivariable logistic regression analysis, valve type was not a risk factor for mortality [odds ratio (OR) 0.62, 95% confidence interval (CI) 0.37-1.05; P = 0.1]. Age (OR 1.03, 95% CI 1.01-1.05; P < 0.05), left ventricular ejection fraction (OR 1.62, 95% CI 1.08-2.42; P < 0.05), creatinine ≥ 200 mg/dl (OR 2.21, 95% CI 1.17-4.04; P < 0.05) and endocarditis (OR 2.66, 95% CI 1.71-4.14; P < 0.05) emerged as risk factors for mortality. CONCLUSIONS: The type of valve initially implanted (mechanical or bioprosthetic) did not determine mortality. Instead, age, left ventricular ejection fraction, renal impairment and endocarditis were significant risk factors for in-hospital mortality.

Trend in mitral valve prostheses of choice and early outcomes in the United Kingdom.

OBJECTIVE: Despite the superiority of mitral valve repair, surgical mitral valve replacement (SMVR) remains an important intervention for patients with valve stenosis, infective endocarditis and complex mitral valve degeneration. There has been an increasing popularity in the worldwide use of biological valves due to the avoidance of long-term anti-coagulation and recent advancements in transcatheter techniques. We aim to evaluate the trend, early clinical outcomes and the choice of prostheses use in isolated SMVR over a 23 years period in the United Kingdom. METHODS: All patients (n = 13,147) who underwent elective or urgent isolated SMVR from March 1996 to April 2019 were identified from the National Adult Cardiac Surgery Audit database. Trends in clinical outcomes, predicted/observed mortality of patients and the utilization of biological prostheses across 5 different age groups: <50, 50-59, 60-69, 70-79 and ≥80 years old were investigated. Early clinical outcomes associated with the use of mechanical and biological mitral valve prostheses in patients between the age of 60-70 years old were analysed. RESULTS: The number of isolated SMVR performed has remained stable with approximately 600 cases annually since 2010. The in-hospital/30-day mortality rate has decreased from 7.41% (1996) to 3.92% (2018), despite the EuroScore II increasing from 1.42% in 1996 to 2.43% in 2018. Biological prostheses usage increased across all age group, and particularly in the 60-69 and 70-79 group, from 17.86% and 53.85% in 1996 to 48.85% and 82.38% in 2018, respectively. The use of mechanical prostheses was reduced in patients between the age of 50-59 from 100% in 1996 to 80.65% in 2018. There were no differences in short term outcomes among patients aged 60-70 years who received either a biological or mechanical prostheses. CONCLUSION: There has been a significant reduction in surgical mitral valve replacement early in-hospital mortality, despite an observed increase in the risk profile of patients over 23 years. A shifting trend in valve replacement choices was observed with a rise in the use of biological prostheses, particularly within the 60-69 and 70-79 age group. Early in hospital outcomes for patients aged 60-70 were not determined by the implanted valve type.

A systematic review and meta-analysis of internal thoracic artery harvesting techniques: Skeletonized vs pedicled.

OBJECTIVES: The aim of this meta-analysis was to compare clinical and angiographic outcomes of skeletonized versus pedicled internal thoracic artery for coronary artery bypass grafting. METHODS: A comprehensive search on Ovid MEDLINE, Ovid EMBASE and Scopus was performed from inception to December 2022. The primary outcome was follow-up mortality and graft failure. Secondary outcomes were repeat revascularization, cardiovascular death and operative mortality, myocardial infarction, stroke, and sternal wound complications (SWCs). Pooled estimate for follow-up outcomes was summarized as incidence rate ratio (IRR) and 95% confidence interval (CI) while short-term outcomes were pooled as odds ratio (OR) and 95% CI. For all outcomes, inverse variance weighting was used for pooling. RESULTS: Twenty-eight studies, including 7 randomized trials and 21 observational studies, for a total of 5664 patients in the skeletonized group and 7434 in the pedicled group, were included in the analysis. At a mean weighted follow-up of 4.8 years, there was no difference in mortality between the two groups (IRR 1.14; 95% CI 0.59-2.20). However, the skeletonized group had a higher incidence of graft failure compared to the pedicled group (IRR 1.87, 95% CI 1.33-2.63) but a lower risk of SWCs (OR 0.42; 95% CI 0.30-0.60). There was no difference in short-term outcomes. CONCLUSIONS: Compared to the pedicled harvesting technique, skeletonization of the internal thoracic artery is associated with higher rate of graft failure and lower risk of SWCs without mortality difference.

Sex-Based Differences in Early Outcomes Following Mitral Valve Surgery for Degenerative Disease.

OBJECTIVES: To determine whether sex-based differences exist following surgery for degenerative mitral valve disease. METHODS: Using a national database, we analysed data on mitral valve surgery for degenerative disease (n = 22,658) between January 2000 and March 2019 in the UK. We split the cohort into men (n = 14,681) and women (n = 7977) and compared background characteristics, intraoperative variables and early postoperative outcomes. Our primary outcome was hospital mortality; secondary outcomes included re-exploration for bleeding, prolonged admission (>10 days) and mitral replacement. We used binary logistic regression models for all outcomes, with multiplicative interaction terms to determine the nature of any differences. RESULTS: Women presented older (70 ± 11 years vs. 67 ± 11 years, p < 0.001) with worse symptom profiles (New York Heart Association Class III-IV 57% vs. 44%, p < 0.001). They had higher rates of preoperative atrial fibrillation (39% vs. 35%, p < 0.001) and tricuspid disease requiring surgery (21% vs. 15%, p < 0.001). They had lower repair rates (66% vs. 76%, p < 0.001), higher mortality (3% vs. 2%, p < 0.001) and were more likely to have a prolonged admission (48% vs. 40%, p < 0.001). Female sex was an independent predictor of mortality (odds ratio (OR): 1.52, 95% CI: 1.21-1.90, p < 0.001). Age and Canadian Cardiovascular Society (CCS) score showed significant interactions with sex. The relationship between advancing age and mortality was found to be more pronounced in women. CONCLUSIONS: (1) Female sex is an independent predictor of hospital mortality, prolonged hospital admission and mitral valve replacement. (2) The relationship between female sex and mortality is exacerbated by worsening CCS score and advancing age. (3) Women have significantly lower repair rates.

Development and Evaluation of a Natural Language Processing System for Curating a Trans-Thoracic Echocardiogram (TTE) Database.

BACKGROUND: Although electronic health records (EHR) provide useful insights into disease patterns and patient treatment optimisation, their reliance on unstructured data presents a difficulty. Echocardiography reports, which provide extensive pathology information for cardiovascular patients, are particularly challenging to extract and analyse, because of their narrative structure. Although natural language processing (NLP) has been utilised successfully in a variety of medical fields, it is not commonly used in echocardiography analysis. OBJECTIVES: To develop an NLP-based approach for extracting and categorising data from echocardiography reports by accurately converting continuous (e.g., LVOT VTI, AV VTI and TR Vmax) and discrete (e.g., regurgitation severity) outcomes in a semi-structured narrative format into a structured and categorised format, allowing for future research or clinical use. METHODS: 135,062 Trans-Thoracic Echocardiogram (TTE) reports were derived from 146967 baseline echocardiogram reports and split into three cohorts: Training and Validation (n = 1075), Test Dataset (n = 98) and Application Dataset (n = 133,889). The NLP system was developed and was iteratively refined using medical expert knowledge. The system was used to curate a moderate-fidelity database from extractions of 133,889 reports. A hold-out validation set of 98 reports was blindly annotated and extracted by two clinicians for comparison with the NLP extraction. Agreement, discrimination, accuracy and calibration of outcome measure extractions were evaluated. RESULTS: Continuous outcomes including LVOT VTI, AV VTI and TR Vmax exhibited perfect inter-rater reliability using intra-class correlation scores (ICC = 1.00, p < 0.05) alongside high R2 values, demonstrating an ideal alignment between the NLP system and clinicians. A good level (ICC = 0.75-0.9, p < 0.05) of inter-rater reliability was observed for outcomes such as LVOT Diam, Lateral MAPSE, Peak E Velocity, Lateral E' Velocity, PV Vmax, Sinuses of Valsalva and Ascending Aorta diameters. Furthermore, the accuracy rate for discrete outcome measures was 91.38% in the confusion matrix analysis, indicating effective performance. CONCLUSIONS: The NLP-based technique yielded good results when it came to extracting and categorising data from echocardiography reports. The system demonstrated a high degree of agreement and concordance with clinician extractions. This study contributes to the effective use of semi-structured data by providing a useful tool for converting semi-structured text to a structured echo report that can be used for data management. Additional validation and implementation in healthcare settings can improve data availability and support research and clinical decision-making.

Osteopontin Activation and Microcalcification in Venous Grafts Can Be Modulated by Dexamethasone.

BACKGROUND: Osteopontin has been implicated in vascular calcification formation and vein graft intimal hyperplasia, and its expression can be triggered by pro-inflammatory activation of cells. The role of osteopontin and the temporal formation of microcalcification in vein grafts is poorly understood with a lack of understanding of the interaction between haemodynamic changes and the activation of osteopontin. METHODS: We used a porcine model of vein interposition grafts, and human long saphenous veins exposed to ex vivo perfusion, to study the activation of osteopontin using polymerase chain reaction, immunostaining, and 18F-sodium fluoride autoradiography. RESULTS: The porcine model showed that osteopontin is active in grafts within 1 week following surgery and demonstrated the presence of microcalcification. A brief pretreatment of long saphenous veins with dexamethasone can suppress osteopontin activation. Prolonged culture of veins after exposure to acute arterial haemodynamics resulted in the formation of microcalcification but this was suppressed by pretreatment with dexamethasone. 18F-sodium fluoride uptake was significantly increased as early as 1 week in both models, and the pretreatment of long saphenous veins with dexamethasone was able to abolish its uptake. CONCLUSIONS: Osteopontin is activated in vein grafts and is associated with microcalcification formation. A brief pretreatment of veins ex vivo with dexamethasone can suppress its activation and associated microcalcification.

Subclinical Leaflet Thrombosis Following Surgical and Transcatheter Aortic Valve Replacement: A Meta-Analysis.

Subclinical leaflets valve thrombosis (SLT) is a recently identified phenomenon with multidetector computer tomography after tissue aortic valve replacement. Whether SLT is more frequent after transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) is currently not known. Thus, the aim of this pairwise meta-analysis was to investigate the incidence of SLT after both TAVR and SAVR, the association with anticoagulation therapy, and the risk for neurological events. We searched PubMed, Google Scholar, and Ovid MEDLINE/Embase (January 02, 2023, last update) (PROSPERO registration: CRD42022383295). Statistical analysis was performed according to a prespecified statistical analysis plan. Time-to-event outcomes were summarized as incidence rate ratios (IRR). Pooled estimates were calculated using inverse variance method and random effect model. Overall, 2 registries, 2 randomized trials, and 1 observational study (1,593 patients) were included in this meta-analysis. There was a statistically significant difference in the incidence rate at follow-up of SLT between patients who underwent TAVR and SAVR (IRR 2.07, 95% confidence interval [CI]: [1.06; 4.03], I2 79%, 95% CI: [44; 92], p = 0.03). Oral anticoagulation therapy was associated with a reduced incidence of SLT (IRR 7.51, 95% CI: [3.24; 17.37], I2 62%, 95% CI: [0; 87], p <0.001). However, the incidence of later neurological events did not differ between patients with or without SLT (IRR 1.05, 95% CI: [0.32; 3.47], p = 0.93). In conclusion, SLT was more frequently detected after TAVR than SAVR. However, it was not associated with an increased risk for neurological events. Oral anticoagulation therapy seemed to reduce the incidence of SLT.

Trends and outcomes of concomitant aortic valve replacement and coronary artery bypass grafting in the UK and a survey of practices.

OBJECTIVES: Concomitant revascularization of coronary artery disease at the same time as treatment for aortic valvopathy favourably impacts survival. However, combined surgery may be associated with increased adverse outcomes compared to aortic valve replacement (AVR) or coronary artery bypass grafting in isolation. METHODS: We retrospectively analyzed all patients who underwent AVR with bypass grafting between February 1996 and March 2019 using data from the National Adult Cardiac Surgery Audit. We used a generalized mixed-effects model to assess the effect of the number and type of bypass grafts associated with surgical AVR on in-hospital mortality, postoperative stroke, and the need for renal dialysis. Furthermore, we conducted an international cross-sectional survey of cardiac surgeons to explore their views about concomitant AVR with coronary bypass grafting interventions. RESULTS: Fifty-one thousand two hundred and seventy-two patients were included in the study. Patients receiving 2 or more bypass grafts demonstrated more significant preoperative comorbidity and disease severity. Patients undergoing 2 and >2 grafts in addition to AVR had increased mortality as compared to patients undergoing AVR and only 1 graft [odds ratio (OR) 1.17, 95% confidence interval (CI) [1.05-1.30], P = 0.005 and OR 1.15, 95% CI [1.02-1.30], P = 0.024 respectively]. A single arterial conduit was associated with a reduction in mortality (OR 0.75, 95% CI [0.68-0.82], P < 0.001) and postoperative dialysis (OR 0.87, 95% CI [0.78-0.96], P = 0.006), but this association was lost with >1 arterial conduit. One hundred and three surgeons responded to our survey, with only a small majority believing that the number of bypass grafts can influence short- or long-term postoperative outcomes in these patients, and an almost equal split in responders supporting the use of staged or hybrid interventions for patients with concomitant pathology. CONCLUSIONS: The number of grafts performed during combined AVR and coronary artery bypass grafting is associated with increased morbidity and mortality. The use of an arterial graft was also associated with reduced mortality. Future studies are needed to assess the effect of incomplete revascularization and measure long-term outcomes. Based on our data, current published evidence, and the collective expert opinion we gathered, we endorse future work to investigate the short and long-term efficacy and safety of hybrid intervention for patients with concomitant advanced coronary and aortic valve disease.

Trend and early clinical outcomes of off-pump coronary artery bypass grafting in the UK.

OBJECTIVES: The popularity of off-pump coronary artery bypass grafting (CABG) varies across the world, ranging from 20% in Europe and the USA to 56% in Asia. We present the trend and early clinical outcomes in off pump in the UK. METHODS: All patients who underwent elective or urgent isolated CABG from 1996 to 2019 were extracted from the National Adult Cardiac Surgery Audit database. The trend in operating surgeons and units volume and training in off pump were analysed. Early clinical outcomes between off- and on-pump CABG were compared using propensity score matching. RESULTS: A total of 351 422 patients were included. The overall off-pump rate during the study period was 15.17%, it peaked in 2008 (19.8%), followed by a steady decreased to 2018 (7.63%). Its adoption varied across centres and surgeons, ranging from <1% to 48.36% and <1% to 85.5%, respectively, of total cases performed. After propensity score matching for the period 1996-2019, off pump, when compared to on pump, was associated with a lower in-hospital/30-day mortality (1.2% vs 1.5%, P < 0.001), return to theatre (3.7% vs 4.5%, P < 0.001), cerebrovascular accident (transient ischaemic attack: 0.3% vs 0.6%, stroke: 0.3% vs 0.6%, P < 0.001) and deep sternal wound infection (0.8% vs 1.2%, P ≤ 0.001). In a sub-analysis from the introduction of EuroScore II (2012-2019), there were no differences in-hospital/30-day mortality (1.0% vs 1.0%, P = 0.71). However, on pump, had a higher return to theatre (4.2% vs 2.7%, P < 0.001), cerebrovascular accident (transient ischaemic attack: 0.4% vs 0.2%, stroke: 0.5% vs 0.3%, P = 0.003) and deep sternal wound infection (1.0% vs 0.6%, P = 0.004). CONCLUSIONS: Our data show a decreasing trend in the use of off pump in the UK since 2008. This is likely to be multifactorial and raises the question of whether it should be a specialized revascularization technique.

Cardiac surgery risk prediction using ensemble machine learning to incorporate legacy risk scores: A benchmarking study.

Objective: The introduction of new clinical risk scores (e.g. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II) superseding original scores (e.g. EuroSCORE I) with different variable sets typically result in disparate datasets due to high levels of missingness for new score variables prior to time of adoption. Little is known about the use of ensemble learning to incorporate disparate data from legacy scores. We tested the hypothesised that Homogenenous and Heterogeneous Machine Learning (ML) ensembles will have better performance than ensembles of Dynamic Model Averaging (DMA) for combining knowledge from EuroSCORE I legacy data with EuroSCORE II data to predict cardiac surgery risk. Methods: Using the National Adult Cardiac Surgery Audit dataset, we trained 12 different base learner models, based on two different variable sets from either EuroSCORE I (LogES) or EuroScore II (ES II), partitioned by the time of score adoption (1996-2016 or 2012-2016) and evaluated on holdout set (2017-2019). These base learner models were ensembled using nine different combinations of six ML algorithms to produce homogeneous or heterogeneous ensembles. Performance was assessed using a consensus metric. Results: Xgboost homogenous ensemble (HE) was the highest performing model (clinical effectiveness metric (CEM) 0.725) with area under the curve (AUC) (0.8327; 95% confidence interval (CI) 0.8323-0.8329) followed by Random Forest HE (CEM 0.723; AUC 0.8325; 95%CI 0.8320-0.8326). Across different heterogenous ensembles, significantly better performance was obtained by combining siloed datasets across time (CEM 0.720) than building ensembles of either 1996-2011 (t-test adjusted, p = 1.67×10-6) or 2012-2019 (t-test adjusted, p = 1.35×10-193) datasets alone. Conclusions: Both homogenous and heterogenous ML ensembles performed significantly better than DMA ensemble of Bayesian Update models. Time-dependent ensemble combination of variables, having differing qualities according to time of score adoption, enabled previously siloed data to be combined, leading to increased power, clinical interpretability of variables and usage of data.

Patterns of cytokine release and association with new onset of post-cardiac surgery atrial fibrillation.

Introduction: Postoperative Atrial Fibrillation (POAF) is a common complication of cardiac surgery, associated with increased mortality, stroke risk, cardiac failure and prolonged hospital stay. Our study aimed to assess the patterns of release of systemic cytokines in patients with and without POAF. Methods: A post-hoc analysis of the Remote Ischemic Preconditioning (RIPC) trial, including 121 patients (93 males and 28 females, mean age of 68 years old) who underwent isolated coronary artery bypass grafting (CABG) and aortic valve replacement (AVR). Mixed-effect models were used to analyze patterns of release of cytokines in POAF and non-AF patients. A logistic regression model was used to assess the effect of peak cytokine concentration (6 h after the aortic cross-clamp release) alongside other clinical predictors on the development of POAF. Results: We found no significant difference in the patterns of release of IL-6 (p = 0.52), IL-10 (p = 0.39), IL-8 (p = 0.20) and TNF-α (p = 0.55) between POAF and non-AF patients. Also, we found no significant predictive value in peak concentrations of IL-6 (p = 0.2), IL-8 (p = >0.9), IL-10 (p = >0.9) and Tumour Necrosis Factor Alpha (TNF-α)(p = 0.6), however age and aortic cross-clamp time were significant predictors of POAF development across all models. Conclusions: Our study suggests no significant association exists between cytokine release patterns and the development of POAF. Age and Aortic Cross-clamp time were found to be significant predictors of POAF.

Comparison of machine learning techniques in prediction of mortality following cardiac surgery: analysis of over 220 000 patients from a large national database.

OBJECTIVES: To perform a systematic comparison of in-hospital mortality risk prediction post-cardiac surgery, between the predominant scoring system-European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, logistic regression (LR) retrained on the same variables and alternative machine learning techniques (ML)-random forest (RF), neural networks (NN), XGBoost and weighted support vector machine. METHODS: Retrospective analyses of prospectively routinely collected data on adult patients undergoing cardiac surgery in the UK from January 2012 to March 2019. Data were temporally split 70:30 into training and validation subsets. Mortality prediction models were created using the 18 variables of EuroSCORE II. Comparisons of discrimination, calibration and clinical utility were then conducted. Changes in model performance, variable-importance over time and hospital/operation-based model performance were also reviewed. RESULTS: Of the 227 087 adults who underwent cardiac surgery during the study period, there were 6258 deaths (2.76%). In the testing cohort, there was an improvement in discrimination [XGBoost (95% confidence interval (CI) area under the receiver operator curve (AUC), 0.834-0.834, F1 score, 0.276-0.280) and RF (95% CI AUC, 0.833-0.834, F1, 0.277-0.281)] compared with EuroSCORE II (95% CI AUC, 0.817-0.818, F1, 0.243-0.245). There was no significant improvement in calibration with ML and retrained-LR compared to EuroSCORE II. However, EuroSCORE II overestimated risk across all deciles of risk and over time. The calibration drift was lowest in NN, XGBoost and RF compared with EuroSCORE II. Decision curve analysis showed XGBoost and RF to have greater net benefit than EuroSCORE II. CONCLUSIONS: ML techniques showed some statistical improvements over retrained-LR and EuroSCORE II. The clinical impact of this improvement is modest at present. However the incorporation of additional risk factors in future studies may improve upon these findings and warrants further study.

A review and meta-analysis of conventional sternotomy versus minimally invasive mitral valve surgery for degenerative mitral valve disease focused on the last decade of evidence.

OBJECTIVES: Early meta-analyses comparing minimally invasive mitral valve surgery (MIMVS) with conventional sternotomy (CS) have determined the safety of MIMVS. We performed this review and meta-analysis based on studies from 2014 onwards to examine the differences in outcomes between MIMVS and CS. Specifically, some outcomes of interest included renal failure, new onset atrial fibrillation, mortality, stroke, reoperation for bleeding, blood transfusion and pulmonary infection. METHODS: A systematic search was performed in six databases for studies comparing MIMVS with CS. Although the initial search identified 821 papers in total, nine studies were suitable for the final analysis. All studies included compared CS with MIMVS. The Mantel - Haenszel statistical method was chosen due the use of inverse variance and random effects. A meta-analysis was performed on the data. RESULTS: MIMVS had significantly lower odds of renal failure (OR: 0.52; 95% CI 0.37 to 0.73, p < 0.001), new onset atrial fibrillation (OR: 0.78; 95% CI 0.67 to 0.90, p < 0.001), reduced prolonged intubation (OR: 0.50; 95% CI 0.29 to 0.87, p = 0.01) and reduced mortality (OR: 0.58; 95% CI 0.38 to 0.87, p < 0.01). MIMVS had shorter ICU stay (WMD: -0.42; 95% CI -0.59 to -0.24, p < 0.001) and shorter time to discharge (WMD: -2.79; 95% CI -3.86 to -1.71, p < 0.001). CONCLUSION: In the modern era, MIMVS for degenerative disease is associated with improved short-term outcomes when compared to the CS.

Efficacy and safety of carbon dioxide insufflation for brain protection for patients undergoing planned left-sided open heart valve surgery: protocol for a multicentre, placebo-controlled, blinded, randomised controlled trial (the CO2 Study).

INTRODUCTION: Brain injury is common following open heart valve surgery. Carbon dioxide insufflation (CDI) has been proposed to reduce the incidence of brain injury by reducing the number of air microemboli entering the bloodstream in surgery. The CO2 Study will evaluate the efficacy and safety of CDI in patients undergoing planned left-sided open heart valve surgery. METHODS AND ANALYSIS: The CO2 Study is a multicentre, blinded, placebo-controlled, randomised controlled trial. Seven-hundred and four patients aged 50 years and over undergoing planned left-sided heart valve surgery will be recruited to the study, from at least eight UK National Health Service hospitals, and randomised in a 1:1 ratio to receive CDI or medical air insufflation (placebo) in addition to standard de-airing. Insufflation will be delivered at a flow rate of 5 L/min from before the initiation of cardiopulmonary bypass until 10 min after cardiopulmonary bypass weaning. Participants will be followed up until 3 months post-surgery. The primary outcome is acute ischaemic brain injury within 10 days post-surgery based on new brain lesions identified with diffusion-weighted MRI or clinical evidence of permanent brain injury according to the current definition of stroke. ETHICS AND DISSEMINATION: The study was approved by the East Midlands-Nottingham 2 Research Ethics Committee in June 2020 and the Medicines and Healthcare products Regulatory Agency in May 2020. All participants will provide written informed consent prior to undertaking any study assessments. Consent will be obtained by the principal investigator or a delegated member of the research team who has been trained in the study and undergone Good Clinical Practice training. Results will be disseminated through peer-reviewed publications and presentations at national and international meetings. Study participants will be informed of results through study notifications and patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN30671536.

Mitral repair versus replacement: 20-year outcome trends in the UK (2000-2019).

OBJECTIVES: Using a large national database, we sought to describe outcome trends in mitral valve surgery between 2000 and 2019. METHODS: The study cohort was split into mitral valve repair (MVr) or replacement, including all patients regardless of concomitant procedures. Patients were grouped by four-year admission periods into groups (A to E). The primary outcome was in hospital mortality and secondary outcomes were return to theatre, postoperative stroke and postoperative length of stay. We investigated trends over time in patient demographics, comorbidities, intraoperative characteristics and postoperative outcomes. We used a multivariable binary logistic regression model to assess the relationship between mortality and time. Cohorts were further stratified by sex and aetiology. RESULTS: Of the 63 000 patients in the study cohort, 31 644 had an MVr and 31 356 had a replacement. Significant demographic shifts were observed. Aetiology has shifted towards degenerative disease; endocarditis rates in MVr dropped initially but are now rising (period A = 6%, period C = 4%, period E = 6%; P < 0.001). The burden of comorbidities has increased over time. In the latest time period, women had lower repair rates (49% vs 67%, P < 0.001) and higher mortality rates when undergoing repair (3% vs 2%, P = 0.001) than men. Unadjusted postoperative mortality dropped in MVr (5% vs 2%, P < 0.001) and replacement (9% vs 7%, P = 0.015). Secondary outcomes have improved. Time period was an independent predictor for reduced mortality in both repair (odds ratio: 0.41, 95% confidence interval: 0.28-0.61, P < 0.001) and replacement (odds ratio: 0.50, 95% confidence interval: 0.41-0.61, P < 0.001). CONCLUSIONS: In-hospital mortality has dropped significantly over time for mitral valve surgery in the UK. MVr has become the more common procedure. Sex-based discrepancies in repair rates and mortality require further investigation. Endocarditis rates in MVS are rising.

Assessment of post-infarct ventricular septal defects through 3D printing and statistical shape analysis.

Background: Post-infarct ventricular septal defect (PIVSD) is a serious complication of myocardial infarction. We evaluated 3D-printing models in PIVSD clinical assessment and the feasibility of statistical shape modeling for morphological analysis of the defects. Methods: Models (n = 15) reconstructed from computed tomography data were evaluated by clinicians (n = 8). Statistical shape modeling was performed on 3D meshes to calculate the mean morphological configuration of the defects. Results: Clinicians' evaluation highlighted the models' utility in displaying defects for interventional/surgical planning, education/training and device development. However, models lack dynamic representation. Morphological analysis was feasible and revealed oval-shaped (n = 12) and complex channel-like (n = 3) defects. Conclusion: 3D-PIVSD models can complement imaging data for teaching and procedural planning. Statistical shape modeling is feasible in this scenario.

Following heart attacks, the heart muscle becomes scarred and weaker, making it prone to tearing under high pressures. These tears are known as 'post-infarct ventricular septal defects'. Their shape varies greatly as the heart beats. The approach to fixing these can range from plugging them with a device or patching them by open heart surgery. We created 15 3D-printed models of hearts with these kinds of defects and made digital reconstructions of the tears to see the different sizes/shapes that they can have. Doctors agreed that 3D-printed models could help in planning repairs and training other doctors. The digital reconstructions of the tears showed that many were round, but some had irregular shapes which would mean devices used to fix them may not fit.