Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial.

BACKGROUND: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. METHODS: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. RESULTS: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. CONCLUSIONS: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Limited versus full sternotomy for aortic valve replacement.

BACKGROUND: Aortic valve disease is a common condition easily treatable with cardiac surgery. This is conventionally performed by opening the sternum ('median sternotomy') and replacing the valve under cardiopulmonary bypass. Median sternotomy is well tolerated, but as less invasive options become available, the efficacy of limited incisions has been called into question. In particular, the effects of reducing the visibility and surgical access have raised safety concerns with regard to the placement of cannulae, venting of the heart, epicardial wire placement, and de-airing of the heart at the end of the procedure. These difficulties may increase operating times, affecting outcome. The benefits of smaller incisions are thought to include decreased pain; improved respiratory mechanics; reductions in wound infections, bleeding, and need for transfusion; shorter intensive care stay; better cosmesis; and a quicker return to normal activity. This is an update of a Cochrane review first published in 2017, with seven new studies. OBJECTIVES: To assess the effects of minimally invasive aortic valve replacement via a limited sternotomy versus conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement. SEARCH METHODS: We performed searches of CENTRAL, MEDLINE and Embase from inception to August 2021, with no language limitations. We also searched two clinical trials registries and manufacturers' websites. We reviewed references of primary studies to identify any further studies of relevance. SELECTION CRITERIA: We included randomised controlled trials comparing aortic valve replacement via a median sternotomy versus aortic valve replacement via a limited sternotomy. We excluded trials that performed other minimally invasive incisions such as mini-thoracotomies, port access, transapical, transfemoral or robotic procedures. Although some well-conducted prospective and retrospective case-control and cohort studies exist, these were not included in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial papers to extract data, assess quality, and identify risk of bias. A third review author provided arbitration where required. We determined the certainty of evidence using the GRADE methodology and summarised results of patient-relevant outcomes in a summary of findings table. MAIN RESULTS: The review included 14 trials with 1395 participants. Most studies had at least two domains at high risk of bias. We analysed 14 outcomes investigating the effects of minimally invasive limited upper hemi-sternotomy on aortic valve replacement as compared to surgery performed via full median sternotomy. Upper hemi-sternotomy may have little to no effect on mortality versus full median sternotomy (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.45 to 1.94; 10 studies, 985 participants; low-certainty evidence). Upper hemi-sternotomy for aortic valve replacement may increase cardiopulmonary bypass time slightly, although the evidence is very uncertain (mean difference (MD) 10.63 minutes, 95% CI 3.39 to 17.88; 10 studies, 1043 participants; very low-certainty evidence) and may increase aortic cross-clamp time slightly (MD 6.07 minutes, 95% CI 0.79 to 11.35; 12 studies, 1235 participants; very low-certainty evidence), although the evidence is very uncertain. Most studies had at least two domains at high risk of bias. Postoperative blood loss was probably lower in the upper hemi-sternotomy group (MD -153 mL, 95% CI -246 to -60; 8 studies, 767 participants; moderate-certainty evidence). Low-certainty evidence suggested that there may be no change in pain scores by upper hemi-sternotomy (standardised mean difference (SMD) -0.19, 95% CI -0.43 to 0.04; 5 studies, 649 participants). Upper hemi-sternotomy may result in little to no difference in quality of life (MD 0.03 higher, 95% CI 0 to 0.06 higher; 4 studies, 624 participants; low-certainty evidence). Two studies reporting index admission costs concluded that limited sternotomy may be more costly at index admission in the UK National Health Service (MD 1190 GBP more, 95% CI 420 GBP to 1970 GBP, 2 studies, 492 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence was of very low to moderate certainty. Sample sizes were small and underpowered to demonstrate differences in some outcomes. Clinical heterogeneity was also noted. Considering these limitations, there may be little to no effect on mortality. Differences in extracorporeal support times are uncertain, comparing upper hemi-sternotomy to full sternotomy for aortic valve replacement. Before widespread adoption of the minimally invasive approach can be recommended, there is a need for a well-designed and adequately powered prospective randomised controlled trial. Such a study would benefit from also performing a robust cost analysis. Growing patient preference for minimally invasive techniques merits thorough quality of life analyses to be included as end points, as well as quantitative measures of physiological reserve.

Minithoracotomy vs Conventional Sternotomy for Mitral Valve Repair: A Randomized Clinical Trial.

Importance: The safety and effectiveness of mitral valve repair via thoracoscopically-guided minithoracotomy (minithoracotomy) compared with median sternotomy (sternotomy) in patients with degenerative mitral valve regurgitation is uncertain. Objective: To compare the safety and effectiveness of minithoracotomy vs sternotomy mitral valve repair in a randomized trial. Design, Setting, and Participants: A pragmatic, multicenter, superiority, randomized clinical trial in 10 tertiary care institutions in the UK. Participants were adults with degenerative mitral regurgitation undergoing mitral valve repair surgery. Interventions: Participants were randomized 1:1 with concealed allocation to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon. Main Outcomes and Measures: The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) version 2 physical functioning scale 12 weeks after the index surgery, assessed by an independent researcher masked to the intervention. Secondary outcomes included recurrent mitral regurgitation grade, physical activity, and quality of life. The prespecified safety outcomes included death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year. Results: Between November 2016 and January 2021, 330 participants were randomized (mean age, 67 years, 100 female [30%]); 166 were allocated to minithoracotomy and 164 allocated to sternotomy, of whom 309 underwent surgery and 294 reported the primary outcome. At 12 weeks, the mean between-group difference in the change in the SF-36 physical function T score was 0.68 (95% CI, -1.89 to 3.26). Valve repair rates (≈ 96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year with no difference between groups. The composite safety outcome occurred in 5.4% (9 of 166) of patients undergoing minithoracotomy and 6.1% (10 of 163) undergoing sternotomy at 1 year. Conclusions and relevance: Minithoracotomy is not superior to sternotomy in recovery of physical function at 12 weeks. Minithoracotomy achieves high rates and quality of valve repair and has similar safety outcomes at 1 year to sternotomy. The results provide evidence to inform shared decision-making and treatment guidelines. Trial Registration: isrctn.org Identifier: ISRCTN13930454.

Determinants of outcomes following surgery for type A acute aortic dissection: the UK National Adult Cardiac Surgical Audit.

AIMS: Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK. METHODS AND RESULTS: We identified 4203 patients undergoing TAAAD surgery in the UK (2009-18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02-1.03; P < 0.001]; malperfusion (OR 1.79, 95% CI 1.51-2.12; P < 0.001); left ventricular ejection fraction (moderate: OR 1.40, 95% CI 1.14-1.71; P = 0.001; poor: OR 2.83, 95% CI 1.90-4.21; P < 0.001); previous cardiac surgery (OR 2.29, 95% CI 1.71-3.07; P < 0.001); preoperative mechanical ventilation (OR 2.76, 95% CI 2.00-3.80; P < 0.001); preoperative resuscitation (OR 3.36, 95% CI 1.14-9.87; P = 0.028); and concomitant coronary artery bypass grafting (OR 2.29, 95% CI 1.86-2.83; P < 0.001). We found a significant inverse relationship between surgeons but not centre annual volume with outcomes. CONCLUSIONS: Patient characteristics, intraoperative factors, cardiac centre, and high-volume surgeons are strong determinants of outcomes following TAAAD surgery. These findings may help refining clinical decision-making, supporting patient counselling and be used by policy makers for quality assurance and service provision improvement.

A survey of minimally invasive cardiac surgery during the COVID-19 pandemic.

BACKGROUND: Lack of scientific data on the feasibility and safety of minimally invasive cardiac surgery (MICS) during the COVID-19 pandemic has made clinical decision making challenging. This survey aimed to appraise MICS activity in UK cardiac units and establish a consensus amongst front-line MICS surgeons regarding standard best MICS practise during the pandemic. METHODS: An online questionnaire was designed through the 'googleforms' platform. Responses were received from 24 out of 28 surgeons approached (85.7%), across 17 cardiac units. RESULTS: There was a strong consensus against a higher risk of conversion from minimally invasive to full sternotomy (92%; n = 22) nor there is increased infection (79%; n = 19) or bleeding (96%; n = 23) with MICS compared to full sternotomy during the pandemic. The majority of respondents (67%; n = 16) felt that it was safe to perform MICS during COVID-19, and that it should not be halted (71%; n = 17). London cardiac units experienced a decrease in MICS (60%; n = 6), whereas non-London units saw no reduction. All London MICS surgeons wore an FP3 mask compared to 62% (n = 8) of non-London MICS surgeons, 23% (n = 3) of which only wore a surgical mask. London MICS surgeons felt that routine double gloving should be done (60%; n = 6) whereas non-London MICS surgeons held a strong consensus that it should not (92%; n = 12). CONCLUSION: Whilst more robust evidence on the effect of COVID-19 on MICS is awaited, this survey provides interesting insights for clinical decision-making regarding MICS and aids to facilitate the development of standardised MICS guidelines for an effective response during future pandemics.

Activation of the innate immune response and organ injury after cardiac surgery: a systematic review and meta-analysis of randomised trials and analysis of individual patient data from randomised and non-randomised studies.

BACKGROUND: It is unclear whether the innate immune response represents a therapeutic target for organ protection strategies in cardiac surgery. METHODS: A systematic review of trials of interventions targeting the inflammatory response to cardiac surgery reporting treatment effects on both innate immune system cytokines and organ injury was performed. The protocol was registered at the International Prospective Register of Systematic Reviews: CRD42020187239. Searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were performed. Random-effects meta-analyses were used for the primary analysis. A separate analysis of individual patient data from six studies (n=785) explored sources of heterogeneity for treatment effects on cytokine levels. RESULTS: Searches to May 2020 identified 251 trials evaluating 24 interventions with 20 582 participants for inclusion. Most trials had important limitations. Methodological limitations of the included trials and heterogeneity of the treatment effects on cytokine levels between trials limited interpretation. The primary analysis demonstrated inconsistency in the direction of the treatment effects on innate immunity and organ failure or death between interventions. Analyses restricted to important subgroups or trials with fewer limitations showed similar results. Meta-regression, pooling available data from all trials, demonstrated no association between the direction of the treatment effects on inflammatory cytokines and organ injury or death. The analysis of individual patient data demonstrated heterogeneity in the association between the cytokine response and organ injury after cardiac surgery for people >75 yr old and those with some chronic diseases. CONCLUSIONS: The certainty of the evidence for a causal relationship between innate immune system activation and organ injury after cardiac surgery is low.

Does Blood Transfusion Have an Effect on Outcomes After Aortic Valve Replacement Surgery?

OBJECTIVE: Long-term outcomes following surgical aortic valve replacement (AVR) are excellent. However, there is a significant early morbidity burden. Red cell transfusion is common in the perioperative period and deleterious effects of receiving a transfusion on early postoperative morbidity are well described in observational studies. This study aimed to assess the effect of transfusion on ischaemic or infective outcomes after aortic valve replacement. METHODS: Data from 270 patients enrolled in the Manubrium-limited ministernotomy versus conventional sternotomy for aortic valve replacement (MAVRIC) randomised controlled trial was used to create two cohorts, patients that received red cell transfusions following AVR and those that did not. Propensity score matching was performed to limit the effect of confounding variables. Strict transfusion thresholds were maintained, with patients receiving a transfusion if haemoglobin concentration fell below 80 g/L, or if significant bleeding or haemodynamic instability occurred. The primary outcome was a composite of ischaemic event (myocardial infarction, permanent stroke, gut ischaemia or acute kidney injury) or serious infection (sepsis, endocarditis, respiratory tract or wound infection). Patients were followed for 12 weeks following surgery. RESULTS: Sixty-three (63) of 270 patients received a red cell transfusion (23.3%). Transfused patients had significantly lower body mass index (BMI), a higher proportion of females, a lower preoperative haemoglobin and haematocrit, a higher EuroSCORE II score, worse renal function and were more likely to have undergone urgent surgery compared to the unadjusted control cohort. Once matched, there was no difference in the primary outcome between cohorts. There was a significantly increased length of hospital stay in the transfused group (median 7 days transfused, median 5 days not-transfused, p=0.001). CONCLUSIONS: Red cell transfusion, using a transfusion threshold of 80 g/L, does not appear to be associated with adverse ischaemic or infective outcomes after aortic valve replacement.

Early and Late Outcomes After Minimally Invasive Mitral Valve Repair Surgery.

BACKGROUND AND AIM OF THE STUDY: The practice of thoracoscopic assisted minimally invasive mitral valve repair surgery is less common in the United Kingdom than in Europe or the USA. The main reasons for this are concerns around increased operative risk, feasibility and durability of valve repair. The study aim was to report the early and late outcomes of minimally invasive mitral valve repair surgery at a single U.K. center. METHODS: Patients undergoing isolated minimally invasive mitral valve repair between 2003 and 2013 were reviewed retrospectively. Data were obtained from a prospectively maintained institutional database, a comprehensive review of individual case notes, echocardiograms, intensive care charts, clinic letters, discharge summaries, and the authors' follow up database (based on data supplied by the UK Office for National Statistics). RESULTS: A total of 190 patients (mean age 61 years; mean EuroSCORE 3.9) underwent the procedure. The mean cardiopulmonary bypass and aortic cross-clamp times were 153 and 108 min, respectively. Rates of major postoperative complications were: reoperation for bleeding 3.7%, stroke 1.6%, intra-aortic balloon pump 2.1%, and venovenous hemofiltration 2.6%. The median intensive care stay was one day, and the median hospital stay five days (21.8% of patients were discharged by day 3). The 30-day mortality was 1.1% (n = 2). Echocardiography performed at discharge or six weeks postoperatively showed less than mild mitral regurgitation (MR) in 91.3%. The median duration of follow up was 57 months. During the entire follow up period, four patients (2.1%) underwent repeat surgery for recurrent MR (between 15 months and five years). Of 188 patients discharged from hospital, nine (4.8%) died during follow up: median 5.3 years (range 1.3- 10.7 years) post surgery. CONCLUSION: These data are the first from the U.K. demonstrating early and late outcomes after thoracoscopic assisted minimally invasive mitral valve repair surgery. The data establish the safety and efficacy of the technique and, importantly, lend further support towards a prospective randomized comparison of minimally invasive versus conventional mitral valve repair surgery.

Feasibility study of rehabilitation for cardiac patients aided by an artificial intelligence web-based programme: a randomised controlled trial (RECAP trial)-a study protocol.

INTRODUCTION: Cardiac rehabilitation (CR) delivered by rehabilitation specialists in a healthcare setting is effective in improving functional capacity and reducing readmission rates after cardiac surgery. It is also associated with a reduction in cardiac mortality and recurrent myocardial infarction. This trial assesses the feasibility of a home-based CR programme delivered using a mobile application (app). METHODS: The Rehabilitation through Exercise prescription for Cardiac patients using an Artificial intelligence web-based Programme (RECAP) randomised controlled feasibility trial is a single-centre prospective study, in which patients will be allocated on a 1:1 ratio to a home-based CR programme delivered using a mobile app with accelerometers or standard hospital-based rehabilitation classes. The home-based CR programme will employ artificial intelligence to prescribe exercise goals to the participants on a weekly basis. The trial will recruit 70 patients in total. The primary objectives are to evaluate participant recruitment and dropout rates, assess the feasibility of randomisation, determine acceptability to participants and staff, assess the rates of potential outcome measures and determine hospital resource allocation to inform the design of a larger randomised controlled trial for clinical efficacy and health economic evaluation. Secondary objectives include evaluation of health-related quality of life and 6 minute walk distance. ETHICS AND DISSEMINATION: RECAP trial received a favourable outcome from the Berkshire research ethics committee in September 2022 (IRAS 315483).Trial results will be made available through publication in peer-reviewed journals and presented at relevant scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN97352737.

Antithrombotic therapy after heart valve surgery: contemporary practice in the UK.

OBJECTIVES: There is a lack of high-quality data informing the optimal antithrombotic drug strategy following bioprosthetic heart valve replacement or valve repair. Disparity in recommendations from international guidelines reflects this. This study aimed to document current patterns of antithrombotic prescribing after heart valve surgery in the UK. METHODS: All UK consultant cardiac surgeons were e-mailed a custom-designed survey. The use of oral anticoagulant (OAC) and/or antiplatelet drugs following bioprosthetic aortic valve replacement or mitral valve replacement, or mitral valve repair (MVrep), for patients in sinus rhythm, without additional indications for antithrombotic medication, was assessed. Additionally, we evaluated anticoagulant choice following MVrep in patients with atrial fibrillation. RESULTS: We identified 260 UK consultant cardiac surgeons from 36 units, of whom 103 (40%) responded, with 33 units (92%) having at least 1 respondent. The greatest consensus was for patients undergoing bioprosthetic aortic valve replacement, in which 76% of surgeons favour initial antiplatelet therapy and 53% prescribe lifelong treatment. Only 8% recommend initial OAC. After bioprosthetic mitral valve replacement, 48% of surgeons use an initial OAC strategy (versus 42% antiplatelet), with 66% subsequently prescribing lifelong antiplatelet therapy. After MVrep, recommendations were lifelong antiplatelet agent alone (34%) or following 3 months OAC (20%), no antithrombotic agent (20%), or 3 months OAC (16%). After MVrep for patients with established atrial fibrillation, surgeons recommend warfarin (38%), a direct oral anticoagulant (37%) or have no preference between the 2 (25%). CONCLUSIONS: There is considerable variation in the use of antithrombotic drugs after heart valve surgery in the UK and a lack of high-quality evidence to guide practice, underscoring the need for randomized studies.

Minimal Access Aortic Valve Surgery.

Minimally invasive approaches to the aortic valve have been described since 1993, with great hopes that they would become universal and facilitate day-case cardiac surgery. The literature has shown that these procedures can be undertaken with equivalent mortality rates, similar operative times, comparable costs, and some benefits regarding hospital length of stay. The competing efforts of transcatheter aortic valve implantation for these same outcomes have provided an excellent range of treatment options for patients from cardiology teams. We describe the current state of the art, including technical considerations, caveats, and complications of minimal access aortic surgery and predict future directions in this space.

Impact of gender, ethnicity and social deprivation on access to surgical or transcatheter aortic valve replacement in aortic stenosis: a retrospective database study in England.

OBJECTIVE: To assess gender, ethnicity, and deprivation-based differences in provision of aortic valve replacement (AVR) in England for adults with aortic stenosis (AS). METHODS: We retrospectively identified adults with AS from the English Hospital Episode Statistics (HES) between April 2016 and March 2019 and those who subsequently had an AVR. We separately used HES-linked Clinical Practice Research Datalink (CPRD) to identify people with AVR and evaluate the timeliness of their procedure (CPRD-AVR cohort). ORs for AVR in people with an AS diagnosis were estimated using multivariable logistic regression adjusted for age, region and comorbidity. AVR was considered timely if performed electively and without evidence of cardiac decompensation before AVR. RESULTS: 183 591 adults with AS were identified in HES; of these, 31 436 underwent AVR. The CPRD-AVR cohort comprised 10 069 adults. Women had lower odds of receiving AVR compared with men (OR 0.65; 95% CI 0.63 to 0.66); as did people of black (OR 0.70; 95% CI 0.60 to 0.82) or South Asian (OR 0.75; 95% CI 0.69 to 0.82) compared with people of white ethnicities. People in the most deprived areas were less likely to receive AVR than the least deprived areas (OR 0.8; 95% CI 0.75 to 0.86). Timely AVR occurred in 65% of those of white ethnicities compared with 55% of both those of black and South Asian ethnicities. 77% of the least deprived had a timely procedure compared with 58% of the most deprived; there was no gender difference. CONCLUSIONS: In this large, national dataset, female gender, black or South Asian ethnicities and high deprivation were associated with significantly reduced odds of receiving AVR in England. A lower proportion of people of minority ethnicities or high deprivation had a timely procedure. Public health initiatives may be required to increase clinician and public awareness of unconscious biases towards minority and vulnerable populations to ensure timely AVR for everyone.

Prehabilitation in elective patients undergoing cardiac surgery: a randomised control trial (THE PrEPS TRIAL) - a study protocol.

INTRODUCTION: Prehabilitation prior to surgery has been shown to reduce postoperative complications, reduce length of hospital stay and improve quality of life after cancer and limb reconstruction surgery. However, there are minimal data on the impact of prehabilitation in patients undergoing cardiac surgery, despite the fact these patients are generally older and have more comorbidities and frailty. This trial will assess the feasibility and impact of a prehabilitation intervention consisting of exercise and inspiratory muscle training on preoperative functional exercise capacity in adult patients awaiting elective cardiac surgery, and determine any impact on clinical outcomes after surgery. METHODS AND ANALYSIS: PrEPS is a randomised controlled single-centre trial recruiting 180 participants undergoing elective cardiac surgery. Participants will be randomised in a 1:1 ratio to standard presurgical care or standard care plus a prehabilitation intervention. The primary outcome will be change in functional exercise capacity measured as change in the 6 min walk test distance from baseline. Secondary outcomes will evaluate the impact of prehabilitation on preoperative and postoperative outcomes including; respiratory function, health-related quality of life, anxiety and depression, frailty, and postoperative complications and resource use. This trial will evaluate if a prehabilitation intervention can improve preoperative physical function, inspiratory muscle function, frailty and quality of life prior to surgery in elective patients awaiting cardiac surgery, and impact postoperative outcomes. ETHICS AND DISSEMINATION: A favourable opinion was given by the Sheffield Research Ethics Committee in 2019. Trial findings will be disseminated to patients, clinicians, commissioning groups and through peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN13860094.

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.

A randomised controlled, feasibility study to establish the acceptability of early outpatient review and early cardiac rehabilitation compared to standard practice after cardiac surgery and viability of a future large-scale trial (FARSTER).

OBJECTIVE: To determine the acceptability and feasibility of delivering early outpatient review following cardiac surgery and early cardiac rehabilitation (CR), compared to standard practice to establish if a future large-scale trial is achievable. METHODS: A randomised controlled, feasibility trial with embedded health economic evaluation and qualitative interviews, recruited patients aged 18-80 years from two UK cardiac centres who had undergone elective or urgent cardiac surgery via a median sternotomy. Eligible, consenting participants were randomised 1:1 by a remote, centralised randomisation service to postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control), or postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention). The primary outcome measures related to trial feasibility including recruitment, retention, CR adherence, and acceptability to participants/staff. Secondary outcome measures included health-rated quality of life using EQ-5D-5L, NHS resource-use, Incremental Shuttle Walk Test (ISWT) distance, 30- and 90-day mortality, surgical site complications and hospital readmission rates. RESULTS: Fifty participants were randomised (25 per group) and 92% declared fit for CR. Participant retention at final follow-up was 74%; completion rates for outcome data time points ranged from 28 to 92% for ISWT and 68 to 94% for follow-up questionnaires. At each time point, the mean ISWT distance walked was greater in the intervention group compared to the control. Mean utility scores increased from baseline to final follow-up by 0.202 for the intervention (0.188 control). Total costs were £1519 for the intervention (£2043 control). Fifteen participants and a research nurse were interviewed. Many control participants felt their outpatient review and CR could have happened sooner; intervention participants felt the timing was right. The research nurse found obtaining consent for willing patients challenging due to discharge timings. CONCLUSION: Recruitment and retention rates showed that it would be feasible to undertake a full-scale trial subject to some modifications to maximise recruitment. Lower than expected recruitment and issues with one of the clinical tests were limitations of the study. Most study procedures proved feasible and acceptable to participants, and professionals delivering early CR. TRIAL REGISTRATION: ISRCTN80441309 (prospectively registered on 24/01/2019).

Which antithrombotic strategy provides the best outcomes after mitral valve repair in patients who remain in sinus rhythm?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'in the first 3-months after mitral valve repair (MVRep) which antiplatelet and/or anticoagulant strategy should be instigated in patients who remain in normal sinus rhythm'. Altogether 77 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that there remains a lack of high-quality randomized studies, controlling for postoperative cardiac rhythm, comparing vitamin K antagonists (VKA) and antiplatelet therapy in the early postoperative period following isolated MVRep. Current guidelines are based on limited evidence or expert consensus alone. Based on the currently available evidence, the authors conclude that antiplatelet therapy (e.g. aspirin) is safe and appropriate to use in the 3-month postoperative period following isolated MVRep, in those without preoperative, or postoperative atrial fibrillation. Rates of thromboembolic events are comparable between these patient groups (i.e. VKA versus aspirin), whilst VKA therapy is associated with increased rates of major bleeding events and mortality.

Long-term outcomes of mini-sternotomy versus conventional sternotomy for aortic valve replacement: a randomized controlled trial.

OBJECTIVES: Aortic valve replacement (AVR) for severe symptomatic aortic stenosis is one of the most common cardiac surgical procedures with excellent long-term outcomes. Multiple previous studies have compared short-term outcomes of AVR with mini-sternotomy versus AVR with conventional sternotomy. We have previously reported the results of the randomized MAVRIC trial, which aimed to evaluate early postoperative morbidity among patients undergoing mini-sternotomy and conventional sternotomy AVR. We now report the long-term all-cause mortality, reoperation, MACE outcomes and echocardiographic data from this trial. METHODS: The prospective, randomized, single-centre, single-blind MAVRIC (manubrium-limited mini-sternotomy versus conventional sternotomy for aortic valve replacement) trial compared manubrium-limited mini-sternotomy and conventional median sternotomy for the treatment of patients with severe aortic stenosis. The previously reported primary outcome was the proportion of patients receiving red cell transfusion postoperatively and within 7 days of the index procedure. Currently reported exploratory analyses of a combined long-term all-cause mortality and reoperation were compared between groups via the log-rank test. Sensitivity analyses reviewed individual components of the combined end point. The primary analysis and long-term exploratory analyses were based on an intention-to-treat principle. RESULTS: Between March 2014 and June 2016, 270 patients were enrolled and randomized in a 1:1 fashion to undergo mini-sternotomy AVR (n = 135) or conventional median sternotomy AVR (n = 135). At the median follow-up of 6.1 years, the composite outcome of all-cause mortality and reoperation occurred in 18.5% (25/135) of patients in the conventional sternotomy group and in 17% (23/135) of patients in the mini-sternotomy group. The incidence of chronic kidney disease, cerebrovascular accident and myocardial infarction was not significantly different between 2 groups. Follow-up echocardiographic data suggested no difference in peak and mean gradients or incidence of aortic regurgitation between 2 approaches. CONCLUSIONS: This exploratory long-term analysis demonstrated that, in patients with severe aortic stenosis undergoing isolated AVR, there was no significant difference between manubrium-limited mini-sternotomy and conventional sternotomy with respect to all-cause mortality, rate of reoperation, MACE events and echocardiographic data at the median of 6.1-year follow-up.

Getting the best from the Heart Team: guidance for cardiac multidisciplinary meetings.

The purpose of this document is to update the existing joint British Societies recommendations on multidisciplinary meetings (MDMs) published in 2015 to reflect changes in practice. We aim to provide guidance on the structure and function of MDMs which should be taking place in every cardiac surgical centre. Out of scope are MDMs that do not require the routine presence of a cardiac surgeon such as electrophysiology MDMs and those which are not provided in every centre, such as complex aortic surgery.

Non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement: a single-centre retrospective study.

BACKGROUND: Iron deficiency has deleterious effects in patients with cardiopulmonary disease, independent of anemia. Low ferritin has been associated with increased mortality in patients undergoing cardiac surgery, but modern indices of iron deficiency need to be explored in this population. METHODS: We conducted a retrospective single-centre observational study of 250 adults in a UK academic tertiary hospital undergoing median sternotomy for non-emergent isolated aortic valve replacement. We characterised preoperative iron status using measurement of both plasma ferritin and soluble transferrin receptor (sTfR), and examined associations with clinical outcomes. RESULTS: Measurement of plasma sTfR gave a prevalence of iron deficiency of 22%. Patients with non-anemic iron deficiency had clinically significant prolongation of total hospital stay (mean increase 2.2 days; 95% CI: 0.5-3.9; P = 0.011) and stay within the cardiac intensive care unit (mean increase 1.3 days; 95% CI: 0.1-2.5; P = 0.039). There were no deaths. Defining iron deficiency as a plasma ferritin < 100 µg/L identified 60% of patients as iron deficient and did not predict length of stay. No significant associations with transfusion requirements were evident using either definition of iron deficiency. CONCLUSIONS: These findings indicate that when defined using sTfR rather than ferritin, non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement. Further studies are required to clarify the role of contemporary laboratory indices in the identification of preoperative iron deficiency in patients undergoing cardiac surgery. An interventional study of intravenous iron targeted at preoperative non-anemic iron deficiency is warranted.

Endoscopic vein harvesting.

Coronary artery bypass grafting is the most common cardiac surgical procedure performed worldwide and the long saphenous vein the most common conduit for this. When performed as an open vein harvest (OVH), the incision on each leg can be up to 85cm long, making it the longest incision of any routine procedure. This confers a high degree of morbidity to the procedure. Endoscopic vein harvest (EVH) methods were popularised over two decades ago, demonstrating significant benefits over OVH in terms of leg wound complications including surgical site infections. They also appeared to hasten return to usual activities and wound healing and became popular particularly in North America. Subgroup analyses of two trials designed for other purposes created a period of uncertainty between 2009-2013 while the impact of endoscopic vein harvesting on vein graft patency and major adverse cardiac events was scrutinised. Large observational studies debunked the findings of increased mortality in the short-term, allowing practitioners and governing bodies to regain some confidence in the procedure. A well designed, adequately powered, randomised controlled trial published in 2019 also definitively demonstrated that there was no increase in death, myocardial infarction or repeat revascularisation with endoscopic vein harvest. Endoscopic vein harvest is a Class IIa indication in European Association of Cardio-Thoracic Surgery (EACTS) and a Class I indication in International Society of Minimally Invasive Cardiac Surgery (ISMICS) guidelines.