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Background Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. Methods For this multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled feasibility trial, adults with OAC (including Siewert I–II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. Results A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low‐density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0·83 (95 per cent c.i. −1·4 to −0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow‐up. Adverse events were similar between the groups. Quality‐of‐life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non‐randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. Conclusion This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

Background: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear., Methods: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis., Results: A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients., Conclusions: In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.)., (Copyright © 2024 Massachusetts Medical Society.)

Aims: Diabetes and obesity are common conditions which can influence outcomes after coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the influence of diabetes and obesity, and their interactions, on ten-year outcomes following CABG., Methods and Results: Patients enrolled in the Arterial Revascularisation Trial (ART) were stratified by diabetes and obesity at baseline. Diabetes was further stratified into insulin and non-insulin dependent. The primary outcome was all-cause mortality at 10 years of follow-up. Secondary outcomes were the composite of all-cause mortality, myocardial infarction or stroke at 10 years, and sternal wound complications at 6 months follow-up. A total of 3096 patients were included in the analysis (24% with diabetes, 30% with obesity). Patients in the "diabetes/no obesity" group had a higher risk of all-cause mortality following CABG (adjusted hazard ratio [aHR] 1.33, 95% confidence interval [CI] 1.08-1.64, p = 0.01) compared to the reference group of "no diabetes/no obesity". No excess risk was observed in the "no diabetes/obesity" or "diabetes/obesity" groups. Patients with insulin dependent diabetes had a significantly higher ten-year mortality risk compared to no diabetes (aHR 1.85, 95% CI 1.41-2.44, p = 0.00). Patients in the "diabetes/no obesity" and "diabetes/obesity groups" had a higher risk of sternal wound complications (HR 2.29, 95% CI 1.39-3.79, p < 0.001 and HR 3.21, 95% CI 1.89-5.45, p < 0.001 respectively). The composite outcome results were consistent with the mortality results., Conclusion: Diabetes, especially insulin dependent diabetes, is associated with a higher ten-year mortality risk after CABG, in contrast to obesity which does not appear to increase long term mortality compared to non-obese. The interaction between diabetes and obesity shows an apparent "protective" effect of obesity irrespective of diabetes on mortality. Both conditions are associated with a higher risk of post-operative sternal wound infections., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: In a recent meta-analysis of randomized controlled trials, routine use of veno-arterial ECMO (VA-ECMO) did not improve outcomes in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS), while a microaxial flow pump reduced mortality in a selected group of patients with AMI-CS in the DanGer-Shock trial., Methods and Results: Individual patient data of patients included in four randomized clinical trials investigating the routine use of VA-ECMO in AMI-CS were centrally analysed. For the purpose of this sub-analysis, DanGer-Shock-like patients were analysed (STEMI only, presumed low likelihood of brain injury). The primary endpoint was 180-day all-cause mortality. A total of 202 patients (106 randomized to VA-ECMO and 96 to control) were included. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. Mortality after 6 months was numerically lower with VA-ECMO between the groups [45% in VA-ECMO group vs. 51% in control group; hazard ratio, 0.84; 95% confidence interval (CI), 0.56-1.26], while major bleeding (OR, 2.24; 95% CI, 1.08-4.64) and peripheral vascular complications (OR, 3.65; 95% CI, 1.15-11.56) were increased with the use of VA-ECMO., Conclusion: In this exploratory subgroup analysis in patients with CS, STEMI, and a low likelihood of brain injury, there was no mortality benefit with the routine use of VA-ECMO. However, as indicated by the large confidence intervals, the statistical power was limited to draw definite conclusions., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS., Methods: In this individual patient data meta-analysis, randomised controlled trials of potential interest were identified, without language restriction, by querying the electronic databases MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Embase, as well as ClinicalTrials.gov, up to Jan 26, 2024. All randomised trials with 6-month mortality data comparing early routine active MCS (directly in the catheterisation laboratory after randomisation) versus control in patients with AMICS were included. The primary outcome was 6-month all-cause mortality in patients with AMICS treated with early routine active percutaneous MCS versus control, with a focus on device type (loading, such as venoarterial extracorporeal membrane oxygenation [VA-ECMO] vs unloading) and patient selection. Hazard ratios (HRs) of the primary outcome measure were calculated using Cox regression models. This study is registered with PROSPERO, CRD42024504295., Findings: Nine reports of randomised controlled trials (n=1114 patients) were evaluated in detail. Overall, four randomised controlled trials (n=611 patients) compared VA-ECMO with a control treatment and five randomised controlled trials (n=503 patients) compared left ventricular unloading devices with a control treatment. Two randomised controlled trials also included patients who did not have AMICS, who were excluded (55 patients [44 who were treated with VA-ECMO and 11 who were treated with a left ventricular unloading device]). The median patient age was 65 years (IQR 57-73); 845 (79·9%) of 1058 patients with data were male and 213 (20·1%) were female. No significant benefit of early unselected MCS use on 6-month mortality was noted (HR 0·87 [95% CI 0·74-1·03]; p=0·10). No significant differences were observed for left ventricular unloading devices versus control (0·80 [0·62-1·02]; p=0·075), and loading devices also had no effect on mortality (0·93 [0·75-1·17]; p=0·55). Patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality with MCS use (0·77 [0·61-0·97]; p=0·024). Major bleeding (odds ratio 2·64 [95% CI 1·91-3·65]) and vascular complications (4·43 [2·37-8·26]) were more frequent with MCS use than with control., Interpretation: The use of active MCS devices in patients with AMICS did not reduce 6-month mortality (regardless of the device used) and increased major bleeding and vascular complications. However, patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality after MCS use. Therefore, the use of MCS should be restricted to certain patients only., Funding: The Heart Center Leipzig at Leipzig University and the Foundation Institut für Herzinfarktforschung., Competing Interests: Declaration of interests HT is the current president of the German Cardiac Society. JEM reports lecture fees from Abbott and Boehringer Ingelheim; institutional research grants from Abiomed and Novo Nordisk Foundation; travel support from Abiomed; equipment from Abiomed; and served as a data and safety monitoring board member for DanHeart. JB reports speaker fees from Resuscitec and Getinge. DB reports payment for travel expenses from Abiomed; and institutional support for steering committee membership. MF reports grants paid to their institution from the European Commission. HE reports speaker fees from Novartis; and travel expenses from Abbott paid to their institution. PO reports speaker fees from Getinge, Abiomed, Fresenius, Edwards Lifesciences, and AOP; and is the president of the Czech Society of Cardiology. PCS reports lecture fees from Abiomed and Abbott; and institutional research support from Abiomed. JP reports institutional research grants from the German Cardiac Society, Schwiete Foundation, German Heart Research Foundation, and Maquet. CH reports lecture fees from Abiomed. MH reports research support paid to their institution from the Heart Center Leipzig. AP reports lecture fees and institutional research grants from Abiomed. NM reports lecture fees from Abbott, Abiomed, AstraZeneca, B Braun, Biotronik, the British Society of Cardiovascular Imaging, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, and Sanofi Genzyme; grants paid to their institution from Abiomed; and unrestricted educational grants from Abiomed and BSCI. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: This article identifies minimal clinically important differences (MCIDs) in quality of life (QoL) measures among patients who had coronary artery bypass grafting (CABG) and were enrolled in the arterial revascularization trial (ART)., Methods and Results: The European Quality of Life-5 Dimensions (EQ-5D) and the Short Form Health Survey 36-Item (SF-36) physical component (PC) and mental component (MC) scores were recorded at baseline, 5 years and 10 years in ART. The MCIDs were calculated as changes in QoL scores anchored to 1-class improvement in the New York Heart Association functional class and Canadian Cardiovascular Society scale at 5 years. Cox proportional hazard models were used to evaluate associations between MCIDs and mortality. Patient cohorts were examined for the SF-36 PC (N = 2671), SF-36 MC (N = 2815) and EQ-5D (N = 2943) measures, respectively. All QoL scores significantly improved after CABG compared to baseline. When anchored to the New York Heart Association, the MCID at 5 years was 17 (95% confidence interval: 17-20) for SF-36 PC, 14 (14-17) for the SF-36 MC and 0.12 (0.12-0.15) for EQ-5D. Using the Canadian Cardiovascular Society scale as an anchor, the MCID at 5 years was 15 (15-17) for the SF-36 PC, 12 (13-15) for the SF-36 MC and 0.12 (0.11-0.14) for the EQ-5D. The MCIDs for SF-36 PC and EQ-5D at 5 years were associated with a lower risk of mortality at the 10-year follow-up point after surgery., Conclusions: MCIDs for CABG patients have been identified. These thresholds may have direct clinical applications in monitoring patients during follow-up and in designing new trials that include QoL as a primary study outcome., Clinical Trial Registration Number: ISRCTN46552265., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS)., Methods: Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months., Results: The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9-2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9-72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01)., Conclusions: A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference., Trial Registration Number: NCT03707314., Competing Interests: Competing interests: NC has received unrestricted grants from HeartFlow, Boston Scientific, Haemonetics and Beckman Coulter; speaker fees from Abbott and Boston Scientific; and travel sponsorship from Edwards Lifesciences, Boston Scientific, Abbott and Biosensors., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate., Methods: Randomised clinical trials comparing early routine use of VA-ECMO versus optimal medical therapy alone in patients presenting with infarct-related cardiogenic shock were identified by searching MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and trial registries until June 12, 2023. Trials were included if at least all-cause death rate 30 days after in-hospital randomisation was reported and trial investigators agreed to collaborate (ie, providing individual patient data). Odds ratios (ORs) as primary outcome measure were pooled using logistic regression models. This study is registered with PROSPERO (CRD42023431258)., Findings: Four trials (n=567 patients; 284 VA-ECMO, 283 control) were identified and included. Overall, there was no significant reduction of 30-day death rate with the early use of VA-ECMO (OR 0·93; 95% CI 0·66-1·29). Complication rates were higher with VA-ECMO for major bleeding (OR 2·44; 95% CI 1·55-3·84) and peripheral ischaemic vascular complications (OR 3·53; 95% CI 1·70-7·34). Prespecified subgroup analyses were consistent and did not show any benefit for VA-ECMO (p interaction ≥0·079)., Interpretation: VA-ECMO did not reduce 30-day death rate compared with medical therapy alone in patients with infarct-related cardiogenic shock, and an increase in major bleeding and vascular complications was observed. A careful review of the indication for VA-ECMO in this setting is warranted., Funding: Foundation Institut für Herzinfarktforschung., Competing Interests: Declaration of interests HT is President of the German Cardiac Society. PO reports lecture fees from Abiomed, Getinge, Edwards, and Xenios/Fresenius. JB reports lecture fees from Abiomed, Resuscitec, and Xenios. DA reports funding to support a clinical research fellow from Abbott Vascular; has received funding from AstraZeneca for unrelated research; has conducted unrelated consultancy for General Electric; holds patents for medical devices, including a cardiac assist device (EP3277337A1, PCT/GB2017/050877, UK patent application number 2211616.4); received royalties from Elsevier for The ECG Made Practical and ECG Problems books; is Chair of the ESC-ACVC SCAD Study Group and ESC-EORP SCAD Registry; and reports participation on an advisory board for Beat SCAD. MS reports consultant fees from Abbott Vascular and iVascular. AB reports that the EURO SHOCK trial received European Commission Horizons 2020 funding (reference number 754946-2), University of Leicester as beneficiary. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: The fragmentation and loss of elastic fibre in the tunica media of the aorta are pathological hallmarks of Marfan syndrome (MFS) but the dynamics of elastin degradation and its relationship to aortic size and physiological growth remain poorly understood., Methods and Results: In this post hoc analysis of the AIMS randomized controlled trial, the association of plasma desmosine (pDES)-a specific biomarker of mature elastin degradation-with age and aortic size was analysed in 113 patients with MFS and compared to 109 healthy controls. There was a strong association between age and pDES in both groups, with higher pDES levels in the lower age groups compared to adults. During childhood, pDES increased and peaked during early adolescence, and thereafter decreased to lower adult levels. This trend was exaggerated in young individuals with MFS but in those above 25 years of age, pDES levels were comparable to controls despite the presence of aortic root dilation. In MFS children, increased aortic diameter relative to controls was seen at an early age and although the increase in diameter was less after adolescence, aortic root size continued to increase steadily with age. In MFS participants, there was an indication of a positive association between baseline pDES levels and aortic root dilatation during up to 5 years of follow-up., Conclusion: This study has shown that developmental age has a significant effect on levels of elastin turnover as measured by pDES in MFS individuals as well as healthy controls. This effect is exaggerated in those with MFS with increased levels seen during the period of physiologic development that plateaus towards adulthood. This suggests an early onset of pathophysiology that may present an important opportunity for disease-modifying intervention., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation., Aims: The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI)., Methods: This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure., Results: Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively)., Conclusions: Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.

Objective: To evaluate the association between sternal wound complications (SWC) and long-term mortality in the Arterial Revascularization Trial., Methods: Participants in the Arterial Revascularization Trial were stratified according to the occurrence of postoperative SWC. The primary outcome was all-cause mortality at long-term follow-up. The secondary outcome was major adverse cardiovascular events., Results: Three thousand one hundred two patients were included in the analysis; the median follow-up was 10 years. 115 patients (3.7%) had postoperative SWC: 85 (73.9%) deep sternal wound infections and 30 (26.1%) sterile SWC that required sternal reconstruction. Independent predictors of SWC included diabetes (odds ratio [OR], 2.77; 95% CI, 1.79-4.30; P < .001), female sex (OR, 2.73; 95% CI, 1.71-4.38; P < .001), prior stroke (OR, 2.59; 95% CI, 1.12-5.98; P = .03), chronic obstructive pulmonary disease (OR, 2.44; 95% CI, 1.60-3.71; P < .001), and use of bilateral internal thoracic artery (OR, 1.70; 95% CI, 1.12-2.59; P = .01). Postoperative SWC was significantly associated with long-term mortality. The Kaplan-Meier survival estimate was 91.3% at 5 years and 79.4% at 10 years in patients without SWC, and 86.1% and 64.3% in patients with SWC (log rank P < .001). The rate of major adverse cardiovascular events was also higher among patients who had SWC (n = 51 [44.3%] vs 758 [25.4%]; P < .001). Using multivariable analysis, the occurrence of SWC was independently associated with long-term mortality (hazard ratio, 1.81; 95% CI, 1.30-2.54; P < .001)., Conclusions: In the Arterial Revascularization Trial, postoperative SWC although uncommon were significantly associated with long-term mortality., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients with diabetes and obesity are at higher risk of adverse long-term outcomes following coronary artery bypass grafting. The use of bilateral internal thoracic arteries (BITA) can potentially offer survival benefit in higher risk patients compared to single internal thoracic artery (SITA), but BITA is not routinely used due to lack of clear evidence of efficacy and concerns over sternal wound complications., Methods: Medline, Embase and the Cochrane Library were searched for studies comparing the efficacy and safety of BITA and SITA grafting in patients with diabetes and obesity. Meta-analysis of mortality and sternal wound complications was performed., Results: We identified eight observational and ten propensity matched studies, and one RCT, comparing BITA and SITA which included patients with diabetes (n = 19,589); two propensity matched studies and one RCT which included patients with obesity (n = 6,972); mean follow up was 10.5 and 11.3 years respectively. Meta-analysis demonstrated a mortality reduction for BITA compared to SITA in patients with diabetes (risk ratio [RR] 0.79; 95% confidence interval [CI] 0.70-0.90; p = 0.0003). In patients with obesity there was a non-significant reduction in mortality in the BITA group (RR 0.73, 95% CI 0.47-1.12; p = 0.15). There was a significantly higher rate of sternal wound complications following BITA observed in patients with diabetes (RR 1.53, 95% CI 1.23-1.90; p = 0.0001) and obesity (RR 2.24, 95% CI 1.63-3.07; p < 0.00001)., Conclusions: BITA is associated with better long-term survival in patients with diabetes. The effects of BITA grafting in patients with obesity are uncertain. BITA is associated with higher rates of sternal wound complications compared to SITA in both patients with diabetes and obesity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Aim: Transfemoral Trans-catheter Aortic Valve Replacement (TF-TAVR) is a safe and effective therapy compared with surgical aortic valve replacement (SAVR) in patients across all risk profiles using balloon-expandable valves (BEV) and self-expanding valves (SEV). Our aim was to compare safety and efficacy of BEV vs. SEV in high-risk patients undergoing TF-TAVR., Methods and Results: We searched PubMed, EMBASE, Clinicaltrials.gov, Scopus, and Web of sciences for studies on patients with severe aortic stenosis undergoing TAVR. Primary outcome was 30-day all-cause mortality. Secondary outcomes defined by Valve Academic Research Consortium 2 (VARC-2) criteria were also examined. Six studies with 2,935 patients (1,439 to BEV and 1,496 to SEV) were included. BEV was associated with lower risk of all-cause mortality (2.2% vs. 4.5%; RR: 0.51; 95% CI: 0.31-0.82; p  < 0.006) and cardiovascular mortality [(2.5% vs. 4.3%; RR: 0.54; 95% CI: 0.32-0.90; p  = 0.01) at 30 days compared with SEV. Implantation of more than one valve per procedure (0.78% vs. 5.11%; RR: 0.15; 95% CI: 0.07-0.31; p  < 0.00001), and moderate/severe AR/PVL (2.5% vs. 9.01%; RR: 0.3; 95% CI: 0.17-0.48); p  < 0.00001) were also lower in the BEV arm., Conclusion: BEV TAVR is associated with reduced all-cause mortality (High level of GRADE evidence), cardiovascular mortality (very low level) at 30 days compared with SEV TAVR in high surgical risk patients. Data are necessary to determine if the difference in outcomes persists in longer-term and if the same effects are seen in lower-risk patients., Systematic Review Registration: identifier, CRD42020181190., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Senguttuvan, Bhatt, Balakrishnan, Krishnamoorthy, Goel, Reddy, Subramanian, Claessen, Kumar, Majmundar, Ro, Lerakis, Jayaraj, Kalra, Flather, Dangas and Tang.)

Background: The reproducibility of mitral regurgitation (MR) quantification by cardiovascular magnetic resonance (CMR) imaging using different software solutions remains unclear. This research aimed to investigate the reproducibility of MR quantification between two software solutions: MASS (version 2019 EXP, LUMC, Netherlands) and CAAS (version 5.2, Pie Medical Imaging). Methods: CMR data of 35 patients with MR (12 primary MR, 13 mitral valve repair/replacement, and ten secondary MR) was used. Four methods of MR volume quantification were studied, including two 4D-flow CMR methods (MR MVAV and MR Jet ) and two non-4D-flow techniques (MR Standard and MR LVRV ). We conducted within-software and inter-software correlation and agreement analyses. Results: All methods demonstrated significant correlation between the two software solutions: MR Standard (r=0.92, p<0.001), MR LVRV (r=0.95, p<0.001), MR Jet (r=0.86, p<0.001), and MR MVAV (r=0.91, p<0.001). Between CAAS and MASS, MR Jet and MR MVAV , compared to each of the four methods, were the only methods not to be associated with significant bias. Conclusions: We conclude that 4D-flow CMR methods demonstrate equivalent reproducibility to non-4D-flow methods but greater levels of agreement between software solutions., Competing Interests: Competing interests: Dr P Garg is a clinical advisor for Pie Medical Imaging and Medis Medical Imaging., (Copyright: © 2023 Grafton-Clarke C et al.)

Aortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria., Competing Interests: Conflict of interest: G.B.-Z. has consulted for Cardionovum, Crannmedical, Innovheart, Guidotti, Meditrial, Opsens Medical, Replycare, Teleflex, and Terumo. D.Y.T. has consulted for Medtronics Inc (Canada) and Edwards Life Sciences (Canada). M.G. has received research grants from the Canadian Institute of Health Research and the National Institute of Health. S.F. has received grants from the the Canadian Institute of Health Research and is the site co-Principal Investigator for the Medtronic SURTAVI, Medtronic Low Risk, and Boston NeoAccurate IDE trials. The other authors have no conflicts to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Measurement of peak velocities is important in the evaluation of heart failure. This study compared the performance of automated 4D flow cardiac MRI (CMR) with traditional transthoracic Doppler echocardiography (TTE) for the measurement of mitral inflow peak diastolic velocities., Methods: Patients with Doppler echocardiography and 4D flow cardiac magnetic resonance data were included retrospectively. An established automated technique was used to segment the left ventricular transvalvular flow using short-axis cine stack of images. Peak mitral E-wave and peak mitral A-wave velocities were automatically derived using in-plane velocity maps of transvalvular flow. Additionally, we checked the agreement between peak mitral E-wave velocity derived by 4D flow CMR and Doppler echocardiography in patients with sinus rhythm and atrial fibrillation (AF) separately., Results: Forty-eight patients were included (median age 69 years, IQR 63 to 76; 46% female). Data were split into three groups according to heart rhythm. The median peak E-wave mitral inflow velocity by automated 4D flow CMR was comparable with Doppler echocardiography in all patients (0.90 ± 0.43 m/s vs 0.94 ± 0.48 m/s, P = 0.132), sinus rhythm-only group (0.88 ± 0.35 m/s vs 0.86 ± 0.38 m/s, P = 0.54) and in AF-only group (1.33 ± 0.56 m/s vs 1.18 ± 0.47 m/s, P = 0.06). Peak A-wave mitral inflow velocity results had no significant difference between Doppler TTE and automated 4D flow CMR (0.81 ± 0.44 m/s vs 0.81 ± 0.53 m/s, P = 0.09) in all patients and sinus rhythm-only groups. Automated 4D flow CMR showed a significant correlation with TTE for measurement of peak E-wave in all patients group (r = 0.73, P < 0.001) and peak A-wave velocities (r = 0.88, P < 0.001). Moreover, there was a significant correlation between automated 4D flow CMR and TTE for peak-E wave velocity in sinus rhythm-only patients (r = 0.68, P < 0.001) and AF-only patients (r = 0.81, P = 0.014). Excellent intra-and inter-observer variability was demonstrated for both parameters., Conclusion: Automated dynamic peak mitral inflow diastolic velocity tracing using 4D flow CMR is comparable to Doppler echocardiography and has excellent repeatability for clinical use. However, 4D flow CMR can potentially underestimate peak velocity in patients with AF., (© 2023. The Author(s).)

Aims: To evaluate the impact of multiple arterial grafting (MAG) vs. single arterial grafting (SAG) in a post hoc analysis of 10-year outcomes in patients with diabetes mellitus (DM) from the Arterial Revascularization Trial (ART)., Methods and Results: The primary endpoint was all-cause mortality and the secondary endpoint was a composite of major adverse cardiac events (MACE) at 10-year follow-up. Patients were stratified by diabetes status (non-DM and DM) and grafting strategy (MAG vs. SAG). A total of 3020 patients were included in the analysis; 716 (23.7%) had DM. Overall, 55.8% non-DM patients received MAG and 44.2% received SAG, while 56.6% DM patients received MAG and 43.4% received SAG. The use of MAG compared with SAG was associated with lower 10-year mortality for both non-DM [17.7 vs. 21.0%, adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.72-1.06] and DM patients (21.5 vs. 29.9%, adjusted HR 0.65, 95% CI 0.48-0.89; P for interaction = 0.12). For both groups, the rate of 10-year MACE was also lower for MAG vs. SAG. Overall, deep sternal wound infections (DSWIs) were uncommon but more frequent in the MAG vs. SAG group in both non-DM (3.3 vs. 2.1%) and DM patients (7.9 vs. 4.8%). The highest rates of DSWI were in insulin-treated patients receiving MAG (9.6 vs. 6.3%, when compared with SAG)., Conclusion: In this post hoc analysis of the ART, MAG was associated with substantially lower mortality rates at 10 years after coronary artery bypass grafting in patients with DM. Patients with DM receiving MAG had a higher incidence of DSWI, especially if insulin dependent., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: We aim to validate four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) peak velocity tracking methods for measuring the peak velocity of mitral inflow against Doppler echocardiography., Method: Fifty patients were recruited who had 4D flow CMR and Doppler Echocardiography. After transvalvular flow segmentation using established valve tracking methods, peak velocity was automatically derived using three-dimensional streamlines of transvalvular flow. In addition, a static-planar method was used at the tip of mitral valve to mimic Doppler technique., Results: Peak E-wave mitral inflow velocity was comparable between TTE and the novel 4D flow automated dynamic method (0.9 ± 0.5 vs 0.94 ± 0.6 m/s; p = 0.29) however there was a statistically significant difference when compared with the static planar method (0.85 ± 0.5 m/s; p = 0.01). Median A-wave peak velocity was also comparable across TTE and the automated dynamic streamline (0.77 ± 0.4 vs 0.76 ± 0.4 m/s; p = 0.77). A significant difference was seen with the static planar method (0.68 ± 0.5 m/s; p = 0.04). E/A ratio was comparable between TTE and both the automated dynamic and static planar method (1.1 ± 0.7 vs 1.15 ± 0.5 m/s; p = 0.74 and 1.15 ± 0.5 m/s; p = 0.5 respectively). Both novel 4D flow methods showed good correlation with TTE for E-wave (dynamic method; r = 0.70; P < 0.001 and static-planar method; r = 0.67; P < 0.001) and A-wave velocity measurements (dynamic method; r = 0.83; P < 0.001 and static method; r = 0.71; P < 0.001). The automated dynamic method demonstrated excellent intra/inter-observer reproducibility for all parameters., Conclusion: Automated dynamic peak velocity tracing method using 4D flow CMR is comparable to Doppler echocardiography for mitral inflow assessment and has excellent reproducibility for clinical use., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To validate the k-adaptive-t autocalibrating reconstruction for Cartesian sampling (kat-ARC), an exclusive sparse reconstruction technique for four-dimensional (4D) flow cardiac magnetic resonance (CMR) using conservation of mass principle applied to transvalvular flow., Methods: This observational retrospective study (2020/21-075) was approved by the local ethics committee at the University of East Anglia. Consent was waived. Thirty-five patients who had a clinical CMR scan were included. CMR protocol included cine and 4D flow using Kat-ARC acceleration factor 6. No respiratory navigation was applied. For validation, the agreement between mitral net flow (MNF) and the aortic net flow (ANF) was investigated. Additionally, we checked the agreement between peak aortic valve velocity derived by 4D flow and that derived by continuous-wave Doppler echocardiography in 20 patients., Results: The median age of our patient population was 63 years (interquartile range [IQR] 54-73), and 18/35 (51%) were male. Seventeen (49%) patients had mitral regurgitation, and seven (20%) patients had aortic regurgitation. Mean acquisition time was 8 ± 4 min. MNF and ANF were comparable: 60 mL (51-78) versus 63 mL (57-77), p = 0.310). There was an association between MNF and ANF (rho = 0.58, p < 0.001). Peak aortic valve velocity by Doppler and 4D flow were comparable (1.40 m/s, [1.30-1.75] versus 1.46 m/s [1.25-2.11], p = 0.602) and also correlated with each other (rho = 0.77, p < 0.001)., Conclusions: Kat-ARC accelerated 4D flow CMR quantified transvalvular flow in accordance with the conservation of mass principle and is primed for clinical translation., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)