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In a porcine experimental model of myocardial infarction, a localised, layer-specific, circumferential left ventricular strain metric has been shown to indicate chronic changes in ventricular function post-infarction more strongly than ejection fraction. This novel strain metric might therefore provide useful prognostic information clinically. In this study, existing clinical volume indices, global strains, and the novel, layer-specific strain were calculated for a large human cohort to assess variations in ventricular function and morphology with age, sex, and health status. Imaging and health data from the UK Biobank were obtained, including healthy volunteers and those with a history of cardiovascular illness. In total, 710 individuals were analysed and stratified by age, sex and health. Significant differences in all strain metrics were found between healthy and unhealthy populations, as well as between males and females. Significant differences in basal circumferential strain and global circumferential strain were found between healthy males and females, with males having smaller absolute values for both (all (Formula presented.) 0.001). There were significant differences in the functional variables left ventricular ejection fraction, end-systolic volume, end-systolic volume index and mid-ventricular circumferential strain between healthy and unhealthy male cohorts aged 65–74 (all (Formula presented.) 0.001). These results suggest that whilst regional circumferential strains may be useful clinically for assessing cardiovascular health, care must be taken to ensure critical values are indexed correctly to age and sex, due to the differences in these values observed here.

BackgroundCardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT-CMR). Here we develop a CMR compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states.Methods10 porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D printed chamber and perfusion circuit re-established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT-CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT-CMR data using fiducial markers.ResultsRegular sustained contraction was successfully established in 6/10 hearts, including the final 5 hearts. Imaging was performed in 4 hearts and one underwent the full protocol including co-localised histology. Image quality was good and there was good agreement between DT-CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2, DT-CMR measures and an increase in mass was consistent with development of myocardial edema resulting in failure to achieve a true diastolic-like state. A contiguous stack of 313 5μm histological sections at and a 100μm thick section showing cell morphology on 3D fluorescent confocal microscopy co-localised to DT-CMR data were obtained.ConclusionsA CMR compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent co-localised histology without the need for onsite pre-clinical facilities.

Background Large animal models of acute myocardial infarction (MI) offer an important platform to test novel therapies. Consistency of infarct size between animals is critical to ensure an accurate assessment of therapies against control. However, anatomical variation challenges the ability to achieve a consistent infarct size and care must be taken to respect the principles of the 3Rs through minimisation of interventional fatalities. Purpose To standardise the approach of a closed chest model of balloon occlusion-facilitated MI. Novel 3-dimensional quantitative coronary angiography (3DQCA) software has been used retrospectively to identify a correlation between coronary volume occlusion and the extension of the myocardial scar. Methods Twenty-four Yorkshire pigs (mean weight 63.1±3 kg) underwent a closed chest MI model via percutaneous occlusion of the mid portion of the left anterior descending artery (LAD) for 60 minutes. The evaluation of the myocardial damage was obtained via cardiac magnetic resonance imaging (CMR) between 24 and 48 hours after the MI model (Acute) and at 4–5 weeks after MI (Chronic). Troponin I was also measured at multiple timepoints. 3DQCA reconstruction (QAngio XA 3D, Medis medical imaging systems NL) was generated from 2 angiographic projections with segmental analysis of all 3 major epicardial vessels including lumen volume, reference diameters, and segment length. The occlusive volume and vessel length was identified through co-registration of balloon position. Results At the short term timepoint, a significant correlation was found between the LAD volume occluded and the scar size as percentage of the LV mass (Spearman correlation 0.72, p value 20% (Fig. 2). At chronic phase the correlation between these two variables was not significant, although there was a trend towards significance (p value = 0.06, Cor = 0.54). No significant correlation was found with serum Troponin I. Conclusions There is a significant correlation between the LAD volume occluded and the overall scar size in the acute phase and at least 32.8% of the LAD volume should be occluded to determine a scar volume >20% of the entire LV. This indicates that a prospective measure of occluded LAD volume might minimise the intra-experimental variability in studies aiming to reduce infarct size and acute myocardial injury. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This research work was supported by grants awarded to Professor Ascione: the British Heart Foundation (BHF) (BHF IG/14/2/30991, BHF RM/13/2/30158), and the Medical Research Council (MRC) (MRC MR/L012723/1).

Ca2+ handling within cardiac myocytes underpins coordinated contractile function within the beating heart. This protocol enables high spatial and temporal Ca2+ imaging of ex vivo multicellular myocardial strips. The endocardial surface is retained, and strips of 150–300-µm thickness are dissected, loaded with Ca2+ indicators and mounted within 1.5 h. A list of the equipment and reagents used and the key methodological aspects allowing the use of this technique on strips from any chamber of the mammalian heart are described. We have successfully used this protocol on human, pig and rat biopsy samples. On use of this protocol with intact endocardial endothelium, we demonstrated that the myocytes develop asynchronous spontaneous Ca2+ events, which can be ablated by electrically evoked Ca2+ transients, and subsequently redevelop spontaneously after cessation of stimulation. This protocol thus offers a rapid and reliable method for studying the Ca2+ signaling underpinning cardiomyocyte contraction, in both healthy and diseased tissue. This protocol describes how to undertake high spatial and temporal Ca2+ imaging of ex vivo multicellular myocardial strips that include the endocardial surface, allowing the study of the Ca2+ signaling that underpins cardiomyocyte contraction.

Funder: EPSRC DTP, Funder: Developmental pathway funding scheme (DPFS), To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5–6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

Aim Reduced Left Ventricular Ejection Fraction (LVEF) is a risk factor for patients undergoing Coronary Artery Bypass Grafting (CABG). The aim of our study was to compare short term outcomes and long-term (20 years) survival rates of patients with reduced LVEF undergoing CABG. Method Between 1996 and 2015, 5016 patients with reduced LVEF underwent CABG: 1024 (20.4%) had poor LVEF (< 30%) and 3992 (79.6%) had moderate LVEF dysfunction (30-49%). After excluding reoperations and combined procedures, the final sample consisted of 3867 patients. Our primary outcomes were early in-hospital mortality and complications and long-term survivals. Results In-hospital mortality rate was 4.4%, stroke rate 1.4% and renal failure 2.9%. Survival rates at 1, 5, 10 and 20 years were 91.1%, 76.7%, 55.1% and 22.1% respectively. Additive Euroscore and Logistic Euroscore (AUC 0.78) is less reliable compared to normal LV patients. Complete revascularization was an independent factor affecting long term survival (HR: 0.85). No difference between OPCABG and ONCABG were found. Conclusions CABG is still safe and most likely the best treatment option for patients with reduced LVEF. Completeness of revascularization plays an important role in long term outcomes while OPCABG has no significant advantages. Euroscore has a reduced predicting ability in this group of patients.

Introduction: Following myocardial infarction, an acute immune response occurs, and infiltrating monocytes and monocyte-derived macrophages migrate into the infarct. Under the influence of intricate pro- and anti-inflammatory stimuli, macrophages drive cardiac fibroblast (CF) activation. The interaction between macrophages and CFs regulates fibrosis-driven wound healing. Hypothesis: We hypothesised that pro- and anti-inflammatory macrophages divergently effect CF activation. We aimed to identify macrophage proteins that regulate CFs as potential intervention targets. Methods: Monocytes from healthy volunteers were differentiated towards pro- or anti-inflammatory macrophages using GM-CSF (20 ng/mL) and M-CSF (20 ng/mL) or M-CSF (40 ng/mL) alone, respectively. CF activation was characterised by α-SMA expression, contraction, and migration. Proteomics were performed on macrophage secretome and subjected to bioinformatics (IPA, Qiagen). CFs were cultured with macrophage-conditioned medium (CM) in the presence of recombinant proteins or neutralising antibodies, as indicated. Results: Pro-inflammatory macrophage CM enhanced CF activation, as evidenced by elevated α-SMA expression (1.6-fold change, pin vitro (33% reduction in 2 hours, 37 o C), which, subsequently, abrogated the suppression of α-SMA expression by CXCL10 in CFs. Conclusions: Our findings indicate that macrophage phenotype exerts divergent effects on CF behaviour, with pro-inflammatory macrophages promoting CF activation, through enhanced CTSZ secretion and associated CXCL10 cleavage, revealing both proteins as potential targets for modulating fibrosis-driven wound healing.

Inhibition of SK channel function is being pursued in animal models as a possible therapeutic approach to treat atrial fibrillation (AF). However, the pharmacology of SK channels in human atria is unclear. SK channel function is inhibited by both apamin and UCL1684, with the former discriminating between SK channel subtypes. In this proof-of-principle study, the effects of apamin and UCL1684 on right atrial myocytes freshly isolated from patients in sinus rhythm undergoing elective cardiac surgery were investigated. Outward current evoked from voltage clamped human atrial myocytes was reduced by these two inhibitors of SK channel function. In contrast, membrane current underlying the atrial action potential was affected significantly only by UCL1684 and not by apamin. This pharmacology mirrors that observed in mouse atria, suggesting that mammalian atria possess two populations of SK channels, with only one population contributing to the action potential waveform. Immuno-visualization of the subcellular localization of SK2 and SK3 subunits showed a high degree of colocalization, consistent with the formation of heteromeric SK2/SK3 channels. These data reveal that human atrial myocytes express two SK channel subtypes, one exhibiting an unusual pharmacology. These channels contribute to the atrial action potential waveform and might be a target for novel therapeutic approaches to treat supraventricular arrhythmic conditions such as atrial fibrillation.

To identify early predictors of late left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used. LVR was assessed by cardiac magnetic resonance imaging (CMRI) at baseline, 12–48 hours (acute), and 5–6 weeks (chronic) post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories,21 of which correlated with LV equatorial circumferential strain rate (ECSR). The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2 (CG-RP-2), and secreted frizzled-related protein 1 (sFRP1). Results indicate that early changes in regional peak ACS predict late LV remodelling and LVR post-MI is associated with augmented levels of D-3PGDH and sFRP1, which show the strongest association with peak ECSR. These findings might help to prevent LVR post-MI by influencing/directing LV unloading strategies or by pharmacological control of tissue levels of D-3PGDH and sFRP1.

The cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischaemia/reperfusion of isolated perfused heart. We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). 8-Br (10 μM) was administered to Langendorff-perfused rat hearts for 5 min either before or at the end of 30 min regional ischaemia. Ca2+-induced mitochondria swelling (a measure of MPTP opening) and binding of hexokinase II (HKII) to mitochondria were assessed following the drug treatment at preischaemia. Haemodynamic function and ventricular arrhythmias were monitored during ischaemia and 2 h reperfusion. Infarct size was evaluated at the end of reperfusion. 8-Br administered before ischaemia attenuated ventricular arrhythmias, improved haemodynamic function, and reduced infarct size during ischaemia/reperfusion. Application of 8-Br at the end of ischaemia protected the heart during reperfusion. 8-Br promoted binding of HKII to the mitochondria and reduced Ca2+-induced mitochondria swelling. Thus, 8-Br protects the heart when administered before regional ischaemia or at the beginning of reperfusion. This effect is associated with inhibition of MPTP via binding of HKII to mitochondria, which may underlie the protective mechanism.

Aims Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein-coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known. Methods and results To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischaemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidification of the intracellular milieu. Furthermore, pharmacological inhibition, or haploinsufficiency of the monocarboxylate transporter 1 (MCT1) significantly decreased succinate efflux from the reperfused heart. Conclusion Succinate release upon reperfusion of the ischaemic heart is mediated by MCT1 and is facilitated by the acidification of the myocardium during ischaemia. These findings will allow the signalling interaction between succinate released from reperfused ischaemic myocardium and SUCNR1 to be explored.

Human saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV. Decellularisation effectiveness was measured in vitro by nuclear counting, DNA content, residual cell viability, extracellular matrix integrity and mechanical strength. Cytotoxicity was assessed on human and porcine cells. The most effective SDS concentration was used to prepare D-hSV grafts that underwent preliminary in vivo testing using a porcine carotid artery replacement model. Effective decellularisation was achieved with 0.01% SDS, and D-hSVs were biocompatible after seeding. In vivo xeno-transplantation confirmed excellent mechanical strength and biocompatibility with recruitment of host cells without mechanical failure, and a 50% patency rate at 4-weeks. We have developed a simple biocompatible methodology to effectively decellularise hSVs. This could enhance vascular tissue engineering toward future clinical applications.

Aims Coronary microvascular smooth muscle cells (SMCs) respond to luminal pressure by developing myogenic tone (MT), a process integral to the regulation of microvascular perfusion. The cellular mechanisms underlying poor myogenic reactivity in patients with heart valve disease are unknown and form the focus of this study. Methods and results Intramyocardial coronary micro-arteries (IMCAs) isolated from human and pig right atrial (RA) appendage and left ventricular (LV) biopsies were studied using pressure myography combined with confocal microscopy. All RA- and LV-IMCAs from organ donors and pigs developed circa 25% MT. In contrast, 44% of human RA-IMCAs from 88 patients with heart valve disease had poor ( Conclusion These data demonstrate the first use of atrial and ventricular biopsies from patients and pigs to reveal that impaired coronary MT reflects a switch of viable SMCs towards a synthetic phenotype, rather than a loss of SMC viability. These arteries represent a model for further studies of coronary microvascular contractile dysfunction.

To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify experimental studies comparing the mitigating effect of ketosis (intervention) vs non‐ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary endpoints were a reduction in neuronal damage and dysfunction, and an “aggregated advantage” (composite of all primary and secondary endpoints). Hedge’s g was the effect measure. Subgroup analyses evaluated the modulatory effect of age, insult type, and injury site. Meta‐regression evaluated timing, type, and magnitude of intervention as predictors of neuroprotection. The selected publications were 49 experimental murine studies (period 1979‐2020). The intervention reduced mortality (g 2.45, SE 0.48, p

PurposeVolume indices and left ventricular ejection fraction (LVEF) are routinely used to assess cardiac function. Ventricular strain values may provide additional diagnostic information, but their reproducibility is unclear. This study therefore compares the repeatability and reproducibility of volumes, volume fraction, and regional ventricular strains, derived from cardiovascular magnetic resonance (CMR) imaging, across three software packages and between readers.MethodsSeven readers analysed 16 short-axis CMR stacks of a porcine heart. Endocardial contours were manually drawn using OsiriX and Simpleware ScanIP and repeated in both softwares. The images were also contoured automatically in Circle CVI42. Endocardial global, apical, mid-ventricular, and basal circumferential strains, as well as end-diastolic and end-systolic volume and LVEF were compared.ResultsBland-Altman analysis found systematic biases in contour length between software packages. Compared to OsiriX, contour lengths were shorter in both ScanIP (-1.9 cm) and CVI42 (-0.6 cm), causing statistically significant differences in end-diastolic and end-systolic volumes, and apical circumferential strain (all pConclusionOsiriX and CVI42 gave consistent results for all strain and volume metrics, with no statistical differences found between OsiriX and ScanIP for mid-ventricular, global or basal strains, or left ventricular ejection fraction. However, volumes were influenced by the choice of contouring software, suggesting care should be taken when comparing volumes across different software.

Background Typically, subgroup analyses in clinical trials are conducted by comparing the intervention effect in each subgroup by means of an interaction test. However, trials are rarely, if ever, adequately powered for interaction tests, so clinically important interactions may go undetected. We discuss the application of Bayesian methods by using expert opinions alongside the trial data. We applied this methodology to the VeRDiCT trial investigating the effect of preoperative volume replacement therapy (VRT) versus no VRT (usual care) in diabetic patients undergoing cardiac surgery. Two subgroup effects were of clinical interest, a) preoperative renal failure and b) preoperative type of antidiabetic medication. Methods Clinical experts were identified within the VeRDiCT trial centre in the UK. A questionnaire was designed to elicit opinions on the impact of VRT on the primary outcome of time from surgery until medically fit for hospital discharge, in the different subgroups. Prior beliefs of the subgroup effect of VRT were elicited face-to-face using two unconditional and one conditional questions per subgroup analysis. The robustness of results to the ‘community of priors’ was assessed. The community of priors was built using the expert priors for the mean average treatment effect, the interaction effect or both in a Bayesian Cox proportional hazards model implemented in the STAN software in R. Results Expert opinions were obtained from 7 clinicians (6 cardiac surgeons and 1 cardiac anaesthetist). Participating experts believed VRT could reduce the length of recovery compared to usual care and the greatest benefit was expected in the subgroups with the more severe comorbidity. The Bayesian posterior estimates were more precise compared to the frequentist maximum likelihood estimate and were shifted toward the overall mean treatment effect. Conclusions In the VeRDiCT trial, the Bayesian analysis did not provide evidence of a difference in treatment effect across subgroups. However, this approach increased the precision of the estimated subgroup effects and produced more stable treatment effect point estimates than the frequentist approach. Trial methodologists are encouraged to prospectively consider Bayesian subgroup analyses when low-powered interaction tests are planned. Trial registration ISRCTN, ISRCTN02159606. Registered 29th October 2008.

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Correction for ‘Design, development, testing at ISO standards and in vivo feasibility study of a novel polymeric heart valve prosthesis’ by Joanna R. Stasiak et al., Biomater. Sci., 2020, DOI: 10.1039/d0bm00412j.

Clinically available prosthetic heart valves are life-saving, but imperfect: mechanical valves requiring anticoagulation therapy, whilst bioprosthetic valves have limited durability. Polymer valves offer the prospect of good durability without the need for anticoagulation. We report the design and development of a polymeric heart valve, its bench-testing at ISO standards, and preliminary extra-vivo and in vivo short-term feasibility. Prototypes were manufactured by injection moulding of styrenic block copolymers to achieve anisotropic mechanical properties. Design was by finite element stress-strain modelling, which has been reported previously, combined with feedback from bench and surgery-based testing using various combinations of materials, valve geometry and processing conditions. Bench testing was according to ISO 5840:2015 standards using an in vitro cardiovascular hydrodynamic testing system and an accelerated fatigue tester. Bench comparisons were made with a best-in-class bio-prosthesis. Preliminary clinical feasibility evaluations included extra-vivo and short-term (1-24 hours) in vivo testing in a sheep model. The optimised final prototype met the requirements of ISO standards with hydrodynamic performance equivalent to the best-in-class bioprosthesis. Bench durability of greater than 1.2 billion cycles (30 years equivalent) was achieved (still ongoing). Extra-vivo sequential testing (n = 8) allowed refinement of external diameter, 3D shape, a low profile, flexibility, suturability, and testing of compatibility to magnetic resonance imaging and clinical sterilisation. In vivo short-term (1-24 hours) feasibility (n = 3) confirmed good suturability, no mechanical failure, no trans-valvular regurgitation, competitive trans-valvular gradients, and good biocompatibility at histopathology. We have developed and tested at ISO standards a novel prosthetic heart valve featuring competitive bench-based hydrodynamics and durability, well beyond the ISO requirements and comparable to a best-in-class bioprosthesis. In vivo short-term feasibility testing confirmed preliminary safety, functionality and biocompatibility, supporting progression to a long-term efficacy trial.

OBJECTIVES: This study was conducted to clarify the relationship between body mass index and mitral valve (MV) surgery and to determine whether an 'obesity paradox' exists in the context of surgery for degenerative MV disease. METHODS: In this retrospective single-centre study, we analysed data from 715 patients who underwent mitral surgery for degenerative disease from 2000 to 2015. Patients were classified according to body mass index: underweight (-30 kg/m2). Early and long-term results were investigated. Multivariable analysis was conducted to identify risk factors for long-term mortality. RESULTS: Mean follow-up was 67 ± 44 months (range 0190 months). There were no differences between groups regarding 30-day mortality (P = 0.35), stroke (P = 0.45), reoperation for bleeding (P = 0.9) and length of hospital stay (P = 0.31). Obese patients were at increased risk of acute kidney injury when compared with normal weight patients (17% vs 5%; P = 0.03) but not when compared with the other groups; this was confirmed within the subgroup with depressed ejection fraction (42% vs 10%, P = 0.02). No differences in long-term survival were found across groups for all patients (P = 0.62) and for patients with depressed ejection fraction (P = 0.6), with a trend towards worse survival in obese patients undergoing MV repair (P = 0.06). Survival in obese patients undergoing repair was significantly worse than that in obese patients undergoing replacement (P = 0.04). CONCLUSIONS: An 'obesity paradox' was not demonstrated after surgery for degenerative MV disease. Obese patients are more prone to acute kidney injury and have worse late survival after MV repair.

OBJECTIVES: To investigate the in-hospital health outcome and 10-year survival in patients undergoing redo coronary surgery with (redo-CABG) or without (redo-OPCAB) cardiopulmonary bypass.METHODS: A total of 349 redo coronary surgery patients were identified from our registry. Of these, 143 redo-OPCAB patients (40.97%) were compared with 206 redo-CABG patients. To minimize the bias, we also conducted propensity score matching. In Matched Analysis A, 111 redo-OPCAB patients with any type of primary cardiac operation were compared with 111 redo-CABG cases. In Matched Analysis B, 84 redo-OPCAB patients with isolated coronary surgery as their primary operation were compared with 84 redo-CABG patients. We assessed for all 3 analyses a composite of in-hospital mortality, acute kidney injury, stroke and severe low cardiac output requiring intra-aortic balloon pump. In addition, we assessed 1-, 5-, and 10-year survival.RESULTS: In the unmatched analysis, redo-CABG was associated with higher usage of intra-aortic balloon pump (10 vs 3%, P = 0.01) and composite compared with redo-OPCAB (25 vs 16%, P = 0.06) and similar 10-year survival (67.2 vs 68.5%, log-rank test: P = 0.78). Matched Analysis A showed similar rates of composite (15 vs 21%, P = 0.25) and 10-year survival (65.1 vs 60.8%, log-rank test: P = 0.5). Matched Analysis B showed reduction of the composite (19 vs 8%, P = 0.04), less in-hospital mortality (5 vs 0%, P = 0.13), 4.5 times less need for intra-aortic balloon pump (2 vs 11%, P = 0.02) favouring redo-OPCAB and a similar 10-year survival (71.6 vs 71.7%, log-rank test: P = 0.61).CONCLUSIONS: Redo-OPCAB surgery is feasible, safe and effective with improved in-hospital outcome and similar 10-year survival compared to redo-CABG.

Robot Assisted Surgery is attracting increasing amount of attention as it offers numerous benefits to patients as well as surgeons. Heart surgery requires a high level of precision and dexterity, in contrast to other surgical specialties. Robot assisted heart surgery is not as widely performed due to numerous reasons including a lack of appropriate and intuitive surgical interfaces to control minimally invasive surgical tools. In this paper, finger motion of the surgeon is analyzed during cardiac surgery tasks on an ex-vivo animal model with the purpose of designing a more intuitive master console. First, a custom finger tracking system is developed using IMU sensors, which is lightweight and comfortable enough to allow free movement of the surgeon’s fingers/hands while using instruments. The proposed system tracks finger joint angles and fingertip positions for three involved fingers (thumb, index, middle). Accuracy of the IMU sensors has been evaluated using an optical tracking system (Polaris, NDI). Finger motion of the cardiac surgeon while using a Castroviejo instrument is studied in suturing and knotting scenarios. The results show that PIP and MCP joints have larger Range Of Motion (ROM), and faster rate of change compared to other finger/thumb joints, while thumb has the largest Fingertip WorkSpace (FWS) of all three digits.

OBJECTIVES To investigate the effect of preoperative volume replacement therapy (VRT) on renal function, health outcome and time to fitness for discharge in diabetic patients undergoing coronary artery bypass grafting (CABG). METHODS In 2 parallel randomized controlled trials, diabetic patients were allocated to preoperative VRT (1 ml/kg/h of Hartmann’s solution for 12 h) or usual care. Primary outcome was time to fitness for discharge. Secondary outcomes included acute kidney injury, postoperative complications, patient-reported quality of life (QoL), hospital resource use and markers of renal, cardiac and inflammatory injury. RESULTS In total, 169 patients were randomized (84 VRT, 85 usual care; mean age 64 years; 88% male). Time to fitness for discharge was similar between groups [median 6 days; interquartile range 5.0–9.0 in both groups; hazard ratio 0.95, 95% confidence interval (CI) 0.65–1.38; P = 0.78]. Postoperative acute kidney injury was not statistically different (VRT: 27.7% vs usual care: 18.8%, odds ratio 1.72, 95% CI 0.82–3.59; P = 0.15). Estimated glomerular filtration rate (mean difference −0.92, 95% CI −4.18 to 2.25; P = 0.56), microalbumin/creatinine ratio [geometric mean ratio (GMR) 1.16, 95% CI 0.94–1.42; P = 0.16], N-acetyl-beta-d-glucosaminidase (GMR 1.08, 95% CI 0.83–1.40; P = 0.57), C-reactive protein (GMR 1.00, 95% CI 0.88–1.13; P = 0.94), troponin T (Trop-T; GMR 1.18, 95% CI 0.78–1.79; P = 0.39) and other secondary health outcomes were similar between groups. QoL improved in both groups at 3 months with no difference observed. CONCLUSIONS The use of preoperative VRT is not superior to usual care in diabetic patients undergoing CABG. Clinical trial registration number ISRCTN02159606.

Background This study investigated the impact of combined degenerative mitral valve (DMV) and coronary artery bypass grafting (CABG+DMV) surgery vs DMV surgery only on in-hospital health outcome and 10-year survival. Methods We identified 745 patients with DMV disease. Of these, 186 (24.9%) were affected also by coronary disease and underwent combined DMV+CABG. They were compared with the remaining 559 patients receiving DMV-only surgery in in-hospital and 1-, 5-, and 10-year survival. We evaluated a short-term composite outcome of hospital mortality, acute kidney injury, cerebrovascular events, and low cardiac output requiring postoperative use of intraaortic balloon pump. In addition, we assessed mitral valve repair rates over time and their correlation with long-term survival. To minimize bias, we conducted a propensity score-matching analysis. Results DMV+CABG surgery was associated with a similar incidence of the composite end point compared with DMV-only surgery in the unmatched analysis (6.5% vs 5.4%, P = .71) and matched analysis (7.5% vs 8.2%, P = .82). The 10-year survival was 70.5% vs 68.6% (P = .07) for the unmatched analysis and 64.6% vs 62.5% (P = .9) for the matched analysis, DMV+CABG vs DMV-only, respectively. Mitral valve repair had a beneficial effect on short-term outcomes and long-term mortality rates, regardless the presence of concomitant coronary surgery. Conclusions Combined DMV+CABG surgery is a very effective surgical treatment with high mitral valve repair rate. Early in-hospital outcome and long-term survival are comparable with DMV-only surgery. In these combined procedures, mitral valve repair is associated with better long-term survival.

The mechanisms underlying the protective effects of remote ischemic preconditioning (RIPC) are not presently clear. Recent studies in experimental models suggest the involvement of the autonomic nervous system (ANS) in cardioprotection. The aim of this study was to investigate the changes in ANS in healthy young volunteers divided into RIPC (n = 22) or SHAM (n = 18) groups. RIPC was induced by 1 cycle of 4 min inflation/5 min deflation followed by 2 cycles of 5 min inflation/5 min deflation of a cuff placed on the upper left limb. The study included analysis of heart rate (HR), blood pressure (BP), heart rate variability (HRV), measurements of microcirculation and porphyrin fluorescence in the limb before and after the RIPC. RIPC caused reactive hyperemia in the limb and reduced blood porphyrin level. A mental load (serial sevens test) and mild motor stress (hyperventilation) were performed on all subjects before and after RIPC or corresponding rest in the SHAM group. Reduction of HR occurred during the experiments in both RIPC and SHAM groups reflecting RIPC-independent adaptation of the subjects to the experimental procedure. However, in contrast to the SHAM group, RIPC altered several of the spectral indices of HRV during the serial sevens test and hyperventilation. This was expressed predominantly as an increase in power of the very low-frequency band of the spectrum, increased values of detrended fluctuation analysis and weakening of correlation between the HRV parameters and HR. In conclusion, RIPC induces changes in the activity of ANS that are linked to stress resistance., Highlights • Brief ischemia/reperfusion episodes of distant organs (RIPC) protect other organs. • Mechanism of RIPC is not known but it involves neuronal activity. • RIPC applied to volunteers was interspersed with mild mental and physical stress. • RIPC was confirmed by hyperemia in the limb and metabolic response to hypoxia. • Heart rate variability shows that RIPC modulates ANS to increase stress resistance.

Introduction Coronary artery bypass grafting (CABG) primarily uses autologous human saphenous vein (hSV), despite autologous arteries having better patency rates. However, a lack of arteries, and presence of disease in those which are available, has led to the need to develop alternative tissue engineered conduits. Here we aim to arterialise a vein, by re-seeding a decellularised hSV (DhSV) with arterial-like endothelial cells (EC), which will ultimately prevent early thrombosis and improve late graft patency. Methods Blood outgrowth EC (BOEC) isolated from 350 ml pig blood were expanded for further use. BOEC were subjected to immunocytochemistry (ICC) for EC markers CD31, vWF, VE-Cadherin, and DBA-Lectin, and also vimentin (mesenchymal/fibroblast marker) and CD45 (leukocyte marker). BOEC seeded in plates were exposed to dynamic (D) culture conditions on an orbital shaker (94 hrs) and compared to static (S) culture. EC isolated from pig aorta (PAEC) were used as positive controls. qPCR was performed for CD31, vWF, VE-Cadherin, eNOS, DLL4 (arterial) and NR2F2 (venous). hSV was decellularised using 0.01% SDS. 1 × 106 BOEC were seeded onto DhSV by tying the ends (T) to trap cells luminally, or placing BOEC in the lumen leaving ends untied (UT), before leaving under static (S) or dynamic (D: roller, 1rpm) culture conditions (93 hrs). Seeded DhSV were static cultured for 73 hours, fixed, paraffin wax-embedded and sections subjected to DBA-lectin staining to quantify maximum lumen coverage of BOEC, and anti-CD31 immunohistochemistry. Results BOEC showed classic EC cobblestone morphology, and ICC staining revealed expression of CD31, DBA-Lectin, vWF, vimentin, VE-Cadherin levels were low and CD45 was not detected. CD31 mRNA levels were comparable in BOEC and PAEC (fold-change (FC) 1.2), while vWF (FC 228.3), VE-cadherin (FC 9.3) and NR2F2 (FC 5.5) mRNAs were increased and eNOS (FC 0.2) and DLL4 (FC 0.1) were decreased in BOEC compared to PAEC. Exposing BOEC to shear stress increased expression of all mRNAs investigated (FC CD31:2.6, vWF:1.8, VE-cadherin:1.4, eNOS:3.3, DLL4:1.4, and NR2F2:3.4) compared to static BOEC. Seeding DhSV resulted in partial re-endothelialisation with greatest lumen coverage found by dynamic seeding with cells tied into lumen (91% coverage) and continued culture resulted in a near complete BOEC layer following (97%). CD31 was still expressed in seeded DhSV. ConclusionS BOEC isolated from pig blood show expression of EC markers, and vimentin, and are negative for the leukocyte marker CD45. We have shown that it is possible to repopulate a DhSV with BOEC and, under the correct conditions, obtain a functional monolayer around the lumen. This preliminary data shows the translational potential for this approach in generating a tissue engineered saphenous vein, reendothelialised with BOEC from blood that could be used for CABG. Conflict of interest None