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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).

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.

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 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.

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

OBJECTIVE: To investigate the impact of postoperative acute kidney injury (AKI) on early health outcome and on long-term survival in patients undergoing redo coronary artery bypass grafting (CABG).METHODS: We performed a Cox analysis with 398 consecutive patients undergoing redo CABG over a median follow-up of 7 years (interquartile range, 4-12.2 years). Renal function was assessed using baseline and peak postoperative levels of serum creatinine. AKI was defined according to the risk, injury, failure, loss, and end-stage (RIFLE) criteria. Health outcome measures included the rate of in-hospital AKI and all-cause 30-day and long-term mortality, using data from the United Kingdom's Office of National Statistics. Propensity score matching, as well as logistic regression analyses, were used. The impact of postoperative AKI at different time points was related to survival.RESULTS: In patients with redo CABG, the occurrence of postoperative AKI was associated with in-hospital mortality (odds ratio [OR], 3.74; 95% confidence interval [CI], -1.3 to 10.5; P < .01], high Euroscore (OR, 1.27; 95% CI, 1.07-1.52; P < .01), use of IABP (OR, 6.9; 95% CI, 2.24-20.3; P < .01), and reduced long-term survival (hazard ratio [HR], 2.42; 95% CI, 1.63-3.6; P = .01). Overall survival at 5 and 10 years was lower in AKI patients with AKI compared with those without AKI (64% vs 85% at 5 years; 51% vs 68% at 10 years). On 1:1 propensity score matching analysis, postoperative AKI was independently associated with reduced long term survival (HR, 2.8; 95% CI, 1.15-6.7).CONCLUSIONS: In patients undergoing redo CABG, the occurrence of postoperative AKI is associated with increased 30-day mortality and major complications and with reduced long-term survival.

OBJECTIVES: We aimed to determine whether early outcomes and long-term survival after mitral valve surgery performed by trainee residents are equivalent in terms of safety and efficacy when compared with consultant surgeons. METHODS: Between January 2000 and December 2015, a total of 1742 patients who underwent mitral valve surgery were identified. Of these, 1622 operations were performed by consultants (Group I) and 120 operations were performed by trainees (Group II). A propensity score-matched analysis has been used to minimize selection bias. Early postoperative outcomes were defined as in-hospital mortality, cerebrovascular accident, postoperative requirement of renal replacement therapy, reoperation for bleeding and postoperative length of hospital stay. Long-term outcomes were evaluated using late survival data after discharge. RESULTS: Before matching, the 2 groups differed significantly in terms of gender and reduced left ventricular ejection fraction, but these differences were solved after matching. Also, Group I included significantly more patients with mitral regurgitation (83% vs 62%; P < 0.01), but after matching, this difference was corrected (62% vs 59%; P = 0.71). Consultant group was associated with a higher in-hospital mortality (6% vs 2%; P = 0.04) in the unmatched population. Moreover, in the unmatched cohort, this group had longer cross-clamp time compared with the trainees group (91 ± 38 vs 89 ± 26 min; P = 0.47) and longer cardiopulmonary bypass time (132 ± 58 vs 121 ± 33 min; P = 0.27); these differences were not statistically significant. There were no significant differences in postoperative dialysis, cerebrovascular accident, reoperation for bleeding and length of hospital stay. Even after matching, no significant differences were found in terms of perioperative complications. The Kaplan-Meier survival curves at 1, 5 and 10 years were similar between the 2 groups. CONCLUSIONS: Mitral valve surgery can be safely performed by trainees and provides similar short- and long-term results compared with consultant surgeons.

Translational research is becoming popular even in the field of cardiac surgery, but can a bench-based model change our clinical practice?

T his protocol describes the preparation of highly viable adult ventricular myocardial slices from the hearts of small and large mammals, including rodents, pigs, dogs and humans. Adult ventricular myocardial slices are 100- to 400-mm-thick slices of living myocardium that retain the native multicellularity, architecture and physiology of the heart. This protocol provides a list of the equipment and reagents required alongside a detailed description of the methodology for heart explantation, tissue preparation, slicing with a vibratome and handling of myocardial slices. Supplementary videos are included to visually demonstrate these steps. A number of critical steps are addressed that must be followed in order to prepare highly viable myocardial slices. These include identification of myocardial fiber direction and fiber alignment within the tissue block, careful temperature control, use of an excitationcontraction uncoupler, optimal vibratome settings and correct handling of myocardial slices. Many aspects of cardiac structure and function can be studied using myocardial slices in vitro. Typical results obtained with hearts from a small mammal (rat) and a large mammal (human) with heart failure are shown, demonstrating myocardial slice viability, maximum contractility, Ca2+ handling and structure. This protocol can be completed in 4 h.

Background: Diabetes mellitus is a major risk factor for prolonged hospital stays, renal failure, and mortality in patients having coronary artery bypass grafting (CABG). Complications pose a serious threat to patients and prolong intensive care and hospital stays. Low glomerular filtration rate (GFR) due to existing renal impairment or volume depletion may exacerbate acute renal impairment/failure in these patients. Preoperative volume replacement therapy (VRT) is reported to increase the GFR and we hypothesize that VRT will reduce renal impairment and related complications in diabetic patients. Objective: The objective of this study is to establish the efficacy of preoperative VRT in reducing postoperative complications in diabetic patients undergoing CABG surgery. Time to “fit for discharge”, incidence of postoperative renal failure, cardiac injury, inflammation, and other health outcomes will be investigated. Methods: In this open parallel group randomized controlled trial, 170 diabetic patients undergoing elective or urgent CABG surgery received 1 mL/kg/hour of Hartmann’s solution for 12 consecutive hours prior to surgery, versus routine care. The primary outcome was time until participants were “fit for discharge”, which is defined as presence of: normal temperature, pulse, and respiration; normal oxygen saturation on air; normal bowel function; and physical mobility. Secondary outcomes included: incidence of renal failure; markers of renal function, inflammation, and cardiac damage; operative morbidity; intensive care stay; patient-assessed outcome, including the Coronary Revascularization Outcome Questionnaire; and use of hospital resources. Results: Recruitment started in July 2010. Enrolment for the study was completed in July 2014. Data analysis commenced in December 2016. Study results will be submitted for publication in the summer of 2017. Conclusions: VRT is a relatively easy treatment to administer in patients undergoing surgical procedures who are at risk of renal failure. This experimental protocol will increase scientific and clinical knowledge of VRT in diabetic patients undergoing elective or urgent CABG surgery. Findings supporting the efficacy of this intervention could easily be implemented in the health care system. Clinical Trial: International Standard Randomized Controlled Trial Number (ISRCTN): 02159606; http://www.controlled-trials.com/ISRCTN02159606 (Archived by WebCite at http://www.webcitation.org/6rDkSSkkK) [JMIR Res Protoc 2017;6(6):e119]

Coronary artery bypass grafting (CABG)-related bleeding complications and perioperative coronary events are strongly influenced by the management of antithrombotic therapy before and after CABG. Bleeding but also blood products transfusion increase the risk of death and compromise the long-term benefits of CABG.1 The use of new P2Y12 inhibitors, increasing pre-CABG percutaneous coronary interventions (PCI) with drug eluting stents (DES) requiring specific antiplatelet regimens, and advances in surgical technique has prompted the ESC Working Group on Cardiovascular Surgery and the ESC Working Group on Thrombosis to review the evidence of peri-CABG recommendations on antithrombotic management. Due to the paucity of randomized trials, most of the evidence is still derived from observational studies and expert consensus, further reinforcing the importance of a multidisciplinary consultation for optimal decision making. ### Benefits of preoperative aspirin Aspirin (acetylsalicylic acid, ASA) is recommended as secondary prevention therapy for all patients with proven coronary artery disease (CAD) and without contraindications. Its indication is even stronger for post-CABG patients (recommendation IA).2 The general consensus is that ASA treatment withdrawal has ominous prognostic implications in patients with CAD, especially in those with intracoronary stents, and should be advocated only when the bleeding risk clearly outweighs that of atherothrombotic events.3 The benefits of continuing ASA until the day of CABG (‘preoperative ASA’) are less clear and may explain the wide variability in the management of ASA therapy in the perioperative period and differences between guidelines endorsed by different professional and scientific societies (Supplementary material online, Table S1 ). This was based on the demonstration that ASA started the day before surgery was no more effective than ASA started 6 h after surgery at improving early (7- to 10-day) graft patency, but was associated with increased bleeding complications.4 More recent evidence suggests, however, that ASA use within 5–7 days prior to CABG …

OBJECTIVES: Combined coronary artery bypass grafting and valve surgery requires a prolonged period of cardioplegic arrest (CA) predisposing to myocardial injury and postoperative cardiac-specific complications. The aim of this trial was to reduce the CA time in patients undergoing combined coronary artery bypass grafting and valve surgery and assess if this was associated with less myocardial injury and related complications. METHODS: Participants were randomized to (i) coronary artery bypass grafting performed on the beating heart with cardiopulmonary bypass support followed by CA for the valve procedure (hybrid) or (ii) both procedures under CA (conventional). To assess complications related to myocardial injury, we used the composite of death, myocardial infarction, arrhythmia, need for pacing or inotropes for >12 h. To assess myocardial injury, we used serial plasma troponin T and markers of metabolic stress in myocardial biopsies. RESULTS: Hundred and sixty patients (80 hybrid and 80 conventional) were randomized. Mean age was 66.5 years and 74% were male. Valve procedures included aortic (61.8%) and mitral (33.1%) alone or in combination (5.1%). CA time was 16% lower in the hybrid group [median 98 vs 89 min, geometric mean ratio (GMR) 0.84, 95% confidence interval (CI) 0.77–0.93, P = 0.0004]. Complications related to myocardial injury occurred in 131/160 patients (64/80 conventional, 67/80 hybrid), odds ratio 1.24, 95% CI 0.54–2.86, P = 0.61. Release of troponin T was similar between groups (GMR 1.04, 95% CI 0.87–1.24, P = 0.68). Adenosine monophosphate was 28% lower in the hybrid group (GMR 0.72, 95% CI 0.51–1.02, P = 0.056). CONCLUSIONS: The hybrid procedure reduced the CA time but myocardial injury outcomes were not superior to conventional approach. TRIAL REGISTRATION: ISRCTN65770930.

Coronary artery chronic total occlusions (CTOs) are an exacerbation of stable coronary artery disease (CAD) with advanced calcification. CTOs are defined as 100% coronary occlusions with Thrombolysis in Myocardial Infarction grade 0 flow persisting for >3 months.1 National database registries and large single-center series suggest that in patients with CAD the overall incidence of CTOs may vary from 16% to 19% in Japan2 and 29% to 33% in North America,3 making this a common problem globally. Treatment of CTOs should be considered if associated with symptoms or viable/ischemic myocardial territories. Historically, treatments have been via coronary artery bypass grafting (CABG) or medical therapy.3–9 Response by Weintraub and Garratt on p 1817 The use of percutaneous coronary intervention (PCI) to treat CTOs (CTO-PCI) against established practice is controversial.10 This controversy is facilitated by the poor evidence available and by lack of clarity in the European and American guidelines for revascularization, including those for patients with stable CAD.11–15 The lack of robust evidence and the unclear guidelines can lead to ill-defined clinical indications determining serious geographical discrepancies in CTO-PCI medical practice. In a recent report from Japan, >61% of patients diagnosed with CTOs (19% of all CAD patients) were treated with CTO-PCI.2 This is a significant increase compared with a previous report from North America in which only 6% to 9% of all CTOs (29%–33% of all CAD cases) were treated with CTO-PCI (range, 1%–16% by geographical area/center).3 The report by Yamamoto and coworkers2 suggests widespread use of CTO-PCI in patients with multivessel CAD. This is likely to be at the expense of more established treatments such as CABG. The difference in CTO-PCI practice observed between Japan and North America is not easily explained. Contributing factors may be differences …

The article by Weintraub and Garratt includes the following key points: (1) the use of coronary artery bypass graft (CABG) to treat chronic total occlusions (CTOs) is limited; (2) surgeons ignore CTOs, simply bypassing them if viability and coronary size >1mm are confirmed; (3) CABG-CTOs can be justified in the setting of multivessel disease; and (4) the concluding remark …

Objective:To assessthe safety and efficacy of on-pump beating heart coronary surgery on organ function, and early and late health outcome as compared with conventional technique. Methods: A total of 81 patients were randomised to (1) coronary surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) (on-pump with CA, n = 41) or to (2) CPB without CA (on-pump without CA, n = 40). Primary outcomes included serial measurement of interleukins (IL-6, IL-8 and IL-10) for inflammation, troponin I for myocardial injury, protein S100 for cerebral injury and creatinine clearance (CrCl) and urinary N-acetyl-b-D-glucosaminidase (NAG) for renal injury. In-hospital health outcome and 5-year event-free survival were secondary outcomes. Results: Baseline and intra-operative characteristics were similar between groups. A marked release of ILs was observed in both groups, but no significant differences between the groups were found (IL-6 +9%, 95% confidence interval (CI) � 15% to +39%, p = 0.49; IL-8 +4%, 95% CI � 34% to +63%, p = 0.86; IL-10 � 0.1%, 95% CI � 19% to +21%, p = 0.93). Troponin I rose in both groups and was on average 34%higherintheon-pumpwithoutCAgroupbutthisdidnotreachstatisticalsignificance(95%CI � 0.4%to+87%,p = 0.08).S100proteinwashigher in the on-pump without CA group at 12 h (p = 0.04) but did not differ at other times (p = 0.16). The level of CrCl was higher 1 h in the on-pump without CA group (+23%, 95% CI +1% to +50%, p = 0.04), but not thereafter. NAG release was similar in both groups (+1% 95% CI � 23% to +33%, p = 0.91). Early and 5-year health outcomes were similar. Conclusions: On-pump without CA coronary surgery does not provide any obvious advantage when compared with the conventional technique of on-pump with CA in elective patients. Both techniques provide a comparable degree of inflammatory activation, myocardial, cerebral and renal injury with similar 5-year event-free survival. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background— Derangement of glucose metabolism after surgery is not specific to patients with diabetes mellitus. We investigated the effect of different degrees of blood glucose control (BGC) on clinical outcomes after cardiac surgery. Methods and Results— We analyzed 8727 adults operated on between April 1996 and March 2004. The highest blood glucose level recorded over the first 60 hours postoperatively was used to classify patients as having good (250 mg/dL) BGC; 7547 patients (85%) had good, 905 (10%) had moderate, and 365 (4%) had poor BGC. Patients with inadequate BGC were more likely to present with advanced New York Heart Association class, congestive heart failure, hypertension, renal dysfunction, and ejection fraction P ≤0.001). We found that 52% of patients with poor, 31% with moderate, and 8% with good BGC had diabetes mellitus. Inadequate BGC, but not diabetes mellitus ( P =0.79), was associated with in-hospital mortality (good, 1.8%; moderate, 4.2%; poor, 9.6%; adjusted odds ratio: poor versus good BGC, 3.90 [95% confidence interval, 2.47 to 6.15]; moderate versus good BGC, 1.68 [95% confidence interval, 1.25 to 2.25]). Inadequate BGC also was associated with postoperative myocardial infarction (eg, odds ratio, poor versus good BGC: 2.73 [95% confidence interval, 1.74 to 4.26]) and with pulmonary and renal complications in patients without known diabetes mellitus (eg, odds ratio, poor versus good BGC: 2.27 [95% confidence interval, 1.65 to 3.12] and 2.82 [95% confidence interval, 1.54 to 5.14] respectively). Conclusions— More than 50% of patients with moderate to poor BGC after cardiac surgery were not previously identified as diabetic. Inadequate postoperative BGC is a predictor of in-hospital mortality and morbidity.

The strategic management of primary lung cancer in patients with poor cardiopulmonary status is still controversial. The aim of this study was to ascertain the early and late results of wide-margin wedge resection with curative intent in this group of patients. Between January 1995 and January 2002, 24 patients (13 males; mean age, 69.96 years) with baseline poor cardiopulmonary status underwent wide-margin wedge resection of preoperatively diagnosed primary lung cancer. All patients suffered from chronic obstructive pulmonary disease and 9 (37.5%) also had symptomatic ischemic heart disease. Eight patients were in New York Heart Association class III and 12 were in class IV. There were no post-operative deaths. Complications included chest infection in 3, surgical emphysema with prolonged air leak in 1, and atrial fibrillation in 6. Overall 7-year survival was 23.3%. Three patients with ischemic heart disease suffered late non-cancer-related death due to myocardial infarction at 48, 60, and 60 months postoperatively. Cancer-free 5-year survival was 54.3%, with 7/24 (29%) late recurrences. Our study suggests that wide-margin wedge resection is a valuable surgical option for primary lung cancer in patients with poor cardiopulmonary status.

OBJECTIVE To investigate the changes in cerebral oxygenation during coronary artery bypass grafting (CABG) with normothermic cardiopulmonary bypass (CPB) using near infrared spectroscopy. METHODS Measurement of cerebral cortical oxygenation changes included concentration of deoxygenated haemoglobin [HHb], oxygenated haemoglobin [O(2)Hb], changes in the redox status of the cytochrome c oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation index (TOI), and cerebral blood volume (CBV) as expressed by tissue haemoglobin index (THI). Measurements were performed in 19 consecutive patients undergoing normothermic (34-36 degrees C) CPB. Data were recorded at 0.5s intervals and averaged into 30 s epochs. Data analysis was carried at baseline, 1, 20, and 40 min after start of CPB, at rewarming, on weaning from CPB, and at closing of chest. RESULTS There were no in-hospital death, neurological deficits, or myocardial infarcts. Compared to baseline, during the entire CPB duration, there was a marked reduction in [O(2)Hb] and CBV which reached their worst level 40 min after initiation of CPB (from -3.03+/-5.1 to -9.25+/-7.20 micromol/l for [O(2)Hb], and a 24% reduction for CBV (both P

Objective: Despite refinements of the diagnostic procedures, often surgery remains the only option to ascertain the histopathological nature of solitary pulmonary nodules (SPN). Aim of the present study was to ascertain the value of wide-margin wedge resection (WMWR) with curative intent in a consecutive cohort of patients afflicted by SPN. Methods: From January 1995 to January 2002, 129 patients (74 male, mean age 60.5 ^ 14.4 years) underwent WMWR of a SPN. In-hospital outcome was prospectively collected and retrospectively analyzed. Incidence of malignancy was obtained by histology. Patients found to be afflicted by primary lung cancer (PLC) were sub-grouped according to their preoperative cardiopulmonary status (CPS). In-hospital and mid-term clinical outcome of all the patients is presented. Results: There were 3 (2.3%) in-hospital deaths. Distribution of histology included 61 (47.3%) PLC (41 poor CPS), 20 (15.5%) secondary lung cancer (SLC), and 48 (37.2%) miscellaneous benign lesions. Twenty patients with PLC were fit and underwent completion lobectomy within 2 weeks following WMWR. Hospital length of stay was longer in patients with PLC as compared to patients with SLC ðP ¼ 0:04Þ: There were 17/61 (27%) recurrences in the PLC group. Of these, 2 occurred in fit patients undergone previous WMWR-lobectomy, and 15 in patients with poor baseline CPS. All these patients were referred for adjuvant therapy. Overall 5-year survival of the PLC group was 66% (61.1% for those with poor CPS and 82.5% for those with good CPR (P ¼ NS). Seven out of 20 (35%) patients with SLC had late recurrent disease, leading to 1 re-operation. The overall 5-year survival in this group was 58.8%. There was only 1 non-related late death in the benign group. Conclusions: The WMWR resection of a primarily malignant SPN determines a valuable 5-year survival but a relatively high incidence of late recurrence. WMWR is a safe and effective surgical option for patients presenting with poor cardiopulmonary reserve. q 2004 Elsevier B.V. All rights reserved.

Background The safety of teaching off-pump coronary artery bypass grafting to trainees is best tested in high-risk patients, who are more likely to experience significant morbidity after surgery. This study compared outcomes of off-pump coronary artery bypass grafting operations performed by consultants and trainees in high-risk patients. Methods Data for consecutive patients undergoing off-pump coronary artery bypass grafting were collected prospectively. Patients satisfying at least one of the following criteria were classified as high-risk: age older than 75 years, ejection fraction less than 0.30, myocardial infarction in the previous month, current congestive heart failure, previous cerebrovascular accident, creatinine greater than 150 μmol/L, respiratory impairment, peripheral vascular disease, previous cardiac surgery, and left main stem stenosis greater than 50%. Early morbidity, 30-day mortality, and late survival were compared. Results From April 1996 to December 2002, 686 high-risk patients underwent off-pump coronary artery bypass grafting revascularization. Operations by five consultants (416; 61%) and four trainees (239; 35%) were the focus of subsequent analyses. Nine visiting or research fellows performed the other 31 operations. Prognostic factors were more favorable in trainee-led operations. On average, consultants and trainees grafted the same number of vessels. There were 18 (4.3%) and 5 (1.9%) deaths within 30 days, and 14 (3.4%) and 5 (1.9%) myocardial infarctions in consultant and trainee groups, respectively. After adjusting for imbalances in prognostic factors, odd ratios for almost all adverse outcomes implied no increased risk with trainee operators, although patients operated on by trainees had longer postoperative stays and were more likely to have a red blood cell transfusion. Kaplan-Meier cumulative mortality estimates at 24-month follow-up were 10.5% (95% confidence interval, 7.7% to 14.2%) and 6.4% (95% confidence interval, 3.8% to 10.9%) in consultant and trainee groups, respectively (hazard ratio=0.60 [95% confidence interval, 0.37 to 0.99]; p = 0.05). Conclusions Off-pump coronary artery bypass grafting surgery in high-risk patients can be safely performed by trainees.

Aims Off-pump coronary bypass grafting (OPCAB) has short-term benefits compared to conventional bypass grafting using the heart-lung machine (CABG-CPB) but may compromise longer term outcome. We aimed to compare generic and disease specific quality of life (QoL) two to four years after surgery in participants in two randomised controlled trials of OPCAB vs. CABG-CPB. Methods and results Trial participants were sent four questionnaires (SF-36, EuroQol/EQ5D, Seattle Angina Questionnaire (SAQ) and Coronary Revascularisation Outcome Questionnaire (CROQ)) to assess generic and disease-specific quality of life (QoL). Of 401 participants, 22 (5.5%) had died; of the 379 survivors, 328 responded (86.5%; 159 CABG-CPB and 169 OPCAB). Median duration of follow-up was three years. QoL scores for both groups were very similar and differences between groups were not significant (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p>0.05\) \end{document} for all questionnaires and dimensions). Summary SF-36 scores showed poorer than normal physical QoL but normal mental QoL. Among all responders, there was a tendency for CROQ scores (core total, physical and psychosocial functioning and satisfaction with treatment) to deteriorate with time after the operation (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{\leqslant}0.05\) \end{document}). Conclusion Two to four years after surgery, patients randomised to OPCAB and CABG-CPB had similar symptoms, generic and disease-specific QoL.

Objectives: We sought to investigate the relationship between perioperative factors and the occurrence of ventricular tachycardia (VT) and ventricular fibrillation (VF), as well as the impa...

We investigated the changes occurring in cerebral cortical oxygenation during off-pump coronary artery bypass (OPCAB) surgery using near infrared spectroscopy (NIRS).Measurement of cerebral cortical oxygenation changes included concentration of deoxygenated hemoglobin [HHb], oxygenated hemoglobin [O(2)Hb], changes in the redox status of the cytochrome c oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation index (TOI), and cerebral blood volume (CBV) as expressed by tissue hemoglobin index (THI). Measurements were performed in 23 consecutive patients during grafting of: left anterior descending (LAD setup 1; n = 23), posterior descending (PDA setup 2; n = 17), and Circumflex (Cx setup 3; n = 19) coronary arteries. Measurements were performed before any surgical manipulation (baseline), following positioning of the pressure stabilizer during construction of the distal anastomosis and 2 minutes after the completion of each distal anastomosis with the heart returned to its natural position.There were no in-hospital deaths, neurologic deficits, or myocardial infarcts. Compared to baseline, during LAD grafting there was a marked reduction in [O(2)Hb] [-1.08 (-1.77 to -0.39), mean difference (95% CI) (p0.0008)], without a significant change in [HHb]. There was also a 4% reduction in cerebral saturation and a 3% fall in CBV (both p0.05). Setup 2 (PDA) was associated with a marked decrease of [O(2)Hb] [-1.92 (-2.95 to -0.88) mean difference (95% CI) (p0.0025)], which was accompanied by an increase in [HHb] [1.89 (1.00 to 2.77) mean difference (95% CI) (p0.0025)], and a 4% reduction in cerebral saturation (p0.0008). Grafting of the Cx was associated with a marked increase in [HHb] [2.85 (1.46 to 4.2) mean difference (95% CI) (p0.0025)], with no changes in [O(2)Hb], a 6% reduction in cerebral saturation, and a 12% increase in CBV (both p0.05). In all 3 settings, however, the changes were not associated with a modification in the redox state of [Cyt-Ox]. On returning to baseline condition, the changes in [O(2)Hb] and TOI observed in setup 1 persisted, and a significant reduction was observed in the redox state of the [Cyt-Ox] when compared with baseline [-0.08 (-0.14 to -0.02) mean difference (95% CI) (p0.002)]. For setups 2 and 3 there was recovery of the cerebral cortical oxygenation.Grafting of the LAD on the beating heart is responsible for changes in cerebral cortical oxygenation which persist early after returning the heart to its natural position. Grafting of the Cx and PDA result in transient reversible changes. Trendelenburg positioning and right lateral tilting of the operating table during grafting of lateral and posterior walls might have a protective role in preventing cerebral cortical ischemia. Further studies are needed to assess the clinical importance of these observations.

Background Intermittent antegrade cold blood cardioplegia is superior to warm blood cardioplegia in patients who have aortic valve operation. This study compared the cardioprotective efficacy of intermittent antegrade and retrograde cold blood cardioplegia with emphasis on metabolic stress in the left and right ventricles. Methods Thirty-nine patients who had elective aortic valve replacement were prospectively randomly selected to receive intermittent antegrade or retrograde cold blood cardioplegia. Left and right ventricular biopsies were collected 5 minutes after institution of cardiopulmonary bypass and 20 minutes after cross-clamp removal and were used to determine metabolic changes. Metabolites (adenine nucleotides, amino acids, and lactate) were measured using high-powered liquid chromatography and enzymatic techniques. Serial measurement of troponin I release was also used as a marker of myocardial injury. Results Preoperative characteristics were similar between groups. There was no in-hospital mortality, and no differences were observed in postoperative complications. Preischemic concentration of taurine was significantly higher in left ventricular biopsies, whereas adenosine triphosphate tended to be lower in the left ventricle. At reperfusion adenosine triphosphate levels were significantly lower than preischemic levels in right but not left ventricles irrespective of the route of delivery. The alanine-glutamate ratio was significantly elevated in both ventricles. Myocardial injury as assessed by troponin I release was also significantly increased in both groups. Conclusions Retrograde and antegrade intermittent cold blood cardioplegic techniques are associated with suboptimal myocardial protection. Metabolic stress was more pronounced in the right than the left ventricle irrespective of the cardioplegic route of delivery used.

Patients presenting with severe left ventricular (LV) dysfunction undergoing coronary artery surgery are at increased risk of perioperative morbidity and mortality. The present study investigated early and midterm outcomes in a consecutive series of patients with severe LV dysfunction undergoing coronary surgery at our institution.Data on 5,195 consecutive patients undergoing coronary artery bypass grafting (CABG) alone (in-hospital mortality 1.35%) from April 1996 to August 2002 were prospectively recorded in the Patient Analysis and Tracking System. Two hundred and fifty patients (median age 65 years [interquartile range, 57 to 70]) with preoperative left ventricular ejection fraction less than 30% (74 off pump; 29.6%) were identified and early and midterm clinical outcomes analyzed. Propensity scores were used to take account of the imbalance in the distribution of prognostic factors between the on-pump and off-pump groups.Patients undergoing on-pump surgery were less likely to have current congestive heart failure, insulin-dependent diabetes, a history of hypertension, have had gastrointestinal tract surgery or an ulcer, or unstable angina. They had on average lower Parsonnet scores and New York Heart Association and Canadian Cardiovascular Score ratings. However they were more likely to have more extensive coronary artery heart disease and to require more grafts than those undergoing off-pump surgery. After adjustment for consultant team and propensity scores no differences between groups with regard to in-hospital mortality and morbidity were found. The only in-hospital outcome to show a significant difference after adjustment was the need for intraoperative inotropic support, which was higher in the on-pump group (odds ratio 5.1; 95% confidence interval 2.55 to 10.2; p0.001)). The median follow-up times for the on- and off-pump groups were 3.4 years and 1.4 years respectively. Three-year survival was higher with on-pump surgery (87% on-pump versus 73% off-pump) but this difference did not reach statistical significance after adjustment for prognostic variables (hazard ratio 0.54, 95% confidence interval 0.22 to 1.26, p = 0.16).In-hospital mortality and morbidity in patients presenting with severe LV dysfunction is low with comparable results with both on- and off-pump coronary artery surgery. Midterm clinical outcome is encouraging and seems to justify surgical revascularization for this high-risk group of patients.

ObjectivesThis study sought to quantify the effect of body mass index (BMI) on early clinical outcomes following coronary artery bypass grafting (CABG).BackgroundObesity is considered a risk factor for postoperative morbidity and mortality after cardiac surgery, although existing evidence is contradictory.MethodsA concurrent cohort study of consecutive patients undergoing CABG from April 1996 to September 2001 was carried out. Main outcomes were early death; perioperative myocardial infarction; infective, respiratory, renal, and neurological complications; transfusion; duration of ventilation, intensive care unit, and hospital stay. Multivariable analyses compared the risk of outcomes between five different BMI groups after adjusting for case-mix.ResultsOut of 4,372 patients, 3.0% were underweight (BMI 7 days) (OR = 1.7, 95% CI 1.1 to 2.5). Overweight, obese, and severely obese patients were not at higher risk of adverse outcomes than normal weight patients, and were less likely than normal weight patients to require transfusion (ORs from 0.42 to 0.86).ConclusionsUnderweight patients undergoing CABG have a higher risk of death or complications than normal weight patients. Obesity does not affect the risk of perioperative death and other adverse outcomes compared to normal weight, yet obese patients appear less likely to be selected for surgery than normal weight patients.

Background A new class of nitric oxide donating aspirin (NO-ASA) drugs may increase the therapeutic impact of aspirin in saphenous vein coronary artery bypass grafting (CABG) not only through the inhibition of thrombosis but also through a reduction of vasospasm and inhibition of vascular smooth muscle cell (VSMC) proliferation (effects that are inhibited by NO but not ASA). In order to test this proposal the effect of three NO-ASA drugs (NCX 4040, NCX4050, and NCX4060) on in vitro relaxation and cyclic guanosine monophosphate (cGMP) formation in the human isolated saphenous vein and the proliferation of human VSMCs was investigated. Methods Saphenous vein segments were obtained from 30 patients undergoing CABG (median age, 59 years; range, 49 to 68). The effect of the NO-ASA adducts, ASA alone, and sodium nitroprusside (NO donor) were investigated on (1) relaxation of phenylephrine-stimulated contraction using an organ bath, (2) cyclic guanosine monophosphate (cGMP) formation using an enzyme-linked immunosorbent assay, and (3) the proliferation of VSMCs derived from saphenous vein using bromo-deoxyuridine (BRDU) incorporation. Results All three NO-ASA adducts (at concentrations that inhibited responses by 50% [IC 50 s] between 1 μmol/L and 100 μmol/L) and nitroprusside (at IC 50 s between 0.5 and 10 μmol/L) elicited relaxation of isolated human saphenous vein, promoted cGMP formation, and inhibited VSMC proliferation whereas ASA alone (up to 100 μmol/L) had no effect on any variable. Conclusions These data indicate that the NO-ASA adducts by virtue of their capacity to release NO and stimulate guanylyl cyclase may be useful not only in the prevention of thrombosis following CABG but also the reduction of saphenous vein graft spasm and neointima formation.

The resurgence of off-pump coronary artery bypass (OPCAB) surgery is rapidly changing surgical practice. After an initial phase of ‘healthy skepticism’, the impetus of some developed countries toward OPCAB surgery is remarkable. Hardly any OPCAB procedure was carried out before 1995 in the USA, however, by 1999 more than 11 000 (10%) coronary operations were performed on the beating heart.1 It is estimated that, worldwide, this percentage is currently up to 20–30%, with expectations to reach 50% by 2005.2–3 Many sceptics have becomeoptimists following the development of enabling instruments and the publication of supportive evidence as part of observational, case-matched, and prospective randomised studies. The concept of direct mammary–coronary anastomoses was advocated separately by Demikhov and Murray in animal models in the early 1950s.4–5 The first saphenous vein graft to bypass the right coronary artery was performed by Sabiston on the beating heart in 1962.6 Kolesov performed the first mammary–coronary anastomosis, on the beating heart in a human, in 1964.7 After the advent of the heart–lung machine, few surgeons continued to use the OPCAB technique, and when they did it was for economic reasons.8–9 Among those were Benetti8 and Buffolo9 from South America, who published in the early 1990s the first two large series on OPCAB surgery. These results, as well as the interest in minimally invasive coronary surgery through mini-thoracotomy approaches, prompted the development of enabling systems and devices that ultimately made the OPCAB a safe and routine procedure. Despite advances in perfusion, anaesthetic and surgical techniques, cardiopulmonary bypass (CPB) is still associated with significant morbidity due to its un-physiological nature. The morbidity rate has indeed remained high, particularly in the ever-increasing high-risk surgical population presenting with co-morbidities. Contact of blood components with the artificial surfaces of the bypass circuit, aortic …

Atrial fibrillation (AF) is the most common complication following cardiac surgery and is associated with significant increases in postoperative morbidity, length of stay and cost of care. In a randomized study we assessed the impact of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) (off-pump, n = 100), compared to conventional (on-pump, n = 100) CABG, on the frequency of postoperative AF. Arrhythmias were detected using an automated arrhythmia detector for the first 72 hours following surgery and by four hourly clinical observations thereafter. AF was defined as an irregular narrow complex rhythm (in the absence of bundle branch block) with absence of discrete P waves lasting greater then 10 minutes. There was a significant reduction in the incidence of postoperative AF in the off-pump group (11% versus 45%, P < 0.001) in addition to significant reductions in blood usage, postoperative pneumonia, inotrope requirements, and hospital and intensive care unit stay. Univariate analysis identified all these variables as risk factors for AF, however multivariate regression analysis identified CPB and cardioplegic arrest as the only independent predictor of postoperative AF (OR 7.4; 95% CI 3.4 to 17.9). This study therefore suggests that the inflammatory response to bypass, myocardial ischaemia and atrial cannulation are significant contributory factors to the development of AF following cardiac surgery. In the light of more recent trials it is apparent that this benefit may be most marked in patients with multiple perioperative risk factors for postoperative AF.

Background Right ventricular assist devices (RVADs) have been proposed to improve exposure of the coronary arteries in off-pump surgery. In this study we investigated the impact of the A-Med RVAD on inflammatory response and organ function in patients undergoing coronary artery bypass grafting. Methods Sixty patients were prospectively randomized to conventional surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest, beating heart surgery (off-pump), or beating heart surgery with the RVAD. Serial blood samples were collected postoperatively, for analysis of inflammatory markers, troponin I, protein S100, and free hemoglobin. Renal tubular function was assessed by measuring urine N -acetyl-glucosaminidase activity. Results No hospital deaths or major postoperative complications occurred in the study population. Interleukin-6, interleukin-8, C3a, and troponin I levels after surgery were significantly higher in the CPB group compared with the off-pump and RVAD groups. Free hemoglobin levels immediately after the operation, peak and total S100 levels, and N -acetyl-glucosaminidase activity were also significantly higher in the CPB group. Conclusions Off-pump coronary revascularization, with or without RVAD, reduces inflammatory response, myocardial, neurologic, and renal injury, and decreases hemolysis when compared with conventional surgery with CPB and cardioplegic arrest.

Background . Homocysteine (Hcy) is an independent risk factor for coronary artery disease, but there are no reports on Hcy levels in patients undergoing coronary artery bypass graft (CABG) surgery. Interactions between Hcy and copper may mediate the vasculopathic impact of Hcy, and this may play a role in vein graft failure. The aim of this study was to assess the perioperative levels of Hcy, copper, ceruloplasmin (CP), folate, and vitamin B 12 in patients undergoing myocardial revascularization surgery. Methods . Blood samples were taken from 55 consecutive patients undergoing elective conventional CABG (43 male; mean age, 63.2 ± 5.2 years) 1 day preoperatively and postoperatively at 1 day, 6 days, and 6 weeks. Hcy, copper, CP, red cell folate, vitamin B 12 , creatinine, and C-reactive protein (CRP) were then measured using standard clinical chemistry methods. The same protocol was applied to 10 patients (7 male; mean age, 63.3 ± 5.2 years) undergoing off-pump coronary artery bypass (OPCAB) surgery. Results . In the conventional CABG group, there were significant increases in the plasma concentrations at 6 days and 6 weeks postoperatively of Hcy (from 10.1 to 11.6 and 13.5 μmol/L, respectively), plasma copper (from 13.5 to 20.3 and 18.5 μmol/L), and serum ceruloplasmin (from 0.3 to 0.41 and 0.44 g/L). CRP and vitamin B 12 were elevated at 6 days but not 6 weeks after the operation. In contrast, red cell folate and creatinine were not significantly changed. The subgroup analysis for the OPCAB patients showed the same trend as for the conventional group. Conclusions . Coronary surgery precipitates a significant and sustained increase in the blood concentrations of Hcy and copper, which is not due to a decrease in folate and vitamin B 12 , altered renal function, or inflammation. Further studies are required to establish whether the concomitant increase in Hcy and copper plays an etiological role in vein graft disease.

Off-pump coronary artery bypass (OPCAB) grafting is becoming popular worldwide. The development of exposure and stabilization techniques have made this surgery a simple, safe, and routine procedure. The evolution of OPCAB surgery at our institution is presented and discussed.

Background— Off-pump coronary artery bypass surgery has been demonstrated to reduce morbidity in elective patients. However, high-risk patients might benefit the most from this surgical procedure. Our goal was to investigate the effectiveness of on-pump and off-pump coronary artery bypass surgery on early clinical outcome in a consecutive series of overweight patients. Methods and Results— From April 1996 to April 2001, data on 4321 patients undergoing coronary surgery (mortality 1.4%) were prospectively entered into the Patient Analysis and Tracking System. Data were extracted for all patients with a body mass index ≥25 kg/m 2 . A risk-adjusted analysis was performed to assess the effect of surgical technique in the whole overweight cohort. 2844 patients were identified (2261 male, median age 63, interquartile range 56 to 68). Patients undergoing on-pump surgery (2170, 76.3%) were less likely than those undergoing off-pump surgery to have hypercholesterolemia or left main stem disease and were, on average, less obese. However, they were more likely to have unstable angina and to have had a previous myocardial infarction, and they had more extensive coronary disease and received more grafts (all P P P Conclusions— These results suggest that off-pump surgery is safe and effective and is associated with a reduced in-hospital mortality and morbidity in overweight patients when compared with conventional coronary surgery with cardiopulmonary bypass and cardioplegic arrest.

Background . Stroke is a rare but devastating complication after coronary artery bypass grafting (CABG) and its prevention remains elusive. We used a case control design to investigate the extent to which preoperative and perioperative factors were associated with occurrence of stroke in a cohort of consecutive patients undergoing myocardial revascularization. Methods . From April 1996 to March 2001, data from 4,077 patients undergoing CABG were prospectively entered into a database. The association of preoperative and perioperative factors with stroke was investigated by univariate analyses. Factors observed to be significantly associated with stroke in these analyses were further investigated using multiple logistic regression to estimate the strength of the associations with the occurrence of stroke, after taking account of the other factors. Results . During the study period, 4,077 patients underwent CABG and of these 923 (22.6%) had off-pump surgery. Forty-five patients suffered a perioperative stroke (1.1%). Overall there were 46 in-hospital deaths (1.1%), of whom 6 also suffered a stroke. Brain imaging of the stroke patients showed embolic lesions in 58%, watershed in 28%, and mixed in 14%. Multivariate regression analysis identified several preoperative factors as independent predictors of stroke, ie, age, unstable angina, serum creatinine greater than 150 mcg/ml, previous cerebrovascular accident (CVA), peripheral vascular disease (PVD), and salvage operation. When operative risk factors were added to the adjusted model, off-pump surgery was associated with a substantial, but not significant, protective effect against stroke (odds ratio=0.56, 95% confidence interval 0.20 to 1.55). Survival for stroke patients was 93% and 78% at 1 and 5 years, respectively. Conclusions . Overall incidence of stroke is relatively low in our series. Age, unstable angina, previous CVA, PVD, serum creatinine greater than 150 mcg/ml, and salvage operation are independent predictors of stroke. These factors should be taken into account when informing each individual patient on the possible risk of stroke and in the decision-making process on the surgical strategy.

Coronary artery bypass grafting in high-risk patients carries substantial morbidity. We compared the effectiveness of off-pump revascularization with that of conventional coronary artery bypass grafting using cardiopulmonary bypass and cardioplegic arrest in consecutive high-risk patients.From April 1996 to December 2000, clinical data for consecutive patients undergoing coronary artery revascularization were prospectively entered into a database. Data were extracted for all patients considered to be high risk, defined as the presence of one or more of ten adverse prognostic factors. Hospital mortality and early morbidity were compared between two groups of patients, the on-pump and off-pump groups.The study group comprised 1,570 consecutive high-risk patients, 332 (21.1%) of whom underwent an off-pump operation. Patients in the on-pump group had fewer high-risk factors and lower Parsonnet scores and were less likely to be 75 years of age or older, to have peripheral vascular disease or hypercholesterolemia, or to have sustained a previous transient ischemic attack. However, they were more likely to be assigned to a higher Canadian Cardiovascular Society class and had more extensive coronary artery disease and were more likely to have unstable angina, to require urgent or emergency operations, and to receive more grafts than those undergoing off-pump procedures. Unadjusted odds ratios for intensive care unit or high-dependency unit stay, total length of stay, blood loss of more than 1,000 mL, postoperative hemoglobin and transfusion requirement all showed a highly significant benefit for the off-pump group (por = 0.005; odds ratios, 0.33 to 0.65). After adjustment for prognostic variables, odds ratios remained essentially unaltered (adjusted odds ratio estimates 0.36 to p0.05) except for blood loss of more than 1,000 mL (adjusted odds ratio estimate, 0.82; p = 0.22). Sensitivity analyses confirmed the robustness of these findings.Off-pump coronary artery bypass grafting is safe, effective, and associated with reduced morbidity in high-risk patients compared with conventional coronary artery revascularization.

Objectives: Myocardial protection techniques during cardiac surgery have been largely investigated in the clinical setting of coronary revascularisation. Few studies have been carried out on patients with left ventricular hypertrophy where the choice of delivery, and temperature of cardioplegia remain controversial. This study investigates metabolic changes and myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using antegrade cold or warm blood cardioplegia. Methods: Thirty-five patients were prospectively randomised to intermittent antegrade cold or warm blood cardioplegia. Left ventricular biopsies were collected at 5 min following institution of cardiopulmonary bypass, 30 min after cross-clamping the aorta and 20 min after cross-clamp removal, and used to determine metabolic changes during surgery. Metabolites (adenine nucleotides, amino acids and lactate) were measured using high pressure liquid chromatography and enzymatic techniques. Postoperative myocardial troponin I release was used as a marker of myocardial injury. Results: Ischaemic arrest was associated with significant increase in lactate and alanine/glutamate ratio only in the warm blood group. During reperfusion, alanine/glutamate ratio was higher than preischaemic levels in both groups, but the extent of the increase was considerably greater in the warm blood group. Troponin I release was markedly (P , 0:05, Mean ^ SD) lower at 1, 24 and 48 h postoperatively in the cold compared to the warm blood group (0.51 ^ 0.37, 0.37 ^ 0.22 and 0.27 ^ 0.19 vs. 0.75 ^ 0.42, 0.73 ^ 0.51 and 0.54 ^ 0.38 ng/ml for cold vs. warm group, respectively). Conclusions: Cold blood cardioplegia is associated with less ischaemic stress and myocardial injury compared to warm blood cardioplegia in patients with aortic stenosis undergoing valve replacement surgery. Both cardioplegic techniques, however, confer sub-optimal myocardial protection. q 2002 Elsevier Science B.V. All rights reserved.

From the Cardiology Department, Cardiovascular MRI Unit, and Department of Cardiac Surgery, Bristol Heart Institute, NIHR Cardiovascular BRU, Bristol, United Kingdom. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Oct 29, 2014; accepted for publication Nov 4, 2014; available ahead of print Dec 4, 2014. Address for reprints: Andrea Giuseppe Porto, MD, Bristol Heart Institute, NIHR Biomedical Research Unit, Marlborough St, Bristol, BS 2 8HW, United Kingdom (E-mail: portoandrea@hotmail.it). J Thorac Cardiovasc Surg 2015;149:e31-3 0022-5223/$36.00 Copyright 2015 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2014.11.013

Preoperative renal insufficiency is a predictor of acute renal failure in patients undergoing conventional coronary artery bypass grafting. Off-pump coronary artery bypass operations have been shown to reduce renal dysfunction in patients with normal renal function, but the effect of this technique in patients with preoperative nondialysis-dependent renal insufficiency is unknown.From June 1996 to December 1999, data of 3,250 consecutive patients undergoing coronary artery bypass grafting were prospectively entered into the Patient AnalysisTracking Systems (PATS, Dendrite Clinical Systems, London, UK). Two hundred and fifty-three patients with preoperative serum creatinine more than 150 micromol/L were identified (202 patients on-pump, 51 patients off-pump), and clinical outcomes were analyzed. Serum creatinine and urea, in-hospital mortality, and morbidity were compared between groups. The association of perioperative factors with acute renal failure was investigated by multiple logistic regression analysis.Preoperative characteristics were similar between the groups. Mean number of grafts was 2.9 +/- 0.8 and 2.3 +/- 0.8 in the on-pump and off-pump groups, respectively (p0.0001). Comparison between groups showed a significantly higher incidence of stroke, inotropic requirement, blood loss, and transfusion of red packed cell and platelets in the on-pump group (all p0.05). Postoperative serum creatinine and urea were higher in the on-pump group with a significant difference at 12 hours postoperatively (p0.05). Logistic regression analysis identified cardiopulmonary bypass, serum creatinine level 60 hours postoperatively, inotropic requirement, need for intraaortic balloon pump, transfusion of red packed cell, and hours of ventilation as predictors of postoperative acute renal failure.This study suggests that off-pump coronary artery bypass operations reduce in-hospital morbidity and the likelihood of acute renal failure in patients with preoperative nondialysis-dependent renal insufficiency undergoing myocardial revascularization.

The aim of this study was to compare hospital, early, and late clinical outcomes for patients undergoing one-stage, coronary and abdominal aortic surgical intervention with and without cardiopulmonary bypass.From March 1990 to September 1999, 42 consecutive patients underwent combined operations at a single institution. Cardiopulmonary bypass and cardioplegic arrest were used during coronary revascularization in the first 20 patients (on-pump group), and the next 22 patients received the one-stage operations on the beating heart (off-pump group).Baseline characteristics were similar between groups. Three cardiac-related hospital deaths occurred in the on-pump group and one such death in the off-pump group (p = 0.25). Cardiac-related events, pulmonary complications, inotropic support, blood loss and transfusion requirements, intensive care unit stay, and hospital stay were significantly reduced in the off-pump group (all, p0.05). The actuarial survival rates in the on-pump and off-pump groups were 80% and 95%, respectively, at 1 year (p = 0.13) and 75% and 89%, respectively, at 3 years (p = 0.22). Freedom from cardiac-related events at 1-year follow-up was 91% in the off-pump group and 65% in the on-pump group (p0.05). No difference in cardiac-related events between groups was observed at 3 years.Off-pump coronary surgical procedures decrease postoperative complications in high-risk patients undergoing simultaneous coronary and abdominal aortic operations compared with the conventional one-stage procedure. The early benefits achieved with off-pump surgical intervention are not at the expense of the long-term clinical outcome.