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Objective: Despite the superiority of mitral valve repair, surgical mitral valve replacement (SMVR) remains an important intervention for patients with valve stenosis, infective endocarditis and complex mitral valve degeneration. There has been an increasing popularity in the worldwide use of biological valves due to the avoidance of long-term anti-coagulation and recent advancements in transcatheter techniques. We aim to evaluate the trend, early clinical outcomes and the choice of prostheses use in isolated SMVR over a 23 years period in the United Kingdom., Methods: All patients (n = 13,147) who underwent elective or urgent isolated SMVR from March 1996 to April 2019 were identified from the National Adult Cardiac Surgery Audit database. Trends in clinical outcomes, predicted/observed mortality of patients and the utilization of biological prostheses across 5 different age groups: <50, 50-59, 60-69, 70-79 and ≥80 years old were investigated. Early clinical outcomes associated with the use of mechanical and biological mitral valve prostheses in patients between the age of 60-70 years old were analysed., Results: The number of isolated SMVR performed has remained stable with approximately 600 cases annually since 2010. The in-hospital/30-day mortality rate has decreased from 7.41% (1996) to 3.92% (2018), despite the EuroScore II increasing from 1.42% in 1996 to 2.43% in 2018. Biological prostheses usage increased across all age group, and particularly in the 60-69 and 70-79 group, from 17.86% and 53.85% in 1996 to 48.85% and 82.38% in 2018, respectively. The use of mechanical prostheses was reduced in patients between the age of 50-59 from 100% in 1996 to 80.65% in 2018. There were no differences in short term outcomes among patients aged 60-70 years who received either a biological or mechanical prostheses., Conclusion: There has been a significant reduction in surgical mitral valve replacement early in-hospital mortality, despite an observed increase in the risk profile of patients over 23 years. A shifting trend in valve replacement choices was observed with a rise in the use of biological prostheses, particularly within the 60-69 and 70-79 age group. Early in hospital outcomes for patients aged 60-70 were not determined by the implanted valve type., Competing Interests: Declaration of Competing Interest Nil, (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this meta-analysis was to compare clinical and angiographic outcomes of skeletonized versus pedicled internal thoracic artery for coronary artery bypass grafting., Methods: A comprehensive search on Ovid MEDLINE, Ovid EMBASE and Scopus was performed from inception to December 2022. The primary outcome was follow-up mortality and graft failure. Secondary outcomes were repeat revascularization, cardiovascular death and operative mortality, myocardial infarction, stroke, and sternal wound complications (SWCs). Pooled estimate for follow-up outcomes was summarized as incidence rate ratio (IRR) and 95% confidence interval (CI) while short-term outcomes were pooled as odds ratio (OR) and 95% CI. For all outcomes, inverse variance weighting was used for pooling., Results: Twenty-eight studies, including 7 randomized trials and 21 observational studies, for a total of 5664 patients in the skeletonized group and 7434 in the pedicled group, were included in the analysis. At a mean weighted follow-up of 4.8 years, there was no difference in mortality between the two groups (IRR 1.14; 95% CI 0.59-2.20). However, the skeletonized group had a higher incidence of graft failure compared to the pedicled group (IRR 1.87, 95% CI 1.33-2.63) but a lower risk of SWCs (OR 0.42; 95% CI 0.30-0.60). There was no difference in short-term outcomes., Conclusions: Compared to the pedicled harvesting technique, skeletonization of the internal thoracic artery is associated with higher rate of graft failure and lower risk of SWCs without mortality difference., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Mortality after reoperative aortic valve surgery continues to decline but remains high compared with primary isolated replacement. We sought to examine temporal trends, morbidity, and mortality among patients undergoing isolated first-time reoperative aortic valve surgery., Methods: The study included all patients undergoing reoperative aortic valve surgery in the United Kingdom between January 2007 and March 2019. Patients undergoing isolated reoperative aortic valve replacement (AVR) were compared with a propensity matched cohort of patients undergoing isolated primary AVR. Outcomes measured included inhospital mortality, neurologic dysfunction, postoperative dialysis, deep sternal wound infections, and hospital length of stay., Results: During the study period, 40,858 primary isolated AVRs and 3015 first-time isolated reoperative AVRs were carried out in the United Kingdom. In the propensity matched reoperative group, median age of participants was 69.8 years (60.8-76.2) with median duration between the initial surgery and the reoperation being 7.69 years. Overall mortality was 3.1% (94) for reoperative AVR compared with 1.9% (56) for primary AVR. Mortality of both primary and reoperative AVR declined during the study period. Reoperation, age, New York Heart Association class, and chronic kidney disease were independently associated with early mortality., Conclusions: Reoperative isolated AVR can be performed with acceptable inhospital mortality and provides a benchmark against which alternative strategies should be compared., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Despite advances in cardiac surgery, observational studies suggest that females have poorer post-operative outcomes than males. This study is the first to review sex related outcomes following both coronary artery bypass graft (CABG) and valve surgery with or without combined CABG., Methods: We identified 30 primary research articles reporting either short-term mortality (in-hospital/30 day), long-term mortality, and post-operative stroke, sternal wound infection and myocardial infarction (MI) in both sexes following CABG and valve surgery with or without combined CABG. Reported adjusted odds/hazard ratio were pooled using an inverse variance model., Results: Females undergoing CABG and combined valve and CABG surgery were at higher risk of short-term mortality (odds ratio (OR) 1.40; 95% confidence interval (CI) 1.32-1.49; I 2  = 79%) and post-operative stroke (OR 1.2; CI 1.07-1.34; I 2  = 90%) when compared to males. However, for isolated AVR, there was no difference found (OR 1.19; 95% CI 0.74-1.89). There was no increased risk in long-term mortality (OR 1.04; 95% CI: 0.93-1.16; I 2  = 82%), post-operative MI (OR 1.22; 95%CI: 0.89-1.67; I 2  = 60%) or deep sternal wound infection (OR 0.92; 95%CI: 0.65-1.03, I 2  = 87%). No evidence of publication bias or small study effect was found., Conclusion: Females are at a greater risk of short-term mortality and post-operative stroke than males following CABG and valve surgery combined with CABG. However, there is no difference for Isolated AVR. Long-term mortality is equivalent in both sexes. PROSPERO Registration: CRD42021244603., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: It is unclear whether the innate immune response represents a therapeutic target for organ protection strategies in cardiac surgery., Methods: A systematic review of trials of interventions targeting the inflammatory response to cardiac surgery reporting treatment effects on both innate immune system cytokines and organ injury was performed. The protocol was registered at the International Prospective Register of Systematic Reviews: CRD42020187239. Searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were performed. Random-effects meta-analyses were used for the primary analysis. A separate analysis of individual patient data from six studies (n=785) explored sources of heterogeneity for treatment effects on cytokine levels., Results: Searches to May 2020 identified 251 trials evaluating 24 interventions with 20 582 participants for inclusion. Most trials had important limitations. Methodological limitations of the included trials and heterogeneity of the treatment effects on cytokine levels between trials limited interpretation. The primary analysis demonstrated inconsistency in the direction of the treatment effects on innate immunity and organ failure or death between interventions. Analyses restricted to important subgroups or trials with fewer limitations showed similar results. Meta-regression, pooling available data from all trials, demonstrated no association between the direction of the treatment effects on inflammatory cytokines and organ injury or death. The analysis of individual patient data demonstrated heterogeneity in the association between the cytokine response and organ injury after cardiac surgery for people >75 yr old and those with some chronic diseases., Conclusions: The certainty of the evidence for a causal relationship between innate immune system activation and organ injury after cardiac surgery is low., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Recent studies have shown no benefits from remote ischemic preconditioning (RIPC) in patients undergoing coronary artery bypass surgery. One possible explanation is that given previous exposure to angina and ischemia/reperfusion injury these patients, may be already 'naturally preconditioned'. The role of RIPC in a context of isolated valve intervention, both surgical and particularly transcatheter is less clear and remains under investigated, with few high-quality studies., Methods: A systematic literature review identified 8 candidate studies that met the meta-analysis criteria. We analyzed outcomes of 610 subjects (312 RIPC and 298 SHAM) with random effects modeling. Each study was assessed for heterogeneity. The primary outcome was the extent of periprocedural myocardial injury, as reflected by the area under the curve for serum troponin concentration. Secondary endpoints included relevant intra- and post-operative outcomes; sensitivity and high-quality subgroup analysis was also carried out., Results: Six and two studies reported the effect of RIPC in surgical and transcatheter valve intervention. There was a significant difference between-group in terms of periprocedural Troponin release (standardized mean difference (SMD: 0.74 [95% CI: 0.52; 0.95], p = 0.02) with no heterogeneity (χ 2 2.40, I 2 0%, p = 0.88). RIPC was not associated with any improvement in post-operative outcomes. No serious adverse RIPC related events were reported., Conclusions: RIPC seems to elicit overall periprocedural cardioprotection in patients undergoing valvular intervention, yet with no benefit on early clinical outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction., Methods: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients., Results: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased "cellular component morphogenesis" and a decrease in "blood circulation". Lipidomic analysis did not identify any lipids significantly altered by either intervention., Discussion: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia., Competing Interests: Declaration of competing interest None declared., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background: There is high demand for minimally invasive mitral valve repair; however, it is unclear whether the minimally invasive approach provides the same performance as conventional sternotomy in a context of complex mitral valve disease. Here, we compared outcomes of minimally invasive and sternotomy procedures for bileaflet and Barlow's mitral valve disease., Methods: We performed a pooled meta-analysis of studies reporting early and late follow-up of mitral valve repair for complex mitral valve regurgitation. The primary outcome was moderate mitral valve regurgitation recurrence and need for reoperation. Secondary outcomes included operation time, reopening for bleeding, associated tricuspid procedures, failed repair, and inhospital mortality. Incidence rates were calculated for long-term follow-up. Effect estimates were calculated as incidence rates with 95% confidence intervals. When Kaplan-Meier curves were available, event rates were estimated from the curves with Plot Digitizer software; otherwise, reported event rates were used to calculate incidence rates., Results: Eighteen studies including 1905 patients (654 minimally invasive and 1251 sternotomy) with a mean follow-up of 51.6 months (range, 14 to 138) were meta-analyzed with a random model. There were no significant between-group differences in moderate mitral valve regurgitation recurrence and reoperation (minimally invasive vs sternotomy, 1.7% [95% confidence interval, 1.0% to 2.9%] vs 1.3% [95% confidence interval, 0.9% to 1.8%], P = .22). Patients in the minimally invasive group were exposed to significantly longer cross-clamp and cardiopulmonary bypass times (P < .01); however, there were no additional between-group differences in secondary outcomes., Conclusions: This meta-analysis has demonstrated that minimally invasive and sternotomy approaches produce comparable results for complex mitral valve repair., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the prognostic impact of cardiac magnetic resonance (CMR) and conventional risk factors in patients with myocardial infarction with nonobstructed coronaries (MINOCA)., Background: Myocardial infarction with nonobstructed coronary arteries (MINOCA) represents a diagnostic dilemma, and the prognostic markers have not been clarified., Methods: A total of 388 consecutive patients with MINOCA undergoing CMR assessment were identified retrospectively from a registry database and prospectively followed for a primary clinical endpoint of all-cause mortality. A 1.5-T CMR was performed using a comprehensive protocol (cines, T2-weighted, and late gadolinium enhancement sequences). Patients were grouped into 4 categories based on their CMR findings: myocardial infarction (MI) (embolic/spontaneous recanalization), myocarditis, cardiomyopathy, and normal CMR., Results: CMR (performed at a median of 37 days from presentation) was able to identify the cause for the troponin rise in 74% of the patients (25% myocarditis, 25% MI, and 25% cardiomyopathy), whereas a normal CMR was identified in 26%. Over a median follow-up of 1,262 days (3.5 years), 5.7% patients died. The cardiomyopathy group had the worst prognosis (mortality 15%; log-rank test: 19.9; p < 0.001), MI had 4% mortality, and 2% in both myocarditis and normal CMR. In a multivariable Cox regression model (including clinical and CMR parameters), CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation electrocardiogram (ECG) remained the only 2 significant predictors of mortality. Using presentation with ECG ST-segment elevation and CMR diagnosis of cardiomyopathy as risk markers, the mortality risk rates were 2%, 11%, and 21% for presence of 0, 1, and 2 factors, respectively (p < 0.0001)., Conclusions: In a large cohort of patients with MINOCA, CMR (median 37 days from presentation) identified a final diagnosis in 74% of patients. Cardiomyopathy had the highest mortality, followed by MI. The strongest predictors of mortality were a CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation ECG., (Copyright © 2019. Published by Elsevier Inc.)

After more than thirty years, a hundred randomized studies and dozens of meta-analyses, there is still controversy on the results and benefits of off-pump coronary artery bypass grafting. The present review summarizes the most relevant evidence, the relation of outcomes with surgeon's and institution's experience, addresses regional variations in popularity of the technique, and the need for structural training., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We sought to investigate the impact of incomplete revascularization (IR) on long-term survival after isolated coronary artery bypass grafting (CABG). The possible interaction between IR and off-pump surgery was also explored., Methods: A total of 13,701 patients with multivessel disease undergoing CABG were included in the analysis. All patients received left internal thoracic artery (LITA) to the left anterior descending artery (LAD) territory. IR was defined as at least one diseased arterial territory (right coronary artery [RCA] and/or circumflex [CX] artery) incompletely revascularized., Results: Overall, 3107 (22.7%) patients received IR. After propensity score matching, IR did not increase all-cause death in the overall group (HR 1.09; 95%CI 0.96-1.22; P=0.17). However, when both RCA and CX artery were incompletely revascularized, late survival was significantly lower (HR 2.15; 95%CI 1.57-2.93). IR was associated with a higher risk of death after off-pump (HR 1.26; 95%CI 1.05-1.49) regardless the extent of IR. After on-pump, IR significantly affected survival only when both RCA and CX artery only were incompletely revascularized (HR 2.32; 95%CI 1.27-4.22)., Conclusions: The present analysis shows that in patients with LITA-LAD graft the impact of IR on survival is marginal when only one coronary territory is left ungrafted. When both the RCA and CX territory remain unrevascularized the survival rate is significantly reduced. IR after off-pump CABG is associated with significantly lower survival and affects long-term outcome even when only one coronary territory is not revascularized., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: We sought to compare the incidence of incomplete revascularization (IR) and long-term survival (up to 20years) after off-pump (OPCAB) versus on-pump (ONCAB) coronary artery bypass in a high OPCAB volume centre where OPCAB was introduced in 1996 and has become the preferred strategy over the years., Methods and Results: From 1996 to 2015 a total of 7,427 OPCAB and 7128 ONCAB procedures were performed at Bristol Heart Institute, United Kingdom. We obtained 5423 propensity matched pairs for final comparison. Mixed effect Cox model accounting for clustering due to different surgeon was used to investigate the treatment effect on mortality., Results: OPCAB was associated with higher rate of incomplete revascularization 13.3% versus 6.7%; P<0.0001). Mean follow-up time was 7.8±4.6year [max 17.3]. At 12years OPCAB was associated with a marginal but significant +3% increase in overall mortality (67.4%[95%CI 65.8-69.1] vs 64.4%[95%CI 62.7-66.2]; stratified log-rank P=0.03). When compared to ONCAB with complete revascularization, OPCAB with IR (HR 1.74;95%CI 1.53-1.99; P<0.001) and ONCAB with IR (HR 1.29; 95%CI 1.06-1.57; P=0.01) but not OPCAB with complete revascularization (HR 1.02;95%CI 0.94-1.11; P=0.63) were associated with increased risk of late mortality., Conclusion: Despite completeness of revascularization was achieved in the majority of OPCAB cases, OPCAB remained associated with a significantly higher rate of incomplete revascularization. This translated into a marginal but significant reduction in late survival rates after OPCAB when compared to ONCAB., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The long saphenous vein is the most commonly used conduit in coronary artery bypass graft (CABG) surgery when bypassing multiple diseased arteries; however, its use is complicated by the development of vascular inflammation, intimal hyperplasia and accelerated atherosclerosis leading to compromised graft efficacy. Despite refinement of surgical techniques to improve graft patency, late vein graft failure remains a significant problem. Moreover, there is a lack of pharmacological interventions proven to be effective in the treatment of late vein graft failure. A greater understanding of the molecular nature of the disease and the interactions between endothelial and smooth muscle cells as a result of alterations in local haemodynamics may assist with designing future beneficial pharmacological interventions. Venous endothelial cells (ECs) are physiologically adapted to chronic low shear stress; however, once the graft is implanted into the arterial circulation, they become suddenly exposed to acute high levels of shear stress. A small number of in vitro and ex vivo studies have demonstrated that acute high shear stress is associated with the activation of a pro-inflammatory profile in saphenous vein ECs, which may be mediated by mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways. The impact of acute changes in shear stress on venous ECs and the role of ECs in the development of intimal hyperplasia remains incomplete and is the subject of this review., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys., Methods: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery., Results: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups., Conclusions: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery., Clinical Trial Registration: http://www.controlled-trials.com , ISRCTN 23557269., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Coagulopathic bleeding is common after cardiac surgery and is associated with increased morbidity, mortality and healthcare costs. Implementation of blood management algorithms in which patients with severe bleeding undergo near-patient coagulation testing results in less overall bleeding and transfusion. However, it is unknown whether there is additional value from pre-emptive near-patient testing to predict whether severe bleeding will occur., Objectives: To evaluate how well a comprehensive panel of 28 near-patient platelet and viscoelastometry tests predict bleeding after cardiac surgery, compared to prediction using baseline clinical characteristics alone., Methods: Single-center, prospective cohort study in adults undergoing a range of cardiac surgery procedures. The primary outcome was clinical concern about bleeding (CCB), a composite of high blood loss (chest drain volume >600 mL within 6 hours), re-operation for bleeding or administration of a pro-haemostatic treatment directed by clinician judgement., Results: In 1833 patients recruited between March 2010 and August 2012, the median number of abnormal near-patient test results was 5/28 per patient (range 0-18). CCB occurred in 449/1833 patients (24.5%). The c-statistic for a predictive model for CCB using only baseline clinical characteristics ( baseline-only model) was 0.72 (95% CI 0.69-0.75). Addition of near-patient test results to this model ( baseline-plus-test model) improved the prediction of CCB (c-statistic 0.75 [0.72-0.77]), but increased the number of correctly classified patients by only 18 (0.98%)., Conclusions: Near-patient coagulation testing predicts bleeding in cardiac surgery patients, but offers little improvement in prediction compared to baseline clinical characteristics alone. trial registration: ISRNCTN 20778544 (http://www.isrctn.com/).

Background: Contemporary comparisons on coronary revascularization should take into account the state of the art percutaneous coronary intervention (PCI) with new generation everolimus-eluting stents (EESs) and coronary artery bypass grafting (CABG) with multiple arterial grafts (MAGs). We aimed to compare early outcomes and late survival after EES versus MAG in patients with multivessel coronary artery disease using a single centre institutional database., Methods: In an observational registry study, we identified 3787 patients with multivessel coronary disease. Of these 696 (18.3%) underwent PCI with EES and 3091 (81.7%) CABG with MAG. With the use of propensity-score matching, we identified 483 pairs for final comparison (C-statistic: 0.91)., Results: The two groups were comparable for 30-day mortality (1.6% versus 0.8% in the EES and MAG group respectively, P=0.38). Stroke was not observed in the EES group and it was 0.8% in the MAG group (P=0.13). After a mean follow-up of 3.1years, PCI with EES was associated with a higher risk of late death (HR 2.2; 95% CI 1.18-4.16; P=0.01)., Conclusions: In patients with multivessel coronary disease, CABG with multiple arterial grafts when compared with PCI with new generation drug eluting stent, was associated with significantly improved long-term survival. Further randomized studies are warranted to identify the best revascularization strategies in the current era., (Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Current randomized controlled trials (RCTs) comparing percutaneous coronary intervention with drug eluting stent (DES-PCI) with coronary artery bypass grafting (CABG) in multivessel disease are underpowered to detect a difference in hard clinical end-points such as mortality, myocardial infarction and stroke. We aimed to overcome this limitation by conducting a meta-analysis of contemporary RCTs., Methods: A systematic literature search was conducted for all RCTs comparing DES-PCI versus CABG in multivessel disease published through May 2015. Inverse variance weighting was used to pool data from individual studies (<1 favouring DES-PCI and >1 CABG favouring surgery)., Results: A total of five randomized trials including 4563 subjects were analysed. After an average follow-up of 3.4 years, DES-PCI was associated with a significantly increased risk of overall mortality (HR 1.51; 95%CI 1.23-1.84; P<0.001), MI (HR 2.02; 95%CI 1.57-2.58; P<0.001) and repeat revascularization (HR 2.54; 95%CI 2.07-3.11; P=<0.001). CABG marginally increased the risk of stroke (HR 0.70; 95%CI 0.50-0.98; P=0.04). The absolute risk reduction for all-cause mortality (3.3%) and myocardial infarction (4.3%) with CABG was larger than the absolute risk reduction for stroke (0.9%) with DES-PCI., Conclusion: In patients with multivessel coronary disease, CABG was found to be superior to DES-PCI by reducing the risk of mortality and subsequent myocardial infarction at the expense of a marginally increased risk of stroke., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Coronary artery bypass grafting (CABG) with conventional cardiopulmonary bypass (CPB) induces systemic inflammation. Miniaturized CPB may attenuate systemic inflammatory activation. The intracellular signaling pathways promoting inflammation in cardiac operations and the relative effects of CPB on these processes are uncertain. In this study, induction of reactive oxygen species (ROS) and activation of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK) within leukocytes, and leukocyte accumulation in cantharidin-induced blisters was compared in patients exposed to miniaturized CPB (mCPB) and those who underwent conventional CPB (cCPB)., Methods: Patients undergoing CABG were randomized to receive either cCPB (n = 13) or mCPB (n = 13). Blood samples were collected preoperatively and 5 times after initiating CPB (up to 5 hours) and analyzed by flow cytometry for intracellular markers of activation (ROS, p38-MAPK, and NF-κB phosphorylation)., Results: ROS in lymphocytes were elevated in cCPB compared with mCPB (p < 0.01), whereas ROS in granulocytes and monocytes were similar between groups. After initiation of CPB, p38-MAPK was higher in patients receiving cCPB compared with those receiving mCPB (p < 0.05). NF-κB phosphorylation in leukocyte subsets was similar in patients exposed to cCPB and those exposed to mCPB. Leukocyte accumulation in cantharidin-induced blisters, white cell counts, and serum C-reactive protein (CRP) was enhanced in response to cardiac operations, but no differences were observed between mCPB and cCPB groups. Postoperative serum creatinine levels were reduced in the mCPB group compared with the cCPB group (p < 0.05)., Conclusions: Both p38-MAPK activation and ROS were attenuated with the use of mCPB compared with cCPB, providing a potential mechanism for reduced inflammation in association with CPB miniaturization., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The hypothalamic-pituitary-adrenal (HPA) axis is a neuro-endocrine system that regulates circulating levels of glucocorticoid hormones. These hormones are vital for normal homeostasis and play a pivotal role in the response to stress. Levels of cortisol fluctuate throughout the day in a diurnal rhythm, underlying which is an ultradian rhythm of approximately hourly pulses, and this pulsatility directly affects transcriptional outcomes. Pulsatility is not the result of a 'pulse generator', but is inherent within the system as a result of negative feedback. These patterns of secretion change in both acute and chronic illness as a result of inflammatory mediators, splanchnic nerve output, and central nervous system control. Levels of cortisol in both normal and illness states are highly dynamic and so previously used static assessment tools for diagnosing corticosteroid related critical illness insufficiency (CRCI) are not likely to be useful. Therapeutic regimens have also failed so far, to take secretory patterns into account. In this review we look at the dynamic control and effects of glucocorticoids and frame in this context the current evidence surrounding steroid use in critical care and major surgery.

Background: Acute kidney injury after cardiac surgery is common, has no effective treatments, and is associated with adverse outcomes. The aim of this study was to determine whether administration of the phosphodiesterase-5 inhibitor sildenafil citrate (SDF) would prevent the development of post-cardiopulmonary bypass (CPB) acute kidney injury in swine., Methods: Adult pigs (n = 8 per group) were randomized to undergo sham procedure, CPB, or CPB plus administration of SDF, with recovery and reassessment at 24 hours., Results: Cardiopulmonary bypass resulted in a significant reduction in creatinine clearance relative to sham pigs (mean difference CPB versus sham, -47.9 mL/min; 95% confidence interval [CI]: -93.7 to -2.2; p = 0.039). This was prevented by the administration of SDF during CPB (mean difference CPB+SDF versus CPB, +55.6 mL/min; 95% CI: +6.5 to +104.7; p = 0.024). Cardiopulmonary bypass also resulted in a significant rise in the urinary biomarker interleukin-18 compared with sham procedures (mean difference 209.3 pg/mL; 95% CI: 120.6 to 298.1; p < 0.001) that was prevented by SDF administration. Post-CPB kidney injury was associated with vascular endothelial injury and dysfunction, reduced nitric oxide bioavailability, medullary hypoxia, cortical adenosine triphosphate depletion, inflammation, and evidence of proximal tubule epithelial cell stress manifest as phenotypic change. Administration of SDF to CPB pigs preserved nitric oxide bioavailability and prevented endothelial dysfunction, regional hypoxia, inflammation, and tubular changes., Conclusions: In this model, phosphodiesterase-5 inhibition using SDF prevented post-CPB acute kidney injury by the preservation of nitric oxide bioavailability, and warrants evaluation as a renoprotective agent in clinical trials., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Despite the exploration of a large number of disparate drugs in animal models and clinical trials, no pharmacological intervention, with the exception of aggressive lipid lowering therapy has reduced late vein graft failure in man. The importance of devising more effective strategies is exemplified by the enormous economic consequences of vein graft failure. Worldwide, there are currently more than 1,000,000 coronary artery bypass graft surgery (CABG) operations a year, the same number of patients undergoing infrainguinal bypass for vascular diseases of the lower limb. The pathophysiology of vein graft failure is complex, involving disparate factors that include adhesion of platelets and leukocytes, rheological forces, metalloproteinase expression, proliferation and migration of vascular smooth muscle cells, neointima formation, oxidative stress, hypoxia and neural re-organisation. Although this diverse etiology may seem to preclude any single drug type as being effective in mediating vein graft failure: one factor that is involved in every facet of vein graft pathobiology is endothelin-1 (ET-1). As such a single drug type (ET(A) antagonist) may prove to be the magic bullet in this scenario. Thus, in this review, we will consider the etiology of vein graft disease in relation to ET-1 and will then present an argument (with evidence) that specific ET(A) receptor antagonists constitute a potentially effective means of preventing vein graft failure., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: There is no accepted consensus on the definition of high-risk patients who may benefit from the use of intraaortic balloon pump (IABP) in coronary artery bypass grafting (CABG). The aim of this study was to develop a risk model to identify high-risk patients and predict the need for IABP insertion during CABG., Methods: From April 1996 to December 2006, 8,872 consecutive patients underwent isolated CABG; of these 182 patients (2.1%) received intraoperative or postoperative IABP. The scoring risk model was developed in 4,575 patients (derivation dataset) and validated on the remaining patients (validation dataset). Predictive accuracy was evaluated by the area under the receiver operating characteristic curve., Results: Mortality was 1% in the entire cohort and 18.7% (22 patients) in the group which received IABP. Multivariable analysis showed that age greater than 70 years, moderate and poor left ventricular dysfunction, previous cardiac surgery, emergency operation, left main disease, Canadian Cardiovascular Society 3-4 class, and recent myocardial infarction were independent risk factors for the need of IABP insertion. Three risk groups were identified. The observed probability of receiving IABP and mortality in the validation dataset was 36.4% and 10% in the high-risk group (score >14), 10.9% and 2.8% in the medium-risk group (score 7 to 13), and 1.7% and 0.7% in the low-risk group (score 0 to 6)., Conclusions: This simple clinical risk model based on preoperative clinical data can be used to identify high-risk patients who may benefit from elective insertion of IABP during CABG., (Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative atrial fibrillation is still a common complication in patients undergoing coronary artery bypass grafting. The aim of this study was to evaluate the effect of preoperative statin therapy on new onset of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting., Methods: Of 8,946 patients undergoing isolated coronary artery bypass grafting at the Bristol Heart Institute from April 1996 to September 2006, 6,321 (70.6%) received preoperative statins. Of these, 2,152 patients (statin group) were matched to a control group (no statin) by propensity score analysis., Results: Preoperative characteristics, number of distal anastomoses, and the use of off -pump procedures were similar in both groups. Hospital mortality was 1.3% (56 patients) with no difference between the two groups. Postoperative atrial fibrillation was significantly higher in the statin compared with the no statin group (411, 19.5%, versus 336; 15.8% respectively; p = 0.002). In a multivariate regression analysis, age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), pulmonary disease (OR, 1.42; 95% CI, 1.12-1.82), history of paroxysmal atrial fibrillation (OR, 3; 95% CI, 2.13 to 4.19), preoperative angiotensin-converting enzyme inhibitor therapy (OR, 1.26; 95% CI, 1.07 to 1.49), ejection fraction less than 0.30 (OR, 1.71; 95% CI, 1.22 to 2.38), emergency operations (OR, 4.5; 95% CI, 2 to 10.12), and preoperative statin treatment (OR, 1.31; 95% CI, 1.11 to 1.55) were all independent predictors of postoperative atrial fibrillation., Conclusions: Preoperative statin is associated with a significantly higher incidence of postoperative atrial fibrillation compared with no statin treatment in patients undergoing isolated coronary artery bypass grafting.

Objectives: Epidural anesthesia has been suggested to exert a protective effect against the inflammatory and stress responses associated with surgery. The aim of this study was to evaluate the impact of thoracic epidural anesthesia on myocardial cell damage, inflammatory, and stress responses in patients undergoing off-pump coronary artery bypass graft (OPCABG) surgery., Methods: Seventy-four patients (66 male [89%], mean age 65.2 years [SD 9.6]) undergoing OPCABG surgery were randomly assigned to receive either general anesthesia plus epidural (GAE [n = 36]) or general anesthesia only (GA [n = 38]). Troponin I, 8-isoprostane, cortisol, C3alpha, interleukin (IL)-6, IL-8, and IL-10 were measured preoperatively, at 30 minutes, and 4, 12, 24, and 48 hours postoperatively., Results: Baseline characteristics were similar in the two groups. One patient died in the GAE group, but no other major postoperative complications were recorded in either group. The IL-6 and IL-8 levels were lower in the GAE group (ratio 0.83, 95% confidence interval: 0.68 to 1.02; p = 0.070) than in the GA group (ratio 0.90, 95% confidence interval: 0.78 to 1.02; p = 0.090). The difference in levels of IL-10 between the GAE and GA groups varied over time (p greater, similar 0.001). The C3alpha, troponin I, 8-isoprostane, and cortisol release was similar in the two groups throughout (p > or = 0.12)., Conclusions: Thoracic epidural anesthesia does not provide any additional benefits in terms of reducing myocardial damage, inflammatory, and stress response compared with general anesthesia only in patients undergoing OPCABG surgery.

Background: We sought to investigate the effect of patient prosthesis mismatch on hemodynamic profile using dobutamine stress echocardiography, and to evaluate midterm survival of patients undergoing aortic valve replacement with 19-mm Perimount (Baxter Healthcare, Santa Ana, California) aortic prosthetic valves., Methods: Between December 1, 1999, and August 17, 2005, 147 patients (mean age, 76.8 +/- 5.51 years) had aortic valves replaced with 19-mm Perimount prostheses. Dobutamine stress echocardiography was performed in a subgroup of 24 patients (mean age, 76.6 +/- 5.60 years). Univariable predictors of peak transprosthetic gradient (PTG) under maximum stress, adjusted for resting PTG, were investigated by regression. Survival in the whole cohort was described, and univariable predictors of survival were investigated by Cox regression., Results: In the stress echocardiography subgroup, cardiac output (p < 0.0001), PTG (p < 0.0001), and effective orifice area index increased significantly (p = 0.002) under stress. Peak transprosthetic gradient under stress was strongly associated with PTG at rest (p < 0.0001). After controlling for PTG at rest, no other variables were associated with PTG under stress. In the whole cohort, mean duration of follow-up was 2.21 years; 23 patients died. Neither body surface area nor effective orifice area index was significantly associated with survival., Conclusions: The 19-mm Perimount aortic prosthesis has acceptable hemodynamic performance. Transvalvular gradients were within a clinically acceptable range, both at rest and under stress. These findings suggest that patient-prosthesis mismatch is unlikely to cause a clinically important problem when the prosthesis is used, which is consistent with survival experience in the whole cohort.

Background: Intermittent antegrade cold-blood cardioplegia followed by terminal warm-blood cardioplegic reperfusion or hot-shot is reported to reduce myocardial injury in the setting of coronary surgery. The efficacy of this cardioplegic technique in patients with left ventricular hypertrophy secondary to aortic stenosis remains uncertain., Methods: Thirty-six patients with left ventricular hypertrophy undergoing aortic valve replacement were prospectively randomized to cold-blood cardioplegia either alone (cold-blood cardioplegia group) or with retrograde hot-shot (hot-shot group). Reperfusion injury was assessed by measuring myocardial levels of adenosine triphosphate and lactate in left and right ventricular biopsies taken 5 minutes after institution of cardiopulmonary bypass and 20 minutes after removal of cross-clamp using high-performance liquid chromatography and enzymatic techniques. Myocardial injury was assessed by serial release of troponin I up to 48 hours postoperatively. Overall clinical outcome was prospectively collected., Results: Baseline and intraoperative characteristics were similar between groups. In the hot-shot group, there were no significant changes in the myocardial concentration of adenosine triphosphate and lactate in both left and right ventricular biopsies after reperfusion. In the cold-blood cardioplegia group, there was a trend to a fall in adenosine triphosphate levels in the left and right ventricular biopsies after reperfusion, but this reached statistical significance only in the right ventricle. Troponin I release was raised in both groups at 4 and 12 hours after surgery (p < 0.05), but did not reach levels of myocardial infarction., Conclusions: The terminal retrograde hot-shot reperfusion does not add any extra benefit to antegrade cold-blood cardioplegia in preventing myocardial injury in patients with left ventricular hypertrophy undergoing aortic valve replacement. Nevertheless, it appears to reduce ischemic stress in the right ventricle. There was no difference in clinical outcome between groups.

Background: The purpose of this study was to assess the prognostic effect of coronary collaterals on early and midterm clinical outcomes in patients undergoing first time isolated off-pump coronary artery bypass (OPCAB) surgery., Methods: Preoperative angiograms from 861 patients were evaluated to assess the presence and extent of coronary collaterals (Rentrop classification). Coronary collaterals (CC) were present in 485 (56.3%) patients (CC group). Patients with coronary collaterals had a higher incidence of preoperative myocardial infarction, lower ejection fraction, and higher Parsonnet scores compared with patients without coronary collaterals (no-CC group)., Results: Coronary collaterals were associated with myocardial protection during OPCAB surgery, as evidenced by a significantly lower incidence of intraoperative ST-segment changes (propensity matched cohort, p = 0.008). No other statistically significant differences in in-hospital outcomes were detected between the two groups. Five years after surgery patient survival was 84.8% (95% confidence interval [CI] 79.4 to 88.8) in the CC group compared with 89.2% (95% CI 84.4 to 92.6) in the no-CC group (p = 0.48). Cardiac-related event-free survival after 5 years was 50.6% (95% CI 43.5 to 57.3) in the CC group and 54.5% (95% CI 47.1 to 61.4) in the no-CC group (p = 0.96), with no significant differences between both groups, before or after risk adjustment, or when comparing propensity-matched cohort., Conclusions: Although patients with coronary collaterals had more extensive coronary artery disease, poor left ventricular function, and more cardiac risk factors than patients without collaterals, the early and midterm clinical outcome after OPCAB surgery was comparable between the two groups.

Background: After coronary artery bypass grafting procedures with saphenous vein, there is a protracted elevation of plasma homocysteine and copper. These interact to elicit endothelial dysfunction through promotion of superoxide. It has been suggested that angiogenesis and the formation of a neovasa vasorum is important in mediating vein graft patency. A novel in vitro model of angiogenesis in isolated pig saphenous veins was therefore developed to study the effect of homocysteine and copper and the role of superoxide on tubule growth, an index of angiogenesis., Methods: Two-millimeter rings of porcine saphenous veins were embedded in fibrin, incubated for 2 weeks with homocysteine and copper chloride, and tubules counted., Results: Tubule growth in cultured saphenous veins, which was inhibited by angiostatin, occurred in a time-dependent manner during a 14-day period. Copper chloride alone at 1 microM and 10 microM augmented microtubule formation, whereas homocysteine alone at up to 1 mM had no effect. Homocysteine and copper chloride together markedly inhibited microtubule formation. Significant inhibition of tubule formation and superoxide formation was elicited with inhibitors of nicotinamide adenine dinucleotide phosphate oxidase, mitochondrial respiration, and xanthine oxidase. Copper chloride augmented superoxide formation, but homocysteine had no effect. Homocysteine and copper chloride together also augmented superoxide formation., Conclusions: These data indicate that the increase in plasma homocysteine and copper may exert a deleterious effect on graft patency by preventing the formation of a neovasa vasorum, thereby promoting hypoxia. This effect is mediated by a mechanism independent of superoxide which actually promotes angiogenesis in this model.

In addition to its life-saving effect in hemorrhagic shock, transfusion of allogenic packed red blood cells can be beneficial in situations where a critically low hematocrit is contributing to a state of oxygen-supply dependency. These benefits are countered by the risks of transfusion-associated lung injury, transfusion-associated immunomodulation, and cellular hypoxia after RBC transfusion. The critical hematocrit is patient and organ specific, and varies intraoperatively according to the duration and temperature of bypass, as well as for a variable postoperative period. Future randomized studies must prospectively evaluate regional indicators of tissue oxygenation in transfusion algorithms.

Although ceruloplasmin (CP), a copper containing metalloenzyme, possesses antioxidant properties (e.g. ferroxidase activity), elevated circulating CP is associated with cardiovascular disease (CVD). This ambivalence is possibly due to the capacity of CP, via its coppers, to promote vasculopathic effects that include lipid oxidation, negation of nitric oxide bioactivity and endothelial cell apoptosis. In turn, these effects that are mediated by increased formation of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. There is also evidence that risk factors for CVD (in particular, diabetes mellitus and hyperhomocysteinaemia) may augment the vasculopathic impact of CP. In turn, it appears that ROS disrupt copper binding to CP, thereby impairing its normal protective function while liberating copper which in turn may promote oxidative pathology. The objective of this review, therefore, is to consider the epidemiology and pathophysiology of CP in relation to CVD, with particular emphasis on the relationship between CP and oxidative stress.

Background: The purpose of this study was to investigate the effect of preexisting atrial fibrillation on early and midterm clinical outcome in patients undergoing coronary surgery., Methods: All elective patients undergoing coronary artery bypass grafting surgery between April 1996 and September 2002 were investigated. Patients were grouped according to their preoperative cardiac rhythm: sinus rhythm (SR) or preexisting atrial fibrillation (AF). In-hospital clinical outcomes and 5-year patient survival and cardiac-related event-free survival were compared using regression methods to adjust for differences between the groups. In all, 5,092 patients were identified, 175 (3.4%) with a history of preexisting AF. These patients were older (median, 64 versus 68 years) and had higher Parsonnet scores (median, 4 versus 8) than the SR group. Previous myocardial infarction, cerebrovascular accident, hypertension, diabetes mellitus, renal impairment, peripheral vascular disease, ejection fraction less than 50%, previous surgery, congestive heart failure, and use of angiotensin-converting enzyme inhibitors were also more common in the AF group., Results: There were 60 in-hospital deaths (1.2%), with no difference between the two groups (odds ratio 1.02, 95% CI: 0.35 to 2.94). Atrial fibrillation patients were more likely to need intraoperative inotropes (p = 0.044), postoperative intra-aortic balloon pump (p = 0.038), and were less likely to be discharged within 6 days (p = 0.017). The risk of death in the 5 years after surgery was higher in the AF group (relative risk 1.49, 95% CI: 1.06 to 2.08, p = 0.020). In the AF group, 109 (62.2%) patients were cardioverted spontaneously by surgery, but only 69 (39.4%) remained in SR until discharge. Longer-term rhythm follow-up data were available for 48 of these 69 patients, and only 36 remained in SR at a median follow-up of 1,483 days (interquartile range, 1,120 to 2,209). Spontaneous conversion to SR after surgery did not confer a midterm survival benefit (p = 0.91)., Conclusions: Preexisting AF in patients undergoing coronary artery bypass graft surgery is not associated with increased in-hospital mortality and major morbidity; however, it is a risk factor for reduced 5-year survival. Spontaneous cardioversion to SR during surgery is transient in the majority of patients and is not associated with midterm survival benefit.

Background: The immature heart has a much greater dependence than the adult heart on amino acid transamination in determining its ischemic tolerance. Compared with adult hearts, experimental models of the immature heart have quantified higher resting concentrations of free amino acids (AA) which are depleted by acute hypoxia. However, we have found no clinical studies that have looked at the free AA profile of the immature human heart or the effects of cyanosis, age, and pathology upon this., Methods: One hundred eighty-one pediatric patients (37 cyanotic, 144 acyanotic) undergoing open-heart surgery were recruited. Myocardial biopsies were collected prior to ischemia and analyzed for free AAs (eg, glutamate, aspartate) using high-performance liquid chromatography. The effects of cyanosis, age, and pathology on amino acid concentrations were estimated by multiple regression modeling with and without controlling for diagnosis; the effects of age and pathology were estimated only in acyanotic children., Results: Alanine concentrations were about 20% higher in cyanotic than acyanotic patients (p = 0.04). Cyanosis was not associated with any other amino acid levels. In acyanotic patients, after controlling for diagnosis, concentrations of glutamate, aspartate, and alanine decreased from birth to about 8 to 10 years, then started to increase again (p < 0.05 for both linear and quadratic terms); concentrations of taurine and the branched chain AAs decreased steadily with increasing age (p < 0.05). There were significant effects of pathology on glutamate (p = 0.006), glutamine (p = 0.003), and branched chain AA (p = 0.004) levels., Conclusions: There is no evidence that chronic hypoxia depletes endogenous AAs. Young age is associated with higher resting AA levels.

Background: We investigated the efficacy of coronary surgery with or without cardiopulmonary bypass in protecting the function of the small intestine, liver, and pancreas., Methods: Patients were randomized to off-pump coronary artery bypass grafting (OPCAB) or coronary artery bypass grafting with cardiopulmonary bypass (CABG-CPB). Small intestine function was assessed by differential four sugars (O = methyl-D-glucose, D-xylose, L-rhamnose, and lactulose) permeability and absorption tests. Liver function was assessed by monoethylglycinexylidide/lidocaine ratios and by serial measurements of transaminases (aspartate transaminase and alanine-amino transferase), bilirubin, and alkaline phosphatase. Pancreatic function was assessed by serial measurements of insulin/glucagon ratio, amylase, and glucose. Forty patients were recruited (20 per group)., Results: Permeability and absorption were more impaired in the OPCAB group immediately after surgery, but returned to baseline levels in both groups by postoperative day 5 (interaction of surgery type and time; p = 0.05 and p = 0.02, respectively). Monoethylglycinexylidide/lidocaine ratios were not different in the two groups. Aspartate transaminase and alanine-amino transferase levels were higher in the CABG-CPB group for the first postoperative day, but levels converged by day 3 (interaction of surgery type and time; p < 0.0001 and p = 0.04, respectively). The bilirubin level for the OPCAB group overshot the CABG-CPB group at 36 hours before returning to a similar level 60 hours postoperatively. Amylase levels were higher in the CABG-CPB group than in the OPCAB group (1.17 times; p = 0.03); other markers of pancreatic function showed no differences between the groups., Conclusions: Early small intestine function is worse with OPCAB; all functions recover to similar levels in both groups by day 5. Conversely, pancreatic function is worse with the CABG-CPB group than with the OPCAB group. Hepatic metabolic function does not differ by type of surgery to the end of the operation. Postoperative hepatocellular injury was worse with the CABG-CPB group.

We report a case of posttraumatic aortic valve regurgitation and pseudoaneurysm of the aortic root diagnosed 22 months after a road traffic accident. The surgical treatment consisted of exclusion of the pseudoaneurysm with direct closure of the entry tear in the right coronary sinus followed by insertion of a Toronto stentless prosthesis (St. Jude Medical, St. Paul, MN). This surgical approach aimed to cover the repaired entry tear ensuring exclusion of the site. Recovery was uneventful and 12 month follow-up was unremarkable.

Background: The aim of this study was to compare early and mid-term outcome in patients undergoing off-pump coronary artery bypass surgery who have had complete revascularizations and incomplete revascularizations (IRs)., Methods: Patient and operative data were collected prospectively for all patients who had off-pump coronary artery bypass surgery. Patients with multivessel disease were classified as having IR if the number of diseased coronary systems (left anterior descending coronary artery, circumflex and right coronary artery) exceeded the number of distal anastomoses. In-hospital outcomes, survival, and event-free survival were compared between patients with complete revascularization and IR using propensity scores to take account of differences in prognostic factors., Results: There were 1,479 off-pump coronary artery bypass surgery patients between April 1996 and December 2002 (30% of all coronary artery bypass graft patients), and 16.0% (237 patients) had IRs. Patients with IRs tended to be older and were female, had more extensive disease, worse dyspnea, a higher Parsonnet score, poorer ejection fraction, congestive cardiac failure, asthma or chronic obstructive airways disease, and previous cardiac surgery. The adjusted hazard ratio for patient survival with IRs versus complete revascularizations was 1.56 (95% confidence interval, 1.19 to 2.06; p = 0.001). Analyses for multiple time periods confirmed that IRs had a significantly increased risk of death, but also that the risk disappeared after the first 4 to 6 months of follow-up (p < 0.0001)., Conclusions: Compared with off-pump coronary artery bypass surgery patients with complete revascularizations, those with IRs have reduced survival, but only in the first 4 to 6 months after surgery. Patients' preoperative condition, rather than IR itself, may explain these findings because IRs should have mid-term as well as early effects.

As the risk profile of patients considered for surgical revascularization worsens, the cumulative benefit of off-pump coronary artery bypass (OPCAB) over conventional coronary artery bypass grafting, in terms of lower morbidity and reduced healthcare costs, may increase. There is still resistance to the introduction of OPCAB surgery however, its practice is variable and surgical residents are rarely trained in these techniques. This article considers how the learning curve in OPCAB may be negotiated and prospectively monitored to ensure quality control. The evidence suggests that situations in which suitable senior expertise exists, OPCAB surgery can be introduced into surgical practice and safely taught to trainees without detriment to patients. This is achieved by a progressive increase in the complexity of the case mix and careful early supervision. The introduction of OPCAB has coincided with the increasing use of control charts as quality control tools. Performance monitoring provides reassurance that patients are not being put at risk during the introduction of OPCAB; control chart methods can be used prospectively for real time performance monitoring by consultant surgeons and residents alike. These techniques may ultimately be used to determine proficiency and accreditation. Increasing use of parallel training techniques, the development of structured training programs that encompass OPCAB and other new technologies in cardiac surgery, coupled with objective performance monitoring are warranted to meet the needs of a changing patient population.

Exaggerated vasospasm, platelet activation, and early graft occlusion are significant barriers to successful coronary artery bypass grafting (CABG). Interestingly, vascular smooth muscle and platelets are predominant sources of type-5 phosphodiesterase (PDE5) in the body, and this enzyme is specifically inhibited by PDE5 inhibitors (eg, sildenafil citrate). Together with endogenous nitric oxide, sildenafil can induce pulmonary and coronary vasodilation, precondition the myocardium, reduce platelet activation, and potentially reduce early graft occlusion. Currently, there are no published clinical trials investigating sildenafil in coronary surgery. Recent studies on the potential use of sildenafil strongly support its beneficial effects in a wide range of patients with cardiovascular diseases. Therefore, we sought to review the literature, explore the current hypothesis that the use of sildenafil in coronary surgery patients can be beneficial, and attempt to define its potential place in the setting of CABG.

Background: The purpose of this study is to investigate the effect of cardiopulmonary bypass (CPB) temperature on myocardial reperfusion injury, oxidative stress, and inflammatory response in pediatric open heart surgery., Methods: Fifty-nine children (median age 78 months; interquartile range, 39-130) undergoing correction of simple congenital heart defects were randomized to receive either hypothermic (28 degrees C) or normothermic (35-37 degrees C) CPB. Troponin I and 8-isoprostane, complement activation C3a, interleukin (IL) -6, -8, and -10, were measured preoperatively, on removal of the aortic cross clamp, 30 minutes, 6, and 24 hours postoperatively., Results: Troponin I and 8-isoprostane were significantly raised, compared to baseline, in both groups, and remained high at 24 hours. Overall, troponin I and 8-isoprostane levels were 37% and 84% higher in the hypothermic than in the normothermic group, respectively (ratio 1.37, 95% CI 1.00 to 1.88, p = 0.053 and 1.84, 95% CI 1.22 to 2.78, p = 0.0045, respectively), and there was no evidence to suggest the treatment effect changed significantly over the time points measured (p = 0.63). Adjusting for aortic cross-clamp time reduced the effect of hypothermia on troponin (p = 0.18) but not on 8-isoprostane levels (p = 0.0028). The C3a, IL-6, and IL-8 release was similar in the two groups. The IL-10 release between the groups changed over time (p = 0.059) and examining differences at individual time points highlighted a statistically significant difference at the end of the cross-clamp time (p = 0.0079)., Conclusions: Normothermic CPB is associated with reduced oxidative stress compared with hypothermic CPB, and similar myocardial reperfusion injury and whole body inflammatory response, in children undergoing open heart surgery. A larger study with clinical outcomes as primary end points is now warranted.

Background: The aim of our study was to investigate the independent effect of preoperative exposure to aspirin, heparin, and clopidogrel on early clinical outcomes of in-hospital referral patients undergoing first time coronary artery bypass graft (CABG) surgery., Methods: Outcomes for in-hospital referrals for CABG between January 2001 and January 2002 were prospectively recorded. Exposure to aspirin, heparin, and clopidogrel during the 5 days before surgery was recorded, and their effect on outcome was explored using multiple regression methods. The effect of clopidogrel given within 48 hours before surgery versus stopped at least 48 hours before the operation was also investigated., Results: In-hospital referral patients represented 40% (473 of 1,185) of the total surgical population; 304 (64.7%) were prescribed aspirin, 116 (24.7%) heparin, 91 (19.4%) clopidogrel, and 133 (28.3%) had all anticoagulants stopped 5 days before surgery. In-hospital mortality was 2.3% (95% confidence interval [CI]: 1.1 to 4.1) and was highest among those exposed to clopidogrel (odds ratio 16.9, 95% CI: 2.10 to 136, p = 0.008). Seven of the 11 deaths occurred in patients given clopidogrel. Postoperative intraaortic balloon pump, arrhythmia, reintubation, and stroke were all significantly more common when clopidogrel was prescribed (relative risk estimates all greater than 1.5, p values all < or = 0.021). Blood loss was 37% higher in the patients given clopidogrel (95% CI: +3% to +82%, p = 0.033). Clopidogrel patients were more likely to need a reoperation for bleeding (p < 0.001) and require transfusions (p < or = 0.015). Intubation time and hospital stay were also longer (p = 0.021 and p = 0.019, respectively). Heparin was also associated with longer hospital stay (p < 0.001) and aspirin use with reduced stay (p = 0.041), but for all other outcomes, no association with aspirin or heparin use was found. Comparison of subgroups of clopidogrel patients suggested mortality was highest when clopidogrel was given in the 48 hours before surgery., Conclusions: Our study suggests that among in-hospital referral patients, preoperative exposure to clopidogrel within 5 days before CABG may increase early mortality and morbidity, and that the mortality risk is greatest when the drug is given within 48 hours of surgery.

Objectives: The development of neointimal hyperplasia with subsequent atherosclerotic deposition has been proposed to cause most late vein graft failures. Our unit has previously demonstrated that placement of a macroporous, loose-fitting polyester external stent prevents neointimal thickening in porcine vein grafts, and has been proposed as a therapeutic strategy to prevent late vein graft failure. To reduce any potential long-term complications of the permanent polyester stent, a study was undertaken to investigate the effect of a biodegradable external stent on porcine vein graft thickening at 1 month and to identify its longer term effects at 6 months., Methods: Bilateral saphenous vein to common carotid artery interposition grafting was performed in Large White pigs (25-32 kg; n = 6 per time course group) according to UK Home Office guidelines. A commercially constructed loose-fitting 8-mm-diameter polyglactin stent was placed externally around the vein graft on one side, and the contralateral side remained unstented to serve as control. The external stent was designed to biodegrade and hence disappear within 90 days. Grafts were left in situ for 1 month in 1 group of animals, and for up to 6 months in the other group, before explantation. Graft morphometric features were assessed with computer-aided planimetry., Results: At 1 month the vein grafts fitted with the polyglactin stent demonstrated a statistically significant decrease in neointimal thickening (0.038 mm; interquartile range [IQR], 0.035-0.039 mm) compared with the unstented control grafts (0.13 mm; IQR; 0.11-0.19; P = .0012), and also in medial thickening (0.09 mm; IQR, 0.086-0.093) compared with unsheathed control grafts (0.302 mm; IQR, 0.272-0.414; P = .0012). The 6-month polyglactin stented grafts also demonstrated a statistically significant reduction in neointimal thickening (0.049 mm; IQR, 0.047-0.07; P = .0012) compared with control grafts (0.178 mm; IQR, 0.164-0.19), and also in medial thickening (0.105 mm; IQR, 0.095-0.143) compared with unstented grafts (0.421 mm; IQR, 0.35-0.44; P = .0012, Mann-Whitney U test)., Conclusion: The loose-fitting biodegradable polyglactin external stent reduces porcine vein graft thickening at 1 month, which persists in the long term, even after degradation of the stent itself. This effective removal of the stent may therefore reduce the long-term risks for infection and mechanical complications associated with implanted prosthetic material while still eliciting the primary objective of preventing graft thickening over the long term. Biodegradable external stents therefore have potential advantages over permanent stent material in clinical application., Clinical Relevance: Arteriovenous bypass graft failure has a huge economic effect on health care resources, and a devastating effect o the patient. The attenuation of vein wall thickening, with subsequent luminal narrowing and occlusion, is a major goal in improving the longevity of the venous graft, to reduce secondary percutaneous and surgical interventions. The biodegradable external stent demonstrated in this study has possible clinical applications in bypass procedures with autogenous venous tissue, and represents a novel approach to ameliorating the problem of intimal hyperplasia that plagues these grafts.

Background: Experimental models have established numerous myocardial metabolic changes with chronic hypoxia and maturation. We conducted this study to specifically look at the effects of cyanosis, age, and pathology upon the basal metabolic state of the immature human heart., Methods: One hundred and eighty-one pediatric patients (37 cyanotic, 144 acyanotic) undergoing open heart surgery were recruited. A myocardial biopsy was collected before ischemia and analyzed for adenine nucleotides, purines, and lactate. The effect of cyanosis was estimated by an analysis of age-matched pairs of children with either ventricular septal defects or tetralogy of Fallot, and by multiple regression modeling. The effects of age and pathology were estimated in acyanotic children also by multiple regression modeling (adjustments were made for baseline differences)., Results: The only effect of cyanosis was for lactate where the paired t test, and unadjusted and adjusted regression analyses were all consistent (ranging from 1.33 to 1.48 times higher in cyanotic than acyanotic children). The concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) declined with age, whereas the ATP/ADP ratio increased; these associations remained significant even in the adjusted regression analysis. None of the effects of acyanotic pathology were highly significant (p < 0.01), implying that few important metabolic differences were attributable to pathology., Conclusions: Cyanosis and age are important factors that determine the basal metabolic state of the pediatric heart. Cyanotic patients have higher myocardial lactate concentrations, whereas young age is associated with lower ATP/ADP ratios and higher adenine nucleotide levels.

Left internal mammary artery to left anterior descending coronary artery bypass grafting integrated with percutaneous coronary angioplasty (hybrid procedure) offers multivessel revascularization with minimal morbidity in high-risk patients. This is caused in part by the avoidance of cardiopulmonary bypass-related morbidity and manipulation of the aorta coupled with minimally invasive techniques. Hybrid revascularization is currently reserved for particularly high-risk patients or those with favorable anatomic variants however, largely because of the emergence of off-pump coronary artery bypass grafting, which permits more complete multivessel revascularization, with low morbidity in high-risk groups. The wider introduction of hybrid revascularization is limited chiefly by the high number of repeat interventions compared with off-pump coronary artery bypass grafting, which occurs because of the target vessel failure rate of percutaneous coronary intervention. Other demerits are the costs and logistic problems associated with performing two procedures with differing periprocedural management protocols. Recently, drug-eluting stents have reduced the need for repeat intervention after percutaneous coronary intervention, and this has raised the possibility that the results of hybrid revascularization may now equal or even better those of off-pump coronary artery bypass grafting. Although undoubtedly effective at reducing in-stent restenosis, drug-eluting stents will not address the issues of incomplete revascularization or the logistic problems associated with hybrid. Uncertainty regarding the long-term effectiveness of drug-eluting stents in many patients, as well as their high cost when compared with those of off-pump coronary artery bypass grafting surgery, also militates against the wider introduction of hybrid revascularization.