Statin loading before coronary artery bypass grafting: a randomized trial.

AIMS: Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. METHODS AND RESULTS: This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74-1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69-1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

Redo heart transplantation in a high-risk patient due to severe aortic regurgitation and accompanying right ventricular failure after LVAD implantation and temporary RVAD support.

BACKGROUND: We report a 62-year-old patient who received redo-orthotopic heart transplantation due to worsening severe aortic regurgitation after 19 months of continuous flow left ventricular assist device  (LVAD) (cf-LVAD) and temporary right ventricular assist device (RVAD) support for 1 month. CASE REPORT: The patient received a heartware LVAD (heartware ventricular assist device) and annuloplasty of the tricuspid valve due to end-stage heart failure (as a consequence of dilated cardiomyopathy) and severe tricuspid regurgitation in addition to right-sided extracorporeal membrane oxygenation (ECMO) implantation. Postoperatively due to the inability to wean the implanted ECMO, a temporary RVAD was implanted after which the patient's condition improved so that it had been explanted later and the patient was discharged after 9 months. In immediate postoperative echo, minimal aortic regurgitation was noted but in the follow-up transthoracic echocardiograms, there was a gradual increase in the severity of aortic regurgitation with worsening both right and left ventricular functions. Transcatheter aortic valve implantation was not an option due to unfavorable anatomical issues. That's why the patient was listed for urgent heart transplantation, performed 19 months after the LVAD implantation. The postoperative course was complicated due to acute renal failure. After recompensation, dialysis, and intensive physiotherapy, the patient could be discharged home after 3 months. CONCLUSION: Severe aortic regurgitation is a recognizable complication after cf-LVAD implantation which in our case was managed successfully with orthotopic heart transplantation in this high-risk patient.

Long-Term Outcomes after Thoracic Endovascular Aortic Repair Using Chimney Grafts for Aortic Arch Pathologies: 10 Years of Single-Center Experience.

BACKGROUND: This study reports the early- and long-term outcomes of the thoracic endovascular aortic repair using the Chimney-Graft technique (ChTEVAR) for the treatment of aortic arch pathologies. METHODS: From January 2010 to December 2019, patients who underwent aortic ChTEVAR technique in our institution were included. Early, mid, and long-term outcomes in this group of patients were evaluated. Patient follow-up data were obtained by imaging follow-up that are routinely performed after 3-6 months following initial surgery and then at yearly intervals. RESULTS: Aortic arch repair with a ChTEVAR was performed in 54 patients. The 30-day mortality was 18.5% (n = 10). All-cause 30-day mortality was higher in the subgroup of patients operated urgently (33% vs. 14%) without a significant difference (P = 0.141). Permanent neurological deficit (PND) was observed in 15% (8/54 patients); stroke in 11% (6/54), and paraplegia 4% (2/54). During follow-up the primary and primary-assisted chimney-graft patency was 96.8% and 97.8%, respectively. The multivariate analysis identified the age >70 years and the aortic diameter as independent risk factors for elevated mortality during the follow-up (P = 0.015 and 0.001, respectively). The PND was an independent predictor for 30-day mortality (P = 0.014, hazard ratio 13.5, 95% confidence interval 1.7-106.6). CONCLUSIONS: The ChTEVAR has noninferior results to other open and endovascular aortic arch repair methods with an acceptable long-term survival especially in elective procedures.

Preoperative Statin Therapy for Atrial Fibrillation and Renal Failure after Cardiac Surgery.

BACKGROUND: Performing cardiac surgery in patients with cardiovascular risk factors incorporates a steady risk for the development of postoperative complications. Perioperative statin intake was associated with an improvement of perioperative outcomes in these patients. However, the European Association for Cardio-Thoracic Surgery guidelines regarding the perioperative statin treatment were changed recently due to large studies reporting about relevant adverse effects related to statin therapy. METHODS: All relevant databases were searched including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials. Various registries were screened (National Research Register, the ClinicalTrials.gov, and gray literature) with search on online conference indices of relevant scientific meetings. No language restrictions were applied. RESULTS: We identified 10 randomized controlled studies summarizing 3,468 participants undergoing various kinds of cardiac surgical procedures. All included studies presented with marked differences regarding study design. Pooled analysis indicated that statin pretreatment was associated with a formally reduced incidence of postoperative atrial fibrillation (AF) (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.39-1.00; p = 0.05) but with an increased incidence of renal failure (OR 1.20, 95% CI 1.01-1.44; p = 0.04) compared with control. Substantial heterogeneity was observed among studies reporting about AF. CONCLUSION: Current but sparse evidence reveals that statin pretreatment is associated with a higher rate of postoperative renal failure compared with control therapy but is ineffective to substantially reduce postoperative AF. Given the relevant heterogeneity among included studies, statin pretreatment cannot be generally recommended.

Rapid Deployment Aortic Valve Replacement with the Perceval S and Intuity Elite.

BACKGROUND: Rapid deployment aortic valve replacement (RDAVR) has emerged as an alternative to conventional aortic valve replacement. This single-center study retrospectively analyzed clinical outcomes and hemodynamic performance of the Perceval S (LivaNova) and Intuity Elite (Edwards LifeSciences) rapid deployment valves (RDVs) in a propensity score matched patient cohort. METHODS: A total of 372 consecutive patients with symptomatic aortic valve stenosis underwent RDAVR between 2012 and 2018 at our institution. The Intuity Elite (INT group) and Perceval S (PER group) were implanted in 251 and 121 patients, respectively. After 1:1 propensity score matching for relevant preoperative comorbidities, 107 patient pairs were compared with respect to relevant perioperative data including hemodynamic parameter, postoperative pacemaker implantation, and 30-day all-cause mortality. RESULTS: Propensity score matching resulted in balanced characteristics between groups. Cardiopulmonary bypass and aortic cross-clamp time did not differ between groups, but more patients in the INT group received coronary artery bypass grafting compared with the PER group (56 vs. 42%; p = 0.055). Thirty-day mortality (4.7 vs. 2.2%) and need for permanent pacemaker implantation (7 versus 4.4%) were comparable between the INT and PER groups for isolated AVR and also for combined procedures, respectively. Cerebrovascular events showed comparable low rates for both RDVs (INT group [1.9%] vs. PER group [2.8%]). Indexed effective orifice area was higher in the INT group (0.90 vs. 0.82 cm2/m2) and coupled to a lower peak (17 ± 7 vs. 22 ± 8) and mean (10 ± 5 vs. 12 ± 4) pressure gradients compared with the PER group. CONCLUSIONS: Our propensity score analysis in AVR patients showed good hemodynamic characteristics with comparable 30-day mortality rate and complications rates for both investigated RDVs.

Higher incidence of perivalvular abscess determines perioperative clinical outcome in patients undergoing surgery for prosthetic valve endocarditis.

BACKGROUND: Cardiac surgery for prosthetic valve endocarditis (PVE) is associated with substantial mortality. We aimed to analyze 30-day and 1-year outcome in patients undergoing surgery for PVE and sought to identify preoperative risk factors for mortality with special regard to perivalvular infection. METHODS: We retrospectively analyzed data of 418 patients undergoing valve surgery for infective endocarditis between January 2009 and July 2018. After 1:1 propensity matching 158 patients (79 PVE/79 NVE) were analyzed with regard to postoperative 30-day and 1-year outcomes. Univariate and multivariable analyses were performed to identify potential risk factors for mortality. RESULTS: 315 patients (75.4%) underwent surgery for NVE and 103 (24.6%) for PVE. After propensity matching groups were comparable with regard to preoperative characteristics, clinical presentation and microbiological findings, except a higher incidence of perivalvular infection in patients with PVE (51.9%) compared to NVE (26.6%) (p = 0.001), longer cardiopulmonary bypass (166 [76-130] vs. 97 [71-125] min; p < 0.001) and crossclamp time (95 [71-125] vs. 68 [55-85] min; p < 0.001). Matched patients with PVE showed a 4-fold increased 30-day mortality (20.3%) in comparison with NVE patients (5.1%) (p = 0.004) and 2-fold increased 1-year mortality (PVE 29.1% vs. NVE 13.9%; p = 0.020). Multivariable analysis revealed perivalvular abscess, sepsis, preoperative AKI and PVE as independent risk factors for mortality. Patients with perivalvular abscess had a significantly higher 30-day mortality (17.7%) compared to patients without perivalvular abscess (8.0%) (p = 0.003) and a higher rate of perioperative complications (need for postoperative pacemaker implantation, postoperative cerebrovascular events, postoperative AKI). However, perivalvular abscess did not influence 1-year mortality (20.9% vs. 22.3%; p = 0.806), or long-term complications such as readmission rate or relapse of IE. CONCLUSIONS: Patients undergoing surgery for PVE had a significantly higher 30-day and 1-year mortality compared to NVE. After propensity-matching 30-day mortality was still 4-fold increased in PVE compared to NVE. Patients with perivalvular abscess showed a significantly higher 30-day mortality and perioperative complications, whereas perivalvular abscess seems to have no relevant impact on 1-year mortality, the rate of readmission or relapse of IE.

Single center experience with patients on veno arterial ECMO due to postcardiotomy right ventricular failure.

OBJECTIVES: Right ventricular (RV) failure is associated with poor outcome and increased mortality in cardiac surgery. Aim of our study was to analyze the outcome of veno arterial extracorporeal membrane oxygenation (va ECMO) therapy in patients with isolated RV failure in postcardiotomy cardiogenic shock (PCS) and to evaluate risk factors associated with 30-day-mortality. METHODS: Between August 2006 until August 2016, 64 consecutive patients with va ECMO therapy due to fulminant RV failure in PCS were identified and included in this retrospective observation. Further, outcome data and a comparison of va ECMO survivors and nonsurvivors was conducted. RESULTS: The mean age of the patient cohort was 63 ± 14 years. Patients were treated with va ECMO for 79 ± 61 hours. Twenty-eight patients (44%) were successfully weaned off ECMO support. Overall 30-day-mortality was 88% (56/64). Hemoglobin concentration before ECMO implantation, maximum rise of muscle-brain type creatine kinase during ECMO therapy, as well as lactic acid concentration 24 hours after initiation of va ECMO therapy were predictive for 30-day mortality. CONCLUSION: ECMO therapy in RV failure due to PCS is shown to be associated with an excessive mortality. Regarding our data, va ECMO might only be an appropriate short-term mechanical assist device separating patients form cardiopulmonary bypass with an acceptable weaning rate. Particularly, in case of failed hemodynamic recovery of the right heart on va ECMO, direct RV bypass systems might function as a bailout option. Additionally, cardiac enzymes and lactic acid might provide valuable information in meeting therapy-related decisions.

Managing Traps and Pitfalls During Initial Steps of an ECMO Retrieval Program Using a Miniaturized Portable System: What Have We Learned From the First Two Years?

The aim of this study was to provide early and mid-term results of the newly established extracorporeal membrane oxygenation (ECMO) retrieval service in a tertiary cardiothoracic center using the miniaturized portable Cardiohelp System (Maquet, Rastatt, Germany). A particular attention was paid to organizational and logistic specifics as well as challenges and pitfalls associated with initial phase of the program. From January 2015 until January 2017 a heterogenic group of 28 consecutive patients underwent ECMO implantation in distant hospitals for acute cardiac, pulmonary or combined failure as a bridge-to-decision and were subsequently transported to our institution. Each cannulation was performed bedside on intensive care units (ICU) using the Seldinger's technique. Early outcomes and mid-term overall survival with up to two-year follow-up along with the impact of ongoing cardiopulmonary resuscitation (CPR) on outcome were presented. Also, changes in hemodynamics and tissue perfusion factors 24 h after ECMO implantation were evaluated. ECMO implantations were performed in 15 distant departments with the median distance of 23(10;40) (maximum 60) km. A total of 15 patients (54%) were cannulated under CPR with the median duration of 30(20;110) (maximum 180) min. After 24 h of support there were significant improvements in SvO2 (P = 0.021), mean arterial pressure (P = 0.027), FiO2 (P = 0.001), lactate (P = 0.001), and pH (P < 0.001). The mean ECMO support duration was 96 ± 100 (maximum 384) hours, whereas 11 patients (40%) were weaned off support and discharged from hospital. Overall cumulative survival in patients without the need for CPR was 61.5% at one week and 38.5% at 1 month, 6 month, and 1 year, whereas patients requiring CPR survived in 40% at one week, and 33.3% at 1 month, 6 month, and 1 year (Log-Rank (Mantel-Cox) P = 0.374, Breslow (Generalized Wilcoxon) P = 0.162). Our initial experience shows that launching new ECMO retrieval programs in centers with sufficient ICU capacities and local ECMO experience can be feasible and associated with acceptable "real world" results despite the initial learning curve. Rapid logistical organization and team flexibility are the key points to ensure comparable survival of patients requiring prolonged CPR.

Statin Therapy in Patients Undergoing Coronary Artery Bypass Grafting for Acute Coronary Syndrome.

BACKGROUND: This study evaluates whether preoperative statin therapy improves clinical outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS). METHODS: A total of 1,151 patients undergoing CABG for ACS were prospectively entered into the North-Rhine-Westphalia surgical myocardial infarction registry and subdivided into two groups according to their preoperative statin status (statin naive vs. statin group). A logistic regression model was employed to analyze the impact of a statin therapy and dose for the endpoints in-hospital mortality and major adverse cardiac events (MACE). RESULTS: Demographics, pre- and intraoperative data of the statin-naive group (n = 208; 18%) and statin-treated group (n = 943, 82%) did not differ. In-hospital mortality (12.6 vs. 6.3%, p = 0.002) and MACE rates (22.1 vs. 9.7%, p < 0.001) were significantly higher in statin naive when compared with statin-treated patients with ACS, respectively. Mevalonic acid revealed that both low- and high-dose statin treatment was associated to a reduction in in-hospital mortality and MACE, without a dose-dependent statin effect. CONCLUSION: Statin therapy in patients with ACS undergoing CABG reduces in a dose-independent manner in-hospital mortality and MACE.

Remote ischaemic preconditioning for coronary artery bypass grafting (with or without valve surgery).

BACKGROUND: Despite substantial improvements in myocardial preservation strategies, coronary artery bypass grafting (CABG) is still associated with severe complications. It has been reported that remote ischaemic preconditioning (RIPC) reduces reperfusion injury in people undergoing cardiac surgery and improves clinical outcome. However, there is a lack of synthesised information and a need to review the current evidence from randomised controlled trials (RCTs). OBJECTIVES: To assess the benefits and harms of remote ischaemic preconditioning in people undergoing coronary artery bypass grafting, with or without valve surgery. SEARCH METHODS: In May 2016 we searched CENTRAL, MEDLINE, Embase and Web of Science. We also conducted a search of ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We also checked reference lists of included studies. We did not apply any language restrictions. SELECTION CRITERIA: We included RCTs in which people scheduled for CABG (with or without valve surgery) were randomly assigned to receive RIPC or sham intervention before surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy. We calculated mean differences (MDs), standardised mean differences (SMDs) and risk ratios (RR) using a random-effects model. We assessed quality of the trial evidence for all primary outcomes using the GRADE methodology. We completed a 'Risk of bias' assessment for all studies and performed sensitivity analysis by excluding studies judged at high or unclear risk of bias for sequence generation, allocation concealment and incomplete outcome data. We contacted authors for missing data. Our primary endpoints were 1) composite endpoint (including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both) assessed at 30 days after surgery, 2) cardiac troponin T (cTnT, ng/L) at 48 hours and 72 hours, and as area under the curve (AUC) 72 hours (µg/L) after surgery, and 3) cardiac troponin I (cTnI, ng/L) at 48 hours, 72 hours, and as area under the curve (AUC) 72 hours (µg/L) after surgery. MAIN RESULTS: We included 29 studies involving 5392 participants (mean age = 64 years, age range 23 to 86 years, 82% male). However, few studies contributed data to meta-analyses due to inconsistency in outcome definition and reporting. In general, risk of bias varied from low to high risk of bias across included studies, and insufficient detail was provided to inform judgement in several cases. The quality of the evidence of key outcomes ranged from moderate to low quality due to the presence of moderate or high statistical heterogeneity, imprecision of results or due to limitations in the design of individual studies.Compared with no RIPC, we found that RIPC has no treatment effect on the rate of the composite endpoint with RR 0.99 (95% confidence interval (CI) 0.78 to 1.25); 2 studies; 2463 participants; moderate-quality evidence. Participants randomised to RIPC showed an equivalent or better effect regarding the amount of cTnT release measured at 72 hours after surgery with SMD -0.32 (95% CI -0.65 to 0.00); 3 studies; 1120 participants; moderate-quality evidence; and expressed as AUC 72 hours with SMD -0.49 (95% CI -0.96 to -0.02); 3 studies; 830 participants; moderate-quality evidence. We found the same result in favour of RIPC for the cTnI release measured at 48 hours with SMD -0.21 (95% CI -0.40 to -0.02); 5 studies; 745 participants; moderate-quality evidence; and measured at 72 hours after surgery with SMD -0.37 (95% CI -0.59 to -0.15); 2 studies; 459 participants; moderate-quality evidence. All other primary outcomes showed no differences between groups (cTnT release measured at 48 hours with SMD -0.14, 95% CI -0.33 to 0.06; 4 studies; 1792 participants; low-quality evidence and cTnI release measured as AUC 72 hours with SMD -0.17, 95% CI -0.48 to 0.14; 2 studies; 159 participants; moderate-quality evidence).We also found no differences between groups for all-cause mortality after 30 days, non-fatal myocardial infarction after 30 days, any new stroke after 30 days, acute renal failure after 30 days, length of stay on the intensive care unit (days), any complications and adverse effects related to ischaemic preconditioning. We did not assess many patient-centred/salutogenic-focused outcomes. AUTHORS' CONCLUSIONS: We found no evidence that RIPC has a treatment effect on clinical outcomes (measured as a composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both, assessed at 30 days after surgery). There is moderate-quality evidence that RIPC has no treatment effect on the rate of the composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke assessed at 30 days after surgery, or both. We found moderate-quality evidence that RIPC reduces the cTnT release measured at 72 hours after surgery and expressed as AUC (72 hours). There is moderate-quality evidence that RIPC reduces the amount of cTnI release measured at 48 hours, and measured 72 hours after surgery. Adequately-designed studies, especially focusing on influencing factors, e.g. with regard to anaesthetic management, are encouraged and should systematically analyse the commonly used medications of people with cardiovascular diseases.

Preoperative intra-aortic balloon pump use in high-risk patients prior to coronary artery bypass graft surgery decreases the risk for morbidity and mortality-A meta-analysis of 9,212 patients.

AIMS: Prophylactic intra-aortic balloon pump (IABP) support for high-risk patients before coronary artery bypass grafting (CABG) is controversial. This meta-analysis sought to determine the current role of preoperative IABP support. METHODS: We performed a meta-analysis of randomized (RCT) and observational trials (OT) that fulfilled the following criteria: (1) Group comparison of patients with prophylactic IABP implantation before CABG with a control group; (2) reporting at least one desired clinical endpoint, including all-cause mortality, myocardial infarction, cerebrovascular accident (CVA), and renal failure. Pooled treatment effects (odds ratio [OR] or weighted mean difference, and 95% confidence intervals [95%CI]) were assessed using a fixed or random effects model. RESULTS: A total of 9,212 patients from 23 studies (7 RCT, 16 OT) were identified after a literature search of major databases using a predefined keyword list. Absolute risk reduction for mortality in RCTs was 4.4% (OR 0.43; 95%CI 0.25-0.73; p = 0.0025). Prophylactic IABP use before CABG surgery also decreased the risk for myocardial infarction (OR 0.58; 95%CI 0.43-0.78; p = 0.004), CVA (OR 0.67; 95%CI 0.47-0.97; p = 0.042), and renal failure (OR 0.62; 95%CI 0.47-0.83; p = 0.0014). Length of intensive care unit stay (p < 0.0001) and length of hospital stay (p < 0.0001) were significantly reduced in patients with preoperative IABP use. CONCLUSION: Current evidence from RCT and OT suggests beneficial effects for the IABP in high-risk patients before CABG surgery.

Point-of-care thromboelastography/thromboelastometry-based coagulation management in cardiac surgery: a meta-analysis of 8332 patients.

OBJECTIVES: Severe bleeding related to cardiac surgery is associated with increased morbidity and mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are point-of-care tests (POCT). Bedside ROTEM/TEG can rapidly detect changes in blood coagulation and therefore provide a goal-directed, individualized coagulation therapy. In this meta-analysis, we aimed to determine the current evidence for or against POCT-guided algorithm in patients with severe bleeding after cardiac surgery. METHODS: We performed a meta-analysis of randomized controlled trials and observational trials retrieved from a literature search in PubMed, EMBASE, and Cochrane Library. Only trials comparing transfusion strategy guided by TEG/ROTEM with a standard of care control group undergoing cardiac surgery were included. In addition, at least one clinical outcome had to be mentioned: mortality, surgical re-exploration rate, sternal wound infection, and acute kidney injury (AKI). Also, surrogate parameters such as transfusion requirements and amount of blood loss were analyzed. The pooled treatment effects (odds ratio [OR] and 95% confidence intervals [CI]) were assessed using a fixed or random-effects model. RESULTS: The literature search retrieved a total of 17 trials (nine randomized controlled trial and eight observational trials) involving 8332 cardiac surgery patients. POCT-guided transfusion management significantly decreased the odds for patients to receive allogeneic blood products (OR 0.63, 95% CI 0.56-0.71; P < 0.00001) and the re-exploration rate due to postoperative bleeding (OR 0.56, 95% CI 0.45-0.71; P < 0.00001). Furthermore, the incidence of postoperative AKI (OR 0.77, 95% CI 0.61-0.98; P = 0.0278) and thromboembolic events (OR 0.44, 95% CI 0.28-0.70; P = 0.0006) was significantly decreased in the TEG/ROTEM group. No statistical differences were found with regard to inhospital mortality, cerebrovascular accident, or length of intensive care unit and hospital stay. CONCLUSIONS: TEG/ROTEM-based coagulation management decreases the risk of allogeneic blood product exposure after cardiac surgery. Furthermore, it results in significantly lower re-exploration rate, decreased incidence of postoperative AKI, and thromboembolic events in cardiac surgery patients. Results of this meta-analysis indicate that POCT-guided transfusion therapy is superior to the current standard of care.

Statin Recapture Therapy before Coronary Artery Bypass Grafting Trial: Rationale and study design of a multicenter, randomized, double-blinded controlled clinical trial.

INTRODUCTION: Patients undergoing coronary artery bypass grafting (CABG) are still at significant risk for postoperative major adverse cardiac and cerebrovascular events (MACCEs). Recent clinical evidence shows that cardioprotection in patients receiving a chronic statin treatment can be "recaptured" by a high-dose statin therapy given shortly before an ischemia-reperfusion sequence. Evaluation of this novel therapeutic approach in the setting of CABG seems promising because myocardial ischemia-reperfusion injury plays a pivotal role in poor clinical outcomes that may be improved by a simple preoperative statin recapture treatment. METHODS: The investigator-initiated StaRT-CABG trial is a multicenter, randomized, double-blinded, 2-parallel group controlled clinical study in 2,630 patients. The trial aims to evaluate whether a high-dose statin recapture therapy given shortly before CABG reduces the incidence of MACCE at 30 days after surgery (primary composite outcome: all-cause mortality, nonfatal myocardial infarction, and cerebrovascular events). Consenting patients who are on chronic statin therapy before surgery will be randomized to receive either oral statin reloading therapy or matching placebo 12 and 2 hours before CABG. Key secondary end points include enzymatic myocardial injury; new-onset atrial fibrillation; length of stay in the intensive care unit and hospital; need for repeat coronary revascularization at 30 days; and, finally, all-cause mortality at 12 months after surgery. IMPLICATIONS: The StaRT-CABG trial is expected to provide highly relevant clinical data on the efficacy of this novel therapeutic approach to optimize the care for patients with coronary artery disease undergoing CABG.

Preoperative statin therapy for patients undergoing cardiac surgery.

BACKGROUND: Patients referred to cardiac surgery for cardiovascular disease are at significant risk for the development of major postoperative adverse events despite significant advances in surgical techniques and perioperative care. Statins (5-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitors) have gained a pivotal role in the primary and secondary prevention of coronary artery disease and are thought to improve perioperative outcomes in patients undergoing cardiac surgery. This review is an updated version of a review that was first published in 2012. OBJECTIVES: To determine the effectiveness of preoperative statin therapy in patients undergoing cardiac surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11), MEDLINE (1950 to November 2013 Week 3), EMBASE (1980 to 3 December 2013 (Week 48)) and the metaRegister of Controlled Trials. Additionally, we searched ongoing trials through the National Research Register, the ClinicalTrials.gov registry and grey literature. We screened online conference indices from relevant scientific meetings (2006 to 2014) to look for eligible trials. We applied no language restrictions. SELECTION CRITERIA: All randomised controlled trials comparing any statin treatment before cardiac surgery, for any given duration and dose, versus no preoperative statin therapy (standard of care) or placebo. DATA COLLECTION AND ANALYSIS: Two review authors evaluated trial quality and extracted data from titles and abstracts identified by electronic database searches according to predefined criteria. Accordingly, we retrieved full-text articles of potentially relevant studies that met the inclusion criteria to assess definitive eligibility for inclusion. We reported effect measures as odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). MAIN RESULTS: We identified 17 randomised controlled studies including a total of 2138 participants undergoing on-pump or off-pump cardiac surgical procedures, and added to this review six studies with 1154 additional participants. Pooled analysis showed that statin treatment before surgery reduced the incidence of postoperative atrial fibrillation (AF) (OR 0.54, 95% CI 0.43 to 0.67; P value < 0.01; 12 studies, 1765 participants) but failed to influence short-term mortality (OR 1.80, 95% CI 0.38 to 8.54; P value = 0.46; two studies, 300 participants) or postoperative stroke (OR 0.70, 95% CI 0.14 to 3.63; P value = 0.67; two studies, 264 participants). In addition, statin therapy was associated with a shorter stay for patients on the intensive care unit (ICU) (WMD -3.19 hours, 95% CI -5.41 to -0.98; nine studies, 721 participants) and in the hospital (WMD -0.48 days, 95% CI -0.78 to -0.19; 11 studies, 1137 participants) when significant heterogeneity was observed. Results showed no reduction in myocardial infarction (OR 0.48, 95% CI 0.21 to 1.13; seven studies, 901 participants) or renal failure (OR 0.57, 95% CI 0.30 to 1.10; five studies, 467 participants) and were not affected by subgroup analysis. Trials investigating this safety endpoint reported no major or minor perioperative side effects of statins. AUTHORS' CONCLUSIONS: Preoperative statin therapy reduces the odds of postoperative atrial fibrillation (AF) and shortens the patient's stay on the ICU and in the hospital. Statin pretreatment had no influence on perioperative mortality, stroke, myocardial infarction or renal failure, but only two of all included studies assessed mortality. As analysed studies included mainly individuals undergoing myocardial revascularisation, results cannot be extrapolated to patients undergoing other cardiac procedures such as heart valve or aortic surgery.

Intraoperative stress in cardiac surgery: attendings versus residents.

BACKGROUND: Performing cardiac surgery is associated with stress for surgeons. We investigated stress levels of experienced surgeons and trainees during coronary artery bypass graft teaching procedures. METHODS: We assessed heart rate (HR) and sympathovagal balance (SVB) of experienced surgeons (attendings; n = 7) and residents enrolled in a training program (residents; n = 3) using a one-lead electrocardiogram during a total of 109 elective isolated coronary artery bypass graft procedures. We measured HR and SVB for baseline values at rest and at prespecified phases during the procedure in the role as primary surgeons (n = 10) and assistants (n = 9). RESULTS: All participants were healthy men with a mean age of 41.4 ± 4.3 y. For patients operated on during this study, demographic and intraoperative data were homogeneous. Compared with rest, mean HR and SVB for the whole procedure were higher for surgeons and assistants, with significant differences for HR values (surgeons, 83.7 ± 8.8 beats/min [bpm]; assistants, 85.4 ± 12.7 bpm, P < 0.05 versus 62.3 ± 5.1 bpm). Courses of HR and SVB were comparable for attending and resident groups but values were higher throughout for attendings compared with residents in their role as surgeons during the total procedure, and as assistants during cardiopulmonary bypass. Mean HR and SVB values of attendings assisting the procedure were higher compared with those of residents performing the operation. CONCLUSIONS: Surgical experience is not associated with reduced stress levels. Supervising a teaching case in cardiac surgery can be linked with more stress compared with the resident performing the procedure.

Endoscopic vein harvesting for coronary artery bypass grafting: a systematic review with meta-analysis of 27,789 patients.

BACKGROUND: To determine the current strength of evidence for or against endoscopic vein harvesting (EVH) in patients undergoing coronary artery bypass grafting (CABG). MATERIALS AND METHODS: A meta-analysis of randomized controlled trials (RCT) and observational trials (OT) was performed that reported the impact of EVH on adverse clinical outcomes after CABG. Analyzed postoperative outcomes included wound infection, postoperative pain, myocardial infarction (MI), vein graft failure, length of hospital stay, and mortality. Pooled treatment effects (OR or weighted mean difference (WMD), 95%CI) were assessed using a fixed or random effects model. RESULTS: A total of 27,789 patients from 43 studies (16 RCT, 27 OT) were identified who underwent saphenectomy by endoscopic (46%; n = 12,822) or conventional technique (54%; n = 14,967). Pooled effect estimates revealed a reduced incidence (P < 0.001) for wound infections (OR 0.27; 95% CI 0.22 to 0.32), pain (WMD -1.26, 95% CI -2.07 to -0.44; P = 0.0026), and length of hospital stay (WMD -0.6 d, 95% CI -1.08 to -0.12; P = 0.0152). EVH was associated to an increase of the odds for vein graft failure (OR 1.38; 95% CI 1.01 to 1.88; P = 0.0433), a finding that lost statistical difference after pooled analysis of RCT and studies with high methodological quality. Similarly, graft-related endpoints, including mortality and MI, did not differ between the harvesting techniques. CONCLUSION: The present systematic review underscores the safety of EVH in patients undergoing CABG. EVH reduces leg wound infections without increasing the midterm risk for vein graft failure, MI, or mortality.

Rosuvastatin reloading before cardiac surgery with cardiopulmonary bypass.

BACKGROUND/PURPOSE: Recent evidence suggests that statin-mediated cardioprotection after chronic statin therapy decreases over time and can be reactivated by preprocedural high-dose statin reloading therapy. We tested in a porcine cardiopulmonary bypass (CPB) model whether statin-related cardioprotection is further enhanced by a preoperative rosuvastatin reloading therapy. METHODS: Control (n = 6), rosuvastatin-pretreated (n = 6; 20 mg/day for 7 days p.o.) and rosuvastatin-reloaded (n = 6; p.o. treatment plus 0.10 mg/kg/h i.v. during surgery) pigs (Deutsche Landrasse) were subjected to CPB for 2 h with 1 h of cardioplegic cardiac arrest. Systemic hemodynamics, cardiac index (CI), coronary blood flow (CBF) and left ventricular (LV) function [pressure-volume area (PVA), preload recruitable stroke work (PRSW)] were determined before and 4 h after CPB. Myocardial expression (PCR) and protein content (Western blot) of endothelial NO synthase (eNOS) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) were measured, and right coronary relaxation was assessed postmortem. All data are given as mean ± SD. RESULTS: Preoperative plasma LDL, HDL and cholesterol did not differ between treatment groups. Compared to control, oral treatment improved post-CPB CI, CBF, first derivative of maximal LV-pressure (LVdp/dt) and PVA (p < 0.05). Significant enhancement was achieved with perioperative reloading therapy (CI: 5.2 ± 1.0 vs. 3.9 ± 1.5 l/min/m(2); CBF: 76 ± 32 vs. 43 ± 8 ml/min; LVdp/dt: 1,980 ± 333 vs. 1,249 ± 461 mm Hg/s; PVA: 6,954 ± 941 vs. 3,252 ± 1,822 mm Hg·ml; p < 0.05) with improved in vitro NO-dependent coronary relaxation (102 ± 10 vs. 79 ± 14%; p = 0.003). Irrespective of recapture therapy statin pretreatment augmented myocardial eNOS and PTEN (p < 0.05), but failed to increase cardiac eNOS or PTEN expression after CPB. CONCLUSIONS: Periprocedural statin reloading therapy enhances myocardial and coronary function after cardiac surgery with CPB and may therefore provide a valuable therapeutic approach for the reduction of myocardial ischemia-reperfusion injury.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Enhanced gap junction expression in myoblast-containing engineered tissue.

Transplantation of skeletal myoblasts (SMs) has been investigated as a potential cardiac cell therapy approach. SM are available autologously, predetermined for muscular differentiation and resistant to ischemia. Major hurdles for their clinical application are limitations in purity and yield during cell isolation as well as the absence of gap junction expression after differentiation into myotubes. Furthermore, transplanted SMs do not functionally or electrically integrate with the host myocardium. Here, we describe an efficient method for isolating homogeneous SM populations from neonatal mice and demonstrate persistent gap junction expression in an engineered tissue. This method resulted in a yield of 1.4 × 10(8) high-purity SMs (>99% desmin positive) after 10 days in culture from 162.12 ± 11.85 mg muscle tissue. Serum starvation conditions efficiently induced differentiation into spontaneously contracting myotubes that coincided with loss of gap junction expression. For mechanical conditioning, cells were integrated into engineered tissue constructs. SMs within tissue constructs exhibited long term survival, ordered alignment, and a preserved ability to differentiate into contractile myotubes. When the tissue constructs were subjected to passive longitudinal tensile stress, the expression of gap junction and cell adherence proteins was maintained or increased throughout differentiation. Our studies demonstrate that mechanical loading of SMs may provide for improved electromechanical integration within the myocardium, which could lead to more therapeutic opportunities.

Preoperative statin therapy for patients undergoing cardiac surgery.

BACKGROUND: Patients referred to cardiac surgery for cardiovascular disease are at significant risk for the development of post-operative major adverse events despite significant advances in surgical techniques and perioperative care. Statins (HMG-CoA reductase inhibitors) have gained a pivotal role in the primary and secondary prevention of coronary artery disease, and are thought to improve perioperative outcomes in patients undergoing cardiac surgery. OBJECTIVES: To determine the effectiveness of a preoperative statin therapy in patients undergoing cardiac surgery. SEARCH METHODS: We searched CENTRAL (Issue 2 of 4, 2010 on The Cochrane Library), MEDLINE (1950 to May, Week 1 2010), EMBASE (1980 to 2010 Week 19), and the metaRegister of Controlled Trials. Additionally, ongoing trials were searched through the National Research Register, the ClinicalTrials.gov registry and grey literature. Conference indices from relevant scientific meetings (2006-2009) were screened online for eligible trials. No language restrictions were applied. SELECTION CRITERIA: All randomized controlled trials comparing any statin treatment before cardiac surgery, for any given duration and dose, to no preoperative statin therapy (standard of care) or placebo. DATA COLLECTION AND ANALYSIS: Two authors evaluated trial quality and extracted data from titles and abstracts identified from the electronic database searches according to pre-defined criteria. Accordingly, full text articles of potentially relevant studies that met the inclusion criteria were retrieved to assess definite eligibility for inclusion. Effect measures are reported as odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%-CI). MAIN RESULTS: Eleven randomized controlled studies including a total of 984 participants undergoing on- or off-pump cardiac surgical procedures were identified. Pooled analysis showed that statin pre-treatment before surgery reduced the incidence of post-operative atrial fibrillation (AF) (OR 0.40; 95%-CI: 0.29 to 0.55; p<0.01), but failed to influence short-term mortality (OR 0.98, 95%-CI: 0.14 to 7.10; p=0.98) or post-operative stroke (OR 0.70, 95%-CI: 0.14 to 3.63; p=0.67). In addition, statin therapy was associated with a shorter length of stay of patients on the intensive care unit (ICU) (WMD: -3.39 hours; 95%-CI: -5.77 to -1.01) and in-hospital (WMD: -0.48 days; 95%-CI: -0.85 to -0.11) where significant heterogeneity was observed. There was no reduction in myocardial infarction (OR 0.52; 95%-CI: 0.2. to 1.30) or renal failure (OR 0.41; 95%-CI: 0.15 to 1.12). These results were unaffected after subgroup analysis. No major or minor perioperative statin side-effects were reported from trials investigating this safety endpoint. AUTHORS' CONCLUSIONS: Preoperative statin therapy reduces the odds of post-operative AF and shortens the stay on the ICU and in the hospital. Statin pretreatment had no influence on perioperative mortality, stroke, myocardial infarction or renal failure. Since analysed studies included mainly patients undergoing myocardial revascularizations the results cannot be extrapolated to patients undergoing other cardiac procedures such as heart valve or aortic surgery.