Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

BACKGROUND: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons. METHODS: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHA2DS2-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication. The participants were randomly assigned to undergo or not undergo occlusion of the left atrial appendage during surgery; all the participants were expected to receive usual care, including oral anticoagulation, during follow-up. The primary outcome was the occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or systemic embolism. The participants, research personnel, and primary care physicians (other than the surgeons) were unaware of the trial-group assignments. RESULTS: The primary analysis population included 2379 participants in the occlusion group and 2391 in the no-occlusion group, with a mean age of 71 years and a mean CHA2DS2-VASc score of 4.2. The participants were followed for a mean of 3.8 years. A total of 92.1% of the participants received the assigned procedure, and at 3 years, 76.8% of the participants continued to receive oral anticoagulation. Stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group (hazard ratio, 0.67; 95% confidence interval, 0.53 to 0.85; P = 0.001). The incidence of perioperative bleeding, heart failure, or death did not differ significantly between the trial groups. CONCLUSIONS: Among participants with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. (Funded by the Canadian Institutes of Health Research and others; LAAOS III ClinicalTrials.gov number, NCT01561651.).

Basis-Anforderungen einer Fachabteilung für Herzchirurgie.

The evolution and progress in cardiovascular medicine and substantial changes in the German health care system require both a reflection of the principles of patient-centered care in general and an update of the criteria that define a department of cardiac surgery in Germany. This position paper lists the core requirements for a cardiac surgical department with regard to infrastructure, facilities, necessary staff, and standard of care (processes). This standard may be used by hospitals and health care providers to ensure the safety and quality of cardiac surgical departments in Germany.

Sex differences in outcomes after coronary artery bypass grafting: a pooled analysis of individual patient data.

AIMS: Data suggest that women have worse outcomes than men after coronary artery bypass grafting (CABG), but results have been inconsistent across studies. Due to the large differences in baseline characteristics between sexes, suboptimal risk adjustment due to low-quality data may be the reason for the observed differences. To overcome this limitation, we undertook a systematic review and pooled analysis of high-quality individual patient data from large CABG trials to compare the adjusted outcomes of women and men. METHODS AND RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events, MACCE). The secondary outcome was all-cause mortality. Multivariable mixed-effect Cox regression was used. Four trials involving 13 193 patients (10 479 males; 2714 females) were included. Over 5 years of follow-up, women had a significantly higher risk of MACCE [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.21; P = 0.004] but similar mortality (adjusted HR 1.03, 95% CI 0.94-1.14; P = 0.51) compared to men. Women had higher incidence of MI (adjusted HR 1.30, 95% CI 1.11-1.52) and repeat revascularization (adjusted HR 1.22, 95% CI 1.04-1.43) but not stroke (adjusted HR 1.17, 95% CI 0.90-1.52). The difference in MACCE between sexes was not significant in patients 75 years and older. The use of off-pump surgery and multiple arterial grafting did not modify the difference between sexes. CONCLUSIONS: Women have worse outcomes than men in the first 5 years after CABG. This difference is not significant in patients aged over 75 years and is not affected by the surgical technique.

Wound Infection after CABG Using Internal Mammary Artery Grafts: A Meta-Analysis.

BACKGROUND: Internal mammary arteries show better long-term patency rates than venous grafts. The use of both mammary arteries is associated with a higher risk of sternal wound infections. This meta-analysis was designed to assess the incidence of a wound healing disorder after bilateral compared with single mammary artery bypass grafting. Compared with existing meta-analysis this paper includes more current literature and one randomized controlled trial. METHODS: A literature search was performed using PubMed and the Cochrane Library. The quality of the articles was assessed by the Newcastle Ottawa Scale. The odds ratio was used as a measure of the chance of developing a wound healing disorder after bilateral internal mammary artery (BIMA) surgery. Meta-analyses were performed for different subgroups. RESULTS: Twenty studies met the quality criteria, including one randomized controlled trial. The use of both mammary arteries significantly increased the risk of superficial (odds ratio [OR] 1.72) and deep (OR 1.75) wound healing disorder in the total population (OR 1.80) as well as in the diabetic subgroup (OR 1.38) and with both preparation techniques. The increased risk with BIMA grafting was present independently of the preparation technique (pedicled: OR 1.89, skeletonized: OR 1.37). CONCLUSION: Bilateral internal mammary artery grafting, especially in high-risk and diabetic patients, is associated with an increased risk of wound healing impairment. Skeletonized preparation does not eliminate the elevated wound healing disorder risk after BIMA use.

Sex-related differences in outcomes after coronary artery bypass surgery-A patient-level pooled analysis of randomized controlled trials: rationale and study protocol.

INTRODUCTION: The impact of sex on the outcomes after coronary artery bypass grafting (CABG) is controversial. The majority of CABG studies are retrospectively collected clinical or registry data, women comprise only a minority, and the reported findings represent the male predominated cohort. This individual patient meta-analysis is aimed at evaluating sex-related differences in outcomes after CABG using high quality data from randomized controlled trials (RCTs). METHODS AND ANALYSIS: A systematic literature search will be performed to identify all CABG RCTs (minimum follow-up: 5 years). Detailed specification for the minimum deidentified patient records' data requirements will be provided to RCT primary contact to request their deidentified data for pooling. The pooled analysis will follow the prospective register of systematic reviews (PROSPERO) and the preferred reporting items for systematic reviews and meta-analyses for individual patient data systematic reviews (PRISMA-IPD) recommendations and will compare sex-related outcomes after CABG. The main hypothesis is that outcomes after CABG are worse in women than in men. We will also test whether treatment effects for off-pump and the use of multiple arterial grafts are present within each sex, and also, whether there are differential treatment effects between sexes. The primary endpoint will be a composite of all-cause mortality, myocardial infarction, stroke, and repeat revascularization at long-term follow up. ETHICS AND DISSEMINATION: Ethics approval and participant consent for the study will be obtained locally by each study team if needed. Data will be disseminated and submitted to peer-reviewed scientific journals and meetings irrespective of study outcome.

Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial.

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Stentless Bioprostheses for Aortic Valve Replacement in Octogenarians: The Influence of Coronary Artery Disease.

BACKGROUND: We sought to determine the long-term results of stentless biological heart valve replacement in octogenarians to find out whether coronary artery disease or the coronary artery bypass grafting (CABG) procedure itself influences survival in these aged patients. METHODS: From 4,012 patients undergoing aortic valve replacement (AVR) with a stentless prosthesis (Freestyle, Medtronic) at a single center, 721 patients were older than 80 years. They had a mean age of 83 ± 2 (2,320 patient years), the male/female ratio was 42:58, NYHA (New York Heart Association) class I and II was prevalent in 22.8%, preoperative atrial fibrillation (AF) in 20.6%, coronary artery disease in 56.1%, mitral valve disease in 12.5%, and aortic disease in 3.5%. Follow-up included a total of 11,546 patient years (mean follow-up time: 74 ± 53 months); follow-up mortality data were 96.3% complete. RESULTS: In these aged patients, 30-day mortality in the isolated AVR group (10.3%) was similar to that in the AVR + CABG group (13.4%). Although long-term survival (15 years) in the octogenarian population is low (9% in the AVR group and 6% in the AVR + CABG group), it was not different (p = 0.191) between patients with and without coronary artery disease. The stroke rate and the myocardial infarction rate, respectively, in the AVR + CABG group (0.43%/100 patient years and 0.17%/100 patient years) were only insignificantly higher than that in the isolated AVR group (each 0.01%/100 patient years). The actuarial freedom from reoperation was 99% in both the groups. CONCLUSION: Use of the Freestyle stentless valve prosthesis for AVR is feasible also in octogenarians. The existence of coronary artery disease leads to concomitant bypass surgery, but not a higher level of perioperative or long-term mortality.

A randomized, parallel group, double-blind study of ticagrelor compared with aspirin for prevention of vascular events in patients undergoing coronary artery bypass graft operation: Rationale and design of the Ticagrelor in CABG (TiCAB) trial: An Investigator-Initiated trial.

BACKGROUND: For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial. HYPOTHESIS: Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG. STUDY DESIGN: The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled. SUMMARY: There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on "New frontiers in cardiovascular research".

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients' outcome.

Spatial expression of components of a calcitonin receptor-like receptor (CRL) signalling system (CRL, calcitonin gene-related peptide, adrenomedullin, adrenomedullin-2/intermedin) in mouse and human heart valves.

Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling. Accumulating evidence suggests an important role of calcitonin receptor-like receptor (CRL) signalling in preventing heart damage under several pathological conditions. Thus we investigate the existence of a putative CRL signalling system in mouse and human heart valves by real-time RT-PCR, laser-assisted microdissection, immunofluorescence and NADPH-diaphorase histochemistry. Mouse and human heart valves expressed mRNAs for the CRL ligands adrenomedullin (AM), adrenomedullin-2 (AM-2) and calcitonin gene-related peptide (CGRP) and for their receptor components, i.e., CRL and receptor-activity-modifying proteins 1-3. Immunofluorescence analysis revealed AM-, AM-2- and CRL-immunolabelling in endothelial cells and VIC, whereas CGRP immunoreactivity was restricted to nerve fibres and some endothelial cells. Nitric oxide synthase activity, as demonstrated by NADPH-diaphorase histochemistry, was shown mainly in valvular endothelial cells in mice, whereas in human aortic valves, VIC and smooth muscle cells were positive. Our results showed the presence of an intrinsic AM/AM-2/CGRP signalling system in murine and human heart valves with distinct cellular localization, suggesting its involvement in the regulation of valve stiffness and ECM production and turnover.

[S3-Guideline: Recommendations for intra-aortic balloon pumping in cardiac surgery]. / S3-Leitlinie "Einsatz der intraaortalen Ballongegenpulsation in der Herzchirurgie".

Although intra-aortic balloon pumping (IABP) is the most frequently used mechanical cardiac assist device in cardiothoracic surgery, there are only guidelines for substantive sections of aortic counterpulsation including prophylactic and postoperative use. In contrast, evidence-based recommendations are still lacking concerning intraoperative use, management, contraindication and other relevant issues. According to international surveys, important aspects of IABP usage show a wide variation in clinical practice. The results of a national questionnaire performed before initiation of this guideline confirmed these findings and demonstrated a clear need for the development of a consensus-based guideline. Therefore, the presented multidisciplinary S-3-guideline was developed under the direction of the German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie, DGTHG) to make evidence-based recommendations for the usage of aortic counterpulsation after cardiothoracic surgery according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF) and the Medical Centre for Quality (Ärztliches Zentrum für Qualität - (ÄZQ)). Main topics discussed in this guideline involve IABP support in the prophylactic, preoperative, intraoperative and postoperative setting as well as the treatment of right heart failure, contraindications, anticoagulation, monitoring, weaning, and limitations of IABP therapy. The presented 15 key messages of the guideline were approved after two consensus meetings under moderation of the AWMF with participation of the German Society of Cardiology (DGK), German Society of Anaesthesiology and Intensive Care Medicine (DGAI), German Interdisciplinary Association for Intensive Care (DIVI) and the German Society for Cardiovascular Engineering (DGfK).

Patient-Reported Postoperative Neuropsychological Deterioration After Heart Valve Replacement and Coronary Artery Bypass Grafting.

Background: Postoperative cognitive decline (POCD) after cardiosurgical interventions are well described through objective psychometric tests. However, a patient's subjective perception is essential to clinical assessment and quality of life. This study systematically evaluated patient-reported POCD between subjects undergoing coronary artery bypass grafting and heart valve replacement. Methods: This study was a multicentre, prospective questionnaire survey conducted at the cardiac surgery departments at the Kerckhoff Clinic in Bad Nauheim and the University Hospital in Giessen, Germany. We included patients undergoing elective coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral valve replacement or reconstruction (MVR), and combined surgery (CABG + valve replacement [VR]) with extracorporeal circulation. The Hospital Anxiety and Depression Scale, the Cognitive Failures Questionnaire (CFQ) for Self-assessment (CFQ-S), and the external assessment (CFQ-foreign [F]) were completed preoperatively, as well as at 3 and 12 months postoperatively. Results: A total of 491 patients were available for analyses (CABG = 182, AVR = 134, MVR = 93, CABG + VR = 82). POCD and postoperative depression increase (PODI) were observed for each surgical procedure. (At the 3-month follow-up: CFQ-S [CABG = 7.1%, AVR = 3.7%, MVR = 9.7%, CABG + VR = 9.8%]; CFQ-F [CABG = 9.9%, AVR = 9.7%, MVR = 9.7%, CABG + VR = 15.9%]; PODI [CABG = 7.7%, AVR = 9.7%, MVR = 6.5%, CABG + VR = 8.5%]. At the 12-month follow-up: CFQ-S [CABG = 6.6%, AVR = 7.5%, MVR = 15.1%, CABG + VR = 7.3%]; CFQ-F [CABG = 7.1%, AVR = 14.9%, MVR = 10.8%, CABG + VR = 9.8%]; PODI [CABG = 10.4%, AVR = 11.2%, MVR = 6.5%, CABG + VR = 4.9%]). No significant between-group effects were observed for the CFQ-S, CFQ-F, or the Hospital Anxiety and Depression Scale. Conclusions: For clinicians, paying attention to patients' self-reported experiences of reduced cognitive function and symptoms of depression following cardiac surgery is important. Such reporting is an indication that interventions such as cognitive training or psychotherapy should be considered.

Contexte: Le déclin cognitif postopératoire (DCPO) à la suite d'interventions de chirurgie cardiaque est bien décrit par des évaluations psychométriques objectives. Cependant, la perception subjective du patient est essentielle à l'évaluation clinique et à la qualité de vie. Cette étude visait à évaluer de façon systématique le DCPO déclaré par le patient chez des sujets ayant subi un pontage aortocoronarien ou une chirurgie valvulaire. Méthodologie: Cette étude prospective multicentrique par questionnaire a été menée aux services de chirurgie cardiaque de la clinique Kerckhoff de Bad Nauheim et de l'hôpital universitaire de Giessen, en Allemagne. Elle a porté sur des patients ayant subi un pontage aortocoronarien (PAC), un remplacement valvulaire aortique (RVA), un remplacement ou une reconstruction de la valvule mitrale (RVM) ou une chirurgie combinée (PAC et remplacement valvulaire [RV]) avec circulation extracorporelle, en situation non urgente. L'échelle d'évaluation de l'anxiété et de la dépression à l'hôpital (HADS), le questionnaire d'auto-évaluation des déficits cognitifs (CFQ-S) et le questionnaire d'évaluation externe des déficits cognitifs (CFQ-F) ont été remplis avant l'intervention chirurgicale, ainsi que 3 et 12 mois après la chirurgie. Résultats: Au total, les résultats de 491 patients étaient disponibles aux fins d'analyses (PAC = 182, RVA = 134, RVM = 93, PAC et RV = 82). Des cas de DCPO et une augmentation postopératoire des symptômes de dépression (APOD) ont été observés après chacune des interventions chirurgicales. (Lors du suivi après 3 mois : DCPO selon le CFQ-S [PAC = 7,1 %, RVA = 3,7 %, RVM = 9,7 %, PAC + RV = 9,8 %]; DCPO selon le CFQ-F [PAC = 9,9 %, RVA = 9,7 %, RVM = 9,7 %, PAC + RV = 15,9 %]; APOD [PAC = 7,7 %, RVA = 9,7 %, RVM = 6,5 %, PAC + RV = 8,5 %]. Lors du suivi après 12 mois : DCPO selon le CFQ-S [PAC = 6,6 %, RVA = 7,5 %, RVM = 15,1 %, PAC + RV = 7,3 %]; DCPO selon le CFQ-F [PAC= 7,1 %, RVA = 14,9 %, RVM = 10,8 %, PAC+ RV = 9,8 %]; APOD [PAC = 10,4 %, RVA = 11,2 %, RVM = 6,5 %, PAC + RV = 4,9 %]). Aucun effet intergroupe significatif n'a été observé relativement aux questionnaires CFQ-S et CFQ-F ou à l'échelle HADS. Conclusions: Il est important que les cliniciens portent attention aux déclarations des patients en ce qui concerne la diminution des fonctions cognitives et les symptômes de dépression à la suite d'une chirurgie cardiaque. De telles déclarations sont une indication que des interventions comme l'entraînement cognitif ou la psychothérapie doivent être envisagées.

Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study.

AIMS: Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study". METHODS: We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge. CONCLUSION: The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.

Potentials of Acetylcholinesterase and Butyrylcholinesterase Alterations in On-Pump Coronary Artery Bypass Surgery in Postoperative Delirium: An Observational Trial.

Cardiac surgery is regularly associated with postoperative delirium (POD), affected by neuro-inflammation and changes in cholinergic activity. Therefore, this prospective observational study aimed to evaluate whether pre- and perioperative changes in blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity were associated with POD development in patients undergoing isolated elective coronary artery bypass graft (CABG) surgery. It included 93 patients. Pre- and postoperative blood AChE and BChE activities were measured with photometric rapid-point-of-care-testing. The Intensive Care Delirium Screening Checklist and the Confusion Assessment Method for the Intensive Care Unit were used to screen patients for POD. POD developed in 20 patients (21.5%), who were older (p = 0.003), had higher EuroSCOREs (p ≤ 0.001), and had longer intensive care unit stays (p < 0.001). On postoperative day one, BChE activity decreased from preoperative values more in patients with (31.9%) than without (23.7%) POD (group difference p = 0.002). Applying a cutoff of ≥32.0% for BChE activity changes, receiver operating characteristic analysis demonstrated a moderate prediction capability for POD (area under the curve = 0.72, p = 0.002). The risk of developing POD was 4.31 times higher with a BChE activity change of ≥32.0% (p = 0.010). Monitoring the pre- to postoperative reduction in BChE activity might be a clinically practicable biomarker for detecting patients at risk of developing POD after CABG surgery.

The impact of postoperative cognitive training on health-related quality of life and cognitive failures in daily living after heart valve surgery: A randomized clinical trial.

BACKGROUND: Heart surgery is a risk factor for objectively and subjectively assessable postoperative cognitive decline (POCD), which is relevant for everyday life. The aim of this study was to investigate whether early postoperative cognitive training has an impact on health-related quality of life and cognitive failures in daily living after cardiac surgery. METHODS: The study was a two-arm, randomized, controlled, outcome-blinded trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation (ECC). Recruitment took place at the Departments of Cardiac Surgery of the Kerckhoff Clinic in Bad Nauheim (Germany) and the University Hospital in Giessen (Germany). The patients were randomized (1:1 ratio) to either a paper-and-pencil-based cognitive training group or a control group. We applied the Short Form Health Survey (SF-36) and the Cognitive Failures Questionnaire (CFQ) prior to surgery and 3 months after the cognitive training. Data were analyzed in a per-protocol fashion. RESULTS: Three months after discharge from rehabilitation, the training group (n = 31) showed improvement in health-related quality of life compared to the control group (n = 29), especially in role limitations due to emotional problems (U = -2.649, p = .008, η2  = 0.121), energy and fatigue (F[2.55] = 5.72, p = .020, η2  = 0.062), social functioning (U = -2.137, p = .033, η2  = 0.076), the average of all SF-36 factors (U = -2.374, p = .018, η2  = 0.094), health change from the past year to the present time (U = -2.378, p = .017, η2  = 0.094), and the mental component summary (U = -2.470, p = .013, η2  = 0.102). CONCLUSION: As our cognitive training has shown beneficial effects, this intervention could be a promising method to enhance health-related quality of life after cardiac surgery.

The correlation of age and extension length in DeBakey type I aortic dissection: are older patients over 70 years at a lower risk?

OBJECTIVES: Age-related atherosclerosis has been shown to cause aortic stiffness and wall rigidification. This analysis aimed to correlate age and dissection extension length in a large contemporary multicentre study. We hypothesize that younger patients suffer more extensive DeBakey type I dissection due to aortic wall integrity, allowing unhindered extension within the layers. METHODS: The perioperative data of 3385 patients from the German Registry for Acute Aortic Dissection Type A were retrospectively analyzed with regard to postoperative outcomes and dissection extension. Patients with DeBakey type I aortic dissection (n = 2510) were retrospectively identified and divided into 2 age groups for comparison: ≤69 years (n = 1741) and ≥70 years (n = 769). Patients with DeBakey type II dissection or connective tissue disease were excluded from the analysis. RESULTS: In younger patients (≤69 years), aortic dissection involved the supra-aortic vessels significantly more often (52.0% vs 40.1%; P < 0.001) and extended significantly further downstream the aorta: descending aorta (68.4% vs 57.1%; P < 0.001), abdominal aorta (54.6% vs 42.1%; P < 0.001) and iliac bifurcation (36.6% vs 26.0%; P < 0.001). Consequently, younger patients also presented with significantly higher incidences of preoperative cerebral (P < 0.001), spinal (P < 0.001), visceral (P < 0.001), renal (P = 0.013) and peripheral (P < 0.001) malperfusion. In older patients (≥70 years), dissection extent was significantly more often limited to the level of the aortic arch (40.9% vs 29.2%; P < 0.001). No significant difference was found with regard to 30-day mortality (20.7% vs 23.6%; P = 0.114). CONCLUSIONS: Extensive DeBakey type I aortic dissection is less frequent in older patients ≥70 years than in younger patients. In contrast, younger patients suffer more often from preoperative organ malperfusion and associated complications. Postoperative mortality remains high irrespective of age groups.

Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial).

INTRODUCTION: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies. METHODS AND ANALYSIS: This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites. ETHICS AND DISSEMINATION: The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT05126303.

Modified repair of interrupted aortic arch utilizing retroesophageal right subclavian artery based on a neonatal hybrid approach in hypoplastic left heart complex.

OBJECTIVE: Interrupted aortic arch (IAA) combined with an aberrant right subclavian artery (ARSA) is frequently associated with a hypoplastic ascending aorta. Neonatal surgical therapy carries a high risk particularly for aortic arch obstructions during the further follow-up. METHODS: We performed a modified reconstruction of the aortic arch utilizing the ARSA as a natural substitute in a staged surgical approach. In a novel approach, the distal part of the ARSA is reimplanted into the brachiocephalic trunk. RESULTS: In three patients, a novel arch reconstruction was successfully performed during complete biventricular repair. In a follow-up of 60 to 87 months, the reconstructed aortic arch has grown without any signs of obstruction in all three patients. CONCLUSION: Utilizing the ARSA for surgical aortic arch repair is a satisfactory solution, when postnatal borderline left heart obstruction associated with IAA and ARSA is postponed by an initial hybrid approach.