Male-female differences following concomitant coronary artery bypass grafting and aortic valve replacement surgery.

AIMS: Combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR), and female sex are associated with increased perioperative mortality in clinical risk scores. This study investigated male-female differences in short-term outcome stratified by age groups. METHODS AND RESULTS: All patients undergoing AVR and CABG between January 2001 and June 2021 at our institution were included. 1963 patients were grouped by decades into: 59 years and younger (n = 127), 60-69 (n = 471), 70-79 (n = 1070), and 80 years and older (n = 295). The primary end points of this study were 30 and 180 days mortality. Secondary end points were influence of preoperative risk factors and impact of sex on survival and postoperative major adverse events. Female patients showed higher 30 and 180 days mortality after combined CABG and AVR surgery (8.3% vs. 4.2%, P < 0.01; 15.8% vs. 9.4%, P < 0.01). Stratified by age groups, 30 and 180 days mortality remained significantly higher in septuagenarians (9.6% vs. 2.5%, P < 0.01; 16.3% vs. 7.7%, P < 0.01). Females were significantly older, had better preserved left ventricular function, and higher incidence of diabetes mellitus compared with male patients in this subgroup (P < 0.01; P = 0.01; P < 0.01). Additionally, females received significantly less internal mammary artery (IMA) conduits (P < 0.01). Female sex (OR: 3.33, 95% CI: [1.76-6.31]; 1.93, [1.22-3.06]), higher age (1.28, [1.13-1.45]; 1.16, [1.06-1.26]), diabetes mellitus (1.93, [1.03-3.60]; 1.70, [1.08-2.67]) and LVEF <30% (3.26, [1.48-7.17]; 2.23, [1.24-4.02]) were correlated with 30 and 180 days mortality, respectively. Upon multivariable testing, sex (1.77, [1.21-2.58]) and LVEF <30% (3.71, [2.39-5.76]) remained independent predictors for major adverse postoperative events. Infrequent use of IMA grafts was associated with increased 30 and 180 days mortality as well as adverse events (0.47, [0.25-0.87]; 0.46, [0.29-0.72]; 0.61, [0.42-0.88]). CONCLUSIONS: Sex disparities in baseline characteristics may delay operative intervention in female patients. The inherent risk profiles might be responsible for outcome differences in septuagenarians.

An ex-vivo and in-vitro dynamic simulator for surgical and transcatheter mitral valve interventions.

PURPOSE: Minimally invasive mitral valve surgery (MIMVS) and transcatheter edge-to-edge repair (TEER) are complex procedures used to treat mitral valve (MV) pathologies, but with limited training opportunities available. To enable training, a realistic hemodynamic environment is needed. In this work we aimed to develop and validate a simulator that enables investigation of MV pathologies and their repair by MIMVS and TEER in a hemodynamic setting. METHODS: Different MVs were installed in the simulator, and pressure, flow, and transesophageal echocardiographic measurements were obtained. To confirm the simulator's physiological range, we first installed a biological prosthetic, a mechanical prosthetic, and a competent excised porcine MV. Subsequently, we inserted two porcine MVs-one with induced chordae tendineae rupture and the other with a dilated annulus, along with a patient-specific silicone valve extracted from echocardiography with bi-leaflet prolapse. Finally, TEER and MIMVS procedures were conducted by experts to repair the MVs. RESULTS: Systolic pressures, cardiac outputs, and regurgitations volumes (RVol) with competent MVs were 119 ± 1 mmHg, 4.78 ± 0.16 l min-1, and 5 ± 3 ml respectively, and thus within the physiological range. In contrast, the pathological MVs displayed increased RVols. MIMVS and TEER resulted in a decrease in RVols and mitigated the severity of mitral regurgitation. CONCLUSION: Ex-vivo modelling of MV pathologies and repair procedures using the described simulator realistically replicated physiological in-vivo conditions. Furthermore, we showed the feasibility of performing MIMVS and TEER at the simulator, also at patient-specific level, thus providing new clinical perspectives in terms of training modalities and personalized planning.

Surgical training of minimally invasive mitral valve repair on a patient-specific simulator improves surgical skills.

OBJECTIVES: Minimally invasive mitral valve repair (MVR) is considered one of the most challenging operations in cardiac surgery and requires much practice and experience. Simulation-based surgical training might be a method to support the learning process and help to flatten the steep learning curve of novices. The purpose of this study was to show the possible effects on learning of surgical training using a high-fidelity simulator with patient-specific mitral valve replicas. METHODS: Twenty-five participants were recruited to perform MVR on anatomically realistic valve models during different training sessions. After every session their performance was evaluated by a surgical expert regarding accuracy and duration for each step. A second blinded rater similarly assessed the performance after the study. Through repeated documentation of those parameters, their progress in learning was analysed, and gains in proficiency were evaluated. RESULTS: Participants showed significant performance enhancements in terms of both accuracy and time. Their surgical skills showed sizeable improvements after only 1 session. For example, the time to implant neo-chordae decreased by 24.64% (354 s-264 s, P < 0.001) and the time for annuloplasty by 4.01% (54 s-50 s, P = 0.165), whereas the number of irregular stitches for annuloplasty decreased from 52% to 24%.The significance of simulation-based surgical training as a tool for acquiring and training surgical skills was reviewed positively. CONCLUSIONS: The results of this study indicate that simulation-based surgical training is a valuable and effective method for learning reconstructive techniques of minimally invasive MVR and overall general dexterity.The novel learning and training options should be implemented in the surgical traineeship for systematic teaching of various surgical skills.

Pericardial Closure With Expanded Polytetrafluoroethylene Patch in Left Ventricular Assist Device Surgery.

To reduce adhesions after left ventricular assist device (LVAD) implantation, pericardial closure using an expanded polytetrafluoroethylene (ePTFE) patch has been suggested. However, as foreign material, ePTFE patches could increase the risk of infectious complications. In this single-center retrospective study, we investigated outcomes of pericardial closure using an ePTFE patch in LVAD implantation. We included all patients who underwent LVAD implantation at our center between 2011 and 2020 (n = 166). Primary endpoint was development of mediastinitis at any point of time between LVAD implantation and heart transplantation (HTx) or death. Secondary endpoint was overall survival. Preoperative and postoperative clinical data were collected to ensure comparability between the groups. We included 166 patients with LVAD. A total of 116 patients (70%) underwent pericardial closure using an ePTFE patch. There were significant differences between the groups in treatment setting, previous cardiac surgery, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level, development of driveline infection, and HTx. Patients with an ePTFE patch developed mediastinitis more frequently (16%) than patients without ePTFE patch (4%) ( p = 0.039). A significant difference in overall survival between the groups could not be confirmed ( p = 0.29). The use of PTFE patches for pericardial closure in LVAD implantation was associated with a higher incidence of mediastinitis, but not with a difference in overall survival.

Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats.

BACKGROUND: Heart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes. The inhibition of cathepsin C (CatC) has been shown to block NE-related protease activation. We hypothesized that the CatC inhibitor BI-9740 improves graft function after HTX. METHODS: In a rat model of HTX, the recipient Lewis rats were orally administered with either a placebo (n = 12) or BI-9740 (n = 11, 20 mg/kg) once daily for 12 days. Donor hearts from untreated Lewis rats were explanted, preserved in a cardioplegic solution, and subsequently heterotopically implanted. In vivo left-ventricular (LV) graft function was assessed after 1 h of reperfusion. The proteolytic activity of neutrophil serine proteases was determined in bone marrow lysates from BI-9740-treated and control rats. Additionally, myocardial morphological changes were examined, and heart samples underwent immunohistochemistry and western blot analysis. RESULTS: The NE-related proteolytic activity in bone marrow cell lysates was markedly decreased in the BI-9740-treated rats compared to those of the placebo group. Histopathological lesions, elevated CatC and myeloperoxidase-positive cell infiltration, and nitrotyrosine immunoreactivity with an increased number of poly(ADP-ribose) polymerase (PARP)-1-positive cells were lowered in the hearts of animals treated with BI-9740 compared to placebo groups. Regarding the functional parameters of the implanted graft, improvements were observed in both systolic function (LV systolic pressure 110 ± 6 vs 74 ± 6 mmHg; dP/dtmax 2782 ± 149 vs 2076 ± 167 mmHg/s, LV developed pressure, at an intraventricular volume of 200 µl, p < 0.05) and diastolic function in the hearts of BI-9740 treated animals compared with those receiving the only placebo. Furthermore, the administration of BI-9740 resulted in a shorter graft re-beating time compared to the placebo group. However, this study did not provide evidence of DNA fragmentation, the generation of both superoxide anions and hydrogen peroxide, correlating with the absence of protein alterations related to apoptosis, as evidenced by western blot in grafts after HTX. CONCLUSIONS: We provided experimental evidence that pharmacological inhibition of CatC improves graft function following HTX in rats.

Temporary circulatory support with surgically implanted microaxial pumps in postcardiotomy cardiogenic shock following coronary artery bypass surgery.

Objectives: Patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) surgery may develop postcardiotomy cardiogenic shock. In these cases, implantation of an Impella 5.0 or 5.5 microaxial pump offers full hemodynamic support while simultaneously unloading of the left ventricle. Methods: Preoperative, perioperative, and postoperative data of all patients receiving postoperative support with an Impella 5.0 or 5.5 after CABG surgery between September 2017 and October 2022 were retrospectively collected. Cohort built-up was performed according to the timing of Impella implantation, either simultaneous during CABG surgery or delayed. Results: A total of n = 42 patients received postoperative Impella support, of whom 27 patients underwent simultaneous Impella implantation during CABG surgery and 15 patients underwent delayed Impella therapy. Preoperative left ventricular ejection fraction was similarly low in both groups (26.7 ± 0.7% vs 24.8 ± 11.3%; P = .32). In the delayed cohort, Impella implantation was performed after a median of 1 (1; 2) days after CABG surgery. Survival after 30 days (75.6% vs 47.6%, P = .04) and 1 year (69.4% vs 29.8%, P = .03) was better in the cohort receiving simultaneous Impella implantation. Conclusions: The combined advantages of hemodynamic support and LV unloading with microaxial pumps may lead to a favorable survival in patients with left ventricular failure following CABG surgery. Early implantation during the initial surgery shows a trend toward a more favorable survival as compared with patients receiving delayed support.

Early versus Delayed Surgery in Patients with Left-Sided Infective Endocarditis and Stroke.

BACKGROUND: Timing of surgery remains controversial in patients with infective endocarditis and stroke. Guidelines on infective endocarditis suggest delaying surgery for up to 4 weeks. However, with early heart failure due to progression of the infection or recurrent septic embolism, urgent surgery becomes imperative. METHODS: Out of 688 patients who were surgically treated for left-sided infective endocarditis, 187 presented with preoperative neurological events. The date of cerebral stroke onset was documented in 147 patients. The patients were stratified according to timing of surgery: 61 in the early group (0-7 days) vs. 86 in the delayed group (>7 days). Postoperative neurological outcome was assessed by the modified Rankin Scale. RESULTS: Preoperative sepsis was more prevalent in patients with preoperative neurological complications (46.0% vs. 29.5%, p < 0.001). Patients with haemorrhagic stroke were operated on later (19.8% vs. 3.3%, p = 0.003). Postoperative cerebrovascular accidents were comparable between both groups (p = 0.13). Overall, we observed good neurological outcomes (p = 0.80) and a high recovery rate, with only 5% of cases showing neurological deterioration after surgery (p = 0.29). In-hospital mortality and long-term survival were not significantly different in the early and delayed surgery groups (log-rank, p = 0.22). CONCLUSIONS: Early valve surgery in high-risk patients with infective endocarditis and stroke can be performed safely and is not associated with worse outcomes.

Symptomatic Upper Extremity Deep Venous Thrombosis After Laser Lead Extraction.

INTRODUCTION: Laser lead extraction is a well-established method for removing unwanted leads with low morbidity and mortality. In this small series of cases, we documented our experience with venous thrombosis after laser lead extraction. METHODS: Retrospective data of patients who underwent laser lead extraction with postoperative axillo-subclavian vein thrombosis between May 2010 and January 2020 were analyzed. Demographic, operative, clinical, and follow-up characteristics of those patients were collected from our medical database. RESULTS: Six patients underwent percutaneous laser lead extraction. Mean age of the patients was 64±7 years. And four of them were male. A total of 11 leads with a mean age of 92±43.8 months were extracted. Patients presented with painful arm swelling postoperatively. CONCLUSION: Laser lead extraction may lead to symptomatic upper extremity deep venous occlusion.

Comparative evaluation of three commercially available markerless depth sensors for close-range use in surgical simulation.

PURPOSE: Minimally invasive surgeries have restricted surgical ports, demanding a high skill level from the surgeon. Surgical simulation potentially reduces this steep learning curve and additionally provides quantitative feedback. Markerless depth sensors show great promise for quantification, but most such sensors are not designed for accurate reconstruction of complex anatomical forms in close-range. METHODS: This work compares three commercially available depth sensors, namely the Intel D405, D415, and the Stereolabs Zed-Mini in the range of 12-20 cm, for use in surgical simulation. Three environments are designed that closely mimic surgical simulation, comprising planar surfaces, rigid objects, and mitral valve models of silicone and realistic porcine tissue. The cameras are evaluated on Z-accuracy, temporal noise, fill rate, checker distance, point cloud comparisons, and visual inspection of surgical scenes, across several camera settings. RESULTS: The Intel cameras show sub-mm accuracy in most static environments. The D415 fails in reconstructing valve models, while the Zed-Mini provides lesser temporal noise and higher fill rate. The D405 could reconstruct anatomical structures like the mitral valve leaflet and a ring prosthesis, but performs poorly for reflective surfaces like surgical tools and thin structures like sutures. CONCLUSION: If a high temporal resolution is needed and lower spatial resolution is acceptable, the Zed-Mini is the best choice, whereas the Intel D405 is the most suited for close-range applications. The D405 shows potential for applications like deformable registration of surfaces, but is not yet suitable for applications like real-time tool tracking or surgical skill assessment.

Outcomes in patients with cardiac amyloidosis undergoing heart transplantation: the eurotransplant experience.

BACKGROUND: When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival. METHODS: Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable. RESULTS: Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model. CONCLUSIONS: HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.

Surgical Rehearsal for Mitral Valve Repair: Personalizing Surgical Simulation by 3D Printing.

PURPOSE: The goal of this study was to show possible effects of performing the actual procedure of mitral valve repair (MVR) on personalized silicone models 1 day before operation. DESCRIPTION: Based on preoperative 3-dimensional echocardiography recordings, flexible 3-dimensional replicas of the depicted pathologic mitral valves could be produced and used for a simulation of reconstructive techniques analogous to the upcoming MVR procedure. We integrated this step of personalized surgical planning into the clinical routine of 6 MVR cases with 3 different surgeons. This pilot study was assessed by evaluating questionnaires and by comparing isolated surgical steps with conventional MVRs. EVALUATION: This approach was considered a better preparation for MVRs with overall positive responses from the surgeons. Simulation helped reduce the time of initial inspection of the valve because of better understanding of the valve's pathomorphologic features. Annuloplasty benefited from preoperative sizing by reducing the number of sizing attempts. CONCLUSIONS: These initial findings suggest that simulation-based surgical planning can be implemented into patients' and physicians' clinical workflow as a major technologic advancement for future MVR preparation.

Early outcomes of patients with Marfan syndrome and acute aortic type A dissection.

BACKGROUND: Acute aortic Stanford type A dissection remains a frequent and life-limiting event for patients with Marfan syndrome. Outcome results in this high-risk group are limited. METHODS: The German Registry for Acute Aortic Dissection Type A collected the data of 56 centers between July 2006 and June 2015. Of 3385 patients undergoing operations for acute aortic Stanford type A dissection, 117 (3.5%) were diagnosed with Marfan syndrome. We performed a propensity score match comparing patients with Marfan syndrome with patients without Marfan syndrome in a 1:2 fashion. RESULTS: Patients with Marfan syndrome were significantly younger (42.9 vs 62.2 years; P < .001), predominantly male (76.9% vs 62.9%; P = .002), and less catecholamine dependent (9.4% vs 20.3%; P = .002) compared with the unmatched cohort. They presented with aortic regurgitation (41.6% vs 23.0%; P < .001) and involvement of the supra-aortic vessels (50.4% vs 39.5%; P = .017) more often. Propensity matching revealed 82 patients with Marfan syndrome (21 female) with no significant differences in baseline characteristics compared with patients without Marfan syndrome (n = 159, 36 female; P = .607). Although root preservation was more frequent in patients with Marfan syndrome, procedure types did not differ significantly (18.3% vs 10.7%; P = .256). Aortic arch surgery was performed more frequently in matched patients (87.5% vs 97.8%; P = .014). Thirty-day mortality did not differ between patients with and without Marfan syndrome (19.5% vs 20.1%; P = .910). Multivariate regression showed no influence of Marfan syndrome on 30-day mortality (odds ratio, 0.928; 95% confidence interval, 0.346-2.332; P = .876). CONCLUSIONS: Marfan syndrome does not adversely affect 30-day outcomes after surgical repair for acute aortic Stanford type A dissection compared with a matched cohort. Long-term outcome analysis is needed to account for the influence of further downstream interventions.

Prospective clinical study testing the efficacy and safety of a new formula to increase the precision of oxygen therapy in the initiation phase of cardiopulmonary bypass.

INTRODUCTION: During cardiopulmonary bypass (CPB), supranormal concentrations of oxygen are routinely administered with the intention to prevent cellular hypoxia. However, hyperoxemia may have adverse effects on patient outcome. Oxygen settings are based on the perfusionist's individual work experience rather than profound recommendations and studies analyzing the effect of oxygen levels are in need of methodological improvement. We aimed to advance perfusion technique by developing and clinically applying a formula for tailored oxygen therapy in CPB. METHODS: A formula to precalculate the oxygenator setting before CPB was developed. The newly-derived formula was then evaluated in a prospective, single-center pilot study to test whether a predefined arterial partial oxygen pressure (PaO2) of 150-250 mmHg could be reached. 80 patients were enrolled in the study between April and September 2021. RESULTS: The mean oxygen fraction calculated for the setting of the gas blender was 52% ±0,12. The mean PaO2 after initiation of the CPB was 193 ± 99 mmHg (min-max: 61-484, median 163 mmHg). 38.75% of the values were in the desired PaO2 corridor of 150 to 250 mmHg. 8.75% of all PaO2 values were below <79.9 mmHg, 31.25% between 80 and 149.9 mmHg, 38.75% between 150 and 249.9 mmHg and 21.25%>250 mmHg. CONCLUSIONS: Conceptually, perfusion technique should be goal-directed, guided by objective parameters and formulas. Although the optimal CPB oxygenation target remains unknown, it is nevertheless important to develop strategies to tailor oxygen therapy to aid in creating evidence as to what level of oxygen is best for patients during CPB. The formula we derived needs further adjustments to increase results in the target range.

Analysing and improving preoperative medication management in cardiac surgery.

AIMS: The objective of this study was to analyse the preoperative medication management within the cardiac surgery patient population and measure the effectiveness of an interprofessional intervention in routine care. METHODS: A jointly developed preoperative medication management was implemented in routine care on multiple levels (inclusion in admission letter to primary care, hotline for inquiries, pocket cards for physicians and correspondence with referring centres). The effectiveness was evaluated by analysing preoperative management before and after implementation. The primary endpoint was the number of drugs managed correctly according to the guidelines after implementation. Secondary endpoints consisted amongst others of bleeding on the intensive care unit, re-thoracotomy, postoperative infarction and cerebrovascular complications. Additionally, possible associations between the correct management and different variables were investigated by multivariate analysis. RESULTS: After the implementation, the number of drugs managed correctly according to guidelines increased from 54.0 to 73.5% (P < .001). The effect was more prominent for direct oral anticoagulants and prophylactic aspirin where the guideline adherence increased from 29.2 to 74.5% and from 78.6 to 95.1%, respectively. No difference was seen for sodium-glucose transporter-2 inhibitors, metformin, vitamin-K antagonists and dual-antiplatelet therapy. Secondary endpoints showed no safety signals with regard to bleeding or thrombotic events. In multivariate analysis, the intervention was effective (odds ratio 2.17, 95% confidence interval [1.32-3.62]) after adjusting for possible confounders. CONCLUSION: An interprofessional programme was effective to improve preoperative medication management in cardiac surgery patients. Sodium-glucose transporter-2 inhibitors, metformin and direct oral anticoagulants appear to be especially at risk for incorrect management before cardiac surgery with possible adverse events.

Symptomatic Upper Extremity Deep Venous Thrombosis After Laser Lead Extraction

ABSTRACT Introduction: Laser lead extraction is a well-established method for removing unwanted leads with low morbidity and mortality. In this small series of cases, we documented our experience with venous thrombosis after laser lead extraction. Methods: Retrospective data of patients who underwent laser lead extraction with postoperative axillo-subclavian vein thrombosis between May 2010 and January 2020 were analyzed. Demographic, operative, clinical, and follow-up characteristics of those patients were collected from our medical database. Results: Six patients underwent percutaneous laser lead extraction. Mean age of the patients was 64±7 years. And four of them were male. A total of 11 leads with a mean age of 92±43.8 months were extracted. Patients presented with painful arm swelling postoperatively. Conclusion: Laser lead extraction may lead to symptomatic upper extremity deep venous occlusion.

Redo aortic arch replacement through a second transcostal approach for closure of type 1A endoleak after endovascular treatment of type B aortic dissection in Marfan syndrome.

A 41-year-old woman with Marfan syndrome suffering from chronic expanding type A dissection of the distal aortic arch and pectus excavatum underwent aortic arch replacement through a left parasternal approach. We demonstrate that this approach is also feasible in complex redo surgery on the aortic arch in selected patients.

Bone Marrow Culture-Derived Conditioned Medium Recovers Endothelial Function of Vascular Grafts following In Vitro Ischemia/Reperfusion Injury in Diabetic Rats.

Ischemia/reperfusion injury (IRI) remains a challenge in coronary artery bypass grafting (CABG). Diabetic patients with coronary artery disease are more likely to require CABG and therefore run a high risk for cardiovascular complications. Conditioned medium (CM) from bone marrow-derived mesenchymal stem cells has been shown to have beneficial effects against IRI. We hypothesized that adding CM to physiological saline protects vascular grafts from IRI in diabetic rats. Bone-marrow derived cells were isolated from nondiabetic rat femurs/tibias, and CM was generated. As we previously reported, CM contains 23 factors involved in inflammation, oxidative stress, and apoptosis. DM was induced by streptozotocin administration. Eight weeks later, to measure vascular function, aortic rings were isolated and mounted in organ bath chambers (DM group) or stored in 4°C saline, supplemented either with a vehicle (DM-IR group) or CM (DM-IR+CM group). Although DM was associated with structural changes compared to controls, there were no functional alterations. However, compared to the DM group, in the DM-IR aortas, impaired maximum endothelium-dependent vasorelaxation in response to acetylcholine (DM 86.7 ± 0.1% vs. DM-IR 42.5 ± 2.5% vs. DM-IR+CM 61.9 ± 2.0%, p < 0.05) was improved, caspase-3, caspase-8, caspase-9, and caspase-12 immunoreactivity was decreased, and DNA strand breakage, detected by the TUNEL assay, was reduced by CM. We present the experimental finding that the preservation of vascular grafts with CM prevents endothelial dysfunction after IRI in diabetic rats. Targeting apoptosis by CM may contribute to its protective effect.

Long-Term Outcomes Stratified by Age in Patients with a Mechanical versus Biological Mitral Valve Replacement.

Objectives: Balancing anticoagulation and reoperation risks determines prostheses choice (mechanical/biological) for mitral valve replacement. We aimed to re-evaluate the outcomes after biological versus mechanical mitral valve replacement. Methods: We compared long-term benefits and risks of mechanical and biological prostheses in 2056 patients (52% men, 48% women; 65.4 ± 12.1 years) who underwent mitral valve replacements between 1993−2017, in a retrospective single-centre study. Data sources included prospective institutional database, social registry, general practitioner data and follow-up questionnaire. Patients were stratified by age: < = 39 y (n = 82), 40−49 y (n = 164), 50−59 y (n = 335), 60−69 y (n = 593), 70−79 y (n = 743) and > = 80 y (n = 139). Long-term outcomes (mortality, reoperations, bleeding) were analysed. Results: Altogether, 1308 mechanical (53% men, 47% women; 61.5 ± 11.7 years) and 748 biological (50% men, 50% women; 72.3 ± 9.6 years) valves were implanted. The reason for valve replacement was stenosis in 162, insufficiency in 823 and combined in 323 cases for mechanical, while it was 46, 567 and 135 for biological valves, respectively. Overall cumulative survival was higher with mechanical prosthesis (mean: 139 ± 4 vs. 102 ± 5 months, 10 y: 55% vs. 33%, p < 0.0001). Subgroup analysis revealed higher survival among patients receiving mechanical prosthesis up to 60 years (< = 39 y p = 0.047, 40−49 y p < 0.0001, 50−59 y p = 0.001). In patients 60−69 years, overall survival did not differ; however, in survivors beyond 8 years, mechanical prosthesis showed improved survival (p = 0.014). While between 70−79 years survival was nearly identical, for above 80 years, patients had a higher survival with biological prosthesis (p = 0.014). Conclusion: The present data demonstrated a higher survival of mechanical prosthesis in a wide range of patients after mitral valve replacement.

Monocyte Metabolism and Function in Patients Undergoing Cardiac Surgery.

Objective: Cardiopulmonary bypass (CPB) can lead to systemic inflammation, which is associated with higher morbidity. Therefore, we investigated the metabolism of isolated blood monocytes before and after CPB compared to healthy controls. Methods: In this prospective, monocentric, observational study, we included 30 patients undergoing CPB and 20 controls. We isolated monocytes from heparinized blood and investigated their metabolism by using Seahorse technology before (t0), 4 h (t4), and 24 h (t24) after the start of the CPB. We also examined programmed cell death 1 ligand (PD-L1), PD-L2, V-domain Ig suppressor of T cell activation (VISTA), and human leukocyte antigen-DR isotype (HLA-DR) using fluorescence-activated cell sorting analysis. Additionally, we investigated plasma cytokine levels in patients without and after ex vivo stimulation. Results: CPB-induced inflammatory responses are shown by significantly elevated plasma interleukin-6 levels in the CPB group compared to baseline and controls [t0: 0 ng/ml (95%CI 0-0 ng/ml); t4: 0.16 ng/ml (95%CI 0.1-0.197 ng/ml), p < 0.0001; t24: 0.11 ng/ml (95% CI 0.1-0.16 ng/ml), p < 0.0001, and controls: 0 ng/ml (95% CI 0-0 ng/ml)]. The cytokine release in the ex vivo stimulation is reduced for lipopolysaccharide stimulation at t4 [t0: 35.68 ng/ml (95% CI 22.17-46.57 ng/ml) vs. t4: 15.02 (95% CI 10.25-24.78 ng/ml), p < 0.0001]. Intracellular metabolism of monocytes after CPB showed a protracted shift to aerobic glycolysis [t0: 179.2 pmol/min (95% CI 138.0-205.1 pmol/min) vs. t24: 250.1 pmol/min (95% CI 94.8-300.2 pmol/min), p < 0.0001]. Additionally, we observed an altered metabolism in monocytes in patients undergoing cardiac surgery compared to controls even before any surgical procedure [t0: 179.2 pmol/min (95% CI 138.0-205.1) vs. controls 97.4 (95% CI 59.13-144.6 pmol/min), p = 0.0031]. Conclusion: After CPB, patients' monocytes show a shift in metabolism from oxidative phosphorylation to aerobic glycolysis, which is associated with energy-demanding and proinflammatory processes. This is the first study to show changes in monocyte immunometabolism in cardiac surgery. Monocytes of patients undergoing cardiac surgery were leaning toward aerobic glycolysis even before any surgical procedure was conducted. Leaving the question of the pathophysiological mechanisms for future studies to be investigated and paving the way for potential therapy approaches preventing inflammatory effects of CPB.

Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation.

Demand for organs is increasing while the number of donors remains constant. Nevertheless, not all organs are utilized due to the limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate whether an iron-chelator-supplemented Bretschneider solution could protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage. HTX was performed in foxhounds. The ischemic time was standardized to 4 h, 8 h, 12 h or 16 h, depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, the myocardial high energy phosphate and iron content and the in-vitro myocyte force were evaluated. Iron chelator supplementation proved superior at a routine preservation time of 4 h, as well as for prolonged times of 8 h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine triphosphate content in the supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content. This study shows that an iron-chelator-supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short- as well as long-term conservation.