INTRODUCTION:Left ventricular (LV) ejection fraction (LVEF) and LV end-diastolic diameter (LVEDd) are well-established predictors of adverse cardiovascular events. However, the possible association with survival in patients with infective endocarditis (IE) treated with aortic valve replacement (AVR) is underexplored. Additionally, it is important to investigate whether sex modifies these associations. METHODS:We retrospectively recruited 170 consecutive patients with IE treated with AVR from three cardiac surgery tertiary hospitals in Scandinavia. Echocardiography was performed both pre- and postoperatively. Baseline characteristics, preoperative blood samples, postoperative complications, echocardiographic, and angiographic data were compared between surviving and deceased patients at both short- (1-year) and long-term (5-year) follow-up. RESULTS:The mean age in the entire study population was 58.5 ± 15.1 years, and 80.0% were males. The mean LVEF was 54 ± 11% preoperatively, decreasing to 51 ± 11% postoperatively. The mean baseline LVEDd was 5.8 ± 0.9 cm in males and 5.0 ± 0.9 cm in females (p < 0.001), decreasing to 5.2 ± 0.9 cm in males and 4.7 ± 0.6 cm in females after surgery (p = 0.006). At short-term follow-up, reduced postoperative LVEF (<50%) was more common in non-survivors (46.2% vs. 26.2%, p = 0.040), with the strongest association observed in females (71.4% vs. 25.9%, p = 0.025). Similarly, during long-term follow-up, deceased female patients had a higher prevalence of reduced preoperative LVEF (<50%) compared to surviving female patients (30.0% vs. 4.2%, p = 0.033). LVEDd was significantly greater in female non-survivors compared to survivors at both short-term (5.7 ± 1.1 cm vs. 4.9 ± 0.8 cm, p = 0.043) and long-term follow-up (5.5 ± 0.9 cm vs. 4.8 ± 0.8 cm, p = 0.046), an association not observed in male patients. CONCLUSION:Our study found that both pre- and postoperative LVEF, as well as preoperative LVEDd, were associated with poorer outcomes in patients with IE undergoing AVR, particularly among female patients. These results highlight the importance of tailored clinical management strategies based on sex-specific risk profiles. Further research is needed to validate these findings and develop interventions to mitigate the observed risks.

Aortic valve infective endocarditis (IE) is associated with significant morbidity and mortality. We aimed to describe the clinical profile, risk factors and predictors of short- and long-term mortality in patients with aortic valve IE treated with aortic valve replacement (AVR) compared with a control group undergoing AVR for non-infectious valvular heart disease. Between January 2008 and December 2013, a total of 170 cases with IE treated with AVR (exposed cohort) and 677 randomly selected non-infectious AVR-treated patients with degenerative aortic valve disease (controls) were recruited from three tertiary hospitals with cardiothoracic facilities across Scandinavia. Crude and adjusted hazard ratios (HR) were estimated using Cox regression models. The mean age of the IE cohort was 58.5 ± 15.1 years (80.0

BackgroundMediastinitis after coronary bypass grafting (CABG) increases the risk of the internal mammary artery (IMA) graft obstruction, and has a detrimental effect on long-term survival. The pathogenesis for this increased mortality is poorly understood. In the present study, we aimed to investigate the relationship between mediastinitis and persistently elevated cardiac-specific biomarkers [troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)] and C-reactive protein (CRP) at mid-term follow-up following CABG.Material and methodsThe epidemiologic design was of an exposed (mediastinitis, n = 41) vs. randomly selected non-exposed (non-mediastinitis) controls (n = 41) cohort. Serum samples for measurements of NT-proBNP, TnT, and CRP were obtained at a median follow up time of 2.7 (range 0.5–5.2) years after CABG surgery.ResultsNT-proBNP (mean 65.0 pg/ml vs. 34.8 pg/ml, p = 0.007) and TnT levels (mean 14.7 ng/L vs. 11.2 ng/L, p = 0.004) were significantly higher in the mediastinitis group than in the control group. Patients with mediastinitis had also higher body mass index (BMI) and were more likely to have diabetes and previous myocardial infarction. There was no difference in serum CRP level between the groups. After controlling for potential confounders (previous myocardial infarction, age, and BMI), the presence of mediastinitis was associated with higher levels of log NT-proBNP (p = 0.02) and log TnT (p = 0.04).ConclusionMediastinitis increases the concentrations of cardiac-specific biomarkers NT-proBNP and TnT at mid-term follow-up, representing persistent myocardial injury and impaired cardiac function.

Angiogenesis is critical for tissue repair following myocardial infarction (MI), which is exacerbated under insulin resistance or diabetes. MicroRNAs are regulators of angiogenesis. We examined the metabolic regulation of miR-409-3p in post-infarct angiogenesis. miR-409-3p was increased in patients with acute coronary syndrome (ACS) and in a mouse model of acute MI. In endothelial cells (ECs), miR-409-3p was induced by palmitate, while vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) decreased its expression. Overexpression of miR-409-3p decreased EC proliferation and migration in the presence of palmitate, whereas inhibition had the opposite effects. RNA sequencing (RNA-seq) profiling in ECs identified DNAJ homolog subfamily B member 9 (DNAJB9) as a target of miR-409-3p. Overexpression of miR-409-3p decreased DNAJB9 mRNA and protein expression by 47% and 31% respectively, while enriching DNAJB9 mRNA by 1.9-fold after Argonaute2 microribonucleoprotein immunoprecipitation. These effects were mediated through p38 mitogen-activated protein kinase (MAPK). Ischemia-reperfusion (I/R) injury in EC-specific miR-409-3p knockout (KO) mice (miR-409ECKO) fed a high-fat, high-sucrose diet increased isolectin B4 (53.3%), CD31 (56%), and DNAJB9 (41.5%). The left ventricular ejection fraction (EF) was improved by 28%, and the infarct area was decreased by 33.8% in miR-409ECKO compared with control mice. These findings support an important role of miR-409-3p in the angiogenic EC response to myocardial ischemia.

Background: Deep sternal wound/mediastinitis is a rare but feared complication in coronary artery bypass grafting (CABG) patients and seems to increase the risk of cardiac death, and is also associated with the risk of early internal mammary artery (IMA) graft obstruction. The pathological mechanism explaining the link between mediastinitis and IMA graft obstruction and the impact on mortality is complex, multifactorial, and not fully investigated. Objectives: Mediastinitis has been associated with increased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T (TnT) at mid-term follow-up, representing persistent low-grade myocardial injury and impaired cardiac function. However, whether mediastinitis is associated with all-cause mortality, or whether the association is driven by these cardiac-specific biomarkers (NT-proBNP and TnT), is not investigated. Methods: The present study provides the longest and most complete follow-up data in 82 patients undergoing CABG, including 41 with post-sternotomy mediastinitis. Results: The annualized incidence rate of mediastinitis was 0.14%/year and remained stable at 0.14% throughout the study period. During a mean follow-up of 12.7 ± 3.5 years, a total of 42 deaths occurred (27 [65.9%] in mediastinitis and 15 [36.6%] in non-mediastinitis group, p = 0.008). No association was found between IMA or saphenous vein graft obstruction with all-cause mortality. Mediastinitis was associated with a 1.9-fold increased risk of all-cause mortality. However, in the multivariable-adjusted models, age and higher TnT and NT-proBNP levels, but not mediastinitis per se were associated with all-cause mortality. Conclusions: Mediastinitis after CABG surgery was associated with a poor prognosis during a 15-year follow-up, showing a nearly two-fold higher frequency of all-cause mortality compared with non-mediastinitis group, with the differences in mortality rate occurring primarily after 10 years. The association between mediastinitis and all-cause mortality was modulated by subclinical myocardial damage and stretch, reflected by elevated TnT and NT-proBNP, measured at 2.7-year follow-up, underscoring that these could represent prognostic markers in CABG patients.

A heart murmur in adults is a common reason for referral for echocardiography at most general cardiology clinics in Europe. A murmur may indicate either a mild age-related valvular calcification or regurgitation, or represent a significant heart valve disease requiring valvular intervention. Generally, the correlation between murmurs by auscultation and severity of heart valve disease by echocardiography is poor. Particularly, the severity and characterization of diastolic murmurs by auscultation may poorly correlate with echocardiographic findings. This narrative review aims to summarize the differential diagnoses of physiological and pathological murmurs, describes the current referral practice of murmur patients for echocardiography, and presents a single-center experience on the correlation of auscultation and echocardiographic findings with a particular focus on aortic and mitral valve diseases. A careful auscultation of the heart prior to the echocardiogram is mandatory and may help to predict the echocardiographic findings and their interpretation in view of the clinical information. The correlation between clinical examination, point of care ultrasound and standard echocardiography is a matter of continued exploration.

Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation.Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint.Results:Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci.Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation.

Objective- In response to tissue injury, the appropriate progression of events in angiogenesis is controlled by a careful balance between pro and antiangiogenic factors. We aimed to identify and characterize microRNAs that regulate angiogenesis in response to tissue injury. Approach and Results- We show that in response to tissue injury, microRNA-615-5p (miR-615-5p) is rapidly induced and serves as an antiangiogenic microRNA by targeting endothelial cell VEGF (vascular endothelial growth factor)-AKT (protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling in vitro and in vivo. MiR-615-5p expression is increased in wounds of diabetic db/db mice, in plasma of human subjects with acute coronary syndromes, and in plasma and skin of human subjects with diabetes mellitus. Ectopic expression of miR-615-5p markedly inhibited endothelial cell proliferation, migration, network tube formation in Matrigel, and the release of nitric oxide, whereas miR-615-5p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3' untranslated region reporter and microribonucleoprotein immunoprecipitation assays, and small interfering RNA dependency studies demonstrate that miR-615-5p inhibits the VEGF-AKT/eNOS signaling pathway in endothelial cells by targeting IGF2 (insulin-like growth factor 2) and RASSF2 (Ras-associating domain family member 2). Local delivery of miR-615-5p inhibitors, markedly increased angiogenesis, granulation tissue thickness, and wound closure rates in db/db mice, whereas miR-615-5p mimics impaired these effects. Systemic miR-615-5p neutralization improved skeletal muscle perfusion and angiogenesis after hindlimb ischemia in db/db mice. Finally, modulation of miR-615-5p expression dynamically regulated VEGF-induced AKT signaling and angiogenesis in human skin organoids as a model of tissue injury. Conclusions- These findings establish miR-615-5p as an inhibitor of VEGF-AKT/eNOS-mediated endothelial cell angiogenic responses and that manipulating miR-615-5p expression could provide a new target for angiogenic therapy in response to tissue injury. Visual Overview- An online visual overview is available for this article.

OBJECTIVES:Patients with various inflammatory rheumatic diseases (IRDs) have increased risk of atherothrombotic disease. Lipoprotein (a) (Lp(a)) is a risk factor for atherosclerosis but its role in IRD with accompanying coronary artery disease (CAD) is still unclear. We aimed to examine if serum Lp(a) levels differed between CAD patients with and without accompanying IRD.DESIGN:A cross-sectional observational, patient-based cohort study.SETTING:Referred centre for coronary artery bypass grafting in the South Eastern part of Norway.PARTICIPANTS:67 CAD patients with IRD (CAD/IRD) and 52 CAD patients without IRD (CAD/non-IRD). All patients were Caucasians, aged >18 years, without any clinically significant infection or malignancy.METHODS:Lp(a) levels in serum were analysed by particle enhanced immunoturbidimetric assay, and Lp(a) levels were related to clinical and biochemical characteristics of the patient population.RESULTS:We found no differences in serum levels of Lp(a) between CAD patients with and without IRD. In general, we found that Lp(a) correlated poorly with clinical and biochemical parameters including C reactive protein with the same pattern in the CAD/non-IRD and CAD/IRD groups.CONCLUSIONS:Our data do not support a link between inflammation and Lp(a) levels in CAD and in general Lp(a) levels were not correlated with other risk factors for cardiovascular disease.

Objective. We aimed to summarize the evidence from observational studies examining the risk factors of the incidence of mediastinitis in open heart surgery. Design. The study was a systematic review and meta-analysis of cohorts and case-control studies. Material and methods. We searched the literature and 74 studies with at least one risk factor were identified. Both fixed and random effects models were used. Heterogeneity between studies was examined by subgroup and meta-regression analysis. Publication bias or small study effects were evaluated and corrected by limit meta-analysis. Results. When correcting for small study effect, presence of obesity as estimated from 43 studies had Odds Ratio OR = 2.26. (95% CI: 2.17-2.36). This risk was increasing with decreasing latitude of study place. Presence of diabetes mellitus from 63 studies carried an OR = 1.90 (95% CI: 1.59-2.27). Presence of Chronic Obstructive Pulmonary Disease (COPD) from 30 studies had an OR = 2.59 (95% CI: 2.22-2.85). Presence of bilateral intramammary graft (BIMA) from 23 studies carried an OR = 2.54 (95% CI: 2.07-3.13). This risk was increasing with increasing frequency of female patients in the study population. Conclusion. Evidence from this study showed the robustness of the risk factors in the pathogenesis of mediastinitis. Preventive measures can be implemented for reducing obesity, especially in lower latitude countries. Furthermore, it is mandatory to monitor perioperative hyperglycemias with continuous insulin infusion. Use of skeletonized BIMA carries higher risk of mediastinitis especially in female patients without evidence of beneficial effect on survival for the time being.

Angiogenesis is a critical process in repair of tissue injury that is regulated by a delicate balance between pro- and antiangiogenic factors. In disease states associated with impaired angiogenesis, we identified that miR-135a-3p is rapidly induced and serves as an antiangiogenic microRNA (miRNA) by targeting endothelial cell (EC) p38 signaling in vitro and in vivo. MiR-135a-3p overexpression significantly inhibited EC proliferation, migration, and network tube formation in matrigel, whereas miR-135-3p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3'-UTR reporter and miRNA ribonucleoprotein complex -immunoprecipitation assays, and small interfering RNA dependency studies revealed that miR-135a-3p inhibits the p38 signaling pathway in ECs by targeting huntingtin-interacting protein 1 (HIP1). Local delivery of miR-135a-3p inhibitors to wounds of diabetic db/db mice markedly increased angiogenesis, granulation tissue thickness, and wound closure rates, whereas local delivery of miR-135a-3p mimics impaired these effects. Finally, through gain- and loss-of-function studies in human skin organoids as a model of tissue injury, we demonstrated that miR-135a-3p potently modulated p38 signaling and angiogenesis in response to VEGF stimulation by targeting HIP1. These findings establish miR-135a-3p as a pivotal regulator of pathophysiological angiogenesis and tissue repair by targeting a VEGF-HIP1-p38K signaling axis, providing new targets for angiogenic therapy to promote tissue repair.

Background Rheumatoid Arthritis (RA) patients have increased cardiovascular risk due to accelerated atherosclerosis (ATS), which significantly contributes to excess mortality in RA1. The increased cardiovascular risk cannot be fully explained by traditional risk factors and systemic chronic inflammation appears to play a crucial role. Interestingly, IL-7, a proinflammatory cytokine involved in RA pathogenesis, appears to play a role also in atherosclerosis2 but its effect on cardiovascular disease (CVD) in RA has not been studied yet. Objectives To examine serum IL-7 levels and expression of IL-7, IL-7R, CD3 and CD20 in aortic adventitia of RA and non-RA patients with coronary artery disease (CAD) and to search for relationships between systemic IL-7 levels and expression of vascular markers, cardiovascular risk factors including metabolic and inflammatory markers. Methods We examined 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery included in the Feiring Heart Biopsy Study. Serum IL-7 levels were measured by chemiluminescence (MSD). Biopsies from the adventitia of thoracic aorta from a subset of patients (12 RA and 14 non-RA) were stained for IL-7, IL-7R, CD3 and CD20 by immunohistochemistry and scored per mm2 of tissue. Results Non-RA patients had lower IL-7 serum levels than RA (3.4±3.3 vs. 6.7±3.5, p<0.05). Independently of RA diagnosis, IL-7 significantly correlated with CRP (rho=0.450, p=0.008), triglycerides (TG, rho=0.566, p=0.005), glucose (rho=0.642, p=0.001) and hypertension (p=0.036). Levels of IL-7 were associated with New York Heart Association class (rho=0.429, p=0.014) and this was stronger in non-RA patients (rho=0.577, p=0.010). No associations were found with smoking or markers of CVD severity (i.e. numbers of arteries with significant stenosis or number of previous myocardial infarcts (MI)). The number of IL-7 +and IL-7R+cells/mm2 in adventitia were significantly higher in RA (134.2±45.5 and 144±49.9 respectively) than non-RA patients (46.9±22.8 and 54.4±20.2, p<0.005) and were associated with serum IL-7 levels (rho=0.551 and rho=0.588, p<0.01). Both IL-7 +and IL7R+cells were associated with a positive history of MI (p=0.047 and p=0.005) and IL-7R+cells with the number of previous MIs (rho=0.408, p=0.038). Only in RA patients, IL-7R+cells showed a trend for correlation with TG (rho=0.771, p=0.072). IL-7 +and IL-7R+cells correlated with CD3 (rho=0.688, p=0.013 and rho=0.630 p=0.028), but no correlation was found with CD20. Cholesterol and HDL levels were associated with IL-7 +cells only in non-RA patients (rho=0.729 p=0.04 and rho=0.733, p=0.038). Conclusions Among patients with CAD, those with RA had higher serum IL-7 and a greater expression of both IL-7/IL-7R is aortic adventitia. Systemic levels of IL-7 were related to its vascular expression. Thus, the IL-7/IL-7R axis may play a role in the accelerated atherogenesis observed in RA; further studies are needed to elucidate the precise role of IL-7 and impact of potential IL-7R blockade in CV risk in RA. References [1] Kaplan MJ. Curr. Opin. Rheumatol2006;18(3):289–297. [2] Damås JK, et al. Circulation2003;107(21):2670–2676. Disclosure of Interest None declared

Introduction Rheumatoid Arthritis (RA) patients have increased cardiovascular risk (CV) due to accelerated atherosclerosis (ATS), which significantly contributes to excess mortality in RA.1 The increased CV risk cannot be fully explained by traditional risk factors and systemic chronic inflammation appears to play a crucial role. Interestingly, IL-7, a proinflammatory cytokine involved in RA pathogenesis, appears to play a role also in ATS2 but its effect on cardiovascular disease (CVD) in RA has not been studied yet. Objectives To examine serum IL-7 levels and expression of IL-7, IL-7R, CD3 and CD20 in aortic adventitia of RA and non-RA patients with coronary artery disease (CAD) and to search for relationships between systemic IL-7 levels and expression of vascular markers, cardiovascular risk factors including metabolic and inflammatory parameters. Methods We examined 19 RA and 20 non-RA patients undergoing coronary artery bypass graft surgery included in the Feiring Heart Biopsy Study. Serum IL-7 levels were measured by chemiluminescence (MSD). Biopsies from the adventitia of thoracic aorta from a subset of patients (12 RA and 14 non-RA) were stained for IL-7, IL-7R, CD3 and CD20 by immunohistochemistry and scored per mm2 of tissue. Results Non-RA patients had lower IL-7 serum levels than RA (3.4±3.3 vs. 6.7±3.5, p<0.05). Independently of RA diagnosis, IL-7 significantly correlated with CRP (rho=0.450, p=0.008), triglycerides (TG, rho=0.566, p=0.005), glucose (rho=0.642, p=0.001) and hypertension (p=0.036). Levels of IL-7 were associated with New York Heart Association class (rho=0.429, p=0.014) and this was stronger in non-RA patients (rho=0.577, p=0.010). No associations were found with smoking or markers of CVD severity (i.e., numbers of arteries with stenosis or previous myocardial infarcts (MI)). The number of IL-7 +and IL-7R+cells/mm2 in adventitia were significantly higher in RA (134.2±45.5 and 144±49.9 respectively) than non-RA patients (46.9±22.8 and 54.4±20.2, p<0.005) and were associated with serum IL-7 levels (rho=0.551 and rho=0.588, p<0.01). Both IL-7 +and IL7R+cells were associated with a positive history of MI (p=0.047 and p=0.005) and IL-7R+cells with the number of previous MIs (rho=0.408, p=0.038). Only in RA patients, IL-7R+cells showed a trend for correlation with TG (rho=0.771, p=0.072). IL-7 +and IL-7R+cells correlated with CD3 (rho=0.688, p=0.013 and rho=0.630, p=0.028), but no correlation was found with CD20. Cholesterol and HDL levels were associated with IL-7 +cells only in non-RA patients (rho=0.729, p=0.04 and rho=0.733, p=0.038). Conclusions Among patients with CAD, those with RA had higher serum IL-7 and a greater expression of both IL-7 and IL-7R is aortic adventitia. Systemic levels of IL-7 were related to its vascular expression. Thus, the IL-7/IL-7R axis may play a role in the accelerated ATS observed in RA; further studies are needed to elucidate the precise role of IL-7 in CV risk in RA. References . Kaplan MJ. Curr. Opin. Rheumatol2006;18(3):289–297. . Damås JK, et al. Circulation2003;107(21):2670–2676. Acknowledgements None. Disclosure of interest None declared

Background: Adipose tissue has endocrine properties, secreting a wide range of mediators into the circulation, including factors involved in cardiovascular disease. However, little is known about the potential role of adipose tissue in heart failure (HF), and the aim of this study was to investigate epicardial (EAT) and subcutaneous (SAT) adipose tissue in HF patients.Methods and Results: Thirty patients with systolic HF and 30 patients with normal systolic function undergoing thoracic surgery were included in the study. Plasma was sampled and examined with the use of enzyme-linked immunosorbent assays, whereas SAT and EAT biopsies were collected and examined by means of reverse-transcription polymerase chain reaction and gas chromatography. Significantly higher expressions of mRNA encoding interleukin-6, adrenomedullin, peroxisome proliferator activated receptor a, and fatty acid (FA) binding protein 3, as well as higher levels of monounsaturated FA and palmitoleic acid, were seen in the EAT of HF patients, whereas the levels of docosahexaenoic acid were lower. Palmitoleic acid levels in EAT were correlated with 2 parameters of cardiac remodeling: increasing left ventricular end-diastolic diameter and N-terminal pro B-type natriuretic peptide.Conclusions: Our results demonstrate adipose tissue depot specific alterations of synthesis of FA and inflammatory and metabolic mediators in systolic HF patients. EAT may be a source of increased circulatory and myocardial levels of these mediators through endocrine actions.

Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.

Mediastinitis is treated with either vacuum‐assisted closure (VAC) or traditional closed drainage (TCD) with irrigation. The aim of the study was to determine the effect of the two treatments on mortality and re‐infection rate in a source population, using 21 314 consecutive patients undergoing isolated coronary artery bypass grafting (CABG) from January 1997 to October 2010. Median observation time was 2·9 years in the VAC group and 8·0 years in the TCD group. The epidemiological design was of an exposed (VAC, n = 64) versus non‐exposed (TCD, n = 66) cohort with two endpoints: (1) mortality and (2) failure of sternal wound healing or re‐infection. The crude effect of treatment technique versus endpoint was estimated by univariate analysis. Stratification analysis by the Mantel–Haenszel method was performed to quantify confounders and to pinpoint effect modifiers. Adjustment for confounders was performed using Cox regression analysis. Mediastinitis was diagnosed 6–105 (median 14) days after primary operation in the VAC group and 13 (5–29) days in the TCD group. There was no difference between groups in long‐term survival. Failure of sternal wound healing or re‐infection occurred less frequently in the VAC group (6%) than in the TCD group (21%; relative risk = 0·29, 95% CI = 0·06–0·88, P = 0·01). There are concerns for increase in right ventricle rupture in VAC compared with TCD. There was no difference in survival after VAC therapy and TCD therapy of post‐CABG mediastinitis. Failure of sternal wound healing or re‐infection was more common after TCD therapy.

Mediastinitis after coronary artery bypass grafting (CABG) gives a longstanding chronic inflammation and has a detrimental negative effect on long-term survival. For this reason, we aimed to study the effect of mediastinitis on graft patency after CABG. The epidemiologic design was of an exposed (mediastinitis, n = 41) versus non-exposed (non-mediastinitis, controls, n = 41) cohort with two endpoints: (i) obstruction of saphenous vein grafts (SVG) and (ii) obstruction of the internal mammary artery (IMA) grafts. The graft patency was evaluated with coronary CT-angiography examination at a median follow-up of 27 years. The number of occluded SVG in the mediastinitis group was 189% versus 155% in the control group. Using generalized estimating equations model with exchangeable matrix, and confounding effect of ischaemic time and patients age, we found no significant association between presence of mediastinitis and SVG obstruction [rate ratio (RR) = 096, 95% CI (052-267), P = 0697]. The number of occluded IMA grafts was 105% in the mediastinitis group and 24% in the control group. Using the Poisson regression model, we estimated RR = 548, 95% CI (143-210) and P = 0013. There was a significant association between mediastinitis and IMA graft obstruction, when controlling for the confounding effect of ischaemic time, body mass index, presence of diabetes mellitus and the number of diseased vessels. Presence of mediastinitis increases the risk of IMA graft obstruction. This may confirm the importance of inflammation as a major contributor to the pathogenesis of atherosclerosis and explain the negative effect of mediastinitis on a long-term survival.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used to save patients with severe cardiopulmonary failure at high risk of dying, but the long-term psychiatric outcome of the treatment has not been studied Methods: Twenty-eight adults who survived ECMO were subjected to psychiatric assessment 5 years after ECMO by means of interviews (MM-Neuropsychiatric Interview and Montgomery-Asberg Depression Rating Scale) and psychometrics [Neuroticism and social conformity (EPQ-N+L); General Health Questionnaire (GHQ), Hospital Anxiety Depression Scale; Aggression Questionnaire, Toronto Alexithymia Scale, and Giessener somatic symptom checklist (GBB)]. Results: Fifteen patients (54%) suffered lifetime psychiatric disorders prior to ECMO. After ECMO, 11 subjects (39%) developed new psychiatric disorders, mostly organic mental (18%), obsessive-compulsive disorders (OCD) 15%, and/or post-traumatic stress disorders (PTSD) 11%. These 11 patients reported higher scores on Montgomery-Asberg Depression Rating Scale (MADRS), GHQ, EPQ-N and GBB. Disregarding the presence of psychiatric disorders at follow-up, ECMO patients reported high levels of distress, physical aggression, anger, and alexithyrnic traits. Conclusions: Severe life-threatening cardiovascular or pulmonary failure with subsequent ECMO is associated with an increased prevalence of long-term psychiatric disorders and distress. Studies addressing the etiology and prevalence of psychiatric consequences after ECMO are needed.

BACKGROUND:Mediastinitis is a severe complication of coronary artery bypass grafting. The aim of the present study was to determine incidence of mediastinitis, its risk factors, and its effect on early and long-term survival. METHODS:The study has a dual design, a case-control, and a retrospective cohort, using a source population of 18,532 consecutive patients who underwent coronary artery bypass grafting from January 1989 to December 2000. The closing date was February 1, 2008. Median follow-up was 10.3 (range 8.1 to 18.9) years. Patients with mediastinitis were compared with a random control group without mediastinitis issued from the same source population in a ratio 1:4. The crude effect of mediastinitis was estimated using rate ratio and 95% confidence limits. Adjustment for multiconfounders was done with the Cox model. A logistic model was used to pinpoint risk factors of mediastinitis. Calibration and discrimination of a prognostic model was done. RESULTS:One hundred seven patients (0.6%) developed mediastinitis. Diagnosis was made 12 (9 to 19) days postoperatively. Independent risk factors of mediastinitis using the logistic model were advanced age, male gender, left main stenosis, body mass index 30 kg/m(2) or greater, chronic obstructive pulmonary disease, diabetes, and increased amount of blood transfusion. There was no increased risk of early mortality (odds ratio = 0.58; 95% confidence interval 0.13 to 2.61) (p = 0.48) but there was increased risk of morbidity (intraaortic balloon pump, ventricular and supraventricular arrhythmia, stroke, inotrope, and myocardial infarction). Follow-up had a median observation time of 10.3 years. Survival for patients with mediastinitis was 49.5 +/- 5.0% versus 71.0 +/- 2.2% for controls (p < 0.01). Analysis of specific death causes documented that cardiac deaths were significantly more frequent in mediastinitis patients than in control patients. When controlling for the confounding effect of the other variables (age, cardiopulmonary bypass time, body mass index, chronic obstructive pulmonary disease), the hazard ratio associated with mediastinitis on long-term mortality was 1.59, 95% confidence limits (1.16 and 2.70) (p = 0.003). CONCLUSIONS:The incidence of mediastinitis in 18,532 patients undergoing coronary artery bypass grafting surgery was low. The major preventable risk factor of mediastinitis was amount of blood transfusion. Mediastinitis had an excess risk of early morbidity and was associated with a significant reduced long-term survival. Most deaths were considered to be cardiac.