Troponin T and N-Terminal Pro-Brain Natriuretic Peptide Are Associated with Long-Term All-Cause Mortality in Patients with Post-Sternotomy Mediastinitis following Coronary Artery Bypass Grafting: A 15-Year Follow-Up Study.

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.

Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling.

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.

Increased levels of NT-proBNP and troponin T 2 years after coronary artery bypass grafting complicated by mediastinitis.

Background: Mediastinitis 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 methods: The 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. Results: NT-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). Conclusion: Mediastinitis increases the concentrations of cardiac-specific biomarkers NT-proBNP and TnT at mid-term follow-up, representing persistent myocardial injury and impaired cardiac function.

Correlation between Murmurs and Echocardiographic Findings; From an Imaging Cardiologist Point of View.

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.

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation.

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.

Mediastinitis in open heart surgery: a systematic review and meta-analysis of risk factors.

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.

Levels of Lipoprotein (a) in patients with coronary artery disease with and without inflammatory rheumatic disease: a cross-sectional study.

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.

MicroRNA-615-5p Regulates Angiogenesis and Tissue Repair by Targeting AKT/eNOS (Protein Kinase B/Endothelial Nitric Oxide Synthase) Signaling in Endothelial Cells.

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.

MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells.

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.-Icli, B., Wu, W., Ozdemir, D., Li, H., Haemmig, S., Liu, X., Giatsidis, G., Cheng, H. S., Avci, S. N., Kurt, M., Lee, N., Guimaraes, R. B., Manica, A., Marchini, J. F., Rynning, S. E., Risnes, I., Hollan, I., Croce, K., Orgill, D. P., Feinberg, M. W. MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells.

Altered Levels of Fatty Acids and Inflammatory and Metabolic Mediators in Epicardial Adipose Tissue in Patients With Systolic Heart Failure.

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 α, 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.

Mediastinitis after coronary artery bypass grafting increases the incidence of left internal mammary artery obstruction.

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 2·7 years. The number of occluded SVG in the mediastinitis group was 18·9% versus 15·5% 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) = 0·96, 95% CI (0·52-2·67), P = 0·697]. The number of occluded IMA grafts was 10·5% in the mediastinitis group and 2·4% in the control group. Using the Poisson regression model, we estimated RR = 5·48, 95% CI (1·43-21·0) and P = 0·013. 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.

Mediastinitis after coronary artery bypass grafting: the effect of vacuum-assisted closure versus traditional closed drainage on survival and re-infection rate.

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.

Psychiatric outcome after severe cardio-respiratory failure treated with extracorporeal membrane oxygenation: a case-series.

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 (MINI-Neuropsychiatric Interview and Montgomery-Åsberg 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-Åsberg 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 alexithymic 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.

Mediastinitis after coronary artery bypass grafting risk factors and long-term survival.

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.

Clinical and psychosocial follow-up study of children treated with extracorporeal membrane oxygenation.

BACKGROUND: Serious heart and pulmonary failure may be treated with extracorporeal membrane oxygenation (ECMO). The aim of this follow-up study was a multimodal assessment of outcome in children surviving ECMO at our hospital from 1991 to 2004. METHODS: Twenty-two children were, on average, 1.18 years old (SD = 1.92; range, 0.1 to 7.8) when ECMO was initiated. Average age at follow-up was 7.2 years (range, 1.8 to 13.9). Thirteen children were treated for cardiac and nine for pulmonary failure. Venoarterial ECMO was performed in 21 patients and venovenous ECMO in one patient. The protocol included a review of patients records, clinical, neurologic and neuropsychologic, and radiological examinations, electroencephalogram, and interviews with the parents. RESULTS: Moderate or severe impairment in at least two clinical assessments were found in 16 (72.7%) children. Five (22.7%) children had cerebral palsy and 15 (68.2%) had moderate or severe cognitive impairment. Eight (36%) children had pathological radiologic findings. Pathological electroencephalograms were found in 11 (50%) patients including four (18.2%) with epileptic activity. Children with radiologic findings had a slightly worse cognitive outcome. There was no association between the neurophysiologic findings and the neuropsychologic performance or the radiologic findings. Based on parental assessment, only four children had pathological scores. CONCLUSIONS: All children, except for two, came walking to the follow-up visit. All parents were positive to the ECMO treatment, and reported a good or slightly reduced quality of life for their child. Cerebral sequelae were frequently found in children treated with ECMO. The need for treatment and support should be assessed in order to optimize their physical and psychosocial functioning.

Is it possible to predict outcome in cardiac ECMO? Analysis of preoperative risk factors.

BACKGROUND: Serious heart failure may be treated with extracorporeal membrane oxygenation (ECMO) when other treatment fails. The aim of the present study was to analyse preoperative risk factors of early mortality in patients treated with veno-arterial (VA)-ECMO. METHODS: We studied a total of 18 possible risk factors in 80 patients with severe cardiac insufficiency treated with VA-ECMO. All consecutive cases treated at our institution between Sept.1990 and May 2006 were included. Univariate analysis and multiple logistic regression analysis were performed on 16 risk factors. The endpoint was early mortality (any death within 30 days of ECMO treatment). RESULTS: Thirty patients (37.5%) died within 30 days. Age, gender, cause of cardiac failure, pre-ECMO treatment (ventilator, NO, IABP) did not significantly influence early mortality. A higher SvO2 was associated with survival and remained significant in the multivariate analysis. CONCLUSION: Treatment with VA-ECMO in patients with severe cardiac failure may save lives. It is, however, difficult to predict outcome. In this study, only SvO2 values prior to ECMO were positively associated with survival.

Cerebral outcome in adult patients treated with extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) carries a high risk of brain injury. The aim of this study was to determine the cerebral status in 28 adult survivors on average 5.0 (range, 0.5 to 12) years after ECMO treatment for severe cardiorespiratory failure. METHODS: All 28 patients were investigated at our institution. A comprehensive assessment protocol included a medical history, physical examination, neuropsychological assessment, electroencephalography, and neuroradiologic assessment. RESULTS: All patients were ambulant unaided, and 43% were without any clinical findings. Impaired neuropsychological performance was found in 41%, neuroradiologic findings in 52%, and a pathologic electroencephalogram in 41% of the patients. There was a significant correlation between the cognitive outcome and neuroradiologic findings. The incidence of neuroradiologic findings (cerebral infarction, microemboli or hemorrhage) was significantly higher in the venoarterial group compared with the venovenous group (75% versus 17%). There was no correlation between the type of ECMO and neuropsychological impairment. Electroencephalography findings did not correlate with neuropsychological performance, nor with the neuroradiologic findings. CONCLUSIONS: Late cerebral sequelae were frequently seen in patients treated on venoarterial ECMO. A significant correlation was found between cognitive impairment and neuroradiologic findings.

Complement activation and cytokine and chemokines release during mediastinitis.

BACKGROUND: Mediastinitis after open heart operation is an infrequent, but life-threatening complication with a reported incidence rate between 1% and 4%. Hospital mortality is estimated at 10% to 35%. The aim of the present work was to study the systemic inflammatory reaction as judged by complement activation and cytokine and chemokines release in patients with mediastinitis after open heart operation. METHODS: Seven patients with clinical signs of mediastinitis were included. Three patients had undergone coronary artery bypass grafting, whereas 4 patients had combined coronary artery bypass grafting, valve replacement, or valvuloplasty. Blood samples were drawn before induction of anesthesia and at the time of reoperation, and thereafter daily during the hospital stay. Controls comprised similar patients with an uneventful postoperative course. RESULTS: The terminal SC5b-9 complement complex concentration in the mediastinitis patients was substantially higher compared with the controls (p < 0.001), and the terminal SC5b-9 complement complex values showed no overlap between the two groups. Interleukin-8, stromal cell-derived factor-1alpha and IL-6 concentrations were also significantly higher in the mediastinitis group than in the control group (p < 0.001), but with considerable overlap between the groups. Interleukin-1beta, interleukin-10, and monocyte chemoattractant protein-1 concentrations were slightly higher in the mediastinitis group, and no differences were seen for the tumor necrosis factor-alpha. CONCLUSIONS: During mediastinitis, the complement is activated and the cytokines and chemokines, interleukin-6, interleukin-8, and stromal cell-derived factor-1alpha are released. These proteins may be involved in the pathogenesis of this complication. Terminal SC5b-9 complement complex may be an indicator to discriminate mediastinitis patients from those with uneventful course.

Changes in the cytokine network and complement parameters during open heart surgery.

OBJECTIVES: During cardiac surgery with cardiopulmonary bypass (CBP) there is a systemic inflammatory reaction, involving enhanced release of inflammatory cytokines and complement. However, few studies have analysed the levels of anti-inflammatory mediators and chemokines after CPB. In this study we investigated the complexity of the cytokine network particularly focusing on the balance between interleukin (IL)-10 and inflammatory cytokines and chemokines. METHODS: Blood samples from 20 patients (seven females; 13 males, age 30-81 (median 65) years) who underwent CPB, were collected before, and at several time points after surgery ,and analyzed for plasma levels of inflammatory and anti-inflammatory cytokines and parameters of complement activation. RESULTS: A marked increase in the anti-inflammatory cytokine IL-10, rather than in inflammatory cytokines, characterized the initial phase after CBP. As for the early inflammatory response the most prominent feature was a rise in the inflammatory chemokines IL-8 and monocyte chemoattractant protein-1, while the increase in tumor necrosis factor-alpha was rather modest. In contrast to the rapid 'rise and fall' in most of the markers, significantly raised IL-6 levels persisted throughout the study. Immediately after CPB there was also a marked increase in complement activation, with return to baseline levels on the first postoperative day. CONCLUSION: The present study shows a complex pattern of changes in the cytokine network and complement parameters during CBP with a marked rise in both inflammatory and anti-inflammatory mediators. However, in contrast to cytokine pattern during various infections, the initial phase after CPB was dominated by a marked rise in anti-inflammatory cytokines (i.e. IL-10).