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Background: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes. Objective: To investigate whether HMGB1 and its receptors are expressed in cardiac muscles of elderly patients with CAD with or without IRD. Methods: HMGB1 and its 3 well-known receptors, receptor for advanced glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were measured by Western blot from the cardiac biopsies in 5 patients with and 5 without IRD. Results: Pathologic cytosolic HMGB1 in cardiomyocytes was massively recorded in all patients with IRD, but only slightly expressed in 1 patient without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle biopsies of patients with IRD compared to those without IRD. Furthermore, all 3 HMGB1 receptors were expressed in cardiomyocytes of all patients. Conclusion: The increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD individuals. Thus, the HMGB1 signaling pathways may be more easily activated in elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD patients might reduce the risk for cardiovascular events.

ObjectivesPatients 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.DesignA cross-sectional observational, patient-based cohort study.SettingReferred centre for coronary artery bypass grafting in the South Eastern part of Norway.Participants67 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.MethodsLp(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.ResultsWe 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.ConclusionsOur 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.

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 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 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] Damas 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 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. . Damas JK, et al. Circulation2003;107(21):2670–2676. Acknowledgements None. Disclosure of interest None declared

Background— This article presents an update of the results achieved by modern surgery in congenital heart defects (CHDs) over the past 40 years regarding survival and the need for reoperations, especially focusing on the results from the past 2 decades. Methods and Results— From 1971 to 2011, all 7038 patients P P =0.003), and 5-year cumulative survival was 88.8% versus 95.0% ( P =0.0003). In simple versus complex defects, 434 (11.6%) versus 985 (33.8%) patients needed at least 1 reoperation before 16 years of age. In complex defects, 5-year cumulative freedom of reoperation among patients operated on in 1990 to 1999 versus 2000 to 2011 was 66% versus 73% ( P =0.0001). Conclusions— Highly significant, sequential improvements in survival and reductions in reoperations after CHD surgery were seen. A future challenge is to find methods to reduce the need for reoperations and further reduce long-term mortality.

Objectives. Patients with inflammatory rheumatic diseases (IRDs) have a higher morbidity and mortality from accelerated atherosclerosis than the general population. We hypothesized that patients with the combination of IRD and coronary artery disease (CAD) would have a certain inflammatory phenotype compared with CAD patients without this comorbidity. Methods. Four groups of patients were included: patients with IRD, referred to coronary artery bypass grafting (CABG) (CAD–IRD, n = 67), patients without IRD, referred to CABG (CAD, n = 52), patients with IRD without CAD (IRD, n = 32) and healthy controls (n = 30). Plasma levels of several inflammatory markers were analysed by enzyme immunoassays. Results. (i) Plasma levels of markers of endothelial cell activation [i.e. vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor] and osteoprotegerin (OPG) were significantly increased and plasma levels of CCL21 significantly decreased in CAD–IRD patients as compared with CAD patients without IRD. (ii) Within the CAD–IRD group, acute coronary syndrome was a significant predictor of OPG, suggesting an enhanced inflammatory response during plaque destabilization in CAD–IRD patients. (iii) Plasma levels of VCAM-1, OPG and CCL21, but not lipid parameters, IRD characteristics and several other inflammatory markers (e.g. CRP), were significant predictors of CAD–IRD as opposed to CAD in two logistic regression models. Conclusion. Our findings further support a role for inflammation in the accelerated form of atherosclerosis in IRD patients, and suggest that certain inflammatory pathways, such as the enhanced endothelial cell activation and the RANK ligand/RANK/OPG system, may be of particular importance.

Objective Various inflammatory rheumatic diseases (IRDs) are associated with increased mortality due to cardiovascular disease. The aim of this study was to investigate heart biopsy specimens obtained from patients undergoing coronary artery bypass grafting and compare markers of inflammation and endothelial cell activation in the cardiac and skeletal muscle of patients with and those without IRD. Methods Paired biopsy specimens of cardiac and skeletal muscle were obtained from 22 consecutive patients with IRD and 8 patients without IRD, all of whom were undergoing coronary artery bypass grafting. The biopsy specimens were evaluated in a blinded manner by conventional microscopy and digital image analysis for cell markers (CD3, CD4, CD8, CD68, CD163, and CD31), HLA (HLA–ABC, HLA–DR, and HLA–DQ), adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and proinflammatory cytokines (interleukin-1α, interleukin-1β, and tumor necrosis factor). Results Patients with IRD had significantly higher expression of adhesion molecules, proinflammatory cytokines, and all classes of HLA on cardiomyocytes and endothelial cells but no increase on mononuclear cells in the myocardium compared with patients without IRD. Furthermore, cardiac muscle from patients with IRD displayed significantly higher local expression of inflammation and activation of cardiac microvessels compared with skeletal muscle from the same patients. Conclusion Patients with cardiovascular disease had increased expression of adhesion molecules, HLA, and proinflammatory cytokines in heart tissue, indicating local inflammation involving microvessels and cardiomyocytes that could play a role in the pathogenesis of cardiovascular disease. The more pronounced changes in patients with IRD compared with patients without IRD might contribute to the increased risk of cardiovascular disease and premature death in patients with IRD.

Objective Pentraxin 3 (PTX3), a key component of innate immunity, is a strong marker of disease severity in coronary artery disease (CAD). The aim of this study was to compare levels of serum PTX3 in CAD patients with and without inflammatory rheumatic disease (IRD) and in healthy controls. Methods We examined 69 patients with IRD (CAD/IRD group) and 53 patients without IRD (CAD/non-IRD) referred to coronary artery bypass grafting, and 30 healthy controls. Results The mean ± SD serum PTX3 level in the CAD/IRD group was 1.96 ± 0.98 ng/ml; this was statistically significantly higher than that of the CAD/non-IRD (1.41 ± 0.74 ng/ml) and healthy control (1.21 ± 0.59 ng/ml) groups. In contrast to most other IRDs, serum PTX3 levels were relatively low in patients with systemic lupus erythematosus (SLE) and other systemic connective tissue diseases. In sex- and age-adjusted analysis, IRD, acute coronary syndromes, and low alcohol intake were associated with higher serum PTX3 levels. Conclusion CAD patients with IRD had higher mean serum PTX3 levels than patients without IRD and healthy controls. In addition, acute coronary syndromes and low alcohol intake independently predicted higher serum PTX3 levels. Higher serum PTX3 levels in IRD may be related to the higher cardiovascular risk of IRD patients. Circulating PTX3 could likely be used as a biomarker for severity of cardiovascular disease in IRDs; its importance, however, might be limited in SLE and related disorders.

Background The main aim of the present study was to compare the occurrence of inflammatory cell infiltrates in the aorta, a vessel with a high occurrence of atherosclerosis, with that in the saphenous vein (SV) and internal mammary artery (IMA), which are protected from atherosclerosis. Methods and Results Samples from the aorta, SV, and IMA of 65 patients with inflammatory rheumatic diseases (IRD) and from 51 control patients undergoing coronary artery bypass graft surgery were examined for the presence and location of inflammatory cell infiltrates and atherosclerotic lesions. Mononuclear cell infiltrates (MCIs) in the media or adventitia were observed in 2% IMAs, 17% SVs, and 35% aortic specimens (SV vs IMA: p=0.006; SV vs aorta: p=0.001). Atherosclerotic lesions were present in none IMA, 3% SVs and 18% aortic specimens. IRD and smoking increased the odds of MCI in the aorta (odds ratio (OR)=3.6, 95% confidence interval (CI): 1.6-8.5 and OR=4.0, 95% CI: 1.5-10.9), but not in the SV or IMA. Conclusions The occurrence of medial and adventitial MCI in the aorta, SV, and IMA paralleled each vessel's susceptibility to atherosclerosis: it was highest in the aorta and lowest in IMA. Local vascular inflammation may be involved in atherogenesis, and influence the patency of vascular grafts. (Circ J 2008; 72: 1986 - 1992)

Objective Several inflammatory rheumatic diseases are associated with accelerated atherosclerosis. Atherosclerosis may result from systemic and/or local vascular inflammation. The aim of this study was to evaluate the occurrence of chronic inflammatory infiltrates in the aortas of patients with and those without inflammatory rheumatic disease who had undergone coronary artery bypass graft (CABG) surgery, and to assess the relationship between the infiltrates and other factors thought to play a role in atherosclerosis, such as smoking. Methods Aortic specimens routinely removed during CABG surgery in 66 consecutive patients with inflammatory rheumatic disease and 51 control patients without inflammatory rheumatic disease were examined by light microscopy for the occurrence, location, and severity of chronic inflammatory infiltrates and atherosclerotic lesions. Results Mononuclear cell infiltrates in the inner adventitia (apart from those localized along the epicardium) were more frequent in the group of patients with inflammatory rheumatic disease (47% versus 20%; P = 0.002, odds ratio [OR] OR 3.6, 95% confidence interval [95% CI] 1.6–8.5), and the extent of these infiltrates was greater. Multivariate analyses revealed that the occurrence of mononuclear cell infiltrates was associated with inflammatory rheumatic disease (OR 2.99, P = 0.020) and current smoking (OR 3.93, P = 0.012), and they were observed in 6 of 7 patients with a history of aortic aneurysm. Inflammatory infiltrates in the media were seen only in patients with inflammatory rheumatic disease. The frequency of atherosclerotic lesions, inflammation within the plaques, and epicardial inflammatory infiltrates in the 2 groups was equal. Conclusion Among aortic samples collected during CABG surgery, those obtained from patients with inflammatory rheumatic disease had more pronounced chronic inflammatory infiltration in the media and inner adventitia than those obtained from control patients. Current smoking was an independent predictor of chronic inner adventitial infiltrates. The infiltrates may represent an inflammatory process that promotes atherosclerosis and formation of aneurysms.

Corticosteroids decrease side effects after noncardiac elective surgery. We designed this randomized, double-blinded, placebo-controlled study to test the hypothesis that standard doses of dexamethasone (4 mg x2) would reduce postoperative nausea, vomiting, and pain, decrease the incidence of atrial fibrillation (AF), and improve appetite after cardiac surgery, thereby facilitating the recovery process. A total of 300 patients undergoing coronary revascularization surgery were enrolled in this clinical study. The anesthetic management was standardized in all patients. Dexamethasone (4 mg/mL) or saline (1 mL) was administered after the induction of anesthesia and a second dose of the same study drug was given on the morning after surgery. The incidence of AF was determined by analyzing the first 72 h of continuously recorded electrocardiogram records after cardiac surgery. The patients were assessed at 24- and 48-h intervals after surgery, as well as at the time of hospital discharge, to determine the incidence and severity of postoperative side effects (e.g., nausea, vomiting, pain) and patient satisfaction scores. Dexamethasone significantly reduced the need for antiemetic rescue medication on the first postoperative day (30% versus 42%), and the incidences of nausea (15% versus 26%) and vomiting (5% versus 16%) on the second postoperative day (P0.05). In addition, dexamethasone significantly reduced the percentage of patients with a depressed appetite on the second postoperative day. However, the corticosteroid failed to decrease the incidence of AF (27% versus 32%) or the total dosage of opioid analgesic medication administered in the postoperative period. We conclude that dexamethasone (8 mg in divided doses) was beneficial in reducing emetic symptoms and improving appetite after cardiac surgery. However, this dose of the corticosteroid does not seem to have antiarrhythmic or analgesic-sparing properties.Dexamethasone (8 mg IV) was beneficial in reducing emetic symptoms and increasing appetite after cardiac surgery. However, this dose of the corticosteroid failed to decrease postoperative pain or the incidence of new-onset atrial fibrillation.

Objectives The goals of this study were to assess late clinical outcome and left ventricular ejection fraction (LVEF) after transmyocardial revascularization with CO2laser (TMR). Background During the 1990s TMR emerged as a treatment option for patients with refractory angina not eligible for conventional revascularization. Few reports exist on clinical effects and LVEF >3 years after TMR. Methods One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized 1:1 to receive continued medical treatment or medical treatment combined with TMR. The patients were evaluated at baseline and after 3, 12 and 43 (range: 32 to 60) months with end points to angina, hospitalizations due to acute myocardial infarctions or unstable angina, heart failure and LVEF. Mortality was registered and MOS 36 Short-Form Health Survey answered at baseline and after 3, 6 and 12 months. Results Forty-three months after TMR, angina symptoms were still significantly improved, and unstable angina hospitalizations reduced by 55% (p Conclusions Forty-three months after TMR, angina symptoms and hospitalizations due to unstable angina were significantly reduced, heart failure treatment increased and LVEF and mortality were seemingly unaffected.

Background. The systemic inflammatory reaction (SIR) is assumed to be one of the factors that causes cerebral dysfunction after cardiopulmonary bypass (CPB). The aim of the present study was to evaluate the relationship between the SIR and postoperative cognitive performance at 5 days and 3 months. Methods. One hundred patients undergoing coronary artery bypass grafting were studied. Inflammatory markers and markers of coagulation and fibrinolysis were determined at several time points during and after the operation. Correlation analysis between maximum levels of the different markers and early and late performance was performed. Results. No overall association was found between the maximum levels of the inflammatory markers and early and late function. Conclusions. Notwithstanding limitations of statistical power established markers of systemic inflammatory reaction showed no relationship with outcome at 5-day or 3-month follow-up in this subset of patients. (C) 2001 by The Society of Thoracic Surgeons.

The aim of the present study was to examine postoperative serum levels of cardiac enzymes after transmyocardial laser treatment (TML) and to evaluate any associations between this release, postoperative cardiac events and change in ejection fraction after 3 months' follow-up.Forty-nine patients with angina pectoris Canadian Cardiovascular Society Angina Score Class IIIIV refractory to medical therapy and untreatable by coronary artery bypass or percutaneous transluminal angioplasty treated with CO2 laser were included. Inclusion criteria were age less than 75 years, left ventricular ejection fraction greater than or equal to 30% and myocardial regions with reversible ischemia. Serum levels of aspartate aminotranspherase (ASAT), alanine aminotranspherase (ALAT) and MB-isoenzymes of creatine kinase (CK-MB) were followed during the first 72 h after surgery. Ejection fractions were estimated by multiple-gated acquisition ventriculography at inclusion and 3 months postoperatively.A significant increase in serum markers of myocardial necrosis was observed 8 h after surgery. A subsequent increase from 8 to 24 h after surgery was associated with the presence of postoperative cardiac adverse events. An inverse correlation was found between peak level of cardiac enzymes and change in ejection fraction from baseline to 3 months' follow-up.TML with CO2 laser is followed by a significant increase in serum levels of cardiac enzymes after 8 h. Further significant increases are associated with cardiac adverse events postoperatively. Peak enzyme values are inversely correlated with change in ejection fraction from baseline to 3 months' follow-up.

A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was successfully treated by mechanical offloading of the left ventricle. A nonpulsatile left-heart bypass was undertaken with an implantable centrifugal blood pump. Careful weaning resulted in device removal on the seventh day. Left and right ventricular function is sustained at 7 months. Widespread application of this method depends on the availability of an inexpensive user friendly blood pump, appropriate weaning protocols and emerging strategies to promote sustainabile myocardial recovery.

OBJECTIVES The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Objectives: Over the past decade, the glial protein S-100β has been used to detect cerebral injury in a number of clinical settings including cardiac surgery. Previous investigations suggest that S-100β is capable of identifying patients with cerebral dysfunction after cardiopulmonary bypass. Whether detection of elevated levels S-100β reflects long-term cognitive impairment remains to be shown. The present study evaluated whether perioperative release of S-100β after coronary artery operations with cardiopulmonary bypass could predict early or late neuropsychologic impairment. Methods: A total of 100 patients undergoing elective coronary bypass without a previous history of neurologic events were prospectively studied. To exclude noncerebral sources of S-100β, we did not use cardiotomy suction or retransfusion of shed mediastinal blood. Serial perioperative measurements of S-100β were performed with the use of a new sensitive immunoluminometric assay up to 8 hours after the operation. Patients underwent cognitive testing on a battery of 11 tests before the operation, before discharge from the hospital, and 3 months later. Results: No significant correlation was found between S-100β release and neuropsychologic measures either 5 days or 3 months after the operation. Conclusion: Despite using a sensitive immunoluminometric assay of S-100β, we found no evidence to support the suggestion that early release of S-100β may reflect long-term neurologic injury capable of producing cognitive impairment. (J Thorac Cardiovasc Surg 2000;119:132-7)

Isolated aortic (AVR, N = 71), mitral (MVR, N = 103), tricuspid (TVR, N = 3), pulmonary (PVR, N = 8), combined AVR + MVR (N = 4), or combined MVR + TVR (N = 2) valve replacement with a Carpentier-Edwards porcine bioprosthesis was performed in 191 patients between 1979 and 1986. Mean age was 56.9 +/- 17 (range 5-80) years in the total cohort. The operative mortality rates were 5.6% and 8.7%, respectively, for AVR and MVR. Mean observation time was 8 +/- 4.2 (0-16.7) years (total = 1.467 patient-years). Follow-up was 100% complete with respect to mortality. There were 78 late deaths (44%). Actuarial survival rates at 5 and 10 years were 73.2 +/- 5.2 and 52.1 +/- 6.6 for AVR and 76.7 +/- 4.2 and 61.6 +/- 4.8 for MVR. Coronary artery disease, concomitant coronary artery bypass grafting and emergency operation were significant risk factors of early mortality (p0.05). Postoperatively, sepsis and multiorgan failure were associated with early mortality (p0.05). The 10-year actuarial freedom from structural deterioration for AVR was 89 +/- 4.6 and 76.4 +/- 4.3 for MVR. It is concluded that structural valve failure is the most important factor that adversely affects the performance of Carpentier-Edwards bioprosthesis.

The release of cytokines during cardiopulmonary bypass (CPB) may contribute to haemodynamic alternations encountered after open heart surgery. Regulatory mechanisms exist and include soluble cytokine receptors. We have measured blood levels of tumour necrosis factor (TNF) and its soluble receptor (TNFsr) during and after open heart surgery in children. Correlation analysis to haemodynamic and clinical variables was performed. Using immunoassays the authors registered a significant increase in plasma levels of TNFsr with peak levels 2 h post-operatively at a level of 1702 +/- 170 pg/ml. The concentration of TNFsr remained significantly elevated until 48 h postoperatively but TNF was not significantly elevated. An inverse correlation existed between peak TNFsr and mean arterial pressure (rho = -0.827, P0.05), between TNFsr and cardiac index (rho = -0.8, P0.05), between TNFsr and left ventricular stroke work index (rho = -0.983, P0.01), between TNFsr and weight (rho = -0.85, P0.05) and between TNFsr and body surface area (rho = -0.867, P0.05). The authors demonstrate that the smallest children experienced the highest TNFsr concentration post-operatively. Furthermore cardiac performance, expressed as cardiac index and left ventricular stroke work index, correlated inversely to peak TNFsr level post-operatively.

Objective: The purpose of the study was to evaluate the clinical and hemodynamic effect of intraoperative extracorporeal ultrafiltration (UF) and its potential in reducing the plasma concentration of circulating cytokines and complement activation products following open heart surgery in children. Methods: Eighteen children with congenital heart disease were prospectively randomized into a control group ( n = 9) and a group who underwent UF ( n = 9). Serial plasma samples for measurements of circulating cytokines (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF), and its soluble receptor (sTNF receptor)), and complement factors (C3 activation products (C3a and C3bc) and terminal complement complex (TCC) were obtained before, during and up to 48 h after cardiopulmonary bypass (CPB). A pulmonary artery thermodilution catheter was introduced preoperatively for hemodynamic monitoring. Results: Postoperative hemodynamics were similar in both groups. Plasma levels of IL-6, sTNF receptors, C3a, C3bc and TCC increased significantly perioperatively ( P < 0.01) in both groups. TNF was detected transiently in 16 patients perioperatively and in 4 of the 9 ultrafiltrate samples in concentrations similar to the plasma levels. Complement activating products were not detected in the ultrafiltration samples except for small amounts of C3a in two cases. Compared to the control group the plasma levels of C3a, C3bc and TCC were unaffected by the ultrafiltration procedure. The level of IL-6 and sTNF receptors increased significantly after 15 min of UF but there was no significant difference between the two groups postoperatively. Conclusions: In this study no clinical or hemodynamic effect was registered after UF. TNF and C3a were occasionally detected in the ultrafiltrate but we were unable to demonstrate reduction of these or any of the other markers tested in the group subjected to ultrafiltration.

Cellular activation with release of cytokines such as interleukin-6 (IL-6) occurs during cardiopulmonary bypass. IL-6 regulates a number of physiologic processes, and a possible role of IL-6 was recently postulated in the pathogenesis of changes in serum thyroid hormone concentrations in patients with nonthyroidal illness. The perioperative concentrations of triiodothyronine (T3) and IL-6 were determined in ten children undergoing open-heart surgery. Significant fall in T3 concentration was found postoperatively, while IL-6 increased significantly, peaking 2 hours postoperatively. The total accumulated IL-6 level 2 hours postoperatively was correlated to postoperative T3 concentration. A significant inverse correlation was found between T3 levels 24 and 48 hours postoperatively and total accumulated IL-6, and also between the percentage decrease in T3 concentrations and total accumulated IL-6. IL-6 release thus correlated inversely to T3 levels after cardiopulmonary bypass.

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.

Background. This study examined the midterm results with the CarboMedics prosthetic valve. Methods. From 1987 through 1991 a total of 569 patients received the CarboMedics prosthesis. Results. Early mortality was 4.9% and related to emergency operation, presence of diabetes mellitus, coronary artery disease, preoperative New York Heart Association class, duration of cardiopulmonary bypass, and aortic cross-clamp time. Midterm follow-up with respect to mortality was 100% complete. All patients were followed up in the hospital after 1 year. In addition 86% of the patients responded to a questionnaire. Mean follow-up was 3 years (range, 0 to 5.6 years). Cumulative survival at 1 and 4 years was 91.2% ± 1.2% and 83.7% ± 1.8%, respectively. Five patients experienced obstructive valve thrombosis (0.3%/patient-year), 16 patients had major thromboembolic events (0.9%/patient-year), and 10 patients had major warfarin-related bleeding (0.6%/patient-year) requiring hospitalization or blood transfusions. Eight patients were reoperated on for paraprosthetic leak (0.4%/patient-year). Prosthetic valve endocarditis developed in 4 patients (0.2%/patient-year). No structural valve failure was observed. Conclusions. Midterm follow-up demonstrates that the CarboMedics mechanical prosthesis is reliable and has an acceptable rate of valve-related complications.

Patients with congenital heart disease and univentricular circulation are vulnerable to ventricular dysfunction. In the context of atrioventricular conduction defects, a ventricular pacemaker may be placed, possibly introducing dyssynchronous wall motion and deterioration of ventricular pump function. We describe such a case in which repositioning of the ventricular lead restored synchronicity.

We report two infants who underwent right pneumonectomy in infancy and developed postpneumonectomy syndrome with obstruction of the left main bronchus causing severe airway obstruction in one patient and gastrointestinal reflux due to a displaced and grossly dilated oesophagus in the other patient. Both patients were operated with implantation of an expandable breast prosthesis.

Percutaneous transluminal coronary angioplasty (PTCA) was performed on 725 occasions at the National Hospital of Norway in 1981-1990. Acute surgical intervention was necessary within 24 hours after PTCA in 15 cases, on indications that included coronary artery dissection (8 cases) and acute thrombotic occlusion (5). Electrocardiographic signs of ischemia were present in 11 patients with anginal pain, while two had severe angina but normal electrocardiogram. Two patients had a non-ischemic indication for surgery. Despite surgery, ten of the 15 patients had acute myocardial infarction. One of the ten died. At follow-up nine of 12 patients were free from angina and three had recurrent symptoms.

The aim of this study was to evaluate the long-term outcome of total repair for tetralogy of Fallot. We aimed to characterize late survival and the time-related risk of late reoperation.Operative protocols, patient records, and the database of the department were evaluated from 1951 until 2008. The official death registry of Norway was used for follow-up. Of the patients identified, the follow-up was 99.6% complete.A total of 627 patients were studied. Of these, 570 could be identified for follow-up. There were a total of 41 early and 30 late deaths. The total early (including palliative procedures) mortality was 7.2% and total late mortality was 7.9%. However, during the last 10 years, no early mortality has been observed following repair. A total of 264 patients underwent some form of palliative procedure as their first treatment, and 541 patients had a reparative procedure performed, with an early mortality of 31 (5.7%). In patients subjected to a reparative procedure, there was no difference in freedom from death or reoperation following primary repair versus primary palliation. The use of transannular patch was associated with a highly significant risk of reoperation.Surgical treatment of the tetralogy of Fallot and related congenital cardiac malformations has good long-term prognosis. In this cohort of patients, more than one-third required additional procedures later on, and, in some cases, as many as four additional surgeries. Palliative procedures followed by repair do not influence survival or reoperation-free survival. There are no differences between transatrial versus transventricular repair on survival or re-repair. Any transannular incision increases the risk of re-repair, but does not influence long-time survival. There is an almost linear decrease in reoperation-free survival following any type of repair of tetralogy of Fallot, even for as long as 50 years since the first procedure.

Background . Atrial fibrillation is the most common rhythm disturbance encountered after open heart operations, with a reported incidence up to 40%. Despite its high incidence and clinical relevance its etiology remains obscure. It has been hypothesized that atrial fibrillation might be related to extracorporeal circulation. We performed a retrospective study (January 1, 1997 to December 31, 1997) comparing the incidence of atrial fibrillation in 3 groups of patients revascularized with and without extracorporeal circulation. Methods . The first group comprised patients with coronary artery disease operated on with standard revascularization technique with cardiopulmonary bypass (n = 685). The second group included patients who had minimally invasive coronary artery bypass grafting without the use of extracorporeal circulation (n = 19). Patients in the third group had off-pump transmyocardial laser revascularization (n = 19). Results . There was no significant difference in the incidence of atrial fibrillation in the group that had conventional coronary artery bypass and the group that had minimally invasive coronary artery bypass without cardiopulmonary bypass. The incidence of atrial fibrillation was significantly lower in the transmyocardial laser group compared with the other two groups. Conclusions . The present study found that postoperative atrial fibrillation is not caused solely by extracorporeal circulation, but patients who had transmyocardial laser revascularization had a significantly lower incidence of atrial fibrillation.

The main aim of the present study was to compare the occurrence of inflammatory cell infiltrates in the aorta, a vessel with a high occurrence of atherosclerosis, with that in the saphenous vein (SV) and internal mammary artery (IMA), which are protected from atherosclerosis.Samples from the aorta, SV, and IMA of 65 patients with inflammatory rheumatic diseases (IRD) and from 51 control patients undergoing coronary artery bypass graft surgery were examined for the presence and location of inflammatory cell infiltrates and atherosclerotic lesions. Mononuclear cell infiltrates (MCIs) in the media or adventitia were observed in 2% IMAs, 17% SVs, and 35% aortic specimens (SV vs IMA: p=0.006; SV vs aorta: p=0.001). Atherosclerotic lesions were present in none IMA, 3% SVs and 18% aortic specimens. IRD and smoking increased the odds of MCI in the aorta (odds ratio (OR)=3.6, 95% confidence interval (CI): 1.6-8.5 and OR=4.0, 95% CI: 1.5-10.9), but not in the SV or IMA.The occurrence of medial and adventitial MCI in the aorta, SV, and IMA paralleled each vessel's susceptibility to atherosclerosis: it was highest in the aorta and lowest in IMA. Local vascular inflammation may be involved in atherogenesis, and influence the patency of vascular grafts.

The main aim of the study was to examine whether patients with spondyloarthritides underwent their first coronary artery bypass grafting (CABG) at a younger age than those without spondyloarthritides.Patients who underwent their first CABG at the Feiring Heart Clinic during 2001-2005 were preoperatively screened for spondyloarthritides, and the cardiological assessment was registered. We compared the characteristics of patients with and without spondyloarthritides.Of the 3852 patients undergoing their first CABG, 30 (0.78%) had spondyloarthritides. No statistically significant differences in traditional cardiovascular risk factors were found. The mean ages of patients with and without spondyloarthritides were 60.1 (SD = 8.7) and 66.9 (SD = 10.1) years, respectively. Spondyloarthritis was found by multivariate analysis to be a stronger independent predictor of early CABG than traditional cardiovascular risk factors [adjusted beta -6.2, p0.001, 95% confidence interval (CI) -9.5 to -2.8]. Sixty per cent of spondyloarthritis patients and 52% of control patients had already suffered a myocardial infarction (p = 0.4).Spondyloarthritis was a stronger predictor of early CABG than most of the registered traditional cardiovascular risk factors. The prevalence of spondyloarthritis seemed to be higher in the CABG population than in the general population. These findings may indicate accelerated coronary artery disease (CAD) in spondyloarthritides.

Background. This prospective randomized study compared the inflammatory response in patients undergoing elective on-pump and off-pump coronary artery bypass grafting. Patients and methods. Forty-four patients undergoing elective coronary artery bypass grafting were recruited with 22 patients randomized to on-pump heart surgery and 22 patients to off-pump coronary bypass surgery. Plasma levels of C3bc, the terminal SC5b-9 complement complex, myeloperoxidase, β -thromboglobulin and prothrombin fragment F1 + 2 were measured before the operation, intraoperatively, at termination of the operation, and two hours post-operatively. Results. Complement was markedly activated in the on-pump group as indicated by a significant increase in C3bc and SC5b-9 (p < 0.001 for both), whereas no complement activation was seen in the off-pump group (p = 0.001 between the groups). In contrast, both groups showed significant activation of neutrophils, platelets and coagulation, as indicated by an early increase in myeloperoxidase and a post-operative increase in β-thromboglobulin and F1 + 2, respectively. Notably, there were no inter-group differences with regard to neutrophil and platelet activation, whereas coagulation activation was more pronounced in the off-pump group (p < 0.01). Conclusions. Off-pump surgery completely eliminated the heart-lung machine-induced complement activation. Neutrophils and platelets were equally activated in both groups, whereas coagulation was enhanced post-operatively in the off-pump group. Perfusion (2007) 22, 251—256.

Although the internal mammary artery (IMA) as a coronary graft offers better long-term patency than the saphenous vein, a factor limiting its use has been the length of the artery's pedicle. In an attempt to overcome this limitation, we evaluated the use of retrograde right IMA in a prospective study. In ten patients scheduled for routine coronary artery bypass surgery, bilateral IMA grafting was used, the left IMA in routine fashion, but the right IMA dissected from the level of the first rib, cut there and placed as an inverted graft. Three months postoperatively the patients were clinically evaluated with stress exercise test (n = 10) and coronary angiography (n = 9). No patient had recurrence of angina. Angiography revealed patency of the retrograde right IMA graft in six of nine patients. On the basis of these data we do not recommend routine use of retrograde IMA.

The frequent use of mechanical circulatory assistive devices in the treatment of patients in cardiogenic shock increases the need for advanced air and ground transport services. In this article we describe a critically ill patient with acute myocardial infarction. He was treated with intraaortic balloon pump at the local hospital before transfer to a university hospital by air. Close cooperation between the university hospital, the Norwegian Air Ambulance and the Norwegian aviation authorities has facilitated this service.

A fistula from the pulmonary artery to the left atrium is a very rare congenital anomaly. The communication, almost exclusively arising from the right pulmonary artery, may give rise to a variety of symptoms with cyanosis as the predominant sign. To our knowledge only seven neonates have been reported with this anomaly, and five of them died postoperatively. We present another two neonates with such a fistula which was closed by simple ligation using a transsternal approach and cardiopulmonary bypass. Both patients had an uneventful postoperative course and are alive and well at the age of two and three years, respectively.

The goals of this study were to assess late clinical outcome and left ventricular ejection fraction (LVEF) after transmyocardial revascularization with CO(2) laser (TMR).During the 1990s TMR emerged as a treatment option for patients with refractory angina not eligible for conventional revascularization. Few reports exist on clinical effects and LVEF3 years after TMR.One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized 1:1 to receive continued medical treatment or medical treatment combined with TMR. The patients were evaluated at baseline and after 3, 12 and 43 (range: 32 to 60) months with end points to angina, hospitalizations due to acute myocardial infarctions or unstable angina, heart failure and LVEF. Mortality was registered and MOS 36 Short-Form Health Survey answered at baseline and after 3, 6 and 12 months.Forty-three months after TMR, angina symptoms were still significantly improved, and unstable angina hospitalizations reduced by 55% (p0.001). Heart failure treatment (p0.01) increased, whereas the number of acute myocardial infarctions, LVEF and mortality was not affected. Quality of life was improved 3, 6 and 12 months after TMR.Forty-three months after TMR, angina symptoms and hospitalizations due to unstable angina were significantly reduced, heart failure treatment increased and LVEF and mortality were seemingly unaffected.

Previous studies have reported that mortality and morbidity after transmyocardial laser treatment (TML) mainly occur perioperatively. The present study was designed to evaluate left-ventricular function and identify risk factors for cardiac-related adverse events in this phase.Forty-nine patients were studied. The inclusion criteria were angina pectoris Canadian Cardiovascular Society Angina Score (CCSAS) class III and IV refractory to medical therapy and untreatable by coronary artery bypass graft or percutaneous transluminal coronary angioplasty, age less than 75 years, left ventricular ejection fraction greater than or equal to 30%, and myocardial regions with reversible ischemia. Hemodynamic data and cardiac adverse events were registered. The follow-up time was 30 days.A transient decrease in mean cardiac index (CI) was observed, reaching its minimum immediately after end of the surgical procedure (1.8+/-0.4, p0.01 vs. baseline). Two patients (4%) died during the postoperative period (30 days). Seventeen patients (35%) experienced adverse cardiac-related events, where CCSAS class IV, unprotected left main stem stenosis, and diabetes mellitus were identified as risk factors in a multivariate analysis.A transient impairment of left ventricular function was observed after TML. The morbidity and mortality after TML were almost exclusively cardiac-related, identifying CCSAS class IV, unprotected left main stem stenosis, and diabetes as risk factors.

BACKGROUND The aim of the study was to elucidate the changes in thyroid function during and after cardiopulmonary bypass (CPB) in children. METHODS Triiodothronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined preoperatively, at specific times throughout CPB, and serially up to 48 h postoperatively, in 10 children (median age 35, range 23-68 months) undergoing elective surgery for congenital heart disease. RESULTS T3 decreased from 2.01 +/- 0.08 preoperatively to 0.94 +/- 0.10 nmol/l 24 h postoperatively (P < 0.05). T4 levels followed a pattern similar to changes in T3. FT4 increased from 17.4 +/- 0.7 preoperatively to 30.0 +/- 0.4 pmol/l after 30 min of CPB (P < 0.05). TSH decreased from 2.44 +/- 0.43 preoperatively to 0.93 +/- 0.21 24 h postoperatively (P < 0.05). CONCLUSION T3, T4 and TSH are significantly depressed after open heart surgery in children.

Interleukin-6 (IL-6) and the complement activation products C3bc and terminal complement complex (TCC) were measured in three groups of children undergoing open heart surgery. One group was treated with intraoperative extracorporeal ultrafiltration and postoperative autotransfusion of shed mediastinal blood, one group was subjected to autotransfusion only and in one group none of these procedures were performed. No differences between the groups were observed concerning the degree of complement activation. Peak and total accumulated level of IL-6 was significantly higher in the group subjected to ultrafiltration and autotransfusion compared to the group treated conventionally with no interventions. IL-6 may be a sensitive marker of maneuvres increasing the inflammatory load during and after open heart surgery in children.

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems may be responsible for some of the coagulation disorders and inflammatory sequelae seen after extracorporeal circulation. The activation pattern of these systems was studied in 10 children undergoing open heart surgery with extracorporeal circulation. Blood samples were drawn serially before, during and up to 48 h after surgery. The heparin injection induced a significant elevation of plasmin (PL) (p < 0.05) which stayed elevated during extracorporeal circulation. Antiplasmin (AP) values were reduced at wound closure, while the levels were significantly elevated 48 h postoperatively (p < 0.05). alpha 2-antiplasmin-plasmin (APP) increased significantly perioperatively peaking 10 min after the initiation of cardiopulmonary bypass (p < 0.05). The coagulation markers thrombin-antithrombin (TAT) and the prothrombin fragment F1 & 2 increased significantly, peaking at wound closure and at termination of bypass respectively (p < 0.05). Plasma kallikrein (KK) values increased significantly with subsequent decreased levels of prekallikrein (PKK) and kallikrein inhibitor (KKI) after heparin injection. The KK level stayed elevated during cardiopulmonary bypass (CPB). The proenzyme functional inhibition index (PFI index), defined as the sum of deviations from the control values for proenzyme and functional inhibition values of the coagulation, fibrinolytic and plasma kallikrein-kinin systems, correlated significantly to the duration of cardiopulmonary bypass (p < 0.05). We conclude that open heart surgery in children activates the fibrinolytic, coagulation and plasma kallikrein-kinin systems.

C3 activation products, terminal complement complex (TCC), and cytokines including interleukins 6 and 2 (IL-6, IL-2) and tumour necrosis factor-alpha (TNF), and the soluble IL-2 and TNF receptors were determined serially during and up to 48 h after open heart surgery in children. Significant increases were noted in soluble TNF and IL-2 receptor levels postoperatively (p0.05). No significant increase over preoperative levels was seen in the cytokines, except for IL-6 which was significantly increased postoperatively (p0.01), reaching a maximum 2 h postoperatively. C3 activation products and TCC levels increased significantly after weaning from cardiopulmonary bypass (p0.05). The IL-6 response lagged behind the complement activation. We found a significant correlation between duration of cardiopulmonary bypass and IL-6 levels 48 h postoperatively (r = 0.852, p0.05). We conclude that the concentration of complement activation products, IL-6 and the soluble TNF and IL-2 receptors are significantly increased after open heart surgery in children. The cytokine receptor response probably reflects some sort of regulatory mechanism.

A pericardio-peritoneal window was created to relieve cardiac tamponade by recurrent effusion after heart transplantation. The effect was echocardiographically evaluated. The technique is described. It requires no sternal splitting for pericardial access and no foreign materials such as drains or shunts. The method should be considered for immunologically compromised, infection-prone patients with heart transplantation.