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Abnormal elevation of myocardial necrosis biomarkers after coronary artery bypass grafting without established myocardial infarction assessed by cardiac magnetic resonance.
Oikawa, FTC, Hueb, W, Nomura, CH, Hueb, AC, Villa, AV, da Costa, LMA, de Melo, RMV, Rezende, PC, Segre, CAW, Garzillo, CL, et al
Journal of cardiothoracic surgery. 2017;(1):122
Abstract
BACKGROUND The diagnosis of peri-procedural myocardial infarction is complex, especially after the emergence of high-sensitivity markers of myocardial necrosis. METHODS In this study, patients with normal baseline cardiac biomarkers and formal indication for elective on-pump coronary bypass surgery were evaluated. Electrocardiograms, cardiac biomarkers, and cardiac magnetic resonance imaging with late gadolinium enhancement were performed before and after procedures. Myocardial infarction was defined as more than ten times the upper reference limit of the 99th percentile for troponin I and for creatine kinase isoform (CK-MB) and by the findings of new late gadolinium enhancement on cardiac magnetic resonance. We assessed the release of cardiac biomarkers in patients with no evidence of myocardial infarction on cardiac magnetic resonance. RESULTS Of 75 patients referred for on-pump coronary bypass surgery, 54 (100%) did not have evidence of myocardial infarction on cardiac magnetic resonance. However, all had a peak troponin I above the 99th percentile; 52 (96%) had an elevation 10 times higher than the 99th percentile. Regarding CK-MB, 54 (100%) patients had a peak CK-MB above the 99th percentile limit, and only 13 (24%) had an elevation greater than 10 times the 99th percentile. The median value of troponin I peak was 3.15 (1.2 to 3.9) ng/mL, which represented 78.7 times the 99th percentile. CONCLUSION In this study, different from CK-MB findings, troponin was significantly increased in the absence of myocardial infarction on cardiac magnetic resonance. Thus, CK-MB was more accurate than troponin I for excluding procedure-related myocardial infarction. These data suggest a higher troponin cutoff for the diagnosis of coronary bypass surgery related myocardial infarction. CLINICAL TRIAL REGISTRATION http://www.isrctn.com/ISRCTN09454308 . Registered 08 May 2012.
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Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: Insights from the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial.
Kotsia, AP, Rangan, BV, Christopoulos, G, Coleman, A, Roesle, M, Cipher, D, de Lemos, JA, McGuire, DK, Packer, M, Banerjee, S, et al
The Journal of invasive cardiology. 2015;(10):E204-10
Abstract
BACKGROUND Intermediate saphenous vein graft (SVG) lesions have high rates of progression. The purpose of this study was to examine the impact of extended-release niacin (ER-niacin) vs placebo on intermediate SVG lesions. METHODS Patients with intermediate (30%-60% diameter stenosis) SVG lesions were randomized to ER-niacin vs placebo for 12 months. Quantitative coronary angiography (QCA), intravascular ultrasonography (IVUS), and optical coherence tomography (OCT) were performed at baseline and at 12 months. The primary endpoint was change in percent atheroma volume (ΔPAV). Enrollment was planned for 138 patients for 90% power to detect ≥2.5% difference in the primary endpoint of ΔPAV, but stopped early after publication of two negative outcome trials of ER-niacin, with enrolled patients completing the 12-month trial protocol. RESULTS Thirty-eight patients were randomized to niacin (n = 19) or placebo (n = 19), yielding power of 47% to detect the primary planned treatment effect of 2.5 ± 4.0% difference in ΔPAV. Between baseline and 12-month follow-up, no significant difference was found between study groups in ΔPAV (-1.31 ± 6.05% vs 1.05 ± 17.8%; P=.60). By OCT, the ER-niacin vs placebo group had less plaque rupture within the intermediate SVG lesion (0.0% vs 36.0%; P=.01). CONCLUSION Administration of ER-niacin did not significantly impact intermediate SVG disease, with the notable limitation of compromised statistical power due to early termination of enrollment.
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Antioxidant supplementation attenuates oxidative stress in patients undergoing coronary artery bypass graft surgery.
Stanger, O, Aigner, I, Schimetta, W, Wonisch, W
The Tohoku journal of experimental medicine. 2014;(2):145-54
Abstract
Ischemia-reperfusion has been reported to be associated with augmented oxidative stress in the course of surgery, which might be causally involved in the onset of atrial fibrillation (AF), the most common arrhythmia after cardiac surgery. We hypothesized that supplementation of antioxidants and n-3 polyunsaturated fatty acids (n-3 PUFAs) might lower the incidence of AF following coronary artery bypass graft (CABG) surgery. In the present study, by monitoring oxidative stress in the course of CABG surgery, we analyzed the efficacy of vitamins (ascorbic acid and α-tocopherol) and/or n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid). Subjects (n = 75) were divided into 4 subgroups: control, vitamins, n-3 PUFAs, and a combination of vitamins and n-3 PUFAs. Fluorescent techniques were used to measure the antioxidative capacity, i.e. ability to inhibit oxidation. Total peroxides, endogenous peroxidase activity, and antibodies against oxidized LDL (oLAb) were used as serum oxidative stress biomarkers. Post-operative increase in oxidative stress was associated with the consumption of antioxidants and a simultaneous onset of AF. This was confirmed through an increased peroxide level and a decreased oLAb titer in control and n-3 PUFAs groups, indicating the binding of antibodies to oxidative modified epitopes. In both subgroups that were supplemented with vitamins, total peroxides decreased, and the maintenance of a constant IgG antibody titer was facilitated. However, treatment with vitamins or n-3 PUFAs was inefficient with respect to AF onset and its duration. We conclude that the administration of vitamins attenuates post-operative oxidative stress in the course of CABG surgery.
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The effect of intravenous magnesium sulfate on serum levels of N-terminal pro-brain natriuretic peptide (NT pro-BNP) in elective CABG with cardiopulmonary bypass.
Dabbagh, A, Bastanifar, E, Foroughi, M, Rajaei, S, Keramatinia, AA
Journal of anesthesia. 2013;(5):693-8
Abstract
INTRODUCTION Nowadays, many patients undergo coronary artery bypass grafting (CABG) with a cardiopulmonary bypass (CPB); while a number of therapeutic agents have been used to suppress its related inflammatory process. Magnesium sulfate (MgSO4) solution has been used as an anti-inflammatory agent. Among the cardiac biomarkers, N-terminal pro brain natriuretic peptide (NT Pro-BNP) is one of the most widely recognized. We performed this study to assess the effect of MgSO4 solution on NT Pro-BNP levels in patients undergoing CABG with CPB. MATERIALS AND METHODS In a double-blind clinical trial, after IRB approval for ethical considerations, during a 12-month period, 88 adult patients aged 40-70 years qualified for the study after inclusion and exclusion criteria were considered. After random allocation of the patients between the two groups, anesthesia, surgical procedure, cardiopulmonary bypass (CPB) methods, and postoperative care were made as similar as possible; however, one group received a MgSO4 infusion (15 mg/kg/h) and the other group saline (placebo). Pre- and post-operative levels of NT Pro-BNP were assessed using an electrochemical luminescence immunoassay in an Elecsys 2010 (Roche, Indianapolis, IN, USA). The results were compared using a Student's t-test. A P value less than 5% was considered significant. RESULTS The MgSO4 group had shorter postoperative mechanical ventilation, lower postoperative morphine requirements and lower postoperative pain scores. Also, 24 h postoperative NT Pro-BNP levels were significantly lower in the MgSO4 group. CONCLUSION Administration of MgSO4 in elective CABG with CPB can decrease the postoperative NT Pro-BNP levels; also, it decreases their time of postoperative mechanical ventilation.
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Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial.
Hueb, W, Gersh, BJ, Rezende, PC, Garzillo, CL, Lima, EG, Vieira, RD, Garcia, RM, Favarato, D, Segre, CA, Pereira, AC, et al
BMC cardiovascular disorders. 2012;:65
Abstract
BACKGROUND Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS/DESIGN The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.
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Coronary stenting with MGuard: extended follow-up of first human trial.
Grube, E, Hauptmann, KE, Müller, R, Uriel, N, Kaluski, E
Cardiovascular revascularization medicine : including molecular interventions. 2011;(3):138-146
Abstract
OBJECTIVES To evaluate feasibility and safety of MGuard based percutaneous coronary interventions (PCI) in vein grafts (VG) and native coronaries (NC). BACKGROUND Distal embolization is a frequent complication of PCI of VG and NC during acute coronary syndromes (ACS). MGuard was a stent designed to reduce embolization. METHODS Prospective, single arm, two-center trial assessing the feasibility and safety of MGuard-based PCI with post-PCI clinical and laboratory monitoring including: cardiac biomarkers, ECG and 6-month angiography. RESULTS Forty-one patients with mean age of 68.2±10.1 years were enrolled. Mean VG age (n=23) was 14.4±4.3 years. All patients received heparin, clopidogrel and aspirin; while none received glycoprotein IIb/IIIa inhibitors, or embolic protection device (EPD). Device and procedural success were 100% and 95.1% respectively. Two patients (4.9%) experienced procedure-related creatinine phosphokinase rise. At 6 months one patient had myocardial infarction and 19.5% had target vessel revascularization (TLR). Late follow up (12-27 months) revealed one additional TLR. CONCLUSION MGuard based PCI of NC and VG appears encouraging especially in view of unfavorable patient and lesion characteristics. Efficacy needs to be further established in larger randomized trials.
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Inadequate cytoplasmatic calcium signals in alveolar macrophages after cardiac surgery.
Berger, K, Sander, M, Kohlar, A, Meisel, C, Konertz, W, Volk, T
Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2010;(9):767-73
Abstract
OBJECTIVE AND DESIGN Patients undergoing cardiac surgery have an elevated risk for pulmonary complications. A dysfunction of alveolar macrophages (AM) might promote postoperative infections. Therefore intracellular calcium [Ca(2+)](i) as an important second messenger in cellular signaling was assessed in AM. MATERIALS AND METHODS Twelve patients undergoing elective coronary artery bypass graft surgery (CABG) were enrolled in this clinical trial. After anesthesia induction and 2 h after cardiopulomary bypass (CPB) declamping, the bronchoalveolar lavage (BAL) fluid was collected preoperatively from the right middle lobe and postoperatively from the left lingula of the lung. Cell subpopulations and [Ca(2+)](i) signals were assessed via flow cytometry. To express the changes of [Ca(2+)](i) signals the Fluo4/FuraRed-Ratio was used. RESULTS After surgery the [Ca(2+)](i) baseline in unstimulated AMs were significantly reduced (p < 0.001). A significant signal reduction after fMLP (p = 0.021) and C5a (p = 0.028) stimulation was found in FSC high AMs after surgery, even though all populations showed a trend of less responsiveness. CONCLUSION We suggest that the reduced [Ca(2+)](i) signaling in postoperative AMs is caused by a reduced coupling to membrane channels. These preliminary data suggest an inadequate [Ca(2+)](i) signal of AM after surgery, which may contribute to a local immune dysfunction in the lung.
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Effect of single dose magnesium on arrhythmias in patients undergoing coronary artery bypass surgery.
Hamid, M, Kamal, RS, Sami, SA, Atiq, F, Shafquat, A, Naqvi, HI, Khan, FH
JPMA. The Journal of the Pakistan Medical Association. 2008;(1):22-7
Abstract
OBJECTIVE To evaluate the safety and role of prophylactic administration of magnesium in preventing arrhythmias. METHOD This double blind randomized placebo controlled clinical trial was conducted at Aga Khan University Hospital on coronary artery bypass surgery patients. All patients were connected to holter monitor before induction of anaesthesia and this monitoring continued for 24 hours. Study drug containing either 2-grams of magnesium or normal saline was given after intubation. Levels of serum magnesium was checked preoperatively and then in ICU at 0, 6, 12, and 24 hours. Independent t-test and chi square test were used for analysis. Statistical significance was defined as p-value < 0.05. RESULTS A total of 104 patients consented to participate in the study, 53 patients were randomly allocated in magnesium (Mg) group and 51 in placebo group. Two (3.77%) patients in magnesium group and five patients (9.8%) in placebo group developed atrial fibrillation. Incidence of ventricular and supraventricular tachycardia was also slightly higher in placebo. Mg level after arrival in CICU (Cardiac Intensive Care Unit) showed mean of 2.1 in magnesium group and 1.6 in placebo group (p = 0.6). CONCLUSION Low magnesium levels were noticed in the placebo group after cardiopulmonary bypass and although prophylactic administration of magnesium sulphate was relatively safe but significant benefit on prevention of arrhythmias could not be attained.
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Arterio-jugular differences in serum S-100beta proteins in patients receiving selective cerebral perfusion.
Kunihara, T, Shiiya, N, Bin, L, Yasuda, K
Surgery today. 2006;(1):6-11
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Abstract
PURPOSE The early increase in serum S100beta after cardiopulmonary bypass (CPB) seems to be derived from an extracerebral source. To exclude contamination, we investigated the arterio-jugular differences in S100beta levels in patients receiving selective cerebral perfusion (SCP). We also evaluated the brain-protective effect of SCP by comparing the arterial S100beta levels with those in patients undergoing coronary artery bypass grafting (CABG). METHODS We measured arterial and jugular venous levels of S100beta in ten patients undergoing aortic arch repair with SCP for up to 12 h postoperatively (SCP group). We also measured arterial levels of S100beta in nine patients undergoing CABG (CPB group). RESULTS There was no incidence of hospital death or stroke. The arterial levels of S100beta in both groups were comparable and peaked just after the conclusion of CPB. The arterial and jugular venous levels of S100beta were almost equivalent. The arterio-jugular differences in S100beta levels were negligible, even in our SCP-group patient with postoperative delirium, who had a peak value three times higher than the other patients. CONCLUSIONS The arterio-jugular differences in S100beta did not clarify the origin of their increase. Thus, measuring the jugular venous levels of S100beta in patients without postoperative clinical neurological deterioration would be of little benefit. However, SCP seems to protect the brain against S100beta release as effectively as conventional CPB.
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Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery.
Visser, L, Zuurbier, CJ, Hoek, FJ, Opmeer, BC, de Jonge, E, de Mol, BA, van Wezel, HB
British journal of anaesthesia. 2005;(4):448-57
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BACKGROUND The clinical benefits of glucose-insulin-potassium (GIK) and tight glycaemic control in patients undergoing coronary artery bypass grafting (CABG) may be partly explained by an anti-inflammatory effect. We applied GIK as a hyperinsulinaemic normoglycaemic clamp for >25 h and quantified its effect on systemic inflammation in patients undergoing CABG. METHODS Data obtained in 21 non-diabetic patients with normal left ventricular function scheduled for elective coronary artery surgery, who were randomly allocated to a control or GIK group, were analysed. In GIK patients, regular insulin was infused at a fixed rate of 0.1 IU kg(-1) h(-1). The infusion rate of glucose (30%) was adjusted to maintain blood glucose levels within a target range of 4.0-5.5 mmol litre(-1). Plasma concentrations of interleukins 6, 8 and 10, C-reactive protein (CRP) and serum amyloid A (SAA) were measured on the day of surgery and on the first and second postoperative days (POD1 and POD2). RESULTS In the GIK group hypoglycaemia (glucose <2.2 mmol litre(-1)) did not occur, whereas hyperglycemia (glucose >6.1 mmol litre(-1)) developed in 15% of all measurements. In control patients, hyperglycaemia developed in >80% of all measurements in the presence of low endogenous insulin levels. CRP and SAA levels increased in both groups, with maximum levels measured on POD2. GIK treatment significantly reduced CRP and SAA levels. Interleukin levels increased significantly in both groups following cardiopulmonary bypass, but no differences were found between the groups. CONCLUSION Hyperinsulinaemic normoglycaemic clamp is an effective method of maintaining tight glycaemic control in patients undergoing CABG and it attenuates the systemic inflammatory response in these patients. This effect may partly contribute to the reported beneficial effect of glycaemic control in patients undergoing CABG.