Creatine Kinase MB Isoform Research Articles

A Case of Dematomyositis in a Cancer Patient Presenting as Dysphagia

Dermatomyositis (DM) is a rare idiopathic inflammatory muscle and skin disorder with a 2:1 female predominance, and peak incidence in the 5th and 6th decades of life. DM presents acutely or progressively as painless proximal skeletal muscle weakness and can be associated with the characteristic heliotropic rash around the eyes and Gottron's papules on extensor surface of the hands. Individuals may also present with symptoms of dysphagia, and cardiac or pulmonary involvement. We report a 72-year-old female with renal clear cell carcinoma, breast cancer, and papillary serous carcinoma of the uterus, who presented with progressive weakness, 30 pound weight loss, and difficulty swallowing over the past three months. She also reported difficulty ambulating, facial rash, and inability to extend her fingers. Physical examination revealed a cachectic-appearing woman and areas of hyperpigmentation on her face, arms, and legs. She also had symmetric proximal muscle weakness in both upper and lower extremities. Laboratory findings were significant for an elevated serum creatinine phosphokinase level of 3222 U/L, creatine kinase isoform MB 369.7 ng/mL, aldolase 31.7 U/L, erythrocyte sedimentation rate 40 mm/hr, C-reactive protein 8.41 mg/L, lactate dehydrogenase 804 U/L, and antinuclear antibody positive >1:640. Barium esophagram revealed significant difficulty initiating swallow with laryngeal penetration and aspiration of contrast. Esophagogastroduodenoscopy showed pooling of saliva in the piriform fossa with a normal appearing esophagus. A left biceps muscle biopsy revealed inflammatory myositis with significant necrotizing component suggestive of DM. Further staining with nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) stain identified frequent myofibers with targetoid-like changes consistent with DM. She was treated with intravenous corticosteroids, however, she did not respond to the treatment. Thus, a percutaneous gastrostomy tube was placed for enteral feeding. DM is an inflammatory myopathy with cutaneous manifestations and associated with malignancy. Striated muscle in the oropharynx and upper one-third of the esophagus are affected, which results in oropharyngeal dysphagia. Patients with muscle weakness and progressive dysphagia can be a hallmark of malignancy. In our patient, DM presented as dysphagia with multiple malignancies with lack of a response to corticosteroid treatment, which portends a poor prognosis.Figure 1Figure 2Figure 3

Semi-continuous, real-time monitoring of protein biomarker using a recyclable surface plasmon resonance sensor

Although label-free immunosensors based on, for example, surface plasmon resonance (SPR) provide advantages of real-time monitoring of the analyte concentration, its application to routine clinical analysis in a semi-continuous manner is problematic because of the high cost of the sensor chip. The sensor chip is in most cases regenerated by employing an acidic pH. However, this causes gradual deterioration of the activity of the capture antibody immobilized on the sensor surface. To use sensor chips repeatedly, we investigated a novel surface modification method that enables regeneration of the sensor surface under mild conditions. We introduced a monoclonal antibody (anti-CBP Ab) that detects the conformational change in calcium binding protein (CBP) upon Ca2+ binding (>1mM). To construct a regenerable SPR-based immunosensor, anti-CBP Ab was first immobilized on the sensor surface, and CBP conjugated to the capture antibody (specific for creatine kinase-MB isoform (CK-MB); CBP-CAb) then bound in the presence of Ca2+. A serum sample was mixed with the detection antibody to CK-MB, which generated an SPR signal proportional to the analyte concentration. After each analysis, the sensor surface was regenerated using medium (pH 7) without Ca2+, and then adding fresh CBP-CAb in the presence of Ca2+ for the subsequent analysis. Analysis of multiple samples using the same sensor was reproducible at a rate >98.7%. The dose-response curve was linear for 1.75–500.75ng/mL CK-MB, with an acceptable coefficient of variation of <8.8%. The performance of the immunosensor showed a strong correlation with that of the Pathfast reference system (R2>96%), and exhibited analytical stability for 1 month. To our knowledge, this is the first report of a renewal of a sensor surface with fresh antibody after each analysis, providing high consistency in the assay during a long-term use (e.g., a month at least).

A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD)

Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross-sectional study of two independent cohorts. We discovered biomarkers that correlate with clinical severity and disease burden measured by magnetic resonance imaging. Sixty-eight proteins in the Rochester cohort (n = 48) and 51 proteins in the Seattle cohort (n = 30) had significantly different levels in FSHD-affected individuals when compared with controls (p-value ≤ .005). A subset of these varied by at least 1.5 fold and four biomarkers were significantly elevated in both cohorts. Levels of creatine kinase MM and MB isoforms, carbonic anhydrase III, and troponin I type 2 reliably predicted the disease state and correlated with disease severity. Other novel biomarkers were also discovered that may reveal mechanisms of disease pathology. Assessing the levels of these biomarkers during clinical trials may add significance to other measures of quantifying disease progression or regression.

LncRNA NONRATT021972 involved the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia after myocardial ischemic injury.

Adenosine triphosphate (ATP) acts on P2X receptors to initiate signal transmission. P2X7 receptors play a role in the pathophysiological process of myocardial ischemic injury. Long noncoding RNAs (lncRNAs) participate in numerous biological functions independent of protein translation. LncRNAs are implicated in nervous system diseases. This study investigated the effects of NONRATT021972 small interference RNA (siRNA) on the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia (SG) after myocardial ischemic injury. Our results demonstrated that the expression of NONRATT021972 in SG was significantly higher in the myocardial ischemic (MI) group than in the control group. Treatment of MI rats with NONRATT021972 siRNA, the P2X7 antagonist brilliant blue G (BBG), or P2X7 siRNA improved the histology of injured ischemic cardiac tissues and decreased the elevated concentrations of serum myocardial enzymes, creatine kinase (CK), CK isoform MB (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) compared to the MI rats. NONRATT021972 siRNA, BBG, or P2X7 siRNA treatment in MI rats decreased the expression levels of P2X7 immunoreactivity, P2X7 messenger RNA (mRNA), and P2X7 protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) in the SG compared to MI rats. NONRATT021972 siRNA treatment prevented the pathophysiologic processes mediated by P2X7 receptors in the SG after myocardial ischemic injury.

Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity.

Normalization of elevated cardiac, kidney, and hemolysis plasma markers within 48 h in Mexican Tarahumara runners following a 78 km race at moderate altitude.

ObjectivesThe aim of this study was to examine to what extent extreme endurance exercise results in changes of plasma markers associated with cardiac and renal damage, as well as hemolysis in male, Mexican Tarahumara runners.MethodsTen Tarahumara runners (mean (sd) age of 38 (12) years) participated in a 78 km race in Chihuahua, Mexico at 2,400 m above sea level. Cardiac, kidney, and hematology plasma markers were measured pre-race and <5 min, 1 h, 3 h, 6 h, 24 h, and 48 h post-race. Anthropometry, blood pressure, pulse rate, electrocardiography, HbA1c, hemoglobin and VO2max (estimated from heart rate following step test) were assessed pre-race, while physical activity energy expenditure and intensity were estimated during the race, and oxygen partial pressure saturation (SpO2) <30 min post-race.ResultsEstimated mean VO2max was 48 (9) mLO2 min−1 kg−1 and relative intensity during the race was 68 (11)%VO2max. Mean SpO2 was 92 (3)% <30 min post-race. Plasma concentrations of especially total creatine kinase, creatine kinase-MB isoform, and haptoglobin changed significantly from pre-race values (P < 0.001) up to 24 h post-race, but had returned to pre-race values after 48 h. The plasma concentrations of mid-regional proatrial natiuretic peptide and copeptin returned to pre-race concentrations after 1 and 6 h, respectively.ConclusionsAltered cardiac, renal, and hemolysis plasma markers were normalized after 48 h following 78 km of running, suggesting that the impact of exercise-induced cardiac and kidney damage as well as hemolysis in the Mexican Tarahumara is low. Am. J. Hum. Biol. 26:836–843, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.

Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia

Ethnopharmacological relevanceThe root of Astragalus membranaceus, known as “huang-qi”, is one of the most widely used Chinese herbal medicines for the prevention and treatment of myocardial ischemic diseases. However, the mechanisms governing its therapeutic effects are largely unknown. Aims of the studyThe aims of the present study were to investigate the cardioprotective effect of the root extract of Astragalu membranaceus (EAM) in myocardial ischemia and to explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and in vitro. Materials and methodsThe saponins in EAM were analyzed using HPLC. The tests for the cardioprotective effects of EAM and its mechanisms were performed in vivo and in vitro. In vivo, the rat model of persistent myocardial ischemia was produced by occlusion of the left anterior descending (LAD) coronary artery. In vitro, the cardiomyocyte model of oxidative stress was mimicked by the direct free radical donor, H2O2. ResultsIn vivo, the increased myocardial infarct size and the increased serum levels of lactate dehydrogenase (LDH), creatine kinase isoform MB (CK-MB), and cardiac troponin (cTnI) were significantly decreased by pre-treatment with EAM. Moreover, cardiac function, as assessed by±dP/dt, left ventricular developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP), was dramatically improved. An oxidative stress biomarker, malondialdehyde (MDA), was reduced, and the antioxidant enzyme superoxide dismutase (SOD) was induced. In vitro, H2O2-triggered myocardial cell death and cytoplasm Ca2+ overload were blocked by treatment with EAM. Furthermore, the KATP channel blocker (5-HD, glibenclamide) blocked the anti-apoptotic protective effect of EAM on cardiomyocytes injured by H2O2. ConclusionsThe cardioprotection of EAM was manifested as a protection of tissue structure and as a decrease in serum markers of ischemic injury. The mechanisms underlying the EAM-mediated protective effects may involve improving cardiac function, attenuating the oxidative injury via a decrease in MDA, a maintenance in SOD, and a reduction in free radical-induced myocardial cell injury. Additionally, EAM enhanced the myocardial cell viability via arresting the influx of Ca2+ to block cell death and opening mitochondrial KATP channels to reduce cell apoptosis.

Topical Cooling (Icing) Delays Recovery From Eccentric Exercise–Induced Muscle Damage

It is generally thought that topical cooling can interfere with blood perfusion and may have positive effects on recovery from a traumatic challenge. This study examined the influence of topical cooling on muscle damage markers and hemodynamic changes during recovery from eccentric exercise. Eleven male subjects (age 20.2 ± 0.3 years) performed 6 sets of elbow extension at 85% maximum voluntary load and randomly assigned to topical cooling or sham groups during recovery in a randomized crossover fashion. Cold packs were applied to exercised muscle for 15 minutes at 0, 3, 24, 48, and 72 hours after exercise. The exercise significantly elevated circulating creatine kinase-MB isoform (CK-MB) and myoglobin levels. Unexpectedly, greater elevations in circulating CK-MB and myoglobin above the control level were noted in the cooling trial during 48-72 hours of the post-exercise recovery period. Subjective fatigue feeling was greater at 72 hours after topical cooling compared with controls. Removal of the cold pack also led to a protracted rebound in muscle hemoglobin concentration compared with controls. Measures of interleukin (IL)-8, IL-10, IL-1β, and muscle strength during recovery were not influenced by cooling. A peak shift in IL-12p70 was noted during recovery with topical cooling. These data suggest that topical cooling, a commonly used clinical intervention, seems to not improve but rather delay recovery from eccentric exercise-induced muscle damage.

Serum NT‐proBNP in the early detection of doxorubicin‐induced cardiac dysfunction

Cardiac dysfunction is a major limitation of anthracycline treatment in cancer patients. There are several useful serum markers in other types of cardiomyopathy, including N-terminal pro-brain-natriuretic peptide (NT-proBNP), troponin-T and creatine kinase MB isoform. We investigated the potential application of these serum biomarkers in cancer patients receiving treatment with anthracycline. We collected data from 52 female breast cancer patients receiving doxorubicin and cyclophosphamide every 3 weeks for four cycles. Cardiac function evaluations by echocardiography were done at baseline and at the end of the fourth cycle of chemotherapy. Patients' blood samples were serially measured for cardiac biomarkers. The mean cumulative dose of doxorubicin in this study was 237 mg/m(2) . No symptomatic heart failure was detected during the study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from mean ± SD 70.7 ± 6% at baseline to 67.0 ± 5% (P < 0.001). By clinical toxicity criteria the LVEF decline was grade I in 18% and grade II in 4%. After one dose of chemotherapy, a significant rise of serum NT-proBNP occurred in patients who subsequently developed an LVEF reduction compared with patients with normal LVEF (P = 0.04). A correlation analysis demonstrated that the reduction of fractional shortening was significantly associated with elevated NT-proBNP (r = -0.016, P = 0.014). Asymptomatic reductions in cardiac function are common in breast cancer patients treated with doxorubicin. NT-proBNP may serve as a convenient serum biomarker for the early detection of cardiotoxicity induced by anthracycline.

A Randomly-Controlled Study on the Cardiac Function at the Early Stage of Return to the Plains after Short-Term Exposure to High Altitude

High altitude acclimatization and adaptation mechanisms have been well clarified, however, high altitude de-adaptation mechanism remains unclear. In this study, we conducted a controlled study on cardiac functions in 96 healthy young male who rapidly entered the high altitude (3700 m) and returned to the plains (1500 m) after 50 days. Ninety eight healthy male who remained at low altitude were recruited as control group. The mean pulmonary arterial pressure (mPAP), left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin-1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1α (HIF-1α), 8-iso-prostaglandin F2α (8-iso PGF2α), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m respectively. The results showed that after short-term exposure to high altitude mPAP and Tei index increased significantly, while LVEF and LVFS decreased significantly. These changes were positively correlated with altitude. On the 15th day after the subjects returned to low altitude, mPAP, LVEF and LVFS levels returned to the same level as those of the control subjects, but the Tei index in the returned subjects was still significantly higher than that in the control subjects (P<0.01). We also found that changes in Tei index was positively correlated with mPAP, ET-1, HIF-1α and 8-iso PGF2α levels, and negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These findings suggest that cardiac function de-adapts when returning to the plains after short-term exposure to high altitude and the function recovery takes a relatively long time.

Saliva-based creatine kinase MB measurement as a potential point-of-care testing for detection of myocardial infarction

Myocardial infarction (MI) is the main cause of death all over the world. Biomarkers of cardiac necrosis are of great importance in the diagnosis of MI. The aim of this study was to determine probable changes of creatine kinase MB isoform (CK-MB) levels in saliva of patients with acute MI. A case-control study was carried out on 30 patients with acute MI who were hospitalized in Kamkar-Arabnia Hospital of Qom City and 30 healthy control subjects. CK-MB levels were measured by immunoinhibition assay in saliva and serum of patients and healthy individuals. Statistical analysis of the Student's t test and Pearson correlation coefficient was used. CK-MB levels showed a significant elevation in saliva and serum of patients with acute MI compared to healthy controls. Furthermore, there was a strong correlation between salivary levels of CK-MB and its serum values. Subsequent to an acute MI, there is a rise in salivary levels of CK-MB just as what occurs in the serum. Moreover, salivary levels of CK-MB reflect well its serum values. It seems that cardiac biomarker CK-MB is measurable in the saliva of patients with acute MI. Salivary CK-MB may serve as an easy-to-use diagnostic tool for point-of-care testing of acute MI.

The Comparison of Cardiac Biomarkers Positivities in Hemodialysis Patients without Acute Coronary Syndrome

Aim: We aimed to compare heart-type fatty acid-binding proteins (H-FAB) and other cardiac biomarkers to determine the most reliable cardiac marker in hemodialysis (HD) patients without acute coronary syndrome (ACS). Materials and methods: Sixty HD patients without ACS were included the study. Blood samples were taken before HD session for measurement of H-FAB, troponin I, troponin T, creatine kinase-MB (CK-MB) isoforms. Results: Mean age of patients was 55 ± 15 years. Males were 55%. Mean serum level of blood urea nitrogen was 75 ± 15 mg/dL, mean serum level of creatinine was 8.3 ± 2.5 mg/dL, mean serum level of hematocrit was 33 ± 5%, mean ejection fraction was 54 ± 9%, and mean left ventricular mass index (LVMI) was 136 ± 54 g/m2. H-FAB was positive in 32%, troponin T in 20%, troponin I in 12%, and CK-MB in 5% of all patients. Three or four of all parameters were not positive together in any patient. While 5% of patients had positive troponin T with H-FAB, 3% of patients had positive troponin T with troponin I and 2% of patients had positive troponin I with H-FAB. Conclusion: Our study found that CK-MB had the lowest positivity in the HD patients without ACS. H-FAB had the highest rate of positivity in all markers. If only one marker is assessed it should be CK-MB. But using two parameters in HD patients in ACS diagnosis increases the reliability of diagnosis. If we use two biomarkers it should be CK-MB and troponin I.

Myocardial energy metabolism and functional recovery in coronary bypass surgery: A comparative study between continuous retrograde warm and mild hypothermic blood cardioplegia

The optimal temperature for delivery of continuous retrograde blood cardioplegia is not known. Twenty-two patients admitted to the hospital for elective coronary artery bypass grafting were randomized into the warm (37°) and mild hypothermic (28°C) cardioplegia groups. Changes in myocardial energy metabolism during cardiopulmonary bypass, postoperative efflux of the creatine kinase MB isoform (CK-MB), functional hemodynamic recovery, and postoperative complications were followed. During aortic cross-clamp, the average oxygen consumption was higher in the warm than in the mild hypothermic group (3.4±0.4 vs 2.4±0.3 ml/minute,p=0.06), as was the average transcardiac (outflow-inflow) pCO2-difference (1.1±0.1 vs 0.7±0.1 kPa,p=0.02). The average transcardiac pH-difference during aortic cross-clamp was lower in the warm group (−0.08±0.01 vs −0.06±0.01 U,p=0.02), reflecting more profound tissue acidosis. In accordance with this, warm hearts produced more lactate, especially towards the end of the aortic cross-clamp period (p=0.001). The net efflux of adenosine and its degradation products was more prominent during warm than during mild hypothermic cardioplegia (p=0.016), indicating less degradation of high energy adenylates in the hypothermic group. The functional hemodynamic recovery during the first postoperative day was similar in both patient groups, although the myocardial injury estimated as postoperative leakage of CK-MB was less extensive in the hypothermic group (p=0.011). There were no major differences in the postoperative complications between the study groups. We conclude that continuous retrograde mild hypothermic blood cardioplegia offers better myocardial protection during coronary bypass surgery than does continuous retrograde warm cardioplegia. The clinical significance of this should be tested in a larger series of patients, especially those with recent myocardial infarction, unstable angina, or severely depressed left ventricular function.

Utility of cardiac biomarkers for the diagnosis of type V myocardial infarction after coronary artery bypass grafting: insights from serial cardiac MRI

ObjectivesTo examine, using cardiac magnetic resonance (CMR), the utility of cardiac biomarkers for the determination of myocyte necrosis and function after coronary artery bypass grafting (CABG), and to test the...

Correlates of acute insulin resistance in the early phase of non-diabetic ST-elevation myocardial infarction

The relationship between insulin secretion and acute insulin resistance (as assessed by Homeostatic Model Assessment [HOMA] index) and clinical and biochemical parameters in the early phase of non-diabetic ST-elevation myocardial infarction (STEMI) is so far unexplored. We aimed at assessing this relation in 286 consecutive STEMI patients without previously known diabetes submitted to primary percutaneous coronary intervention (PCI). Insulin resistance (as indicated by HOMA) was detectable in 67.1%. Non-parametric correlation showed that HOMA index was significantly correlated with BMI (r = 0.242; p < 0.0001) and HbA(1c) (r = 0.189; p < 0.001). At multivariable backward linear regression analysis, glycaemia was directly related to leukocyte count (p = 0.0003), age (p = 0.0001), creatine kinase isoform MB (CK-MB) (p = 0.00278) and lactate (p < 0.0001). Insulin was directly and significantly related to glycaemia (p = 0.0006), body mass index (BMI) (p = 0.00028) and lactate (p = 0.0096) In the early phase of STEMI without previously known diabetes the acute glucose dysmetabolism is quite complex, comprising increased glucose values and the development of acute insulin resistance. While insulin secretion is strictly related to BMI, apart from glucose levels, increased glucose values can be mainly related to the acute inflammatory response (as indicated to leukocyte count and C-RP), to age and to the degree of myocardial damage (as inferred by CK-MB).

Elevated Soluble fms-Like Tyrosine Kinase-1 Levels in Acute Coronary Occlusion

Early recognition of an acute coronary occlusion (ACO) improves clinical outcomes. Soluble fms-like tyrosine kinase-1 (sFLT1) is an endothelium-derived protein induced by hypoxia. We tested whether sFLT1 levels are elevated in ACO. Serum sFLT1 levels were measured by enzyme-linked immunosorbent assay in patients with ST-segment elevations and angiographically confirmed ACO, unstable angina/non ST-segment elevation myocardial infarction, and 2 control groups. To further explore sFLT1 release, a mouse model of ACO and in vitro human coronary artery endothelial cell injury were used. sFLT1 levels were increased in ACO compared with unstable angina/non-ST-elevation myocardial infarction, catheterized controls, or healthy volunteers (200.7±15.5 versus 70.7±44.0 versus 10.2±4.0 versus 11.7±1.7 pg/mL respectively, P<0.001 versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (>15 pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of creatine kinase levels >10 ng/mL (P<0.01) and 85% had ultrasensitive troponin I levels >0.05 ng/mL (P<0.05). Within 60 minutes after symptom onset, sFLT1 was more sensitive than the MB isoform of creatine kinase or ultrasensitive troponin I for ACO (100% versus 20% versus 20% respectively; P≤0.01 for each). Within 60 minutes of ACO in mice, sFLT1 levels were elevated. Hypoxia and thrombin increased sFLT1 levels within 15 minutes in human coronary artery endothelial cells. sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.

The role of the heart-type fatty acid binding protein in the early diagnosis of acute coronary syndrome and its comparison with troponin I and creatine kinase-MB isoform

Objectives The aim of this study was to research the effectiveness of the heart-type fatty acid binding protein (H-FABP) in the early diagnosis of acute coronary syndrome (ACS) in patients admitted to emergency service (ES) within 6 hours of onset of chest pain. Equipment and Method A total of 83 patients admitted with chest pain to our ES were included in this study. The patients were divided into 2 groups: those with a diagnosed ACS and those diagnosed with non–cardiac-related chest pain. Patients were also were divided into 2 groups according to the time of admission: those admitted within 0 to 3 hours and 3 to 6 hours of onset of chest pain. Peripheral venous blood samples were obtained from all patients for H-FABP, troponin I, and creatine kinase-MB (CK-MB) serum concentration measurements. Results Of a total of 83 patients, 21.6% (n = 18) were in the control group and 78.3% (n = 65) were in the ACS group. The average H-FABP value for the patients in the control group was 0.86 ± 0.54 ng/mL. When the ACS and control groups were compared in means of cardiac markers for CK-MB ( P = .000) and H-FABP ( P = .000), there was a statistically significant difference, whereas no difference was observed for troponin I ( P = .013). In the ACS group, H-FABP sensitivity for diagnosis was found to be 98% and specificity was 71%; CK-MB sensitivity was 86% and specificity was 52%; and troponin I sensitivity was 77% and specificity was 20%. Conclusions For patients admitted with chest pain to ES, H-FABP was found to be more sensitive and specific than troponin I and CK-MB in the early diagnosis of ACS.

The Association Between Plaque Characterization by CT Angiography and Post-Procedural Myocardial Infarction in Patients With Elective Stent Implantation

This study sought to evaluate the association between volumetric characterization of target lesions by multidetector computed tomography (MDCT) angiography and the risk of post-procedural myocardial injury after elective stent implantation. Previous reports have shown that plaque characterization of the target lesion may provide useful information for stratifying the risk of coronary stenting. A total of 189 consecutive patients were enrolled; they underwent elective stent implantation after volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50 HU); 2) moderate-attenuation plaque (MAP) (50 to 150 HU); 3) lumen (151 to 500 HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque component in the target lesion was calculated using Color Code Plaque. Post-procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 h after percutaneous coronary intervention were also evaluated. The volumes of LAP (87.9+/-94.8 mm3 vs. 47.4+/-43.7 mm3, p<0.01) and MAP (111.6+/-77.5 mm3 vs. 89.8+/-67.1 mm3, p<0.05) were larger in patients with post-procedural myocardial injury (defined as positive TnT) than in those with negative TnT. The volumes of LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume) correlated with biomarkers; the MAP fraction was inversely correlated with biomarkers. The volume of LAP was an independent predictor of positive TnT after adjusting for patient background, conventional IVUS parameters, and procedural factors. Post-procedural myocardial injury was associated with the volume and fraction of LAP as detected by MDCT. The volume of LAP was an independent predictor of positive TnT. Plaque analysis by MDCT would be a useful method for predicting post-procedural myocardial injury after percutaneous coronary intervention.

Intracoronary Electrocardiogram Recording With a Bare-Wire System: Perioperative ST-Segment Elevation in the Intracoronary Electrocardiogram Is Associated With Myocardial Injury After Elective Coronary Stent Implantation

With an intracoronary electrocardiogram (IcECG) recording with insulated polymer-coated guidewire without balloon catheter, we sought to examine the association between ST-segment elevation in the IcECG after elective stenting and myocardial injury. An IcECG is a sensitive method to detect local myocardial ischemia. Occasionally, persistent ST-segment elevation in the IcECG was recorded after successful coronary intervention. Conventionally IcECG was recorded with a guidewire and over-the-wire system. Patients who underwent elective stenting were enrolled (n = 339). The IcECG both at baseline and after procedure were obtained with a guidewire with an insulating coated shaft suitable for IcECG recording. The presence of chest pain after percutaneous coronary intervention was recorded. Cardiac biomarkers were examined 18 h after the procedure. The ST-segment elevation in the IcECG after procedure was recorded in 65 patients, and no change was recorded in 274 patients. Troponin-T, creatine phosphokinase, and creatine kinase MB isoform after the procedure were significantly higher in patients with post-procedural ST-segment elevation in the IcECG than patients without ST-segment elevation. Multivariate analysis demonstrated that ST-segment elevation in the IcECG is an independent predictor of post-procedural myocardial injury. The incidence of ST-segment elevation in the IcECG was significantly higher in patients with post-procedural chest pain than patients without chest pain (p < 0.001). We demonstrated a facile method to record IcECG with a guidewire with a polymer-coated shaft. The IcECG is a useful method for predicting post-procedural myocardial injuries.

Requiem for a Heavyweight

The development of rapid, automated, and accurate laboratory testing for creatine kinase MB (CK-MB) revolutionized the treatment of patients with acute cardiac events in the 1970s and 1980s.1 To clinicians, CK-MB values augmented a thorough history, physical, and ECG findings, and elevations rapidly became the gold standard for identifying cardiac injury.1 CK-MB allowed earlier diagnosis of acute myocardial infarction (AMI), and detection of reinfarction, and measurements could be used to provide a facile clinical estimate of infarct size. Elevations of CK-MB were never intended to be synonymous with myocardial infarction, only indicative of cardiac injury.1 However, because of the relative insensitivity of measurements, increased concentrations occurred predominantly with larger insults such those associated with acute ischemic heart disease. For that reason, AMI was rarely diagnosed, assuming appropriate timing of the samples, in the absence of a CK-MB elevation.2,3 CK-MB assays initially relied on the measurement of enzyme activity, but over time, improved accuracy and ease of use were established by the use of mass assays. Mass assays allowed earlier detection of abnormal values and improved both clinical sensitivity and specificity. However, mass assays unmasked an increased frequency of CK-MB elevations due primarily to skeletal muscle injury because of their increased sensitivity.4–6 Clinical use of the percent relative index was then initiated. This approach improved the specificity of elevations for cardiac muscle injury but was insensitive when concurrent cardiac injury and skeletal muscle injury were present because elevations from skeletal muscle often are of a large magnitude.7–10 A large number of analytical confounds such as macrokinases and interfering substances also were substantial problems with these assays.10,11 Attempts to standardize assays12 have been partially successful, but differences still exist between manufacturers and even between the same testing antibodies used on different analytical platforms (ie, …