Serum Creatine Kinase Isoenzyme MB Research Articles

Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of follow-up in 196 patients: J. Ravkilde, H. Nissen, M. Horder, K. Thygesen. Department of Medicine-Cardiology A, Aarhus Amtssygehus University Hospital, Aarhus, Denmark. J Am Coll Cardiol 1995; 25:574–81

Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of follow-up in 196 patients: J. Ravkilde, H. Nissen, M. Horder, K. Thygesen. Department of Medicine-Cardiology A, Aarhus Amtssygehus University Hospital, Aarhus, Denmark. J Am Coll Cardiol 1995; 25:574–81

Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction: Analysis of 28 months of follow-up in 196 patients

We sought to determine the incidence and independent prognostic value of increased serum levels of sensitive serologic markers in patients in whom a conventionally diagnosed acute myocardial infarction had been ruled out. Increased serum levels of creatine kinase (CK) isoenzyme MB mass and cardiac troponin T in patients with unstable angina pectoris are associated with a poor prognosis. We analyzed data from 196 consecutive patients with suspected acute myocardial infarction, which was later ruled out in 124. Increased serum levels of CK-MB mass, troponin T and myosin light chains were compared with clinical findings, ST-T wave abnormalities and presence of arrhythmias. Of the patients in the noninfarction group, 28% had serum CK-MB mass > or = 6 micrograms/liter, 20% had troponin T > or = 0.20 micrograms/liter, and 26% had myosin light chains > or = 0.4 micrograms/liter (discrimination limits). The cardiac event rate (cardiac death, nonfatal acute myocardial infarction) within 28 months was significantly higher in patients in the noninfarction group with elevated marker levels (range 22% to 24%) than in patients with values below these discriminators (range 3% to 5%) but was not significantly different from that in patients with a definite diagnosis of acute myocardial infarction (29%). Further, significant predictors of cardiac events were previous myocardial infarction; myocardial infarction or angina pectoris, or both; previous congestive heart failure; ST-T wave abnormalities on admission; a transient ST-T wave shift on serial electrocardiograms (ECGs); recurrent chest pain; and occurrence of supraventricular or ventricular tachycardia, or both, during the 1st 48 h after admission. It was found that all three biochemical markers, in the main, convey independent prognostic information with respect to clinical findings and presence of arrhythmias but not ST-T wave abnormalities on admission or a transient ST-T wave shift on serial ECGs. Increased serum levels of CK-MB mass, troponin T and myosin light chains all detect a subgroup of 25% of patients without acute myocardial infarction who have as poor a prognosis as that of patients with a definite diagnosis of acute myocardial infarction. All three biochemical markers provide similar important independent prognostic information with regard to clinical findings and arrhythmias but add no additional prognostic information once ECG ST-T wave changes are considered.

Normal post-race antimyosin myocardial scintigraphy in asymptomatic marathon runners with elevated serum creatine kinase MB isoenzyme and troponin T levels. Evidence against silent myocardial cell necrosis.

Recent epidemiologic studies confirm that heavy physical exertion can trigger myocardial infarction. Diagnosis of acute myocardial injury in marathon runners is complicated by elevations of serum creatine kinase MB isoenzyme activity in asymptomatic finishers with normal post-race infarct-avid myocardial scintigraphy. Such isoenzyme elevations can arise from exertional rhabdomyolysis of skeletal muscle biochemically altered by training, from silent injury to the myocardium or from a combined tissue source. To assess silent myocardial cell necrosis in marathon runners, we performed quantitative anti-myosin myocardial scintigraphy after competition with serum immunoassays for creatine kinase MB isoenzyme and troponin T. Therefore, 8 male marathon runners with a mean age of 52 years underwent quantitative antimyosin myocardial scintigraphy immediately following the 1988 and 1993 Boston Marathons. Serum immunoassays for creatine kinase MB isoenzyme by a chemiluminescent method (CLIA) and troponin T by an enzyme-linked immunosorbent assay were performed in 4 runners after the 1993 race. Quantitative antimyosin myocardial scintigraphy was normal in all runners including 3 who participated after both races 5 years apart. Post-race serum creatine kinase MB isoenzyme and/or troponin T levels were in a range otherwise diagnostic of acute myocardial infarction in 3 of 4 subjects. Normal quantitative antimyosin myocardial imaging in asymptomatic marathon runners excludes silent myocardial cell necrosis as the source of elevated serum protein markers. Such imaging may be the optimal diagnostic modality for detection of myocardial cell necrosis in symptomatic athletes when results of conventional testing are inconclusive.

Early detection of successful coronary reperfusion based on serum myoglobin concentration: Comparison with serum creatine kinase isoenzyme MB activity

The usefulness of serum myoglobin (Mb) concentration for early detection of successful reperfusion was compared with that of creatine kinase isoenzyme MB (CKMB) activity in 49 patients with acute myocardial infarction. To determine accurately the time of reperfusion, we performed coronary angiography every 5 minutes during reperfusion therapy. Reperfusion was obtained in 32 patients (reperfused group) but not in 17 patients (nonreperfused group) until 60 minutes after the initiation of reperfusion therapy. Blood samples were taken before and 15, 30, and 60 minutes after the angiographic confirmation of reperfusion in the reperfused group. In the nonreperfused group, samples were taken before and 15, 30, and 60 minutes after the initiation of treatment. We calculated the Mb ratio (value after reperfusion or treatment initiation to value before) and CKMB ratio (value after to value before). When values >2.4 for the Mb ratio or >2.0 for the CKMB ratio were used as the criteria for reperfusion within 60 minutes after initiation of treatment, the sensitivities were 91% and 56% at 15 minutes after reperfusion, 97% and 84% at 30 minutes, and 100% and 100% at 60 minutes, respectively. For each ratio the specificity of detection was 100% at all times evaluated. Thus the Mb ratio accurately detected the success of reperfusion as early as 15 minutes after reperfusion and may be more useful than the CKMB ratio for detecting the success of reperfusion within 30 minutes.

Creatine kinase isoenzyme MB may be elevated in healthy young women after submaximal eccentric exercise.

Elevations in serum creatine kinase isoenzyme MB (CK MB) after exercise may be of clinical importance for the diagnosis of myocardial infarction. However, CK MB has been observed to increase after exercise in highly trained endurance runners. No data exist relating to the effect of exercise in a heterogeneous female population with regard to CK MB. The purpose of the present investigation was to determine whether an elevation in serum CK MB can be measured in women (heterogeneous for aerobic capacity, estradiol, and lean body mass) and to make a preliminary analysis of the relationships of postexercise serum CK MB concentration and CK activity, estradiol, lean body mass, and peak oxygen consumption. Lean body mass and peak oxygen consumption were measured for 15 college-age women (19 to 29 years) after the performance of a stepping exercise for 40 minutes at 70% of peak oxygen consumption to elicit the efflux of intramuscular enzymes. Serum CK MB concentration, CK activity, and estradiol level were measured before exercise and 24 and 48 hours after exercise. Serum estradiol level was also measured immediately after exercise. Four of the 15 subjects had elevations in CK MB concentrations ranging from 18.4 to 101.2 micrograms/L, many times the upper normal limit (4.7 micrograms/L). All subjects with high serum CK MB concentrations had high CK activity, and the two measures were significantly related (p < 0.01) in the postexercise period. It was concluded that exercise can cause large elevations in serum CK MB in some women.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of serum myoglobin and creatine kinase MB isoenzyme in the detection of acute myocardial infarction

Serum creatine kinase MB isoenzyme (CKMB) and myoglobin have been studied in 35 cases with myocardial infarction. Increased values for both serum CKMB and myoglobin have been found in all the patients in the second sample collected 4 hr. after admission while in 22 patients in the first sample collected immediately after admission. Thus, the present study shows a good correlation between serum CKMB and myoglobin and therefore, suggests the possibility of using the serum myoglobin estimation in early detection of myocardial infarction either alone or in combination with the serum CKMB.

Risk stratification in suspected acute myocardial infarction based on a sensitive immunoassay for serum creatine kinase isoenzyme MB. A 2.5-year follow-up study in 156 consecutive patients.

This prospective study was an evolution of a new sensitive creatine kinase (CK) isoenzyme MB immunoassay in 156 patients, admitted consecutively to the coronary care unit, suspected of having acute myocardial infarction (MI), with regard to clinical applicability and clinical outcome. 42% of the patients had MI based on WHO criteria. The remaining 91 patients could be divided into a group with ischemic heart disease (IHD) without MI being present (n = 65) and a group with non-IHD (n = 26). In the former, a subgrouping based on changing CK MB levels (n = 24) or stable CK MB levels (n = 41) as compared to the non-IHD group could be performed. These patients were not diagnosed using the routine diagnostic procedures. Follow-up was carried out for 30 months (median 22). The prognosis as evaluated by cardiac death was significantly better for patients with stable CK MB levels than for those with changing CK MB levels, inasmuch as the cumulative probability not to suffer cardiac death was 95 +/- 3 and 66 +/- 10% after 2.5 years, respectively (p less than 0.003). It was 52 +/- 6% for the patients with MI, similar to patients with changing CK MB levels (p = 0.15). We conclude that this new CK MB assay can detect a subgroup of patients with IHD, which is not diagnosed using routine diagnostic procedures, with a poor clinical outcome.

Indices of reperfusion in patients with acute myocardial infarction using characteristics of the CK-MB time-activity curve

The purpose of this study was to identify indices of coronary artery reperfusion in patients treated with thrombolytic therapy for acute myocardial infarction (AMI) by means of characteristics from the serum creatine kinase (CK) isoenzyme MB time-activity curve. Frequent blood sampling as performed in three groups with a first AMI: 29 patients treated with intravenous thrombolytic therapy who had a patent infarct-related artery with normal flow (TIMI-3) at acute catheterization (reperfusion group); four patients with a persistently closed infarct-related artery (no reperfusion group); and 44 patients who did not receive any therapy aimed at coronary reperfusion (no thrombolytic therapy group). In the latter group we prospectively estimated that 25% would have spontaneous reperfusion. A physiologically based computer-calculated multi-compartment method was used to determine the characteristics of the serum CK-MB time-activity curve. In addition to demonstrating an earlier increase, a shorter time to peak of serum CK-MB and a lower estimated infarct size in the reperfusion group ( p = 0.025 to 0.00001), the appearance rate constant (k1) and time from estimated initial increase to peak of CK-MB in the blood stream (tRP) were significantly different from those values in the no thrombolytic therapy group ( p < 00001). A cutoff level indicating reperfusion if k1 was >0.185 or tRP was <16.5 hours demonstrated overlapping values between these two groups in only four patients (k1), two patients (tRP), and six patients with a combination. This corresponds to a sensitivity of 86% (k1), 93% (tRP), or 100% (combination) and an estimated specificity of 100% (k1), 100% (tRP), or 89% (combination). The k1 index can be reliably estimated as early as 4 hours after the onset of CK-MB release into the blood stream. Thus these indices reflect the presence or absence of coronary reperfusion and may be useful for monitoring thrombolytic therapy in patients with AMI.

S-100ao protein in serum during acute myocardial infarction

Concentrations in serum of S100ao protein (alpha alpha form of S-100 protein, which is present at high concentrations in heart muscle) were successively measured by enzyme immunoassay in 21 patients with acute myocardial infarction (AMI) and six with angina pectoris (ANP). Results were compared with measurements of creatine kinase isoenzyme MB (CK-MB) concentrations in the same specimens. Mean S100ao concentrations in sera from 100 healthy adults were 0.12 (SD 0.08) microgram/L. In patients with AMI, S100ao concentrations were 4.74 +/- 5.27 micrograms/L at admission, peaked 8 h after admission (23.5 +/- 27.7 micrograms/L), then decreased gradually. Among nine AMI patients who were admitted within an hour after their attack, eight showed abnormally high concentrations of S100ao in serum (greater than 0.5 microgram/L), whereas only four showed abnormally high CK-MB concentrations (greater than 5 micrograms/L) in sera at the time of admission. Serum S100ao concentrations remained within the normal range in all six patients with ANP; however, serum CK-MB concentrations were increased in two of them. Therefore, serum S100ao is useful not only for detection of AMI but also for differentiating AMI from ANP.

At what level of serum total creatine kinase activity can measurement of serum creatine kinase MB isoenzyme activity be omitted in suspected myocardial infarction?

The purpose of this study was to establish a discriminatory limit for serum total creatine kinase activity (CK activity) below which CK isoenzyme fractionation is unnecessary.We looked at 2610 serum samples from 1077 consecutive patients with suspected acute myocardial infraction (AMI). The CK activity was determined according to the Scandinavian recommended method. Isoenzymes of CK were separated by agarose gel electrophoresis, followed by fluorometric scanning.When the threshold for CK activity was 150 U/l, none of the samples had a creatine kinase MB isoenzyme activity (CK-MB activity) equal to or higher than 30 U/l (the diagnostic level), which has been found to differentiate between patients with AMI and those without AMI. Only 14 patients (1.3% of all patients investigated) had CK-MB activity peaks between 10 U/l (detection limit) and 30 U/l. Of these, AMI was only diagnosed in one.We recommend that CK-MB activity should be measured only when CK activity is higher than 150 U/l. This would make about 50% of all CK-MB measurements unnecessary.

Immobilized enzyme assay of creatine kinase with amperometric detection

Serum creatine kinase-MB isoenzyme was determined by an immunoinhibition-amperometric technique in a coupled reaction scheme in which ADP and ATP are recycled and hydrogen peroxide is a product of the reaction. Two enzymes in the scheme, glycerokinase and glycerol-3-phosphate oxidase, were co-immobilized on collagen membrane at the surface of a platinum electrode polarized at 700 mV. The rate of production of hydrogen peroxide in the reaction was measured amperometrically at the electrode and related to the activity of creatine kinase. Calibration curves prepared with human creatine kinase-MB isoenzyme standards were linear from 10 to 500 U liter −1 with a detection limit of 8 U liter −1. Total creatine kinase in serum was also determined by the present method. The precision of the method was 3.1% relative standard deviation at the 10 U liter −1 level of creatine kinase. Interference from adenylate kinase was eliminated by the addition of diadenosine-5′-pentaphosphate to samples.

At what level of serum total creatine kinase activity can measurement of serum creatine kinase MB isoenzyme activity be omitted in suspected myocardial infarction?

The purpose of this study was to establish a discriminatory limit for serum total creatine kinase activity (CK activity) below which CK isoenzyme fractionation is unnecessary. We looked at 2610 serum samples from 1077 consecutive patients with suspected acute myocardial infraction (AMI). The CK activity was determined according to the Scandinavian recommended method. Isoenzymes of CK were separated by agarose gel electrophoresis, followed by fluorometric scanning. When the threshold for CK activity was 150 U/l, none of the samples had a creatine kinase MB isoenzyme activity (CK-MB activity) equal to or higher than 30 U/l (the diagnostic level), which has been found to differentiate between patients with AMI and those without AMI. Only 14 patients (1.3% of all patients investigated) had CK-MB activity peaks between 10 U/l (detection limit) and 30 U/l. Of these, AMI was only diagnosed in one. We recommend that CK-MB activity should be measured only when CK activity is higher than 150 U/l. This would make about 50% of all CK-MB measurements unnecessary.

Serum isoenzyme pattern of creatine kinase and lactate dehydrogenase in various animal species.

The creatine kinase and lactate dehydrogenase isoenzyme pattern were determined in the serum of normal and untreated rats, rabbits, dogs, monkeys and pigs. The relative distribution of all isoenzymes in the serum and an electrophoretic pattern for each animal species are presented. The isoenzyme serum pattern showed a great variation between the species. The diagnostic value of serum creatine kinase isoenzyme MB and lactate dehydrogenase isoenzymes 1 and 2 in predicting cardiac lesions in different animal species is briefly discussed.

A comprehensive estimation of acute myocardial infarct size using enzymatic, electrocardiographic and mechanical methods

This prospective study compares the estimated size of acute myocardial infarction (AMI) by cumulative serum creatine kinase isoenzyme MB (CK-MB), Selvester QRS score, and 2-dimensional (2-D) echocardiographic dyssynergy of the left ventricle in 63 consecutive patients with their first anterior (n = 31) or inferior AMI (n = 32). The correlations among these parameters were good for patients with anterior AMI (r = 0.74 to 0.78, standard error of the estimate = 29 to 33%) but only fair for those with inferior AMI (r = 0.35 to 0.47, standard error of the estimate = 38 to 73%). Based on previous autopsy studies, estimates of CK-MB and QRS score were then converted to percent of infarcted left ventricle. Linear regression analyses between mean percent AMI size by cumulative CK-MB plus QRS score vs the number of dyssynergic segments by 2-D echocardiography were used to develop a comprehensive formula for estimating AMI size by a combination of all 3 techniques. Thus, a formula is proposed that may optimally estimate AMI size derived from leakage of cytosolic enzymes, changes in the sequence of myocardial depolarization, and irregularities of left ventricular contraction.

False increases in serum creatine kinase MB isoenzyme detected in two patients by the Behring CK-MB quantitative immunometric assay.

False increases in serum creatine kinase MB isoenzyme detected in two patients by the Behring CK-MB quantitative immunometric assay.

Changes in serum creatine kinase and lactate dehydrogenase caused by acute perioperative myocardial infarction and by transatrial cardiac surgical procedures

A prospective clinical study was conducted to ascertain if a patient's postoperative elevation in serum creatine kinase MB isoenzyme coupled with determination of the lactate dehydrogenase1/lactate dehydrogenase2 ratio could differentiate whether atrial or ventricular myocardium was the source of these changes. Animal studies have shown that atrial myocardium is as rich a source of creatine kinase MB as is ventricular myocardium. Atrial myocardium has a lactate dehydrogenase1/lactate dehydrogenase2 ratio less than 1.00, whereas in ventricular myocardium the ratio is greater than 1.00. Sixty-four patients were assigned to six groups on the basis of serial electrocardiograms and vectorcardiograms by a cardiologist who was unaware of their clinical courses. The control group (Group 1) consisted of 16 patients admitted to the coronary care unit who had no electrocardiographic changes. Three surgical groups without electrocardiographic or vectorcardiographic evidence of perioperative myocardial infarction were studied: 10 patients undergoing routine coronary artery bypass procedures (Group 2), six adults undergoing repair of secundum atrial septal defect (Group 3), and 13 patients having mitral valve replacement (Group 4). Two groups of surgical patients who had acute perioperative transmural myocardial infarctions confirmed by serial electrocardiograms and vectorcardiograms were studied: 15 patients (Group 5) who had elective coronary artery bypass procedures and four (Group 6) who had mitral valve replacement. This study suggests that serum creatine kinase MB levels in excess of 50 IU/L on the postoperative day 1 and day 2 samples coupled with serum lactate dehydrogenase1/lactate dehydrogenase2 ratios greater than 1.00 on the postoperative day 2 and day 3 samples support the diagnosis of acute myocardial infarction. Patient groups undergoing procedures necessitating atriotomies had average elevations in serum creatine kinase MB and in the lactate dehydrogenase1/lactate dehydrogenase2 ratio, but these were significantly less than those seen when acute perioperative myocardial infarction had occurred.

Serum creatine kinase isoenzyme MB concentration after endomyocardial biopsy

Serum total creatine kinase (CK), CK-MB and myoglobin (Mb) were serially determined in 17 patients who underwent endomyocardial biopsy. Mean total CK levels increased from 36 ± 27 U/l 30 min before biopsy to a maximum of 112 ± 77 U/l 8 h following the procedure ( p < 0.05). Similarly, Mb concentrations rose from 57 ± 55 μg/l to 119 ± 57 μg/l 30 min after biopsy ( p < 0.05). Normalization of total CK and Mb levels occurred within 16 and 8 h, respectively. A new immunoenzymetric assay (IEMA) was used to measure the mass concentration of the CK-MB molecule. The initial CK-MB levels were 0.2 ± 0.4 μg/l; a small but significant elevation was recorded as early as 2 h after biopsy (1.6 ± 1.5 μg/l, p < 0.05). CK-MB returned to initial concentration 16 h after the beginning of the procedure. Comparison with the maximum CK-MB levels recorded in 16 myocardial infarction patients (258 ± 172 μg/l, range 90–680 μg/l) indicated that the modest increase of CK-MB level detected after biopsy probably reflects a limited endomyocardium lesion at the sampling site, excluding any significant myocardial damage. Total CK and Mb, which showed more pronounced elevations than CK-MB, are likely to originate from other sources than the myocardium.

Differentiating muscle damage from myocardial injury by means of the serum creatine kinase (CK) isoenzyme MB mass measurement/total CK activity ratio.

We immunoenzymometrically measured creatine kinase (CK) isoenzyme MB in extracts of myocardium and in homogenates of five different skeletal muscles. CK-MB concentrations in the former averaged 80.9 micrograms/g wet tissue; in the skeletal muscles it varied widely, being (e.g.) 25-fold greater in diaphragm than in psoas. CK-MB in skeletal muscles ranged from 0.9 to 44 ng/U of total CK; the mean for myocardium was 202 ng/U. In sera from 10 trauma and 36 burn patients without myocardial involvement, maximum ratios for CK-MB mass/total CK activity averaged 7 (SEM 1) ng/U and 18 (SEM 6) ng/U, respectively. Except for an infant (220 ng/U), the highest ratio we found for serum after muscular damage was 38 ng/U. In contrast, the mean maximum ratio determined in 23 cases of acute myocardial infarction exceeded 200 ng/U. Among seven determinations performed 8 to 32 h after onset of symptoms, each infarct patient demonstrated at least one ratio greater than or equal to 110 ng/U. Ratios observed after infarct were unrelated to treatment received during the acute phase. We propose a CK-MB/total CK ratio of 80 ng/U as the cutoff value for differentiating myocardial necrosis from muscular injury.

Serum creatine kinase MB (heart) isoenzyme activity in schizophrenia

Serum creatine kinase MB (heart) isoenzyme activity in schizophrenia

Quantitative influence of serum creatine kinase isoenzyme MB estimated infarct size and other prognostic variables on one year mortality after acute myocardial infarction.

The aim of the present study was to determine the strength of the relation between serum creatine kinase isoenzyme MB estimated infarct size, other prognostic variables, and mortality after acute myocardial infarction. Serum creatine kinase MB estimated infarct size and 11 other prognostic variables were obtained in 317 patients. By Cox regression analysis the prognostic variables significantly related to mortality were identified: congestive heart failure, estimated infarct size, New York Heart Association class, number of previous infarcts, and age. Congestive heart failure and estimated infarct size were most strongly related to mortality. The relation between the prognostic variables and mortality was non-linear, and the variables influenced each others' relation to mortality. A prognostic index based on all five prognostic variables provided the best means of estimating the probability of survival after acute myocardial infarct. Neither serum creatine kinase MB estimated infarct size nor any of the other prognostic variables had a significant independent influence on mortality, and the probability of survival was high in the absence of any of the prognostic variables in combination.