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PubMed2001

Myoglobin and creatine kinase isoenzyme MB mass assays: intermethod behaviour of patient sera and commercially available control materials.

The low biological variation of myoglobin and creatine kinase isoenzyme MB mass (CK-MBm) requires accurate measurements. In the standardization process, in order to effectively measure and correct intermethod variability, the intermethod behaviour of control materials must be the same of patient sera, i.e. they must be commutable. In this work we checked the commutability of some commercially available control materials in pairs of methods for myoglobin and CK-MBm measurements; we assessed the impact of commutable and non-commutable control materials when used for equalizing patient sera results by two different methods and discussed the problems related to external quality assessment schemes. Myoglobin and CK-MBm were measured in sets of 49 and 56 patient sera and in 13 commercially available control materials with two automatic analytical systems. The non-commutability rate was 8.3% for myoglobin and 23.1% for CK-MBm. Recalculation of serum samples results with a control material as calibrator lowered or increased the bias originally present according to whether the material itself was commutable or not. We conclude that also for myoglobin and CK-MBm assays it is necessary to check the commutability of materials to be used in external quality assessment schemes, or to normalize patient results by different methods.

Creatine Kinase↗
PubMed2001

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes.

BACKGROUND: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

Adult↗
PubMed2002

Value of a single troponin T at the time of presentation as compared to serial CK-MB determinations in patients with suspected myocardial ischemia.

BACKGROUND: Prior studies with cardiac markers have focused predominantly on subjects presenting to the emergency department with chest pain or unstable angina, and have relied on serial markers for the diagnosis of acute myocardial infarction. We evaluated the diagnostic utility of a single cardiac troponin T (cTnT) determination at the time of presentation as compared to serial creatine kinase (CK) MB determinations in a broad spectrum of patients with suspected myocardial ischemia. METHODS: A total of 267 consecutive patients presenting to the emergency department with suspected myocardial ischemia had a single, blinded cTnT determination drawn at the time of presentation to the emergency department in addition to routine serial electrocardiographic and CK-MB determinations. RESULTS: The specificity (93.7% vs. 87.1%; p<0.05) and positive predictive value (80.0% vs. 69.4%; p<0.05) of a single cTnT determination were superior to that of serial CK-MB determinations without compromising sensitivity. Forty-six percent of patients with confirmed myocardial infarction and an abnormal cTnT at presentation had a normal initial CK-MB determination. Conversely, 20% of patients without acute coronary syndromes had an abnormal CK-MB determination in the setting of a normal cTnT. The initial cTnT was abnormal in all patients with confirmed myocardial infarction and a symptom duration of at least 3.5 h. CONCLUSIONS: In a heterogeneous population of patients with suspected myocardial ischemia, the initial cTnT determination drawn at the time of presentation is a powerful diagnostic tool that, when used in context with symptom duration, allows for more rapid and accurate triage of patients than serial CK-MB determinations.

Adult↗
PubMed2003

Elevated cell-free serum DNA detected in patients with myocardial infarction.

BACKGROUND: Cell-free DNA is detectable in the circulation. Increased cell-free DNA has been detected in cancer patients and individuals with trauma. We want to know whether patients with myocardial infarction (MI) also have increased cell-free DNA in their blood. METHODS: We used a QIAamp blood kit for DNA extraction from serum and the PicoGreen DNA kit for quantification. DNA patterns of serum DNA were established by gel electrophoresis on 2.5% metarphor gel. RESULTS: The average serum DNA in MI patients (N=55) was 511+/-398 ng/ml, more than 10-fold higher than normal (36.3+/-23.8 ng/ml, n=274). Patients with increased CK-MB (>4%) were associated with highly increased concentrations of cell-free DNA (93.4%). There was no correlation between the concentration of cell-free DNA and the concentrations of CK-MB, troponin I and C-reactive protein. In serial specimens, we found that the cell-free DNA rose early, but peaked behind CK-MB. A slightly diffused DNA ladder could be found with pooled cell-free DNA from MI patients by electrophoresis with the smallest DNA band at only a few hundred base pairs. CONCLUSIONS: Cell-free DNA in MI patients is increased in patients diagnosed with MI, and may complement troponin and CK-MB in a multiple marker test format.

Biomarkers↗
PubMed2002

Myoglobin, creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain.

OBJECTIVES: Measurements of myoglobin and creatine kinase (CK)-MB isoforms have been suggested to be sensitive tests for the early diagnosis of myocardial infarction (MI). We have investigated the utility of myoglobin, creatine kinase (CK)-MB isoforms and creatine kinase MB mass (CK-MBm) in early diagnosis of MI using cardiac troponin T (cTnT) positivity as a reference. DESIGN AND METHODS: The study population comprised 440 patients who had had chest pain for less than 12 h. Patients were divided into cTnT negative (cTnT-) or cTnT positive (cTnT+) patients (concentration of cTnT >0.1 microg/L at two different time points during 72 h). RESULTS: At the time of admission to the emergency department receiver operating characteristics (ROC) curves of CK-MB isoforms and CK-MBm were not better than that of myoglobin. Six hours after admission CK-MB isoforms and CK-MBm provided statistically significantly larger areas under the curve (AUC) than myoglobin (p < 0.01). When ROC curves were related to the onset of chest pain (< 3 h, 3-6 h, and > 6 h) there were no significant differences between the cardiac markers studied. CONCLUSIONS: According to the present findings, CK-MB isoforms or myoglobin offer no advantage over CK-MBm as early markers of myocardial infarction.

Aged↗
PubMed2002

Trypanosoma cruzi: host selenium deficiency leads to higher mortality but similar parasitemia in mice.

Selenium is an essential trace element and its deficiency was implicated in heart diseases. We recently showed low Se levels in chronic chagasic patients with cardiomyopathy. Herein, mice were depleted in Se by feeding the mothers with chow containing only 0.005 mg Se/kg and maintaining this diet for offspring, that were further infected with Trypanosoma cruzi. Survival rate was significantly lower in Se deficient than in control mice. Parasitemia was similar in all groups. Necrotic heart lesions were found after infection (high CK-MB levels). No outbreaks of parasite growth were detected in chronic survivors submitted or not to a second Se depletion. The present results confirm our hypothesis that a nutritional deficiency in Se is associated to a higher mortality during T. cruzi infection. The potential beneficial effect of Se supplementation is a perspective. Hypothesis to explain the higher susceptibility of Se-depleted mice to T. cruzi infection are discussed.

Animals↗
PubMed2003

Myocardial viability twenty-four hours after orthotopic heart transplantation from non-heart-beating donors.

OBJECTIVES: Using a new preservation strategy, we investigated the performance of hearts from non-heart-beating donors during an observation period of 24 hours after orthotopic heart transplantation in a pig model. METHODS: In the control group (n = 6) beating donor hearts were harvested with Bretschneider's HTK solution and transplanted orthotopically without reperfusion modifications. In the non-heart-beating donor group (n = 6) hearts were perfused with leukocyte-depleted blood cardioplegia after 30 minutes of normothermic ischemia. Blood cardioplegia was supplemented with a sodium-hydrogen exchange inhibitor and adenosine. After transplantation, a second controlled reperfusion with blood cardioplegia was performed. RESULTS: Preload recruitable stroke work of the left ventricle 24 hours after transplantation in the control versus non-heart-beating donor group was 108% +/- 24% versus 103% +/- 18% of baseline values. Myocardial blood flow of the left and right ventricle was increased to 146% +/- 32% and 176% +/- 51% in the control group versus 176% +/- 29% and 194% +/- 27% in the non-heart-beating donor group. Myocardial oxygen consumption was 11.2 +/- 2.1 versus 12.8 +/- 2.2 mL/100 g per minute at baseline and 11.6 +/- 2.6 versus 13.2 +/- 3.1 mL/100 g per minute after 24 hours (not significant). Histologic examination with Luxol fast blue staining revealed that 2.6% +/- 4.8% of myocytes in the control group versus 1.8% +/- 1.9% in the non-heart-beating donor group were damaged irreversibly. CONCLUSIONS: Recovery of donor hearts from non-heart-beating donors is comparable with recovery of organs harvested from heart-beating donors if the above-mentioned preservation technique is used. These results could encourage the use of marginal donor hearts and help to expand the limited donor pool.

Animals↗
PubMed2003

Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study.

OBJECTIVES: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk of myocardial necrosis after coronary artery bypass graft surgery. METHODS: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients > or =18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and > or =2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. RESULTS: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P =.027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P =.005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P =.033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. CONCLUSIONS: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.

Adolescent↗
PubMed2003

A new role for cardioplegic buffering: should acidosis or calcium accumulation be counteracted to salvage jeopardized hearts?

OBJECTIVES: Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood cardioplegic solution containing the natural erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or 7.2 (nonbuffered), and this was tested alone and after pretreatment with Na(+)-H(+) exchange blockade (cariporide) to define their protective effects. METHODS: Twenty-four Yorkshire-Duroc pigs (27-34.5 kg) underwent 30 minutes of normothermic global ischemia, followed by 30 minutes of aortic clamping during protection with buffered (n = 12) or nonbuffered (n = 12) glutamate-aspartate-enriched blood cardioplegic solution. Twelve hearts (6 buffered and 6 nonbuffered) were pretreated with intravenous cariporide (5 mg/kg) 15 minutes before ischemia. RESULTS: Severe and comparable left ventricle dysfunction followed buffered or nonbuffered cardioplegia: Preload recruitable stroke work recovered to 56% +/- 21% and 45% +/- 20% of baseline levels; creatine kinase MB, conjugated dienes, and myeloperoxidase activity markedly increased; moderate myocardial edema occurred; and endothelin-1 increased 2-fold more than baseline values. Cariporide pretreatment caused a similar return of preload recruitable stroke work to 86% +/- 9% and 90% +/- 6% after buffered or nonbuffered cardioplegia (P <.05 vs nonpretreated groups), allowed only minor creatine kinase MB and conjugated diene changes, and reduced endothelin-1 release 3-fold compared with hearts without sodium-hydrogen exchange blockage. CONCLUSIONS: The severe ischemia-reperfusion injury of 30 minutes of normothermic ischemia is not altered by an acidic or alkalotic pH cardioplegic solution. Correction of damage is achieved by adding Na(+)-H(+) exchange blocker therapy before treatment with buffered and nonbuffered solutions; thus, sodium-hydrogen exchange inhibition plays a more vital role in recovery than pH management.

Acidosis↗
PubMed2003

Prognostic significance of elevated creatine kinase MB after coronary bypass surgery and after an acute coronary syndrome: results from the GUARDIAN trial.

OBJECTIVE: To determine if the correlation between magnitude of creatine kinase-myocardial band release after coronary artery bypass surgery and 6-month mortality is comparable to that of patients admitted with an acute coronary syndrome. METHODS: The GUARDIAN trial tested the efficacy of cariporide, an Na+/H+ exchange inhibitor, on reduction of myocardial ischemia or death in high-risk patients. We compared 6-month survival in a cohort of 2332 GUARDIAN patients scheduled for coronary artery bypass surgery at entry with 4233 acute coronary syndrome patients stratified by level of creatine kinase-myocardial band release. Cumulative 6-month survival by creatine kinase-myocardial band categories was performed using life table analysis, adjusting for variables known to impact prognosis using Cox regression. RESULTS: The 6-month mortality rates for coronary artery bypass surgery patients with peak creatine kinase-myocardial band ratios of <1, > or =1 and <5, > or =5 and <10, and > or =10 upper limits of normal (ULN) were 5.8, 2.8, 5.9, and 12.0%, respectively (P <.0001). The 6-month mortality rates for acute coronary syndrome patients with peak creatine kinase-myocardial band ratios of <1, > or =1 and <5, > or =5 and <10, and > or =10 ULN were 6.3, 9.8, 10.0, and 12.3%, respectively (P <.0001). Patients with coronary artery bypass surgery or acute coronary syndrome had similar adjusted 6-month survival estimates at normal creatine kinase-myocardial band levels and when the creatine kinase-myocardial band level was > or =10 ULN. Patients with coronary artery bypass surgery had significantly better survival at intermediate enzyme levels (> or =1 and <10 ULN; P <.001). CONCLUSIONS: Modest elevations of creatine kinase-myocardial band release (> or =1 and <10 ULN) after coronary artery bypass surgery are not associated with adverse 6-month survival, in contrast to that seen in acute coronary syndrome patients. Routine creatine kinase-myocardial band sampling should be considered in all higher-risk patients undergoing coronary artery bypass surgery procedures to identify the sizable cohort of patients with creatine kinase-myocardial band release > or =10 ULN; these patients may benefit from postoperative angiotensin-converting enzyme inhibitor and beta-blocker therapy. Newer cardioprotective agents that reduce the number of patients with marked creatine kinase-myocardial band release are currently being tested in large randomized controlled clinical trials.

Acute Disease↗
PubMed2003

A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting.

BACKGROUND: Total arterial grafting is increasingly preferred in coronary artery bypass grafting, but it increases blood loss. Aprotinin (Trasylol; Bayer Corp, Leverkusen, Germany) reduces blood loss in cardiac surgery but has not been subjected to a randomized trial in total arterial grafting. METHODS: A single-center, randomized, double blind, placebo-controlled trial of aprotinin administration in total arterial grafting was performed. The primary outcome variable was postoperative blood loss, and the secondary outcome variable was the number of units of donor blood or coagulant products transfused. The incidence of myocardial injury was determined from serial measurements of cardiac troponin T and creatine kinase-MB and renal injury from serum creatinine. RESULTS: The placebo group (n = 34) and aprotinin group (n = 36) were similar with respect to all preoperative and intraoperative comparisons. One patient in each group underwent reexploration for bleeding. Open-label aprotinin was administered to 9 patients in the placebo group (26%) and to 2 patients in the aprotinin group (6%). There was a highly significant reduction in the median (interquartile range) blood loss in the aprotinin group compared with the placebo group (785 mL [590-1025 mL] vs 1525 mL [1175-1920 mL], respectively). Similarly, the aprotinin group demonstrated a marked reduction in the need for blood transfusion (77% vs 39%; P =.0001), the mean number of transfused blood units (2.6 vs 0.8, P <.001), and the number of patients requiring coagulant products (24% vs 3%; P <.001). There was no difference in myocardial injury in the 2 groups. Four patients in the aprotinin group had persistently elevated creatinine levels in the postoperative period (3 of whom had elevated preoperative creatinine levels and perioperative complications). CONCLUSIONS: Aprotinin significantly reduces blood loss and the need for blood component transfusion in patients undergoing total arterial grafting without increasing the risk of myocardial injury. Aprotinin should be considered routinely in patients undergoing total arterial grafting but cautiously in patients with an elevated preoperative creatinine level.

Aprotinin↗
PubMed2003

Significance of assessment of serum cardiac troponin I and interleukin-8 in scorpion envenomed children.

In the present study, 41 children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with 15 apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination, full blood count and arterial blood gases analysis. According to severity of scorpion envenomation, 17 children had manifestations of severe envenomation and clinical signs of toxic myocarditis (severe cases), 14 children had moderate manifestations of envenomation without clinical evidence of carditis (moderate cases) and 10 cases showing only mild symptoms of envenomation (mild cases). The serum levels of cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside the enzymatic activities of creatine phosphokinase (CPK), CPK-isoenzyme-MB (CPK-MB) and lactate dehydrogenase (LDH) were determined once for mild cases and controls on admission and twice for severe and moderate cases on admission and after 24. Electrocardiography and measurements of echocardiographic (Echo) of % fractional shortening of left ventricule (% SF), left ventricular ejection fraction (LVEF) and cardiac chambers dilatation were done for severe and moderate cases. All the envenomed victims showed significantly higher mean values of CPK, CPK-MB, LDH, and IL-8 on admission in comparison to control group. cTnI was not detectable in the sera of control group as well as patients of mild envenomation. The mean values of CPK, CPK-MB, LDH, and IL-8 were significantly higher in severe cases while only IL-8 and CPK-MB were significantly higher in moderate cases in comparison with mild cases. The mean values of IL-8, cTnI, CPK, CPK-MB and LDH were significantly higher in severe cases both on admission and on follow-up comparing with moderate cases. The case fatality rate was 12.5% and all were from severe cases with toxic myocarditis. The non-survivors victims showed significant higher mean values of only cTnI on admission and both cTnI and IL-8 on follow up in comparison to the survivors. Significant reduction of % SF and LVEF were noticed among the non-survivors in comparison to survivors. The cTnI showed 100% specificity and sensitivity for diagnosis of myocardial injury in relation to Echo finding in the envenomed victims. In severe cases, cTnI was positively correlated with IL-8 while negatively correlated with %SF and LVEF. In conclusion, cTnI is a specific marker for diagnosis of myocardial injury in scorpion envenomation while other biochemical markers did not show such specificity. Also, IL-8 may be involved in the pathogenesis of myocardial injury of scorpion envenomation. Both cTnI and IL-8 may be useful to forecast the fatal outcome in scorpion envenomation.

Animals↗
PubMed2002

B-type natriuretic peptide after percutaneous transluminal septal myocardial ablation.

BACKGROUND: Plasma level of B-type natriuretic peptide is a sensitive marker of left ventricular dysfunction and the level is markedly elevated in patients with hypertrophic obstructive cardiomyopathy. Percutaneous transluminal septal myocardial ablation, a catheter-based treatment of hypertrophic obstructive cardiomyopathy, has been widely used as a new therapeutic option for the disease. This study was designed to evaluate clinical implications of natriuretic peptides after the new treatment. METHODS: Seven consecutive patients with hypertrophic obstructive cardiomyopathy unresponsive to usual medical treatments (age: 57.9+/-22.0 years) were enrolled in the study. Serial changes in atrial and B-type natriuretic peptide in plasma were examined after percutaneous transluminal septal myocardial ablation. RESULTS: Atrial and B-type natriuretic peptides levels (pg/ml, mean+/-S.D.) at baseline were higher in hypertrophic obstructive cardiomyopathy than in control (80.0+/-43.0 vs. 12.8+/-5.2, P<0.0001; 858.0+/-458.4 vs. 12.4+/-7.0, P<0.0001; respectively). Left ventricular outflow-tract pressure gradient (mmHg) immediately decreased from 115.3+/-23.3 to 30.6+/-12.4 (P<0.0001) after the treatment and concomitantly B-type natriuretic peptide level decreased (858.0+/-458.4 to 264.1+/-137.7, P=0.0084). The level re-increased and peaked at the 2nd day (634.4+/-429.6) and gradually decreased again until 4 weeks. Reduction rate of left ventricular outflow-tract pressure gradient between before and 4 weeks after percutaneous transluminal septal myocardial ablation positively correlated with that of B-type natriuretic peptide (r(2)=0.817, P=0.0053). Changes in atrial natriuretic peptide were not significant in contrast to those of B-type natriuretic peptide. CONCLUSIONS: Plasma B-type natriuretic peptide level could be useful to predict the effects of percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy.

Adolescent↗
PubMed2003

Cardiac troponin T and myocardial injury during routine cardiac catheterisation in children.

BACKGROUND: This study aims to investigate whether intracardiac catheterization produces myocardial damage on pediatric heart. METHODS: Five blood samples were collected (basal, immediate post procedure, at 4, 12 and 24 h after the procedure) for troponin T and creatine kinase MB (CKMB) from 48 consecutive patients (age: 5.34+/-6.03 years). The effect of age, duration of procedure, pulmonary hypertension, cyanosis, and medication taken for congestive heart failure on the levels of troponin T and CKMB were sought. RESULTS: The increase in CKMB (basal CKMB: 3.93+/-3.70 ng/ml; peak CKMB: 8.68+/-10.89 ng/ml; P<0.0001) and troponin levels (basal troponin: 0.002+/-0.003 ng/ml; peak troponin: 0.11+/-0.23 ng/ml; P<0.0001) over time was significant in the study group. Additionally younger patients (</=1 year), patients with pulmonary hypertension (mean pulmonary artery pressure >25 mmHg), longer procedure time (>30 min), and patients taking anti-congestive heart failure therapy had significantly higher levels of CKMB and troponin (P>0.05). CONCLUSION: All patients undergoing cardiac catheterization are under risk of myocardial injury, and younger patients with pulmonary hypertension and especially with compensated cardiac failure have increased risk of myocardial damage, and need to be handled carefully.

Adolescent↗
PubMed2003

Brugada-type ECG with polymorphic ventricular tachycardia: a red herring for isolated right ventricular infarction.

We present a patient with Brugada-type ECG abnormalities and recurrent polymorphic ventricular tachycardia (VT). Subsequent investigations confirmed the diagnosis of isolated right ventricular myocardial infarction. The VT resolved after the 1st day and was not inducible subsequently. This case illustrates the importance of a careful study of the ECG to exclude other conditions in a patient with Brugada-type ECG abnormalities.

Adult↗