Biochemical Markers Of Myocardial Damage Research Articles

Usefulness of transesophageal echocardiography using a combined probe when converting atrial fibrillation to sinus rhythm

We studied the feasibility and efficacy of transesophageal echocardiography (TEE) combined with transesophageal cardioversion (TEC). Secondary aims were to study left atrial flow velocities before and 1 and 5 minutes after TEC, biochemical markers of myocardial damage, and patient tolerability. TEC after a short period of anticoagulation and exclusion of a clot with TEE was safe. TEC was well tolerated and efficacious. The use of a combined probe for TEE and TEC therefore can save time and be more effective. A custom-made probe for combined TEE plus TEC was used. TEC was performed with a step-up protocol (20 J to between 30 and 50 J) and with biphasic shocks. Presence of spontaneous echo contrast was scored. Cumulative energy needed to achieve sinus rhythm was calculated. Discomfort was scored on a scale of 0 to 10. Twenty-six patients underwent combined TEE/TEC. Sinus rhythm was achieved in 24 of 26 patients (92%) with a mean cumulative energy of 42.3 J. Sixteen of 26 patients were cardioverted with a 20-J shock, and 6 of these patients had early recurrence of atrial fibrillation. All biochemical markers were unaffected, and TEE/TEC was well tolerated. Left atrial appendage velocity decreased significantly after TEC. Thus, the use of a TEE/TEC probe offers effective cardioversion with low energy levels, is well tolerated, and hemodynamics during and immediately after cardioversion can be monitored. Early cardioversion after exclusion of a clot with this combined probe is time saving and cost effective.

External Quality Assessment for biochemical markers of myocardial damage: an Italian experience

In 1999 the Centre of Biomedical Research (CRB) in co-operation with the Italian interdisciplinary and intersociety Working Group on Markers of Myocardial Damage proposed a national external quality assurance scheme that was granted in accordance with the UK Clinical Pathology Accreditation Standards in 2001. The scheme, which stresses the importance of educational aspects in quality assurance, was scientifically designed to ensure that it would provide an objective assessment of participants' performance and promote quality improvements to meet the needs of participants. The present paper reports on the data collected in EQA cycles conducted to evaluate improvements in the performance of participants and in related methods. The findings obtained demonstrate that during the 4-year experience the scheme provided opportunities to improve the performance of laboratories and promoted an efficient, more satisfactory approach to analytical aspects. The number of unacceptable performances decreased from 11.6% to 5.6% for troponin I, from 19.5% to 9.0% for myoglobin and from 13.2% to 4.3% for creatine kinase myocardial isoenzyme (CK-MB). During cycles in 2001 and 2002, inter-variability (coefficient of variation, CV%) data for all markers appeared satisfactory and showed a significant improvement (lower than 10%), in particular for procedures automated on Dade Behring Dimension and Beckman Access systems. However, reference values/decisional limits declared by laboratories and those suggested by the manufacturers are not comparable, even within the same diagnostic system. The findings demonstrate that participation in EQA schemes provided an opportunity for participating laboratories to continuously improve the quality of their services.

Interpretative comments and reference ranges in EQA programs as a tool for improving laboratory appropriateness and effectiveness

Introduction: Laboratory information is generated when a meaning is given to certain data. This is usually achieved by comparing a laboratory test result with the reference range/decisional limit (RL), and by providing consultation for the interpretation of data, advice, and follow-up testing. Aim: In this paper, we investigate factors affecting the conversion of data into useful information with regard to biochemical markers of myocardial damage (CK-MB mass, myoglobin, and troponins), in view of their importance in detecting myocardial necrosis. Our aim was to report results obtained in order to verify the consensus between laboratories with reference to interpretative comments and the reference ranges/decisional limits added to clinical reports. Methods: A questionnaire and simulated medical reports on three different patients were distributed to participants (94 laboratories) in the 2001 cycle of the External Quality Assessment (EQA). Moreover, we analysed 113 medical reports sent by laboratories during the most recent EQA cycle 2002, and checked the number of different RLs used, both independent and within the diagnostic system used. We also compared each laboratory result of a control sample, obtained in the 2002 cycle, with declared RL in order to verify the clinical significance of results (“normal” or “pathological”) for troponin I and CK-MB. Results: Our findings show that few laboratories regularly add interpretative comments to medical reports. On the contrary, they cooperate with clinicians who require consultation, advice, and information for the appropriate use of biochemical markers. There is a general consensus among participants regarding probable syndromes suggested by the interpretation of the same result and most laboratories also agree on further investigations to be carried out for several diseases. Concerning RL, the data demonstrate that numerous different RLs are used to report the results of the biochemical markers evaluated, both when considered independent of the diagnostic system used and within the diagnostic system used. Discussion and conclusions: The biochemist does not have the opportunity to verify the efficacy of the interpretation that he/she provided. An audit of this activity is therefore required to allow the laboratory to monitor its own performance and to assure good practice. The evaluation of interpretative comments, through specific surveys, should be a prime objective of EQA organisers. Well-designed EQA programs can, moreover, support laboratories in establishing appropriate RL and in verifying the clinical significance of their results with respect to that of other laboratories. Our survey on interpretative comments and the analysis of the RLs further demonstrate how laboratory medicine can contribute to the objective evaluation of the patients' health status.

Propofol Preservation of Myocardial Function in Patients Undergoing Coronary Surgery Using Cardiopulmonary Bypass is Dose Dependent

In Reply:—We appreciate the interest of Drs. Ansley and Xia regarding our study on the preservation of myocardial function by sevoflurane in coronary surgery patients. 1Transient myocardial dysfunction after coronary bypass surgery is a well known phenomenon, 2but its pathophysiologic mechanisms still are not fully elucidated. Although its causes are multifactorial, reperfusion injury is thought to play an important role.Recently, increasing evidence has indicated that anesthetic agents may have a potential beneficial role in the prevention and/or treatment of reperfusion injury. Volatile anesthetics have been shown to directly precondition or indirectly enhance ischemic preconditioning, resulting in protection of the myocardium, with the adenosine triphosphate– regulated potassium channel playing an important role. Central to the pathogenesis of ischemia–reperfusion injury is the production of free radicals. Several reports have demonstrated that propofol may enhance antioxidant capacity, and this property has been claimed to protect the myocardium. However, data on this subject are essentially experimental, and, to date, few studies have demonstrated a potential beneficial effect of anesthetic agents in myocardial stunning in the clinical situation.For the volatile anesthetics, the beneficial effects were demonstrated on both functional hemodynamic parameters and biochemical markers of myocardial damage. For propofol, the evidence of a myocardial protective effect is mainly circumstantial. Several studies have, indeed, demonstrated that propofol increases the antioxidant capacity of erythrocytes and tissue. However, the possible implications of this increase in antioxidant capacity for preservation of tissue function remain to be demonstrated.Ebel et al. 3found no protective effect of propofol (at clinically relevant concentrations) against myocardial reperfusion injury, but Ko et al. 4demonstrated that propofol at higher concentrations (100 μm) attenuated mechanical, biochemical, and histologic changes caused by myocardial ischemia and reperfusion. In a recent publication, Ansley et al. 5observed that high-dose propofol (a 2–2.5-mg/kg bolus followed by a continuous infusion of 200 μg · kg−1· min−1) enhances erythrocyte antioxidant capacity during cardiopulmonary bypass in humans. Erythrocyte antioxidant capacity with low-dose propofol or isoflurane anesthesia, on the contrary, was similar.Ansley and Xia related this increased antioxidant capacity in the high-dose propofol group to improved myocardial function (higher cardiac index) 12 h postoperatively. However, the cardiac index in the low-dose propofol group was similar, despite the difference observed in the antioxidant capacity. It seems, therefore, that the suggested relation between improved cardiac function with propofol and its antioxidant properties is not supported by the data presented. Instead, it seems more likely that differences in cardiac loading conditions are responsible for the observed differences in cardiac index between the isoflurane and propofol groups.In our study, 1propofol was administered by means of a target-controlled infusion system, which was set to achieve a target plasma propofol concentration of 2–4 μg/ml. This plasma concentration is far beyond the concentration at which Ansley and Xia have observed “cardioprotective” effects (12 μg/ml). Still, it is the concentration that is clinically applied in patients with compromised cardiac function, which is not the case for concentrations up to 12 μg/ml. From a clinical point of view, the agents that have potential beneficial effects on ischemia–reperfusion injury should also exert their action at clinically relevant concentrations.Under the conditions of our study, sevoflurane at clinically relevant concentrations protected against the transient myocardial dysfunction related to coronary surgery, whereas propofol did not (lower cardiac index until the end of the operation). The suggestion that the title of our article, “Sevoflurane but Not Propofol Preserves Myocardial Function in Coronary Surgery Patients,” is misleading is therefore not correct. The data and conclusions clearly refer to clinically relevant concentrations and do not comment on possible properties at concentrations that are much higher than those used in clinical practice.

Strategy of IFCC standardization and use of cardiac markers in acute coronary syndromes

Although the use of troponin to diagnose acute myocardial infarction (AMI) has been previously proposed, the Committee on Standardization of Markers of Cardiac Damage (C-SMCD) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) made a recommendation in 1999 to expand on the enzyme diagnostic criteria for AMI to include cardiac-specific proteins. In September 2000, a joint committee of the European Society of Cardiology and the American College of Cardiology (ESC/ACC) published a new definition of AMI that for first time officially included troponin. According to these criteria, as the best biochemical indicator for detecting myocardial necrosis is "a concentration of cardiac troponin exceeding the decision limit (defined as the 99th percentile of a reference control group) on at least one occasion during the first 24 hours after the onset of clinical event". The use of creatine kinase MB (CK-MB), measured by mass assays, is still considered as an acceptable alternative only if cardiac troponin assays are not available. It is very important to standardize the clinical use of troponin in diagnosis and management of acute coronary syndromes and to clearly define decision thresholds. Two strategies have competed as the most appropriate for the use of new markers. The first relies on the use of a combination of two markers - a rapid rising marker such as myoglobin, and a marker that takes longer to rise but is more specific, such as cardiac troponin - to enable detection of AMI in patients who present early and late after symptom onset. In the second strategy, only measurement of cardiac troponin is suggested. One of the most important problems in the practical use of the cardiac-specific troponin is the right definition of decision limits. As diagnostic cut-off for clinical use, the IFCC C-SMCD recommends for troponin assays a total imprecision, expressed as coefficient of variation (CV), of <10% at the 99th percentile of a reference control group. For troponin assays that cannot presently meet the 10% CV at the 99th percentile value, a predetermined higher concentration that meets this imprecision goal should be used as cut-off for AMI until the goal of a 10% CV can be achieved at the 99th percentile. It is very important that clinically relevant biomarker, such as cardiac troponin, on which critical decisions will rest, can be measured with highly reliable and standardized methods. There are problems in assay standardization, imprecision interference, and of pre-analytical variability. Cardiac troponin is currently the most sensitive and specific biochemical marker of myocardial damage and is the best marker for diagnosis, risk stratification, and guidance of therapy in acute coronary syndromes.

N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation

ObjectivesThe study evaluated the prognostic value of single measurement of N-terminal pro brain natriuretic peptide (NT-proBNP) obtained on admission in patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation. BackgroundPatients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation constitute a large and heterogeneous population. Early risk stratification has been based on clinical background factors, electrocardiography (ECG) and biochemical markers of myocardial damage. The neurohormonal activation has, so far, received less attention. MethodsThe NT-proBNP was analyzed on admission in 755 patients admitted because of chest pain and no ST-segment elevation. Patients were followed concerning death for 40 months (median). ResultsThe median NT-proBNP level was 400 (111 to 1646) ng/l. Compared to the lowest quartile, patients in the second, third and fourth quartiles had a relative risk of subsequent death of 4.2 (1.6 to 11.1), 10.7 (4.2 to 26.8) and 26.6 (10.8 to 65.5), respectively. When NT-proBNP was added to a Cox regression model including clinical background factors, ECG and troponin T, the NT-proBNP levels were independently associated with prognosis. ConclusionsA single measurement of NT-proBNP on admission will substantially improve the early risk stratification of patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation. A combination of clinical background factors, ECG, troponin T and NT-proBNP obtained on admission will provide a highly discerning tool for risk stratification and further clinical decisions.

Cardioplegic arrest with l-arginine improves myocardial protection: results of a prospective randomized clinical trial

Background. Blood cardioplegic arrest remains the method of choice for myocardial protection. l-arginine has been suggested to improve protection through an increase in nitric oxide production. Methods. A prospective, randomized, double-blinded clinical trial comparing standard blood cardioplegic solution to l-arginine-enriched solution (7.5 g/500 mL) enrolled 200 patients undergoing coronary artery bypass grafting. Clinical data and biochemical markers of ischemia were recorded. Warm blood cardioplegia (33°C) was administered in 74% of patients and cold blood (20°C) was used in 26% of patients. Both groups averaged three grafts per patient. Results. There were two (2%) deaths in both groups. There were four (4%) myocardial infarctions (MI) in the control group and six (6%) infarctions in the l-arginine group ( p = 0.5). For the 190 patients without MI, serum levels of troponin T averaged 0.40 ± 0.43, 0.38 ± 0.42, and 0.39 ± 0.50 μg/L in control patients compared with 0.28 ± 0.22, 0.24 ± 0.18, and 0.27 ± 0.20 μg/L in l-arginine patients, respectively, 12, 24 and 48 hours after coronary artery bypass grafting ( p = 0.03). The cardiac index averaged 2.7 ± 0.8 L · min −1 · m −2 in control patients and 2.9 ± 0.7 L · min −1 · m −2 in arginine patients immediately after surgery ( p = 0.09). Intensive care unit and hospital length of stay averaged 3.5 ± 5 days and 7.3 ± 6 days in control patients compared with 2.5 ± 3 days and 6.1 ± 4 days in arginine patients ( p = 0.09). Conclusions. l-arginine-supplemented blood cardioplegic solution is associated with reduced release of biochemical markers of myocardial damage, suggesting improved myocardial protection.

Determinación de marcadores específicos de lesión miocárdica en la enfermedad cerebrovascular aguda

It is thought that any acute damage to the central nervous system and, more particularly, acute cerebrovascular disease (ACVD) can give rise to a myocardial lesion. Our aim is to apply the latest biochemical markers (troponin T, troponin I and myoglobin) to the study of this problem. We conducted a retrospective study of 42 patients who were consecutively admitted to hospital with ACVD. The pathological antecedents and the clinical and electrocardiographic variables were considered in each case. A single determination of CK, CK MB, myoglobin, troponin T and troponin I was performed for each patient. The determination of the new biochemical markers was positive in a higher number of cases than CK and its MB fraction, or electrocardiographic alterations. This positivity, together with the troponin T and troponin I values correlate with mortality. We present the first research work to be published in Spanish that studies the new biochemical markers of myocardial damage in ACVD. We urge researchers to carry out further analyses on more extensive series in order to determine the influence myocardial damage has on mortality and to establish suitable therapeutic measures. This will also allow us to find out whether a certain location or size of the lesion can give rise to a higher predisposition to this kind of damage

Cardioversión eléctrica externa y sistemas de cardioversión interna: evaluación prospectiva y comparativa del daño celular con troponina I

In this study we measured the concentrations of cardiac troponin I (cTnI) and several biochemical markers of myocardial damage after elective external cardioversion or internal cardioversion by specific catheters or automatic defibrillators. Biochemical markers were analyzed prospectively for 30 consecutive patients after electrical cardioversion. Concentrations of cTnI, myoglobin, creatine kinase (CK), CK-MB and the MB/CK ratio were determined in samples before cardioversion and 2, 8 and 24 h later. The shock energy ranged from 50 to 360 joules (235 106 joules) in external cardioversions and from 3 to 37 joules (15 8 joules) in internal cardioversions. We detected abnormal concentrations of CK, myoglobin, CK-MB and MB/CK in 33% of the patients after external cardioversion. The concentrations of cTnI remained within normal limits at all times, with no elevations detected. Whereas no abnormal concentration of any biochemical marker was detected in any patient who required internal cardioversion for atrial fibrillation, two patients who underwent external cardioversion from an automatic defibrillator did have abnormal concentrations of CK-MB, myoglobin, and even of cTnI. The concentration of cTnI remained below the detection limit after external cardioversion, even though the other more non-specific markers changed. No enzyme alteration was detected in patients who underwent internal cardioversion of atrial fibrillation.

Markers of myocardial damage in acute coronary syndromes—therapeutic implications

Patients admitted with suspicion of an acute coronary syndrome (ACS) still constitute a diagnostic, prognostic and therapeutic challenge for the treating physician. The final diagnosis ranges from a noncardiac diagnosis to a full-blown myocardial infarction (MI). Biochemical markers of myocardial damage are essential for diagnosis and, especially troponin T and troponin I, have been shown to be valuable for early risk stratification and for selection of treatment in ACS. Patients identified to be at low risk of future cardiac events might be discharged early, and unnecessary investigations and treatments avoided. On the contrary, a more intense treatment can be started in patients identified to be at high risk. Unstable angina patients with, compared to without, elevation of troponin, have a more activated coagulation system and more frequently complex lesions and visible thrombus in their coronary arteries. Accordingly, antithrombotic and antiplatelet therapies, i.e. l.m.w heparin and GP IIb/IIIa receptor antagonists, have been proved to have beneficial effects in troponin positive patients, but little or no beneficial effects in troponin negative patients. Also, the beneficial effects of an invasive compared to a noninvasive approach seem to be much more pronounced in troponin positive patients. In patients with ST-elevation MI, an elevated troponin T level at admission are associated with an increased mortality. However, the therapeutic implications of this finding remain speculative. Patients admitted with chest pain and left bundle branch block (LBBB) and who develop an MI have a poor prognosis. Current guidelines in acute myocardial infarction state that these patients should receive thrombolysis. Despite that, only a minority of these patients do receive thrombolysis, most probably because of the great diagnostic uncertainty. Rapid testing with a cardiac marker, e.g. myoglobin, would most probably increase the proportion of patients with chest pain and LBBB who receive appropriate reperfusion treatment.

Cardiac markers and risk stratification: an integrated approach

Risk stratification of patients with acute coronary syndromes (ACS) is pivotal for correct allocation of health resources and for maximizing the benefit of available treatment modalities. However, clinical and electrocardiographic indicators of high risk lack sufficient sensitivity for the detection of major cardiac events. The complementary information provided by the measurement of different biomarkers is believed to be very useful. Specifically, elevations of cardiac troponin I (cTnI) and T (cTnT) are strongly associated with a high-risk profile both at short- and long-term. This has been definitely demonstrated in many studies as well as in cumulative meta-analysis. The role of different biomarkers, such as those reflecting activation of hemostasis and the presence of inflammation, is however less defined. At the moment, no study has prospectively evaluated these biomarkers in the whole spectrum of unselected patients with ACS. It is also unclear whether these biomarkers add independent prognostic value to the clinical and electrocardiographic indicators of adverse outcome and whether they offer additional information when compared to each other. The Early Prognostic Value of Biochemical Markers of Myocardial Damage, Activation of Hemostatic Mechanism and Inflammation in Acute Ischemic Syndromes (EMAI) study has been prospectively designed to solve these issues. In this study, we have evaluated the prognostic value of cTnI and cTnT, d-dimer, prothrombin fragment 1+2 (F1+2), thrombin–antithrombin complex (TAT) and C-reactive protein (CRP) in patients with ACS at the time of admission. We have enrolled in 31 Italian Coronary Care Units 1971 patients with rest anginal pain within 12 h from admission and electrocardiographic evidence of myocardial ischemia. Of these, 730 patients resulted to have ST-segment elevation myocardial infarction eligible for a reperfusion strategy and 1241, an acute coronary syndrome without persisting ST-segment elevation. Primary outcome measure of the study is the composite of death and non-fatal MI within 30 days from admission, which has occurred in 8.9% of the study population.

An overview of biochemical markers in acute coronary syndromes

The cardiac troponins (cTns), cTnT and cTnI, are currently regarded as being the most useful diagnostic and prognostic biochemical markers of myocardial damage in patients with suspected acute coronary syndromes (ACSs). In spite of the evidence-based nature of this observation, the uptake of serum cTn measurement in routine clinical practice--in both the UK and elsewhere, is patchy, indeed, there still exists wide variability in the range of testing and sampling strategies involving usage of the many existing cardiac markers. For evaluating suspected acute myocardial infarction (AMI) and other ACSs, international opinion favours either serum cTnT or cTnI (measured 12-24 h after admission to the emergency room)--together with a short-time window marker such as serum creatine kinase (CK) (measured on admission and perhaps again within the 12-24 h window). Translation of this strategy into universal clinical practice would require not only formulation of, but also strict adherence to, agreed clinical decision-making protocols which, in turn, would need to be backed by adequate funding.

Clinical, electrocardiographic, and biochemical data for immediate risk stratification in acute coronary syndromes.

The recent evolution in therapeutic options for acute coronary syndromes (ACS) mandates early risk stratification in order to select the appropriate treatment strategy for individual patients. Simple clinical data derived from the patient's medical history and physical examination, a standard twelve-lead electrocardiogram (ECG), and determinations of biochemical markers of myocardial damage can be obtained in the emergency room and serve as a guide for deciding appropriate medical management and optimal use of available resources. Even the most important classification of the ACS is based upon a simple and dichotomous description of the ECG, where the presence of ST-segment elevation mandates an immediate attempt to restore coronary perfusion (either pharmacologically or mechanically), whereas its absence suggests pharmacological stabilization before further evaluation. Across the whole spectrum of ACS, clinical history data (such as older age, previous coronary events, and diabetes) and clinical variables (such as higher heart rate, lower blood pressure, and higher Killip class) are the most powerful prognostic determinants at multivariate analyses derived from large databases. The ECG adds significant and independent prognostic information using the analysis of qualitative (direction of ST-segment shift, associated T-wave inversion, and presence of conduction disturbances) and quantitative (number of leads involved, amount of ST- segment shifts, duration of QRS) characteristics. Biochemical markers of myocardial damage have also been identified as independent predictors of events. In addition, retrospective analyses of clinical trials have suggested that biochemical markers might serve as a guide to select pharmacological therapy. However, how to best combine electrocardiographic and biochemical data for immediate risk stratification remains to be further elucidated.

Detection of Myocardial Damage – are the Troponins the Ultimate Solution?

Biochemical markers of myocardial damage are together with the clinical history, the physical examination and the 12-lead ECG key elements in the clinical evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome (ACS). In this situation the detection of myocardial damage, even very minor, is of importance, not only for diagnosis, but also for risk assessment and selection of treatment. The new markers of myocardial damage, troponin T and I, have been shown to offer some advantages over the conventional markers in ACS and there is also an increasing interest for troponins in other clinical situations, e.g. after surgery and percutaneous coronary intervention. This paper will discuss the role of troponins in these different clinical situations.

Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial

The Fragmin and Fast Revascularisation during Instability in Coronary artery disease II trial (FRISC II) compared an early invasive with an early non-invasive strategy in unstable coronary-artery disease. We report outcome at 1 year. 2457 patients were randomly assigned invasive or non-invasive treatment and 3 months of dalteparin or placebo. Complete information at 1 year was available for 1222 in the invasive group and 1234 in the non-invasive group. Analyses were by intention to treat. Revascularisation was done within the first 10 days in 71% of the invasive group and 9% of the non-invasive group and within the first year in 78% and 43%. During the first year, 27 (2.2%) patients in the invasive group and 48 (3.9%) in the non-invasive group died (risk ratio 0.57 [95% CI 0.36-0.90], p=0.016). 105 (8.6%) versus 143 (11.6%) had myocardial infarction (0.74 [0.59-0.94], p=0.015). The composite of death or myocardial infarction occurred in 127 (10.4%) versus 174 (14.1%) patients (0.74 [0.60-0.92], p=0.005). There were also reductions in readmission (451 [37%] vs 704 [57%]; 0.67 [0.62-0.72]), and revascularisation after the initial admission (92 [7.5%] vs 383 [31%]; 0.24 [0.20-0.30]). The results did not interact with the dalteparin/placebo allocation. After 1 year in 100 patients, an invasive strategy saves 1.7 lives, prevents 2.0 non-fatal myocardial infarctions and 20 readmissions, and provides earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischaemia on electrocardiography or raised levels of biochemical markers of myocardial damage.

Rapid Measurement of Cardiac Markers on Stratus CS

Biochemical markers of myocardial damage are of fundamental importance in ruling in and ruling out diagnostic strategies for acute coronary diseases, particularly when electrocardiographic findings do not allow a diagnosis. An increasing body of evidence has demonstrated the value of strategies based on specific (cardiac troponin I or T) and sensitive [myoglobin (Myo)] assays in the diagnosis (1), prognosis, and monitoring (2) of patients with acute coronary syndrome. The impact of laboratory information on the management of patients has led to the development and definition of recommendations designed to reduce the therapeutic turnaround time, thus improving the medical outcome for patients. Because of the delay often associated with transport-related problems, the concept of point-of-care testing has been introduced for the measurement of cardiac markers (3). Some requirements, which seem to be of value in assuring quality for devices and diagnostic systems designed for point-of-care testing of cardiac markers, require whole blood or heparinized specimens for effective therapeutic turnaround time and must guarantee quantitative, accurate, and precise results comparable to those provided by central laboratories. The aim of our study, therefore, was to evaluate the analytical performance of the Stratus CS (SCS; Dade Behring), a fluorometric enzyme immunoassay analyzer based on solid-phase radial partition immunoassay technology, for quantitative measurement of creatine kinase isoenzyme MB mass concentration (CK-MB), Myo, and troponin I (TnI) in whole blood samples collected using lithium heparinate as anticoagulant. The samples may be processed automatically by the analyzer, which provides for centrifugation on board before the analytical phase, or heparinized plasma may be dispensed directly into a sample cup for analysis. Briefly, after the first antibody is added to a glass fiber paper linked to the dendrimer, the sample and the second antibody are pipetted. Finally, enzyme activity is started by the substrate wash solution with the simultaneous …

Acute management--how should we intervene?

A crucial question in the acute management of the patient with unstable coronary artery disease (UCAD) is whether to carry out early intervention, performing angiography soon after presentation and following this with revascularization where appropriate, or whether to follow a noninvasive medical strategy as far as possible unless symptoms necessitate intervention. The body of literature addressing this question is sparse, but the recent Fast Revascularization during InStability in Coronary artery disease (FRISC II) study has provided new insights into the problem. Using a factorial design to randomize patients to invasive or noninvasive management strategies, and to short- or long-term treatment with the low-molecular-weight heparin (LMWH) dalteparin sodium (Fragmin), it was shown in FRISC II that early invasive treatment (within 7 days), when combined with optimal medical pretreatment with dalteparin sodium, aspirin, and appropriate antianginal medication, is associated with improved clinical outcomes, relative to a "watchful waiting" approach based on noninvasive therapy. Thus, an early invasive approach following aggressive medical pretreatment should be the preferred strategy for patients with UCAD who present with signs of ischemia on the electrocardiogram or raised biochemical markers of myocardial damage at admission.

Comparison of Immunoreactivity of Five Human Cardiac Troponin I Assays toward Free and Complexed Forms of the Antigen: Implications for Assay Discordance

Troponin, consisting of three components, troponin C (TnC), troponin I (TnI), and troponin T (TnT), is a major component of the structural proteins involved in striated and cardiac muscle contraction (1)(2). TnI and TnC bind tightly to each other in the presence of Ca2+ with an association constant, K a, of ∼108-109 L/mol (1)(2)(3). TnT binds to both TnC and TnI, although less weakly than the binding between TnC and TnI. The cardiac isoforms of TnI (cTnI) and TnT are structurally different from the corresponding skeletal isoforms, and therefore they have recently established themselves as biochemical markers of myocardial damage (4)(5)(6)(7). The currently available cTnI assays produce differing results (8)(9)(10). One important reason is that the assays may differ in their responses to the various isoforms of cTnI present in circulation or in biochemical preparations. In addition to “free” cTnI (I) and its binary and ternary complexes with TnC and TnT (IC or ICT) (8)(11)(12), cTnI may exist in phosphorylated (13), oxidized (14), and proteolytically degraded (8)(11)(12) forms. The latter modified forms of cTnI also may exist as binary or ternary complexes. All of these forms may have different recognition patterns in different immunoassays. The predominant form of cTnI in acute myocardial infarction (AMI) patients is the binary complex IC (8)(11). Samples treated with a Ca2+ chelator such as EDTA would contain mostly free cTnI because chelation of Ca2+ disrupts IC and ICT complexes. We explored the possibility that the sera from patients with different pathological conditions may contain different …

Contemporary approach to management of unstable angina

Unstable angina pectoris is one of the commonest diseases requiring hospital admission in Western countries, the estimated incidence being 2 per 1000 admissions annually. 1 Chierchia S Current therapeutic strategies in unstable angina. Eur Heart J. 1999; 1: 2-6 Google Scholar The course of the disease is highly variable; in some patients an anginal attack progresses rapidly to myocardial infarction or death, whereas in others there is uneventful recovery in 24 h. How best to manage patients is of crucial importance because of the high risk of myocardial infarction (15–20%) and death (15%) in the ensuing 3 months. 2 Théroux P Lidon RM Unstable angina:pathogenesis, diagnosis and treatment. Curr Probl Cardiol. 1993; 18: 159-214 Summary Full Text PDF Scopus (31) Google Scholar Endothelial dysfunction, plaque erosion and rupture, platelet adhesion and aggregation, and thrombus formation contribute to the pathogenesis of unstable angina. The goal of medical therapy is to relieve symptoms (primarily with classic antianginal agents such as nitrates, β-blockers, or calcium antagonists alone or in combination) and to stabilise plaque. Anticoagulation with intravenous heparin or low-molecular-weight heparin given together with aspirin and, more recently, glycoprotein IIb/IIIa inhibitors reduces the likelihood of myocardial infarction, with a trend towards reduced mortality. 3 PRISM PLUS Study Investigators.Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave infarction. N Engl J Med. 1998; 338: 1488-1497 Crossref PubMed Scopus (1647) Google Scholar The rationale for the use of heparin (fractionated or unfractionated) is based on many trials and meta-analyses. 4 Oler S Whooley MA Oler J Grady D Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. JAMA. 1996; 276: 811-815 Crossref PubMed Google Scholar In the Fragmin during Instability in Coronary Artery Disease (FRISC) study, dalteparin was superior to placebo in reducing the incidence of death and myocardial infarction in patients presenting with unstable angina. 5 Fragmin during Instability in Coronary Artery Disease (FRISC) study group.Low-molecular-weight heparin during instability in coronary artery disease. Lancet. 1996; 347: 561-568 Summary PubMed Google Scholar How long to give heparin remained uncertain until the FRISC II medical-management study, reported in this issue of The Lancet, showed that 3 months of dalteparin lowered the risk of death and myocardial infarction and need for revascularisation by about 13% at the end of that period (this benefit being due largely to the reduced need for revascularisation). Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre studyThe early invasive approach should be the preferred strategy in most patients with unstable coronary-artery disease who have signs of ischaemia on electrocardiography or raised biochemical markers of myocardial damage. Full-Text PDF Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre studyLong-term dalteparin lowers the risk of death, myocardial infarction, and revascularisation in unstable coronary-artery disease at least during the first month of therapy. These early protective effects could be used to lower the risk of events in patients waiting for invasive procedures. Full-Text PDF

Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study

<h2>Summary</h2><h3>Background</h3> In unstable coronary-artery disease early invasive procedures are common, despite lack of evidence for the superiority of this approach. We compared an early invasive with a non-invasive treatment strategy in unstable coronary-artery disease. <h3>Methods</h3> In a prospective randomised multicentre study, we randomly assigned 2457 patients in 58 Scandinavian hospitals (median age 66 years, 70% men) an early invasive or non-invasive treatment strategy with placebo-controlled long-term low-molecular-mass heparin (dalteparin) for 3 months. Coronary angiography was done within the first 7 days in 96% and 10%, and revascularisation within the first 10 days in 71% and 9% of patients in the invasive and non-invasive groups, respectively. We followed up patients for 6 months. Analysis was by intention to treat. <h3>Findings</h3> After 6 months there was a decrease in the composite endpoint of death or myocardial infarction of 9·4% in the invasive group, compared with 12·1% in the non-invasive group (risk ratio 0·78 [95% Cl 0·62–0·98], p=0·031). There was a significant decrease in myocardial infarction alone (7·8 <i>vs</i> 10·1%, 0·77 [0·60–0·99]; p=0·045) and non-significantly lower mortality (1·9 <i>vs</i> 2·9%, 0·65 [0·39–1·09]; p=0·10). Symptoms of angina and re-admission were halved by the invasive strategy. Results were independent of the randomised dalteparin treatment. The greatest advantages were seen in high-risk patients. <h3>Interpretation</h3> The early invasive approach should be the preferred strategy in most patients with unstable coronary-artery disease who have signs of ischaemia on electrocardiography or raised biochemical markers of myocardial damage.