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

doi:10.1016/0002-8703(91)90992-Q

American Heart Journal

Volume 122, Issue 2, August 1991, Pages 400-408

https://doi.org/10.1016/0002-8703(91)90992-Q Get rights and content

Abstract

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.

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Cited by (26)

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He encouraged young scientists not only to conceive papers and submit them for peer review, but also encouraged them to serve as reviewers rather early in their careers. He was also a very productive scientist: during the period 1976 to 2016 he authored 526 papers in peer-reviewed biomedical journals [1–526], of which 397 were original scientific articles. Many of Dr. Wagner’s papers were developed as part of his mentoring of young scientists, many others in various cooperative settings with other researchers.
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Since then, uncountable visits over the years followed, either alone or accompanied by colleagues. Several publications resulted [21,59–74]. Already as a post doc, Dr. Clemmensen and Dr. Wagner started to recruit new talented researchers, many of whom we co-mentored over the next 3 decades leading to many completed Ph.D. and doctoral theses.
This paper describes a substantial part of the international mentoring network of students and young investigators in electrocardiology that developed around Dr. Galen Wagner (1939–2016), including many experiences of his mentees and co-mentors.
The paper is meant to stimulate thinking about international mentoring as a means to achieve important learning experiences and personal development of young investigators, to intensify international scientific cooperation, and to stimulate scientific production.
Non-invasive methods to assess reperfusion in acute myocardial infarction: Enzymes and cardiac imaging gammagraphy with MIBI-SPECT
1998, Revista Espanola de Cardiologia
Diversos estudios señalan la importancia de la denominada angioplastia o fibrinólisis de rescate en el caso de que la trombólisis haya sido ineficaz en el infarto agudo de miocardio. Para ello es necesario disponer de nuevos métodos no invasivos de valorar la reperfusión, que documenten de forma segura que dicho tratamiento no ha sido efectivo.
Presentamos un trabajo basado en la valoración de pacientes con infarto agudo de miocardio tratados con fibrinólisis o sin fibrinólisis. Se realizaron perfiles enzimáticos cardíacos de creatinfosfocinasa y su fracción MB (tiempos, pico y la constante de elevación enzimática tiempoactividad: K1). Con gammagrafías cardíacas con isonitrilos pre y postratamiento se calculaban el miocardio en riesgo, el salvado y la relación entre ambos.
En los pacientes con infarto tratados con fibrinólisis el miocardio salvado fue superior (8,3% frente a 3,0%; p < 0,05). Considerando que una mejoría en el defecto de perfusión (miocardio salvado/miocardio en riesgo) mayor del 30% puede considerarse como reperfusión efectiva, vemos que en el grupo de pacientes con infartos tratados con fibrinólisis se necesitó reperfusión en el 45,8%, y del grupo sometidos a tratamiento convencional únicamente en el 6,7%. Los pacientes tratados con trombólisis presentan unos tiempos elevación-pico y dolor-pico mucho más cortos, tanto para la creatinfosfocinasa (p < 0,0001) como para la MB (p < 0,001). Los pacientes sometidos a reperfusión presentan un rápido incremento de la actividad enzimática, como lo demuestran las variables tiempo dolor-pico y la constante de aparición enzimática tiempo-actividad, con diferencias muy significativas para esta última (p < 0,0001). Respecto de la gammagrafía, unos valores de K1 mayores o iguales de 0,19 para la creatinfosfoscinasa y 0,14 para la MB, obtuvieron una sensibilidad del 83% y del 91% y una especificidad del 85% y del 80%, respectivamente, en predecir la reperfusión.
Creemos que tanto la gammagrafía cardíaca con isonitrilos como la determinación de la constante de aparición enzimática tiempo-actividad pueden ser útiles en la monitorización del tratamiento fibrinolítico en pacientes con infarto. Son necesarios nuevos estudios que valoren estos mismos aspectos, con un menor número de determinaciones enzimáticas.
Several studies point out the importance of what is called rescue angioplasty or fibrinolysis when thrombolysis has been ineffective in acute myocardial infarction. Therefore, it is necessary to make use of new non-invasive methods to asses reperfusion and to safely establish that such a treatment has not been effective.
We present a work which is based on the assessment of patients with acute myocardial infarction treated with or without fibrinolysis. After determining cardiac enzimatic profiles of creatin kinase and MB isoform (time course, peak, appearance rate constant time-activity: K1). With cardiac imaging gammagraphies 99mTc-isonitrile- single-photon emission computed tomography pre and post treatment after to calculating myocardium at risk, salvage and relationship.
In patients treated with fibrinolysis, the salvage myocardium was higher (8.3% vs 3.0%; p < 0.05). Considering that an improvement in perfusion defect (salvaged myocardium/myocardium at risk) higher than 30% can be viewed as an effective reperfusion, we can see that the percentage in the group treated with fibrinolysis being 45.8%, and the percentage in the group under conventional treatment being just 6.7%. Patients with acute myocardial infarction treated with fibrinolysis show much shorter start of rise-peak time and pain-peak time, all this with very significant differences for the creatin kinase (p < 0.0001) as well as for the MB (p < 0.001). Patients with reperfusion show a rapid increase in activity enzymatic, as demostred by the pain-peak time variable and the appearance rate constant time-activity (K1), with very significant differences in the latter (p < 0.0001). In relation with gammgraphy, values of K1 higher or equal to 0.19 for the creatin kinase and 0.14 for the MB isoform, achieved a sensibility of 83% and 91%, and a specificity of 85% and 80% respectively, to asses reperfusion.
We think that cardiac imaging gammagraphy with isonitriles as well as as determination of the appearance rate enzymatic constant time-activity, can be useful in monitoring treatment with fibrinolysis in infarction patients. New studies are needed to assess these same aspects, with a lesser number of enzymatic determinations.
Early noninvasive identification of failed reperfusion after intravenous thrombolytic therapy in acute myocardial infarction
1998, Journal of the American College of Cardiology
Objectives. This study sought to evaluate a biochemical approach to the early noninvasive assessment of reperfusion.
Background. In patients with an acute myocardial infarction, a rapid noninvasive method of detecting failure of intravenous thrombolytic therapy to restore early Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery (IRA) is needed.
Methods. Serial blood samples were collected to assay creatine kinase-MB fraction (CKMB mass), cardiac troponin T and myoglobin concentrations in 105 patients with a myocardial infarction who underwent early angiography after intravenous streptokinase. The ratios of the 60- and 90-min concentrations to prethrombolytic values were used to determine an index that could identify failure to achieve TIMI grade 3 flow in the IRA at 90 min.
Results. Significant increases in serum concentrations of markers at 60 min were more likely with TIMI grade 3 flow (59 patients) than with TIMI grade 0 to 2 flow (46 patients). Ratios ≤5 at 60 min after thrombolysis detected failure to achieve 90-min TIMI grade 3 flow with 92% to 97% sensitivity, 43% to 60% specificity and 63% to 76% positive and 86% to 94% negative predictive values. Ratios ≤10 at 90 min showed 88% to 95% sensitivity, 49% to 65% specificity and 61% to 69% positive and 86% to 94% negative predictive values for TIMI flow grade <3. The overall predictive values were thus similar for all three markers.
Conclusions. In acute myocardial infarction treated with intravenous streptokinase, a simple measurement of increased serum concentrations of CKMB mass, cardiac troponin T or myoglobin at 60 and 90 min can accurately predict failure to achieve TIMI grade 3 flow in the IRA at 90 min.
Diagnostic application of CK-MB mass determination
1998, Clinica Chimica Acta
Recent advances in analytic techniques have increased the diagnostic value of creatine kinase MB (CK-MB), enabling earlier and more sensitive results. The CK-MB mass immunoassays, that utilise the monoclonal anti-CK-MB in conjunction with anti-M or anti-B antibodies, are able to measure accurately small changes during the early hours after myocardial infarction (MI). CK-MB has two main limitations in diagnosing MI neither of which however undermines its established clinical value: CK-MB is not perfectly specific to cardiac injury, with increase occurring also during massive musculoskeletal injury; furthermore, the early release pattern of CK-MB limits its value for the late MI diagnosis. For the foreseeable future evidence is compelling for greater access to rapid testing capabilities in emergency situations, using protocols incorporating CK-MB mass evaluation together with other biochemical markers, i.e. myoglobin and troponins.
Laboratory monitoring of success and failure of thrombolytic therapy in acute myocardial infarction
1995, Fibrinolysis and Proteolysis
In clinical practice it would be desirable to monitor the clinical course and outcome of thrombolytic therapy by use of non-invasive laboratory methods. From the test systems available, the determination of specific myocardial necrosis markers seem to be at the moment of highest clinical value. Markers of thrombin activation might indicate failure of therapy and/or tendency for thrombotic reocclusion with all commercially available fibrin specific or non-specific thrombolytic agents but have failed to be of prognostic value for the individual patient or have not been investigated in sufficient numbers of patients. No clinical usefulness has been found so far for determination of markers of plasmin activation. Accordingly, specific control parameters of thrombolytic therapy with rt-PA have not been shown to be useful as predictive marker for clinical outcome of thrombolytic therapy in the individual patient with acute myocardial infarction. However, determination of t-PA and PAI-1 plasma levels is of interest with respect to investigation of pathophysiological contexts and their influence on efficacy of thrombolysis and should, therefore, be taken into account in clinical trials using t-PA or related substances for thrombolytic therapy.

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^☆: Supported in parts by grants from the Danish Heart Foundation and the Danish Research Council.

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

Abstract

Lancet

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am Heart J

Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction

Lancet

Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2

Lancet

Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction

N Engl J Med

Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction

Br Med J

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty

N Engl J Med