Estimation of enzymatic infarct size: Direct comparison of the marker enzymes creatine kinase and α-hydroxybutyrate dehydrogenase

doi:10.1016/S0002-8703(98)70335-7

American Heart Journal

Volume 135, Issue 1, January 1998, Pages 1-9

https://doi.org/10.1016/S0002-8703(98)70335-7 Get rights and content

Abstract

Background Estimation of infarct size with serum-time activity curves of creatine kinase (CK) (or CKMB) or α-hydroxy- butyrate dehydrogenase (HBDH) is widely used in clinical trials. However, an independent variable such as left ventricular function has not been directly compared with CK and HBDH infarct size measurements in the same group of patients. Methods and Results Infarct size was calculated by the CK area under the curve (AUC) and by the cumulative release of HBDH in 90 patients with acute myocardial infarction undergoing early thrombolysis. Infarct size estimates by CK AUC and HBDH release were closely correlated (r = 0.88, p < 0.0001). HBDH release was significantly better (p < 0.001) correlated to angiographically assessed ejection fraction 8 days after infarction (r = 0.74) than to CK AUC (r = 0.60), as was maximum HBDH (r = 0.71) compared with CK maximum (r = 0.59). In contrast to CK, maximum levels of HBDH only slightly overestimate myocardial damage in patients with early reperfusion. Data reanalyzed from the former placebo-controlled Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study revealed significant differences in favor of streptokinase for CK and CKMB AUC and for HBDH maximum, but no difference for CK and CKMB maximums. Conclusions For comparative clinical trials HBDH appears to be the preferable marker enzyme for estimates of infarct size and measure of reperfusion effectiveness. In clinical practice one routine measure of HBDH serum activity on the second day after infarction may be a useful approximate value of infarct size. (Am Heart J 1998;135:1-9.)

Section snippets

Patients

During the study period, patients with acute myocardial infarction lasting <6 hours and treated with intravenous thrombolysis who had no interventional procedures and survived at least 5 days were included. In addition to the typical clinical findings, inclusion criteria were ST elevations of ≥0.1 mV in two extremity electrocardiographic leads or ≥0.2 mV in two contiguous precordial leads, persistent after administration of sublingual nitroglycerin. Of 107 patients, 17 were excluded because of

Results

The mean values of enzymatic infarct size in all 90 patients were 803 ± 608 IU/L for mean HBDH release and 18.9 ± 19.6 IU/ml × hour for CK AUC. Comparison of both enzymatic infarct size measurements displayed a close correlation (r = 0.88, Fig. 1).

. Correlation between infarct sizes measured by CK AUC and mean HBDH release for all 90 study patients.

Compared with CK AUC, however, cumulative HBDH release correlated better (differences between the correlations p < 0.001) with parameters of left

Discussion

In the early 1970s, two methods to assess enzymatic infarct size were reported.9, 11 The method of Shell et al.⁹ is based on a total CK recovery of only 15% to 30%.¹⁰ The method developed by Witteveen et al.¹¹ is based on a two-compartment model for circulating enzymes and complete recovery of enzymes released from the infarcted myocardial tissue.11, 14 The actual estimates of infarct sizes are consistent with both methods, but the formulations used are different.12, 13 The validity of using

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Preoperative serum alpha-hydroxybutyrate dehydrogenase level as a predictor of postoperative mortality and morbidity after noncardiac surgery: A propensity-adjusted analysis
2022, Surgery (United States)
Preoperative serum alpha-hydroxybutyrate dehydrogenase is reportedly associated with myocardial infarction. Myocardial injury after noncardiac surgery is independently associated with postoperative mortality. However, the association between preoperative alpha-hydroxybutyrate dehydrogenase and outcomes after noncardiac surgery has not been researched. We aimed to assess the association between preoperative serum alpha-hydroxybutyrate dehydrogenase levels and mortality and morbidity after noncardiac surgery.
We conducted a retrospective cohort study on patients undergoing noncardiac surgery from 2018 to 2020 in Sichuan University West China Hospital. After multivariate adjustment, the alpha-hydroxybutyrate dehydrogenase level was verified to be associated with postoperative outcomes by logistic regression analyses and propensity score weighting methods.
We obtained data from 130,880 patients. An elevated preoperative serum alpha-hydroxybutyrate dehydrogenase level was associated with increasing mortality (odds ratio 1.244, 1.190–1.300; P < .001), myocardial injury after noncardiac surgery (odds ratio 1.198, 1.141–1.257; P < .001), and intensive care unit admission (odds ratio 1.138, 1.111–1.166; P < .001) in logistic regression analyses. The covariate balancing generalized propensity score methodology demonstrated similar results. After classifying alpha-hydroxybutyrate dehydrogenase as a binary variable with a cut-off value of 182, we found that mortality, myocardial injury after noncardiac surgery, and intensive care unit admission >24 hours were significantly higher in the elevated alpha-hydroxybutyrate dehydrogenase group (5.458% vs 0.737%; odds ratio 1.771, 1.533–2.046; P < .001), (3.598% vs 0.572%; odds ratio 1.636, 1.393–1.922; P < .001), and (18.182% vs 6.442%; odds ratio 1.430, 1.327–1.542; P < .001), respectively. Similarly, the inverse-probability-of-treatment weighted estimation demonstrated similar results.
Our results suggest that the preoperative serum alpha-hydroxybutyrate dehydrogenase level was associated with in-hospital mortality, myocardial injury after noncardiac surgery, and intensive care unit admission after noncardiac surgery.
Circulating MIF Levels Predict Clinical Outcomes in Patients With ST-Elevation Myocardial Infarction After Percutaneous Coronary Intervention
2019, Canadian Journal of Cardiology
The purpose of the study was to assess the value of admission macrophage migration inhibitory factor (MIF) levels in predicting clinical outcomes in ST-elevation myocardial infarction (STEMI) patients.
For this study we recruited 498 STEMI patients after they received percutaneous coronary intervention (PCI), 40 with stable angina pectoris and 137 healthy participants. Plasma MIF levels were measured at admission and after PCI. The primary end points were in-hospital mortality and major adverse cardio-and/or cerebrovascular events (MACCE) during hospitalization and 3.2-year follow-up period.
Admission MIF levels were elevated in 88.4% of STEMI patients over the upper reference limit of healthy controls and it was 3- to 7-fold higher than that in stable angina pectoris and control groups (122 ± 61 vs 39 ± 19 vs 17 ± 8 ng/mL; P < 0.001). Admission MIF levels were significantly higher in patients who died after myocardial infarction vs survivors. For predicting in-hospital mortality using the optimal cutoff value (127.8 ng/mL) of MIF, the area under the receiver operating characteristic curve for MIF was 0.820, similar area under the receiver operating characteristic curve values for predicting short-term outcomes were observed for high-sensitivity troponin T, CK-MB, N-terminal probrain natriuretic peptide, and Global Registry of Acute Coronary Events (GRACE) score. Although peak high-sensitivity troponin T and N-terminal probrain natriuretic peptide also predicted MACCE during the follow-up period, only higher admission MIF levels predicted in-hospital mortality and MACCE during the 3.2-year follow-up. Multivariate regression analysis showed the independent predictive value of a higher admission MIF level (≥ 127.8 ng/mL) on in-hospital mortality (odds ratio, 9.1; 95% confidence interval, 1.7-47.2) and 3.2-year MACCE (hazard ratio, 2.8; 95% confidence interval, 1.5-5.6).
A higher admission MIF level is an independent predictor for in-hospital mortality and long-term MACCE in STEMI patients who underwent PCI.
L’étude visait à évaluer l’utilité du dosage du facteur d’inhibition de la migration des macrophages (MIF) effectué lors de l’admission à l’hôpital aux fins de pronostic des résultats cliniques chez les patients ayant souffert d’un infarctus du myocarde avec élévation du segment ST (STEMI).
Pour les besoins de cette étude, nous avons recruté 498 patients ayant souffert de STEMI après qu’ils eurent subi une intervention coronarienne percutanée (ICP), 40 patients atteints d’angine de poitrine stable et 137 sujets en bonne santé. Les concentrations plasmatiques de MIF ont été mesurées lors de l’admission à l’hôpital et après l’ICP. Les paramètres d’évaluation principaux étaient la mortalité intrahospitalière et la survenue d’événements cardiovasculaires et/ou cérébrovasculaires indésirables majeurs (MACCE) au cours de l’hospitalisation et d’une période de suivi de 3,2 ans.
Lors de l’admission à l’hôpital, les concentrations de MIF étaient élevées chez 88,4 % des patients qui avaient souffert de STEMI; elles se situaient au-delà de la limite supérieure de référence mesurée chez les sujets témoins en bonne santé et étaient de 3 à 7 fois plus élevées que celles notées chez les patients atteints d’angine de poitrine stable et les sujets témoins (122 ± 61 vs 39 ± 19 vs 17 ± 8 ng/ml, p < 0,001). Les concentrations de MIF lors de l’admission à l’hôpital étaient significativement plus élevées chez les patients qui sont décédés après avoir souffert d’un infarctus du myocarde que chez les survivants. Pour le pronostic de mortalité intrahospitalière en fonction de la concentration de MIF constituant la valeur seuil optimale (127,8 ng/ml), l’aire sous la courbe ROC était de 0,820. Une aire sous la courbe ROC similaire a été observée pour le pronostic des résultats à court terme en fonction des concentrations de troponine T hypersensible, de CK-MB et de NT-proBNP (propeptide natriurétique de type B N-terminal) et en fonction du score GRACE (Global Registry of Acute Coronary Events). Même si les concentrations maximales de troponine T hypersensible et de NT-proBNP étaient aussi prédictives des MACCE durant la période de suivi, seules les concentrations plus élevées de MIF lors de l’admission à l’hôpital constituaient un marqueur pronostique de mortalité intrahospitalière et de MACCE durant la période de suivi de 3,2 ans. L’analyse de régression multivariée a montré qu’une concentration plus élevée de MIF lors de l’admission à l’hôpital (≥ 127,8 ng/ml) constitue un marqueur pronostique indépendant de mortalité intrahospitalière (rapport des risques instantanés de 9,1; intervalle de confiance à 95 % de 1,7 à 47,2) et de MACCE sur une période de 3,2 ans (rapport de cotes de 2,8; intervalle de confiance à 95 %, de 1,5 à 5,6).
Une concentration plus élevée de MIF lors de l’admission à l’hôpital constitue un marqueur pronostique indépendant de mortalité intrahospitalière et de MACCE à long terme chez les patients qui ont souffert d’un STEMI et subi une ICP.
Association between the ratio of anti-angiogenic isoform of VEGF-A to total VEGF-A and adverse clinical outcomes in patients after acute myocardial infarction
2018, IJC Heart and Vasculature
Vascular endothelial growth factor-A (VEGF-A) promotes neovascularization and is attracting considerable attention as a remarkable risk factor in patients after acute myocardial infarction (AMI). In contrast, the association between VEGF-A₁₆₅b, which is the main anti-angiogenic isoform of VEGF-A, and adverse clinical outcomes after AMI remains unclear. The present study aimed to investigate the association between serum VEGF-A₁₆₅b and major adverse cardiac and cerebrovascular events (MACCEs) after percutaneous coronary intervention (PCI) for AMI.
We evaluated 23 patients with AMI who underwent primary percutaneous coronary intervention. VEGF-A and VEGF-A₁₆₅b levels were measured on admission (day 1) and at days 3, 7, and 30 after PCI.
The levels of total VEGF-A tended to be lower, while the ratio of VEGF-A₁₆₅b to total VEGF-A tended to be higher in patients with MACCEs than in those without. The patients with a high ratio of VEGF-A₁₆₅b to total VEGF-A had a significantly higher risk of MACCEs using the cut-off values for MACCEs at day 30 after PCI (0.87 vs. 0.25, log-rank test, p = 0.0058).
The assessment of VEGF-A₁₆₅b combined with VEGF-A may be a valuable screening tool for predicting MACCEs in clinical practice.
Discrepancy between MRI and echocardiography in assessing functional left ventricular parameters and scar characteristics in patients with chronic ischemic cardiomyopathy
2015, Egyptian Heart Journal
Citation Excerpt :
In addition, poor T1 nulling of normal myocardium, as well as low signal-to-noise ratios in general, can increase the amount of intermediate-intensity pixels, and thereby falsely increase the gray zone size.17 The LVEF in this study and others18–21 is inversely related to total infarct size, although the strength of this relationship may be weak. Many factors affect LVEF aside from infarct size, such as preload, afterload, autonomic factors, medications, and post-infarction remodeling.22
Studies have demonstrated that infarct size estimated by CMR-LGE was an independent determinant of adverse LV remodeling and dysfunction.
We sought to assess relationship between different scar characteristics and left ventricular remodeling and dysfunction using late gadolinium enhancement CMR (LGE-CMR) and echocardiography in patients with ischemic cardiomyopathy.
Forty-eight patients with post-infarction left ventricular (LV) dysfunction underwent CMR and 2D echocardiographic studies. Various scar characteristics were assessed by a freely available software and were correlated with functional parameters.
All patients had LGE in CMR indicating prior myocardial infarction (MI). A statistically significant but modest negative association was found between left ventricular ejection fraction (LVEF) and number of segments with LGE (r = −0.4, p = 0.005). Additionally, there was a statistically significant modest to moderate positive relationship between LV end diastolic volume (LV EDV) and absolute total scar mass (r = 0.38, p = 0.007), absolute scar core mass (r = 0.32, p = 0.026), peri-infarct zone as absolute (r = 0.45, p = 0.001) and as percent of LV (r = 0.29, p = 0.045) and number of segments with LGE (r = 0.32, p = 0.029). Similarly, statistically significant modest positive correlations were observed between LV end systolic volume (LV ESV) and absolute total scar mass (r = 0.37, p = 0.009), absolute scar core mass (r = 0.32, p = 0.02), peri-infarct zone as absolute (r = 0.4, p = 0.004) and number of segments with LGE (r = 0.38, p = 0.007). There was a mild to moderate correlation between LVEF as assessed by TTE and LVEF measured by CMR (r = 0.49, p < 0.001). The mean difference in LVEF between the two methods was 7.5 ± 9.2% with a p value <0.001. Bland–Altman limits were wide ranging from −10.5 to 25.5%.
Different scar characteristics as assessed by CMR were associated with the extent of LV remodeling and dysfunction. This highlights the potential importance of myocardial scarring assessment in risk stratification of patients with ischemic cardiomyopathy.
Wide agreement limits for ejection fraction assessment by TTE and CMR suggest that both methods are not interchangeable. Given its 3D approach and superior image quality, CMR may be the preferred technique for volume and ejection fraction estimation.
Endothelial nitric oxide synthase genotypes modulate peripheral vasodilatory properties after myocardial infarction
2015, Gene
Studies in population genetics suggest an important relationship between the eNOS G894T polymorphism and occurrence of acute myocardial infarction (AMI), with little known on its influence on the post-AMI period.
To investigate the association of allelic variants produced by the G894T transversion in eNOS (rs1799983) with post-AMI variables.
Cross-sectional analyses of anthropometric, clinical and laboratory assessments obtained within the first 24 h and after 5 and 30 days of the AMI event across T carriers and G homozygotes of eNOS in 371 consecutive cases of AMI with ST-segment elevation admitted to a Brazilian emergency service in cardiology. Genotypes were determined by polymerase chain reaction followed by enzymatic restriction.
Despite no difference between genotypic groups on aspects as Killip–Kimbal classification scores, extension of infarcted mass, lipid profile or pattern of medication use, an increase in serum nitric oxide from admission to day 5 was higher for T carriers (p < 0.001). Thirty days post-AMI, peripheral blood flow reserve was larger among T carriers either by flow- (p = 0.037) and nitrate-mediated (p = 0.040) dilation testing.
Our results suggest an association of the eNOS 894T allele with an apparent improvement in late arterial function in post-AMI patients.
Evolution of myocardial perfusion during primary angioplasty in spontaneously reperfused infarct-related artery: Impact on long-term clinical outcomes and left ventricular function recovery
2011, International Journal of Cardiology
Citation Excerpt :
Serum level of creatine kinase MB (CK-MB, U/l) was determined at least three times within the first 24 h, and then after 36 and 48 h. The area under the curve of CK-MB release in the first 48 h (AUC, U/l × h) was calculated [17]. Two-dimensional echocardiography was performed at rest to evaluate LV ejection fraction (LVEF, %) by the biplane Simpson's method.
TIMI myocardial perfusion grade (TMPG) reflects the integrity of microvasculature in ST-elevation myocardial infarction (STEMI). We sought to investigate whether TMPG evolution during primary angioplasty (pPCI) in spontaneously reperfused STEMI patients might predict long-term outcomes.
392 patients with TIMI-3 flow before pPCI were analyzed. According to pre- and post-pPCI TMPG four reperfusion patterns were created: A. TMPG deterioration from grade 2/3 to 0/1 after pPCI (n = 55, 14.0%), B. TMPG-0/1 before and after pPCI (n = 111, 28.3%), C. TMPG improvement from grade 0/1 to 2/3 (n = 52, 13.3%), D. TMPG-2/3 before and after pPCI (n = 174, 44.4%). 30-day and 1-year mortality and heart failure requiring hospitalization (HF-hosp) were recorded. Left ventricular ejection fraction (LVEF) was measured at first day (1D) and after 6 months (6M).
1D-LVEF was similar in A–D groups. After 6M, LVEF improved in pattern D (7.5 ± 5.4%, p < 0.01) and C (3.7 ± 3.4%, p < 0.05), deteriorated in pattern A (5.2 ± 3.9%, p < 0.01) and did not change in pattern B. 6M-LVEF increased (p < 0.001) and frequency of 1-year HF-hosp decreased (p < 0.001) in stepwise fashion among A–D patterns. A 30-day mortality rate for A–D patterns was 9.1%, 2.7%, 1.9% and 0%, respectively (p < 0.001). 1-year mortality was 16.3%, 7.2%, 5.8% and 0.6%, respectively (p < 0.001). By multivariate analysis (c-index = 0.79), TMPG evolution was independent predictor of 1-year mortality (HR = 2.5, 95%CI 1.3–4.0, p = 0.006).
Maintaining TMPG-2/3 or improving TMPG-0/1 through pPCI in STEMI implies LV function recovery and good long-term survival. In contrast, substantial deterioration of TMPG is associated with lack of LV function recovery, and the highest mortality rate.

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^☆: From the Department of Cardiopulmology, Klinikum Benjamin Franklin, Free University Berlin.

^☆☆: Reprint requests: Rolf Schröder, MD, Klinikum Benjamin Franklin Free University Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.

^★: 4/1/87276

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Estimation of enzymatic infarct size: Direct comparison of the marker enzymes creatine kinase and α-hydroxybutyrate dehydrogenase☆,☆☆,★

Abstract

Section snippets

Patients

Results

Discussion

Am Heart J

J Am Coll Cardiol

Am Heart J

Am Heart J

Am Heart J

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

A prospective trial of intravenous streptokinase in acute myocardial infarction (ISAM)

N Engl J Med

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

Br Med J

Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinse in acute myocardial infarction

Circulation

Nachweis der Wiedereröffnung eines Infarktgefäßes durch serielle CK-MB- und CK-Bestimmung

Herz/Kreisl

Different effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct-related patency-the GUSTO enzyme substudy

Eur Heart J

Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial creatine phosphokinase activity

J Clin Invest