Prognostic significance of an early rise to peak creatine kinase after acute myocardial infarction

Because an early rise to peak creatine kinase (CK) is regarded as a noninvasive marker of early coronary reperfusion, the short- and long-term significance of this phenomenon was studied. In a series of consecutive patients admitted between 1974 and 1976 with acute myocardial infarction (AMI), 2 hourly CK estimations were performed. Complete CK curves were obtained in 102 patients, all of whom have been followed for 10 years. Without reference to their clinical course or follow-up, patients were divided into those with CK curves peaking less than or equal to 15 hours (mean 11 hours; n = 41) and those with curves peaking greater than 15 hours (mean 21 hours; n = 61). There were no differences in age, Norris index, location of AMI or past history of coronary artery disease between the groups; however, the mean peak CK was higher in the late peak group (p less than 0.05) and there were more non-Q-wave infarcts in the early peak group (p less than 0.01). In the first 9 months of follow-up there were fewer cardiac deaths in the early peak group (5 vs 13%), but this difference was not significant, and at 12 months the survival curves crossed. At 10 years, survival was 42% in the early peak group and 65% in the late peak group (p less than 0.05). Cox regression analysis showed that early peaking of the CK curve was an independent marker for cardiac death overall (relative risk 2.3, p less than 0.02). In 1-year survivors the relative risk increased to 3.8 (p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic significance of a low peak serum creatine kinase level in acute myocardial infarction

To assess the prognostic significance of a low peak creatine kinase (CK) level, 723 consecutive patients admitted with acute myocardial infarction (AMI) within 16 hours after onset of symptoms were studied. Thrombolytic therapy was not attempted during the study. Patients were dichotomized according to their peak CK levels, determined from a cluster analysis of peak CK distribution among the population of patients who died within 3 years after hospital discharge. The 139 patients with low peak CK (less than or equal to 650 IU/liter) (group 1) were compared to the 584 patients with high peak CK (greater than 650 IU/liter) (group 2). Patients in group 1 were older and had a higher incidence of previous AMI, angina pectoris before AMI and non-Q-wave AMI. Despite a lower incidence of in-hospital complications and a nonsignificantly lower hospital mortality rate (4 vs 9%) the group 1 three-year posthospital mortality rate was higher (26 vs 17%; p less than 0.02), especially in the subgroup of patients with a Q-wave infarct (mortality 31% in group 1 vs 16% in group 2; p less than 0.001). Among the 491 patients who had a first Q-wave AMI, 55 had a peak CK less than or equal to 650 IU/liter. Compared to the 436 patients with a higher peak CK, these 55 patients had a higher incidence of early postinfarction angina (31 vs 14%; p less than 0.01), a similar hospital mortality (4 vs 7%) but a higher 3-year posthospital mortality (23 vs 12%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of elevated MB isoenzyme with normal creatine kinase in acute myocardial infarction

The significance of elevated levels of the MB isomer of creatine kinase (CK-MB) when creatine kinase (CK) level is normal was studied in 400 patients with suspected acute myocardial infarction (AMI). In 350 patients both CK and CK-MB were elevated (group 1), in 21 only CK-MB was elevated (group 2), in 24 neither enzyme was elevated (group 3) and in 5 only CK was elevated (group 4). In 57% of patients in group 2 the CK level was doubled, with a characteristic enzyme curve, within the normal range, suggesting that an increase in CK had been missed because arbitrary definitions of "normal" were used. The median CK increase (60 IU/liter) in group 2 was greater than that in group 3 (23 IU/liter) (p less than 0.001). Patients in group 1 with small AMIs had a relative increase in CK similar to that in group 2. However, patients in group 2 had a lower baseline CK level so that peak CK did not become abnormally high despite a 5-fold increase in some patients. In patients in group 1 with small AMIs, CK was elevated in fewer samples than CK-MB. If only 2 samples were obtained in all patients, elevation of CK levels would have been missed in 63 group 1 patients, erroneously increasing the number of patients in group 2 fourfold (to 84 of 400, or 21%, instead of 21 of 400, or only 5%). Conversely, if patients in group 2 with a doubling of CK are excluded, the prevalence of elevated CK-MB with normal CK would be only 9 of 400 (2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic significance of time-delay to peak creatine kinase after direct percutaneous coronary intervention in acute myocardial infarction patients

The aim of the present study was to investigate the prognostic significance of time-delay to peak creatine kinase (CK) after successful direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Our 240 consecutive first AMI attack subjects admitted within 5 hours from onset were successfully reperfused by direct PCI therapy. Subjects were divided into two groups according to the upper quartile value of peak-CK time from onset, the early peak-CK group (peak-CK time < or = 16 hours from onset, n = 180) and the late peak-CK group (peak-CK time > 16 hours, n = 60). (I) The early ST-segment resolution rate was lower in the late peak-CK group compared with the early peak-CK group (P < 0.05), and there were significantly fewer patients with preinfarction angina pectoris in the late peak-CK group than in the early peak-CK group (P < 0.01). (II) LVEF in the chronic stage was significantly lower in the late peak-CK group than in the early peak-CK group (49 +/- 13% versus 57 +/- 13%, P < 0.001). (III) There were significantly more patients with major complications in the late peak-CK group than in the early peak-CK group (required CABG: 10% versus 3%, P < 0.05; cardiac death: 18% versus 3%, P = 0.0001). (IV) Multivariate analysis identified late peak-CK as an independent predictor of cardiac death (Odds ratio 7.91, 95% C.I. 1.40-44.11, P < 0.05). In patients with AMI, the time-delay to peak-CK after successful direct PCI may be closely related to left-ventricular systolic dysfunction and poor patient outcome, including mortality.     

Noninvasive detection of reperfusion in acute myocardial infarction based on plasma activity of creatine kinase MB subforms

Successful thrombolytic therapy is associated with an accelerated release of creatine kinase (CK) MB from necrotic myocardium. With use of a previously validated assay, the plasma kinetics of the myocardial subform (MB2) and the plasma-modified subform (MB1) were determined in blood samples obtained from 56 patients with acute Q wave myocardial infarction: 33 patients who received thrombolytic therapy (group A) and 23 patients managed conservatively (group B). Plasma MB2 activity increased more rapidly in the group A patients, but there was substantial overlap with group B. Plasma MB1 activity did not differ significantly between the two groups. The MB2/MB1 ratio was significantly higher in group A patients than in group B patients between 2 and 10 h after the onset of infarction. Among group A patients, the ratio increased from 2.4 +/- 1.6 to 4.6 +/- 2.0 in the 1st h after therapy (p less than 0.001). The peak ratio was 6.3 +/- 2.5 in group A patients and 3.1 +/- 1.2 in group B patients. Twenty-seven of the 33 group A patients had a peak ratio greater than 3.8 versus 5 of the 23 group B patients (p less than 0.001). In seven group A patients, the ratio was greater than 3.8 before plasma CK MB activity was out of the normal range. Angiography was performed at 5.0 +/- 3.5 days in 39 patients. Eighteen (90%) of 20 patients with a patent infarct-related artery had a peak ratio greater than 3.8; 17 (89.5%) of 19 patients with an occluded infarct-related artery had a ratio less than 3.8 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of serum myoglobin and creatine kinase MB isoenzyme in early diagnosis of acute myocardial infarction.

We compared the clinical usefulness of serum myoglobin and creatine kinase MB (CK MB) isoenzyme determinations in the early diagnosis of acute myocardial infarction in 109 consecutive patients admitted to a coronary care unit. Of these, 37 patients were diagnosed as having definite infarction, three possible infarction, and 69 no infarction, using World Heath Organisation criteria. Blood samples were taken on admission and two to four hours later, Both CK MB and myoglobin were raised in the initial serum samples in 24 of the 37 patients with definite infarction. In an additional seven patients both CK MB and myoglobin were negative in the first specimen though both were detected in the second sample. In five patients CK MB preceded the appearance of myoglobin while in the remaining patient myoglobin appeared before CK MB. We conclude that the detection of serum myoglobin does not offer any clinical advantage over CK MG as an early indicator of myocardial infarction.     

Contribution of creatine kinase MB mass concentration at admission to early diagnosis of acute myocardial infarction.

OBJECTIVE--To assess the diagnostic value at admission of creatine kinase MB mass concentration, alone or in combination with electrocardiographic changes, in suspected myocardial infarction. DESIGN--Prospective study of all consecutive patients admitted within 12 hours after onset of chest pain to a coronary care unit for evaluation of suspected myocardial infarction. SETTING--Large regional hospital. PATIENTS--In 297 patients creatine kinase and creatine kinase MB activities and creatine kinase MB mass concentration were determined. Myocardial infarction according to the criteria of the World Health Organisation was diagnosed in 154 patients and excluded in 143 patients (including 70 with unstable angina pectoris). RESULTS--Sensitivity/specificity for creatine kinase MB mass concentration in patients admitted within 4 hours and 4-12 hours after onset of chest pain were 45%/94% and 76%/79% respectively. Corresponding values for creatine kinase activity were 20%/89% and 59%/83%, and for creatine kinase MB activity 16%/87% and 53%/87%. Raised creatine kinase MB mass concentration was seen in 17% of patients with unstable angina pectoris. Stepwise logistic regression analysis showed that independent predictors of acute myocardial infarction in patients admitted within 4 hours after onset of chest pain were electrocardiographic changes and creatine kinase MB mass concentration on admission; in patients admitted 4-12 hours after the onset of pain independent predictors were electrocardiographic changes and creatine kinase MB mass concentration and activity. CONCLUSION--Creatine kinase MB mass concentration is a more sensitive marker for myocardial infarction than the activity of creatine kinase and its MB isoenzyme. Electrocardiographic changes on admission in combination with creatine kinase MB mass concentration (instead of creatine kinase and creatine kinase MB activities) are best in diagnosing myocardial infarction.     

Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction

Conventional plasma isoenzyme and enzyme values usually are normal during the first few hours of acute myocardial infarction. Thus definitive diagnosis may be delayed. We have shown recently that infarction in dogs can be detected within 1 hr after coronary occlusion by analysis of relative activities of MM creatine kinase (CK) isoforms in plasma. Isoforms of MM CK evolve through posttranslational modifications in plasma of the form released from tissue (MMA) to MMB and MMC. In this study we quantified changes in isoform profiles in the first available plasma samples from patients with evolving myocardial infarction, from patients with angina, and from normal subjects. In the 26 control subjects, the ratio of MMA to MMC was 1.09 +/- 0.4 (SE) (range 0.31 to 3.1; upper limit of normal [defined as the mean plus 2 SD] 2.5). In the seven control patients with coronary artery disease, the ratio of MMA to MMC was 1.3 +/- 0.3 with a range of 0.5 to 2.5. In contrast, among the 28 patients with acute myocardial infarction, the ratio of MMA to MMC in the first available plasma sample averaged 14.6 +/- 4.5 (p less than .01 compared with both control groups). First available samples were obtained 3.9 +/- 0.4 hr after the onset of pain. In 24 of 28 patients (86%) the ratio of MMA to MMC was greater than 2.5.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic implications of creatine kinase elevation after primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES: We examined the prognostic implications of the absolute level and rate of increase of creatine kinase (CK) elevation after primary percutaneous coronary intervention (PCI). BACKGROUND: Peak creatine kinase (CK(peak)) and the rate of CK increase are related to reperfusion success and clinical outcomes after thrombolytic therapy for acute myocardial infarction (AMI). The utility of routine serial CK monitoring after primary PCI, in which normal antegrade blood flow is restored in most patients, is unknown. METHODS: In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial, 1,529 patients with AMI randomized to either stenting or balloon angioplasty, each with or without abciximab, had CK levels determined at baseline and at 8 +/- 1 h, 16 +/- 1 h, and 24 +/- 1 h after PCI. RESULTS: The CK(peak) occurred at baseline in 3.9% of patients, at 8 +/- 1 h in 69.6%, at 16 +/- 1 h in 20.0%, and at 24 +/- 1 h in 6.5%. The CK levels at all post-procedural time points were significantly higher in patients who died compared with the one-year survivors, as was CK(peak) (mean, 2,865 U/l vs. 1,885 U/l, respectively, p < or = 0.001). By multivariate analysis, CK(peak) was a significant predictor of one-year mortality (hazard ratio = 2.15, p = 0.0002), independent from post-PCI Thrombolysis In Myocardial Infarction (TIMI) flow. Both the improvement in left ventricular ejection fraction from baseline to seven months and its absolute level were inversely correlated with CK(peak) (p < 0.001 for both). In contrast, the time to CK(peak) was not an independent predictor of mortality or myocardial recovery. CONCLUSIONS: The CK(peak) after primary PCI is a powerful predictor of one-year mortality independent of other clinical and angiographic measures.     

Use of rapid serial sampling of creatine kinase MB for very early detection of myocardial infarction in patients with acute chest pain.

To determine how early myocardial infarction can be detected, serial creatine kinase MB concentrations were sampled in 313 patients during triage of acute (less than 12 hours) chest pain. Serum was sampled on hospital arrival (baseline) and hourly for 3 hours (total of four samples). Creatine kinase MB concentrations were subsequently analyzed for their ability to detect infarction. Infarction was present in 70 patients (22%) and was diagnosable from the index electrocardiograms in 27 of these (39%). Sensitivity and specificity for detection of infarction were 76% and 72%, respectively, as determined from baseline MB values only and increased with each additional sample to a maximum of 92% and 96%, respectively, in all four samples. Analysis of two serum samples taken 2 hours apart showed a sensitivity of 94% and a specificity of 91%. If these results are confirmed, improved initial diagnostic accuracy with this rapid assay technique in acute chest pain may (1) conserve resources when initial suspicion of infarction is low, (2) identify patients with infarction appropriate for early intervention, and (3) avoid premature hospital discharge of patients with infarction.     

The creatine kinase curve area and peak creatine kinase after acute myocardial infarction: Usefulness and limitations

We determined creatine kinase (CK) curve areas in 112 patients with acute myocardial infarction. Two-hour sampling was performed for the first 24 hours or until peak CK was reached, and a gamma density function was used to calculate curve areas from all available samples. Attempts to predict CK curve area by means of the portion of the curve prior to peak CK proved to be inaccurate; not until values 2 hours or more beyond peak CK were utilized did predicted and actual CK areas agree well. A good correlation (r = 0.93) was found between CK area and peak CK. To establish an approach for detecting peak CK in the clinical setting, a range of sampling intervals (4 to 24 hours) was assessed; 4-and 6-hour sampling intervals for 48 hours produced maximum CK values at or above 85% of true peak CK in 90% and 89% of patients, respectively, and average maximum CK at both sampling intervals exceeded 94% of that obtained with 2-hour samplings. We conclude that this simplified approach can provide a basis for estimating infarct severity in the individual patient.     

Simultaneous occurrence of the MB isoenzyme of creatine kinase and macro creatine kinase type 1 in a patient with acute myocardial infarction

When the immunoinhibition method is used for differentiation of isoenzymes of creatine kinase, the simultaneous occurrence of the MB isoenzyme and variants of macro creatine kinase may lead to misinterpretation in the diagnosis of acute myocardial infarction. We describe the case of an elderly woman in whom the MB isoenzyme and the type 1 variant of macro creatine kinase were found simultaneously in her serum after acute myocardial infarction. It proved possible to identify the MB isoenzyme rapidly using a fast enzymeimmunoassay.     

Prognosis of patients with different peak serum creatine kinase levels after first myocardial infarction

The extent to which patients with low peak serum creatine kinase(CK) at their first myocardial infarction differ from patientswith high CK levels in terms of risk for subsequent ischaemicevents was investigated in 266 patients who survived the first48 h from the onset of infarction. All patients were followedup for one year. Four groups were formed based on peak CK200,201–400, 401–800 and >800 IU l^-1. During follow-upthe incidence of mortality was 15% (N=39), non-fatal re-infarction9% (N=23), and angina 53% (N=140). Hospital mortality was significantlyhigher (P<0.02) in the highest CK-group (16%), but the incidenceof non-fatal re-infarction, angina pectoris and late mortalitywas similar in the four groups. In hospital survivors, ischaemicST-changes during pre-discharge symptom limited bicycle stresstest and multiple vessel disease were equally distributed inall four groups. We conclude that while hospital mortality is directly relatedto peak CK, there is no relationship between peak CK and latemortality, non-fatal re-infarctions, or recurrent angina. Accordingly,diagnostic and therapeutic procedures in the individual patientsare notinfluenced by the amount of serum CK released duringacute infarction.     

Myoglobin and creatine kinase in acute myocardial infarction

Serum myoglobin concentration and creatine kinase activity were measured serially in 70 consecutive patients presenting within four hours of the onset of symptoms of suspected acute myocardial infarction. Of 36 patients with definite or possible myocardial infarction (WHO criteria), the serum myoglobin concentration was raised (greater than 85 micrograms/l) one hour after the onset of symptoms in 25% and at four hours in 89%. Creatine kinase activity was raised (greater than 140 U/l) one hour after the onset in 25% and at four hours in only 56%. Within 12 hours of the onset of symptoms the myoglobin concentration reached a peak in 83% and the creatine kinase a peak in only 14%. Within 36 hours the myoglobin concentration fell to normal values in 67% while creatine kinase activity fell to normal values in only 3%. Four hours after the onset of symptoms the serum myoglobin concentration distinguished easily those patients with myocardial infarction from those without, whereas when creatine kinase values were used the sensitivity was poor but the specificity high. From the combined results of the two studies and using a single measurement of serum myoglobin concentration at six hours from the onset of symptoms to predict the diagnosis in 114 patients with suspected infarction, the sensitivity was 93% and specificity 89%.     

Characteristics and prognosis of patients with suspected acute myocardial infarction and elevated MB relative index but normal total creatine kinase

"MB Leak" patients who develop an elevated MB relative index with a normal total creatine kinase (CK) level are not as well characterized as those who have diagnostic enzyme elevations in the setting of ST elevation (elevation) or non-ST elevation acute myocardial infarction (AMI). During a 1-year period, we studied all patients hospitalized in an urban academic hospital with suspected AMI who developed an elevated MB relative index within 24 hours of presentation. Of 595 patients, 44% had MB Leak, 34% had non-ST elevation AMI and 22% had ST elevation AMI. Patients with MB Leak and non-ST elevation AMI were significantly older than those with ST elevation AMI (mean ages 69, 71, and 63 years, respectively; p <0.001), and were more likely to have previous AMI (55%, 46%, 12%; p <0.001) or past coronary revascularization (40%, 19%, 12%; p <0.001). The in-hospital death rate of patients with MB Leak was half that of patients with non-ST elevation AMI or ST elevation AMI (6%, 12%, 12%; p = 0.03). By 1 year after presentation, the death rate of patients with MB Leak (17%) was intermediate between that of non-ST elevation AMI (24%) and ST elevation AMI (14%). Within the MB Leak group, those with elevated absolute CK-MB levels were at highest risk. In a multivariable model using MB Leak as the referent, the relative risks for 1 year death were 1.4 (95% confidence interval, 0.9 to 2.2) for patients with non-ST elevation AMI and 1.7 (0.8 to 3.4) for patients with ST elevation AMI. Patients with MB Leak are at high risk for cardiovascular events in the hospital and for death by 1 year. Therefore, they may benefit from early aggressive therapy and risk stratification. These results suggest that CK-MB should be measured in all patients with suspected AMI, regardless of their total CK level.     

Prognostic implications of early spontaneous angina after acute transmural myocardial infarction

We investigated the clinical, electrocardiographic and hemodynamic features and the prognostic implications of early spontaneous angina in 31 consecutive patients after acute myocardial infarction. Re-elevation of ST segments in the area of infarction occurred during angina and during reinfarction in all but one patient. Depression of ST segments, when present during pain, involved the same leads as in the acute infarction. Blood pressure and double product tended to increase during pain in 23 patients. The magnitude of this change, however, often varied from crisis to crisis and there were no increases in these parameters in one or more attacks in 15 patients. Sublingual nitroglycerin, 1.0 mg, failed to relieve one or all anginal episodes in 17 of the 28 patients in whom it was given. In-hospital mortality rate was 10% (3/31) and always followed reinfarction. In-hospital reinfarction rate was 16% (5/31) and followed a larger number of anginal crises (7.2 +/- 1.3 vs 3.0 +/- 2.1, P less than 0.001) and a higher incidence of transient hypotensive episodes than in the rest of patients (3/5 vs 3/26). Three additional patients died after discharge. Of the remaining 25 patients and during a follow-up of 26 months (16-34) only one developed reinfarction. Early resting angina after a transmural infarction is almost invariably associated with ECG evidence of ischemia in the leads overlying the infarcted zone. The inconsistent changes in blood pressure and heart rate during pain render these hemodynamic changes an unlikely cause of this form of angina. While postinfarction angina did not carry a grave short- or long-term prognosis, patients with recurrent crises demonstrated as high a risk of reinfarction and death as those with spontaneous hypotension.