Relationship between initial white blood cell counts,stage of acute myocardial infarction evolution at presentation,and incidence of Thrombolysis In Myocardial Infarction-3 flow after streptokinase

Background The initial white cell counts in patients with acute myocardial infarction (AMI) may reflect the stage of AMI evolution, and may also be related to the efficacy of thrombolytic agents in recanalizing occluded epicardial arteries.Methods In 312 patients with a first AMI, we divided the initial white cell counts into quartiles and investigated their relationship with the time to treatment and the incidence of Thrombolysis In Myocardial Infarction (TIMI)-3 flow at 90 minutes after commencement of streptokinase.Results A longer time from symptom onset to treatment was independently associated with a higher neutrophil count and a lower non-neutrophil count. These times were 2.6, 2.9, and 3.8 hours, respectively, in the lowest, combined second and third (ie, middle), and highest neutrophil quartiles (P = .003), and 4.3, 3, and 1.9 hours, respectively, in the lowest, combined middle, and highest non-neutrophil quartiles (P < .0001). TIMI-3 flow was achieved in 44% of the lowest total white cell quartile, 41% of the combined middle quartile, and 60% of the highest quartile (P = .05). The corresponding figures were 47%, 49%, and 46% (P = .657) for the neutrophil quartiles, and 32%, 46%, and 68% for the non-neutrophil quartiles (P = .001). On multivariable analysis, the incidence of TIMI-3 flow was independently and positively associated with the initial non-neutrophil count. Patients with non-neutrophil counts in the highest quartile had a higher incidence of TIMI-3 flow than those in the lowest quartile (odds ratio 2.86, 95% CI 1.32-6.23, P = .008).Conclusions A longer time from symptom onset to thrombolysis for AMI is associated with a higher neutrophil count and a lower non-neutrophil count at presentation. A higher neutrophil count is not associated with worse epicardial blood flow at 90 minutes after streptokinase, and a higher non-neutrophil count predicts a greater likelihood of achieving TIMI-3 flow. (Am Heart J 2003;145:95-102.)     

Multicenter, dose-ranging study of efegatran sulfate versus heparin with thrombolysis for acute myocardial infarction: The Promotion of Reperfusion in Myocardial Infarction Evolution (PRIME) trial

Background Adjunctive therapies that increase the incidence of normal reperfusion after thrombolysis for acute myocardial infarction (MI) could enhance clinical outcomes. Direct thrombin inhibitors may offer an advantage over standard adjunctive therapies. Methods We randomized 336 patients with acute MI at 33 sites to receive 1 of 5 doses of efegatran sulfate, a direct thrombin inhibitor, or heparin for 72 to 96 hours, both with accelerated alteplase and aspirin. The primary end point was the incidence of thrombolytic failure (death, reinfarction, or TIMI grade 0-2 flow in the infarct artery from 90 minutes to discharge or 30 days, whichever occurred earlier). Results Significantly more patients randomized to efegatran had evidence of heart failure at admission. The lowest-dose efegatran arm was terminated at 15 patients because of unacceptably increased thrombolytic failure. The primary end point occurred in 53.0% of patients treated with heparin, in 53.8% of patients treated with efegatran overall (P = .90), and in 55.4% of patients given intermediate-dose efegatran (P = .74). These findings were unaffected after adjustment was done for baseline differences. Most bleeding was minor; major bleeding and the use of blood transfusions did not differ significantly by treatment. Three patients in the high-dose efegatran group had intracranial hemorrhage, as did 1 patient in the heparin group. Continuous ST monitoring showed a shorter time to recovery for the efegatran group (median 107 minutes) compared with the heparin group (154 minutes; P = .025). Conclusions Efegatran sulfate appeared to offer no clear advantage over heparin as an adjunct to thrombolysis for acute myocardial infarction, although there may be a modest improvement in time to reperfusion. (Am Heart J 2002;143:95-105.)     

Single lead ST-segment recovery: a simple, reliable measure of successful fibrinolysis after acute myocardial infarction

Background

Successful reperfusion after acute ST-elevation myocardial infarction improves prognosis. Among the different electrocardiographic markers of reperfusion, sum ST resolution is considered the hallmark of reperfusion, but is cumbersome to use.

Methods

To assess the usefulness of a single lead ST resolution at 90 minutes after fibrinolysis compared with the sum ST resolution in predicting Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, we used prospectively collected data from the Limitation of Myocardial Injury Following Thrombolysis in Acute Myocardial Infarction (LIMIT-AMI) study. All patients had electrocardiograms recorded at presentation and 90 minutes and a coronary angiogram 90 minutes after fibrinolysis.

Results

Infarction artery patency was assessed in 238 patients with 4 different ST resolution criteria: single lead ST resolution ≥50% and ≥70% and sum ST resolution ≥50% and ≥70%. The most sensitive criteria for TIMI grade 3 flow was single lead ST resolution ≥50% (sensitivity rate, 70%; specificity rate, 54%), whereas sum ST resolution ≥70% was most the specific criteria (sensitivity rate, 45%; specificity rate, 79%). The proportion of patients with TIMI grade 3 flow was similar in all 4 ST resolution groups (P = .84). Pre-discharge infarction size and ejection fraction were also similar. No single lead or sum lead measure of ST resolution was significantly associated with an increased risk of death, heart failure, or reinfarction.

Conclusion

We propose that single lead ST-resolution ≥50% as an optimal electrocardiographic indicator for successful reperfusion 90 minutes after fibrinolysis. This simple electrocardiographic measure should be combined with bedside clinical and hemodynamic assessment to optimize decision making after fibrinolysis.     

Early ST-segment recovery, infarct artery blood flow, and long-term outcome after acute myocardial infarction

Background Early resolution of ST-segment deviation (ST recovery) on the postthrombolytic electrocardiograms and restoration of “normal” blood flow in the infarct-related artery are associated with improved outcomes after myocardial infarction (MI). Methods and Results To evaluate the relationships between ST recovery, infarct-related artery flow, and late survival we studied 766 patients with electrocardiograms recorded at a median of 167 minutes after thrombolytic therapy. Angiography was performed at 3 weeks, and follow-up was done at a median of 6.3 years (interquartile range [IQR] 5.0-8.4). At 10 years, the survival rates were 55% (95% CI 43-70) in patients with <30% ST recovery in the single lead with maximum ST elevation, 71% (95% CI 64-79) in those with 30% to 70% ST recovery, and 74% (95% CI 68-82) in those with >70% ST recovery (P = .0005), whereas ST recovery measured as the sum of voltage changes of either ST deviation (elevation or depression) or ST elevation was not associated with 10-year survival (log-rank test, P = .06 and P = .34, respectively). In patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow, ST recovery of >70% (vs <30% and 30% to 70%) in the lead with maximum ST elevation was associated with increased late survival (P = .04). On multivariate analysis, the predictors, at admission, of 5-year survival were age (P < .001), ST recovery (measured as a continuous variable, P = .001), diabetes (P = .003) and female gender (P = .02). When the ejection fraction (P = .003) and TIMI flow grade (P = .02) at 3 weeks were included in the analysis, the P value for ST recovery was .08. Conclusions ST recovery measured in the single lead with maximum ST elevation was a predictor of late survival, even in patients with TIMI grade 3 flow but ST recovery measured as the sum of voltage changes in all leads with ST deviation was not. This simple electrocardiographic parameter can identify patients with a reduced chance of survival who might benefit from additional therapies. (Am Heart J 2002;143:265-71.)     

Cardiac troponin I: a potential marker of exercise intolerance in patients with moderate heart failure

Background In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. Methods Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% ± 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). Results Patients with moderate heart failure showed an increase of cTnI from 37 ± 49 pg/mL to 73 ± 59 pg/mL (P < .001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P < .05 for each). Conclusion Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated. (Am Heart J 2002;144:351-8)     

Biochemical and clinical predictors of long-term outcome in patients with nonspecific chest pain and nondiagnostic electrocardiograms

Background There are few data assessing the relative value of clinical factors and sensitive cardiac markers in determining the long-term prognosis of patients with chest pain. Likewise, little information exists about the long-term outcome of patients with chest pain who have negative markers of myocardial cell necrosis. This study addresses these issues in a cohort of patients with nonspecific chest pain and nondiagnostic electrocardiograms (ECGs).Methods Eligible subjects (n = 501) had experienced >15 minutes chest pain at rest during the previous 24 hours, but were found to be at low-risk for acute myocardial infarction (AMI) by means of a well-validated clinical algorithm. Cardiac troponin I, creatine kinase MB_mass, myoglobin, and myosin light chain-1 were collected at presentation and 3, 6, and 12 hours later. Patients were observed for a median of 31 months. The composite end point was death or AMI subsequent to the index admission.Results Cardiac troponin I was the best single biochemical predictor of outcome (risk ratio 2.34, 95% CI 1.31-4.17, P = .004), but was of less independent prognostic value than age and an abnormal presenting ECG. It was also inferior to a combination strategy, using all 4 markers tested (risk ratio 2.37, 95% CI 1.44-3.91, P < .001). Fifty of 428 patients (12%) with a cardiac troponin I level ≤0.2 ng/mL and 25 of 287 patients (9%) without elevation of any marker tested sustained an adverse event during follow-up.Conclusions Cardiac troponin I is the most useful single biochemical predictor of long-term outcome, but the best determinants are age, an abnormal presenting ECG, and an “any marker positive” strategy. Patients without elevated cardiac markers have an adverse event rate of approximately 10% in the subsequent 31 months. (Am Heart J 2003;145:88-94.)     

Troponin I elevation and cardiac events after percutaneous coronary intervention

Background Serum troponins are sensitive markers of myonecrosis and ischemia and are now widely used in clinical practice. Although percutaneous coronary intervention (PCI)-related creatine kinase-myocardial band isoenzyme (CK-MB) elevation has been associated with future cardiac events, the significance of troponin elevation in this setting is unknown. We sought to determine whether serum troponin I (Tn-I) elevation after PCI is associated with future cardiac events. Methods and Results Consecutive patients undergoing elective PCI underwent systematic postprocedure measurement of Tn-I and CK-MB levels. Serum levels were correlated with demographic, angiographic, and procedural characteristics and the development of major adverse cardiac events (MACE; defined as death, MI, or need for PCI or coronary bypass graft surgery) at 30 days, 6 months, and 1 year. In 286 consecutive procedures, postintervention myonecrosis-specific Tn-I was elevated in 13.6% of patients, and CK-MB was elevated in 12.9% of patients. Multivariable predictors of Tn-I elevation were procedural side branch occlusion and thrombus formation. Peak Tn-I and CK-MB values were well correlated (r = 0.81, P < .0001). Three-fold elevation of Tn-I after successful PCI was independently predictive of MACE (P = .01). Conclusions Tn-I elevation after elective PCI is relatively common and is associated with procedural complications such as incidental side branch occlusion and thrombus formation. In addition, this study demonstrates that a 3-fold elevation of Tn-I after successful elective PCI is predictive of future cardiac events, especially the need for early repeat revascularization. (Am Heart J 2003;145:522-8.)     

Potential contributing factors to noncompliance with dietary sodium restriction in patients with heart failure

Background Although sodium restriction is considered essential in the management of patients with chronic heart failure (CHF), there are no data available regarding patients awareness of and ability to comply with the sodium restriction guideline. Methods Between May 1999 and August 2000, 50 patients referred to the Parkland Memorial Hospital CHF clinic were assessed by a registered dietitian for (1) awareness of the sodium restriction guideline, (2) ability to read the sodium content from a Nutrition Facts label, and (3) ability to sort 12 food containers, all bearing a Nutrition Facts label, into high- and low-sodium groups. A global measure of dietary sodium knowledge was calculated (“sodium knowledge score,” range 0-10). These tests were repeated after the patient completed one or more educational sessions (mean 2.8 ± 1.5) with the dietitian. Results The proportion of patients aware of the sodium restriction guideline was 14% at baseline and 42% at follow-up (P < .01). The proportion of patients able to read the sodium content from the Nutrition Facts label was 58% at baseline and 92% at follow-up (P < .01). The sodium knowledge score was 3.8 ± 3.4 at baseline and 5.8 ± 3.2 at follow-up (P < .01). The proportion of subjects who achieved a perfect sodium knowledge score of 10 was 8% at baseline and 26% at follow-up (P < .05). The number of food containers sorted accurately was 10.6 ± 1.5 at baseline and 11.3 ± 1.1 at follow-up, P = .09. Conclusions On referral to a specialty CHF clinic, many patients had severe deficiencies in their knowledge base regarding dietary sodium intake that would preclude compliance with the sodium restriction guideline. Directed education focusing on sodium intake corrected many of these deficiencies. (Am Heart J 2002;143:29-33.)     

Slow upsloping ST-segment depression during exercise: does it really signify a positive stress test?

Background Slow upsloping ST-segment depression during stress is thought to represent an ischemic response to exercise treadmill testing (ETT). Aim We used modern single-photon emission computed tomography (SPECT) imaging protocols to determine the incidence of ischemia in patients with slow upsloping ST depression during exercise and whether this response signifies more or less severe coronary artery disease (CAD) and risk in comparison with rapid upsloping ST depression and particularly with horizontal or downsloping ST depression. Methods We enrolled 33 patients (group 1) with rapid upsloping ST depression (>1 mm extending <0.08 seconds beyond J point), 32 patients (group 2) with slow upsloping depression (>1.5 mm extending >0.08 seconds beyond J point), and 35 patients (group 3) with horizontal or downsloping depression (>1 mm at 0.08 seconds beyond J point). Summed stress score (SSS), summed difference score (SDS), stress extent percent (SE%) and reversible extent percent (RE%) of perfusion abnormalities, lung-heart ratio (LHR), and transient ischemic dilatation (TID) were calculated. Results The mean SSS, SDS, SE%, RE%, and LHR were similar between groups 1 and 2 but significantly higher in group 3. Incidence of ischemia was similar in groups 1 and 2 (39% and 25%) but significantly higher in group 3 (77%, P < .001). Evidence of TID was seen in none of the patients in groups 1, in 3% of patients in group 2, and in 23% of patients in group 3. Conclusions Slow upsloping ST depression does not signify more severe ischemia, more extensive CAD, or more stress-induced backward left ventricular failure. Thus, it would be reasonable to consider patients with slow upsloping ST depression during exercise as having a very low likelihood of CAD, similar to patients with rapid upsloping ST depression. (Am Heart J 2002;143:482-7.)     

Do transmyocardial and percutaneous laser revascularization induce silent ischemia? An assessment by exercise testing

Background Transmyocardial and percutaneous laser revascularization (TMR, PTMR) may reduce angina and increase exercise tolerance in otherwise untreatable angina patients, although the mechanism is unknown and the placebo effect may be significant. One other proposed mechanism is cardiac denervation leading to silent ischemia. Methods Electrocardiograms obtained during symptom-limited exercise (ETT, modified Bruce protocol) at baseline and 12 months were analyzed (blinded core laboratory) from 182 patients randomized to TMR (n = 92) or medical therapy alone (MED_TMR, n = 90) and 219 patients randomized to PTMR (n = 109) or medical therapy alone (MED_PTMR, n = 110). Results Exercise duration increased 1 year after TMR or PTMR relative to medically treated patients (6.8 ± 3.4 min vs 8.6 ± 3.5 min for TMR; 7.3 ± 3.1 min vs 9.1 ± 3.6 min for PTMR, P < .05). At baseline, 20% of TMR and MED_TMR subjects had ST depression >1.0 mm, >80% had angina during exercise, but only 3% had ST changes without chest pain (silent ischemia). This did not change after TMR. In the PTMR group, more subjects exercised to >1.0 mm ST depression (from 17% to 34%, P < .05), with no change in MED_PTMR, but the proportion with silent ischemia did not change in either group. Conclusion Exercise tolerance improved after TMR and after PTMR. Relative to PTMR, TMR more effectively suppressed pain during exercise and ischemic ST depression. However, neither TMR nor PTMR induced significant silent ischemia. These results suggest that denervation may not be a significant factor contributing to angina relief after these procedures. The contribution of the placebo effect was not determined by these results. (Am Heart J 2002;143:1052-7.)     

Effectiveness of a novel serotonin blocker,sarpogrelate, for patients with angina pectoris

Background We have recently demonstrated that a single oral administration of sarpogrelate, a 5-HT_2A receptor antagonist, may improve exercise capacity in anginal patients with well-developed collaterals. The aim of the current study was to investigate the effectiveness of 2-week treatment with sarpogrelate on anginal symptoms and exercise capacity in anginal patients. Methods A treadmill exercise test was repeated after a 2-week period with or without sarpogrelate (100 mg 3 times a day) in 20 patients with angiographically proven stable angina. Anginal symptoms and daily physical activity by the specific activity scale (SAS) were also evaluated. Results Treatment with sarpogrelate significantly increased the SAS score and prolonged exercise time to the onset of 0.1-mV ST depression. When data were analyzed in a subgroup of patients (n = 8) with well-developed collaterals, the treatment with sarpogrelate decreased the number of anginal attacks (control vs sarpogrelate, 3.0 ± 2.8 vs 0.9 ± 1.1/2 weeks, P < .05), increased the SAS score (5.2 ± 1.6 vs 6.2 ± 1.3 METS, P < .05), and increased the time to the onset of 0.1-mV ST depression (235 ± 84 vs 295 ± 127 seconds, P < .05). In addition, the double product at the onset of 0.1-mV ST depression increased by 15% (P < .05) after sarpogrelate. In contrast, all parameters were not significantly changed after sarpogrelate treatment in patients (n = 12) without well-developed collaterals. Conclusions These findings indicate the therapeutic effectiveness of sarpogrelate for anginal patients, especially for patients with well-developed collaterals. (Am Heart J 2002;144:e1.)     

Usefulness of an echo-contrast agent for assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery with transthoracic doppler scan echocardiography

Background This study assessed the feasibility of transthoracic Doppler scan echocardiography (TTDE) combined with echo-contrast agent in measuring coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending artery. Methods In 68 consecutive patients who underwent cardiac angiography, TTDE was recorded before and after induction of a hyperemic condition with intravenous administration of adenosine triphosphate (0.14 mg/kg/min). After CFV values returned to baseline, the same measurements were repeated while an echo-contrast agent was continuously infused. CFVR was assessed as the ratio of hyperemic to basal CFV. The pulsed wave Doppler scan quality was graded from 1 to 3 (TTDE score: 1, no signal detection; 2, poor definition of outline; 3, optimal outline definition). Results Before enhancement, CFVR could not be measured in 20 patients. Prevalence of delayed stenosis (Thrombolysis In Myocardial Infarction [TIMI] II grade flow) in these patients (30%) was significantly greater than in those whose CFVRs could be measured without enhancement (2%; P <.01). TTDE scores both at baseline and after hyperemia were significantly improved with contrast enhancement (before, 2.8 ± 0.6; after, 3.0 ± 0.3; P <.01; before, 2.6 ± 0.7; after, 3.0 ± 0.3; P <.01; respectively). Overall contrast enhancement increased the rate of successful CFVR measurement from 70% to 97% (P <.01). Sensitivity and specificity of significant left anterior descending artery stenosis detection with CFVR of <2.0 were 94.4% and 87.8%, respectively. Conclusion These data suggest that administration of echo-contrast agent improves pulse wave Doppler scan quality and thus the feasibility of measuring CFVR. (Am Heart J 2002;143:668-75.)     

Assessment of coronary reperfusion in patients with myocardial infarction using fatty acid binding protein concentrations in plasma

OBJECTIVE—To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes.
DESIGN—Retrospective substudy of the GUSTO trial.
SETTING—10 hospitals in four European countries.
PATIENTS—115 patients were treated with thrombolytic agents within six hours after the onset of acute myocardial infarction. Patency of the infarct related artery was determined by angiography within 120 minutes of the start of thrombolysis.
MAIN OUTCOME MEASURES—First hour rate of increase in plasma FABP concentration after thrombolytic treatment, compared with increase in plasma myoglobin concentration and creatine kinase isoenzyme MB (CK-MB) activity. Infarct size was estimated from the cumulative release of the enzyme α hydroxybutyrate dehydrogenase in plasma during 72 hours, or from the sum of ST segment elevations on admission. Logistic regression analyses were performed to construct predictive models for patency.
RESULTS—Complete reperfusion (TIMI 3) occurred in 50 patients, partial reperfusion (TIMI 2) in 36, and no reperfusion (TIMI 0+1) in 29. Receiver operating characteristic (ROC) curve analyses showed that the best performance of FABP was obtained when TIMI scores 2 and 3 were grouped and compared with TIMI score 0+1. The performance of FABP as a reperfusion marker was improved by combining it with α hydroxybutyrate dehydrogenase infarct size, but not with an early surrogate of infarct size (ST segment elevation on admission). In combination with infarct size FABP performed as well as myoglobin (areas under the ROC curve 0.868 and 0.857, respectively) and better than CK-MB (area = 0.796). At optimum cut off levels, positive predictive values were 97% for FABP, 95% for myoglobin, and 89% for CK-MB (without infarct size, 87%, 88%, and 87%, respectively), and negative predictive values were 55%, 52%, and 50%, respectively (without infarct size, 44%, 42%, and 34%).
CONCLUSIONS—FABP and myoglobin perform equally well as reperfusion markers, and successful reperfusion can be assessed, with positive predictive values of 87% and 88%, or even 97% and 95% when infarct size is also taken into account. However, identification of non-reperfused patients remains a problem, as negative predictive values will generally remain below 70%.


Keywords: myocardial reperfusion; cardiac marker proteins     

Prognostic significance of creatine kinase-MB elevation after percutaneous coronary intervention in patients with chronic renal dysfunction

Background Multiple studies have demonstrated a relationship between creatine kinase-MB (CK-MB) elevation after percutaneous coronary intervention (PCI) and increased late mortality within the general population. Because CK-MB is frequently elevated in renal disease even in the absence of myocardial injury, the clinical significance of CK-MB elevation after PCI in patients with renal insufficiency has been questioned. Methods We sought to examine the association between elevated CK-MB after PCI and late mortality in 190 consecutive patients with chronic renal insufficiency (serum creatinine ≥2.0 mg/dL) undergoing PCI at the Cleveland Clinic between January 1997 and March 2000. Of the total group, 20 patients undergoing PCI for acute myocardial infarction, cardiogenic shock, or both were excluded. Follow-up was 99.4% complete at a mean duration of 24.8 ± 11.2 months (range 5-43 months). Results CK-MB elevation above the upper limit of normal after intervention was detected in 33 patients (19.4%). Baseline characteristics were not significantly different between the CK-MB elevation group and the normal CK-MB group. Late mortality, however, was significantly higher among patients with postprocedural CK-MB elevation (36.4% vs 17.5%, P = .017). Cox proportional hazard model revealed CK-MB elevation as an independent predictor of late mortality (hazard ratio 2.44, 95% CI 1.14-5.24, P = .02), in addition to New York Heart Association class (hazard ratio 1.35, 95% CI 1.05-1.73, P = .02). Conclusions This analysis of patients with chronic renal insufficiency undergoing PCI suggests that postprocedural CK-MB elevation is an independent predictor of late mortality even in the presence of renal dysfunction. (Am Heart J 2002;143:1040-5.)     

Enzymatische Marker der Reperfusion bei akutem Myokardinfarkt

Despite advances in therapy acute myocardial infarction is associated with a mortality rate of up to 30%. Early and complete reperfusion of the infarct related artery (defined as TIMI flow 3 at 90 minutes following therapy) as obtained with thrombolytic therapy in 50 to 80% of patients improves survival and enhances ventricular function. Failure to achieve recanalization should prompt further intervention (second attempt of thrombolysis or rescue-PTCA). Various cardiac markers known from diagnosing acute myocardial infarction or risk stratification in unstable angina pectoris have been assessed in their ability to predict successful reperfusion/failure of therapy. Following reperfusion creatinkinase (CK) and its isoform CK-MB, troponin and myoglobin show an early and rapid rise to a high maximum value with rapid normalization. For creatinkinase time to peak values of less than 9 hours or rates of increase of > 50 U/h (> or = 10 U/h for CK-MB activity) within the first 2.5 hours following thrombolysis have been suggested as useful indicators of successful reperfusion. The same applies for a troponin (T)slope > 0.5 ng/ml/h within the first hour (Table 5). The major limitation in applying either creatinkinase, troponin or even lactatdehydrogenase (LDH) is their comparatively late release (4 to 6 hours) following myocardial infarction. In that respect myoglobin (though not specific for cardiac injury) seems ideal for guidance of intervention after failed thrombolysis. The I.S.A.M. study included 1,741 patients with acute myocardial infarction of less than 6 hours duration being given either streptokinase or placebo. Serial blood samples for measurement of cardiac enzymes were drawn within the first 50 hours. In the streptokinase group the time to peak concentration of CK-MB activity was significantly lower (mean 10.9 hours vs 16.1 hours following initiation of treatment) as was the area under the CK-MB curve indicating reduction of infarct size (Table 2). A substudy investigating the myoglobin release in 120 patients having received streptokinase or placebo demonstrated higher maximum values in the streptokinase group (mean 3008 vs 2097 ng/ml), a shorter time to peak interval following treatment (3.4 vs 6.5 hours) and a reduction in infarct size as suggested by a smaller area under the myoglobin curve (17,377 vs 23,240 ng/ml x h) (Table 3). For LDH/alpha-HBDH the reduction in time to peak intervals was less impressive (Table 4). In angiographic studies with TIMI flow 3 at 90 minutes in the infarct related artery in 22 patients (Figure 5) the maximum myoglobin value was reached in less than 4.2 hours (mean value plus SEM) following treatment (9.5 hours for CK-MB activity). Therefore, myoglobin seems to be the preferred marker in reperfusion assessment.     

Early Noninvasive Identification of Failed Reperfusion After Intravenous Thrombolytic Therapy in Acute Myocardial Infarction

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.     

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.     

Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach

The disposition index, the product of the insulin sensitivity index (S_I) and the acute insulin response to glucose, is linked in African Americans to chromosome 11q. This link was determined with S_I calculated with the nonlinear regression approach to the minimal model and data from the reduced-sample insulin-modified frequently-sampled intravenous glucose tolerance test (Reduced-Sample-IM-FSIGT). However, the application of the nonlinear regression approach to calculate S_I using data from the Reduced-Sample-IM-FSIGT has been challenged as being not only inaccurate but also having a high failure rate in insulin-resistant subjects. Our goal was to determine the accuracy and failure rate of the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the minimal model. With S_I from the Full-Sample-IM-FSIGT considered the standard and using the nonlinear regression approach to the minimal model, we compared the agreement between S_I from the Full- and Reduced-Sample-IM-FSIGT protocols. One hundred African Americans (body mass index, 31.3 ± 7.6 kg/m² [mean ± SD]; range, 19.0-56.9 kg/m²) had FSIGTs. Glucose (0.3 g/kg) was given at baseline. Insulin was infused from 20 to 25 minutes (total insulin dose, 0.02 U/kg). For the Full-Sample-IM-FSIGT, S_I was calculated based on the glucose and insulin samples taken at −1, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 minutes. For the Reduced-Sample-FSIGT, S_I was calculated based on the time points that appear in bold. Agreement was determined by Spearman correlation, concordance, and the Bland-Altman method. In addition, for both protocols, the population was divided into tertiles of S_I. Insulin resistance was defined by the lowest tertile of S_I from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was compared by rank order and κ statistic. We found that the rate of failure of resolution of S_I by the Reduced-Sample-IM-FSIGT was 3% (3/100). For the remaining 97 subjects, S_I for the Full- and Reduced-Sample-IM-FSIGTs were as follows: 3.76 ± 2.41 L mU⁻¹ min⁻¹ (range, 0.58-14.50) and 4.29 ± 2.89 L mU⁻¹ min⁻¹ (range, 0.52-14.42); relative error, 21% ± 18%; Spearman r = 0.97; and concordance, 0.94 (both P < .001). After log transformation, the Bland-Altman limits of agreement were −0.29 and 0.53. The exact agreement for distribution of the population in the insulin-resistant tertile vs the insulin-sensitive tertiles was 92%, κ of 0.82 ± 0.06. Using the nonlinear regression approach and data from the Reduced-Sample-IM-FSIGT in subjects with a wide range of insulin sensitivity, failure to resolve S_I occurred in only 3% of subjects. The agreement and maintenance of rank order of S_I between protocols support the use of the nonlinear regression approach to the minimal model and the Reduced-Sample-IM-FSIGT in clinical studies.     

Predicting outcome after thrombolysis in acute myocardial infarction according to ST-segment resolution at 90 minutes: a substudy of the GUSTO-III trial. Global Use of Strategies To Open occluded coronary arteries

Background Resolution of ST-segment elevation after thrombolysis for acute myocardial infarction has been shown to have prognostic significance 3 hours (180 minutes) after the initiation of therapy. Whether prognostically useful information can be achieved as early as 90 minutes after thrombolysis is unknown. Methods An electrocardiographic substudy of 2352 patients from the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial was undertaken to compare outcomes according to ST-segment resolution at 90 minutes versus 180 minutes after administration of thrombolytic therapy. Results Of 2352 patients in the substudy, 2241 had a baseline and 90-minute electrocardiogram, and 2218 had a baseline and 180-minute ECG. Complete ST-segment resolution occurred in 44.2% of patients at 90 minutes and 56.5% of patients at 180 minutes. ST-segment resolution at both 90 and 180 minutes was associated with lower 30-day and 1-year mortality. Multivariate analysis revealed ST-segment resolution at 90 minutes to be an equally strong predictor of 30-day mortality as resolution at 180 minutes. Patients who were at particularly high risk for mortality were those aged >70 years, those who presented with Killip class >1, and those with anterior infarctions. Conclusions The presence of ST-segment resolution on standard 12-lead electrocardiographic monitoring 90 minutes after thrombolysis is a useful independent predictor of mortality at 30 days and 1 year. The potential for obtaining prognostic results as early as 90 minutes after thrombolysis sets a new precedent for optimum electrocardiographic monitoring times in these patients. (Am Heart J 2002;144:81-8.)     

Incidence of high-risk acute coronary syndromes and eligibility for glycoprotein IIb/IIIa inhibitors among patients admitted for possible myocardial ischemia

Objective Recent studies have demonstrated that glycoprotein (GP) IIb/IIIa inhibitors can reduce cardiac events in patients with acute coronary syndromes (ACS). However, little is known about how many patients are actually eligible for treatment. Our purpose was to determine how many patients admitted for possible myocardial infarction (MI) meet GP IIb/IIIa inhibitor treatment criteria. Methods Patients admitted for possible MI who underwent a standard protocol that included serial sampling of total creatine kinase (CK), CK-MB, and troponin I (TnI) were retrospectively assigned to different treatment algorithms on the basis of criteria from GP IIb/IIIa inhibitor trials: an electrocardiogram (ECG) consistent with acute MI or ischemia, and myocardial marker elevations. Elevated CK-MB was considered diagnostic of MI. High-risk ACS was defined as ischemic ECG changes or troponin elevations without CK-MB elevations. Results A total of 2179 patients were admitted for MI exclusion. MI was identified in 304 patients (14.0%) (123 ST-elevation, 49 ischemic ECG, 132 nonischemic ECG). Another 273 patients (12.5%) without CK-MB criteria for MI met high-risk ACS criteria (172 ischemic ECG, 120 TnI elevations). Ischemic ECGs or elevated myocardial markers identified 454 (21%) patients as eligible for treatment. Inclusion of patients with ST elevation increased eligibility to 26.5%. Of the 454 non-ST-elevation ACS patients, 340 (74%) were identified early by the ECG or the initial markers. Conclusions A large proportion of patients admitted for possible MI met criteria for treatment with GP IIb/IIIa inhibitors. The non-ST-elevation ACS group was >3 times larger than the ST-elevation MI group. These findings have important implications for treatment of patients with ACS. (Am Heart J 2002;143:70-5.)