Prognostic value of isolated troponin elevation across the spectrum of chest pain syndromes

The risk of death or recurrent myocardial infarction (MI) in patients with chest pain and baseline isolated troponin elevation is unclear. To determine the early and short-term risk of death or MI associated with isolated troponin elevation across a spectrum of chest pain syndromes, we used baseline creatine kinase (CK)-MB and troponin data from the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) B troponin substudy, the Global Utilization of Strategies To Open Occluded Coronary Arteries (GUSTO) IIa troponin substudy, and the Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) study. Patients were grouped into 1 of 4 categories based on marker status (troponin-positive/CK-MB-positive, troponin-positive/CK-MB-negative, troponin-negative/CK-MB-positive, or troponin-negative/CK-MB-negative). The adjusted odds of death or MI occurring at 24 hours and 30 days was assessed by baseline marker status using multivariable logistic regression, with the group negative for both markers used as the reference. Patients who were positive for both markers had the highest odds of the 24-hour and 30-day end point. The adjusted odds of the 30-day end point for patients with isolated troponin elevation were 1.3 (95% confidence interval 0.7 to 2.3) and 4.8 (95% confidence interval 1.4 to 16.0) for high- and low-risk patients, respectively. The risk for 24-hour and 30-day death or MI with isolated positive CK-MB results was lower than with isolated positive troponin results, and it was not significantly greater than if the 2 markers were negative. For patients with high- and low-risk chest pain, baseline troponin elevation without CK-MB elevation was associated with increased risk for early and short-term adverse outcomes. This suggests that these patients should be admitted to the hospital and monitored in either an intensive care or step-down unit.     

Significance of elevated cardiac troponin after percutaneous coronary interventions

Assays for cardiac troponin have become a standard for the diagnosis of myocardial damage. Due to their high sensitivity, minor myocardial injury can be frequently detected following percutaneous coronary interventions (PCI). Minor elevations in cardiac enzymes after apparently successful PCI are rather common and even modest increases in creatine kinase myocardial band (CK-MB) elevation identify a population with worse long-term prognosis compared to patients with no enzyme elevation. The significance of troponin elevation in acute coronary syndromes and its prognostic implications on short- and long-term clinical outcomes were previously demonstrated in several clinical studies. Conversely, data regarding troponin elevation after an apparently successful PCI is limited and their relevance in terms of predicting clinical outcomes remains unclear. Given the higher sensitivity of troponin essays, the incidence of troponin elevation after PCI is higher than that of CK-MB. In this review we discuss the significance and implications of post-procedural troponin elevation.     

Prognostic implications of elevated whole blood choline levels in acute coronary syndromes

Troponins I and T represent the current biomarker standard for diagnosis of myocardial infarction. Even small increases of cardiac troponins have prognostic implications, but not all patients at risk are correctly classified, particularly at admission. We identified elevated whole-blood choline as a promising marker and performed a prospective study of 327 patients with a suspected acute coronary syndrome that focused on the analysis of troponin-negative patients. Diagnostic classification of patients and the definition of troponin cutoffs were performed according to the new European Society of Cardiology/American College of Cardiology criteria. Blood was sampled serially and choline was measured using high-performance liquid chromatography mass spectrometry in whole blood. Patients were followed for 30 days. In patients with negative troponin I test results at admission (n = 250), choline was a predictor of cardiac death and nonfatal cardiac arrest (hazard ratio 6.0, p = 0.003), life-threatening arrhythmias (hazard ratio 3.75, p = 0.004), heart failure (hazard ratio 2.87, p = 0.002), and coronary angioplasty (hazard ratio 2.57, p = 0.001). In multivariate analysis of troponin-negative patients, choline was the strongest predictor of cardiac death or arrest (odds ratio 6.05, p = 0.01). Choline was not a marker for myocardial necrosis but indicated high-risk unstable angina in patients without acute myocardial infarction (sensitivity 86.4%, specificity 86.2%). Thus, an increased concentration of choline at hospital admission is a predictor of adverse cardiac events in patients with suspected acute coronary syndromes. Whole blood choline may be useful for early risk stratification of these patients, particularly if troponin results are negative on admission.     

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 elevated troponin in patients with suspected acute coronary syndrome but no critical epicardial coronary disease: a TACTICS-TIMI-18 substudy

OBJECTIVES: The purpose of this study is to determine whether there is clinical significance to elevated troponin I in patients with suspected acute coronary syndromes (ACS) with non-critical angiographic coronary stenosis. BACKGROUND: Elevation of troponin in patients admitted with ACS symptoms with non-critical coronary artery disease (CAD) may result from coronary atherothrombosis not evident using standard angiography or from other ischemic and non-ischemic causes that may confer increased risk for future events. METHODS: Patients with ACS enrolled in the Treat Angina With Aggrastat and Determine Cost of Therapy With Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI)-18 were included. Of 2,220 patients enrolled in the trial, 895 were eligible. Patients were divided into four groups according to troponin status on admission and presence of significant angiographic stenosis. Baseline brain natriuretic peptide (BNP) and C-reactive protein (CRP) were obtained on all patients. RESULTS: The median troponin I levels were 0.71 ng/ml in patients with CAD compared with 0.02 ng/ml in patients without CAD (p <0.0001). Troponin-positive patients with or without angiographic CAD had higher CRP and BNP levels compared with troponin-negative patients (p <0.01 for both). The rates of death or reinfarction at six months were 0% in troponin-negative patients with no CAD, 3.1% in troponin-positive patients with no CAD, 5.8% in troponin-negative patients with CAD, and 8.6% in troponin-positive patients with CAD (p=0.012). CONCLUSIONS: Elevated troponin in ACS is associated with a higher risk for death or reinfarction, even among patients who do not have significant angiographic CAD. The mechanisms conferring this adverse prognosis merit further study.     

Prognostic value of troponin I after elective percutaneous coronary interventions

BACKGROUND: A mild and asymptomatic increase in the troponin level following elective percutaneous coronary interventions (PCI) has been widely reported, however, the prognostic role of this finding has not yet been well established.Aim. To assess prognostic value of troponin I level increase following elective PCI. METHODS: The study group consisted of 90 consecutive patients who underwent elective PCI in our institution. Troponin I level (normal values <0.1 ug/L) was assessed at baseline and 12 as well as 24 hours after the procedure. In addition, CK-MB level was measured 12 and 24 hours following PCI. Left ventricular (LV) systolic performance was assessed echocardiographically at baseline and after 12 months. The incidence of major adverse coronary events (MACE) during one-year follow-up was also evaluated. RESULTS: An increase in troponin I level >0.1 ug/L was observed in 66 (73%) patients; of whom, 8 patients had a marked (>1.0 ug/L) increase of troponin I, with a concomitant significant elevation of the CK-MB level. Patients with a positive troponin test developed systolic LV abnormalities more often than patients with a normal troponin I level following PCI (p<0.001). There were 10 MACE in the troponin-positive group and 2 in the troponin-negative patients (NS). Seven MACE occurred in patients with marked increase in troponin I level (>1.0 ug/L) which was significantly more often than in the troponin-negative patients (p<0.001). CONCLUSIONS: A mild increase in troponin I level following elective PCI was frequent and did not predict poor outcome, however, was associated with the development of LV systolic impairment. A marked (>1.0 ug/L) increase in troponin I level identified patients at risk of MACE. An increase in troponin I level was similar following various types of PCI.     

Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention

Objectives. We examined the relations of elevated creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide.Background. Elevation of cardiac enzymes often occurs after PCI, but its clinical implications are uncertain.Methods. Patients undergoing elective, scheduled PCI for any indication were analyzed. Parallel analyses investigated CK (n = 3,535) and CK-MB (n = 2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days and 6 months were stratified by postprocedure CK and CK-MB (multiple of the site’s upper normal limit).Results. Overall, 1,779 patients (76%) had no CK-MB elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in 323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK-MB was associated with an increased risk of death, reinfarction, or emergency revascularization at 30 days, and of death, reinfarction, or surgical revascularization at 6 months. Elevated total CK to above three times normal was less frequent, but its prognostic significance paralleled that seen for CK-MB. The degree of risk correlated with the rise in CK or CK-MB, even for patients with successful procedures not complicated by abrupt closure.Conclusions. Elevations in cardiac enzymes, including small increases (between one and three times normal) often not considered an infarction, are associated with an increased risk for short-term adverse clinical outcomes after successful or unsuccessful PCI.     

Frequency and clinical implications of discordant creatine kinase-MB and troponin measurements in acute coronary syndromes.

OBJECTIVES: We sought to evaluate the association between discordant cardiac marker results and in-hospital mortality and treatment patterns in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND: Creatine kinase-MB (CK-MB) and cardiac troponins (cTn) are often measured concurrently in patients with NSTE ACS. The significance of discordant CK-MB and cTn results is unknown. METHODS: Among 29,357 ACS patients in the CRUSADE initiative who had both CK-MB and cTn measured during the first 36 hours, we examined relationships of four marker combinations (CK-MB-/cTn-, CK-MB+/cTn-, CK-MB-/cTn+, and CK-MB+/cTn+) with mortality and American College of Cardiology/American Heart Association guidelines-recommended acute care. RESULTS: The CK-MB and cTn results were discordant in 28% of patients (CK-MB+/cTn-, 10%; CK-MB-/cTn+, 18%). In-hospital mortality was 2.7% among CK-MB-/cTn- patients; 3.0%, CK-MB+/cTn-; 4.5%, CK-MB-/cTn+; and 5.9%, CK-MB+/cTn+. After adjustment for other presenting risk factors, patients with CK-MB+/cTn- had a mortality odds ratio (OR) of 1.02 (95% confidence interval [CI] 0.75 to 1.38), those with CK-MB-/cTn+ had an OR of 1.15 (95% CI 0.86 to 1.54), and those with CK-MB+/cTn+ had an OR of 1.53 (95% CI 1.18 to 1.98). Despite variable risk, patients with CK-MB+/cTn- and CK-MB-/cTn+ were treated similarly with early antithrombotic agents and catheter-based interventions. CONCLUSIONS: Among patients with NSTE ACS, an elevated troponin level identifies patients at increased acute risk regardless of CK-MB status, but an isolated CK-MB+ status has limited prognostic value. Recognition of these risk differences may contribute to more appropriate early use of antithrombotic therapy and invasive management for all cTn+ patients.     

Creatine kinase-MB enzyme elevation and long-term clinical events after successful coronary stenting in lesions with ruptured plaque

Patients with acute coronary syndrome are at increased risk of acute and long-term events after stent implantation. We compared the impact of intravascular ultrasound detected plaque rupture on creatine kinase-MB (CK-MB) isoenzyme release and clinical outcomes by comparing 62 patients with ruptured plaques with 62 matched control patients who underwent stent implantation. Two thirds of the patients in each group presented with an acute coronary syndrome. There were no differences in procedural complications between groups, although patients with ruptured plaque had higher CK-MB elevation rates than those without ruptured plaque (1 to 3 times the upper limit of normal CK-MB, 35% vs 10%, p <0.001; >3 times the upper limit, 15% vs 2%, p = 0.02). Independent predictors of CK-MB elevation were presence of ruptured plaque (p = 0.03) and unstable angina (p = 0.04). Patients with ruptured plaque had higher composite rates of late events (target lesion revascularizations/myocardial infarctions/cardiac deaths) than controls (25% vs 9%, p = 0.03). These results were similar when only patients with acute coronary syndrome were studied. Plaque rupture morphology is associated with higher periprocedural CK-MB release and worse 1-year clinical outcome in patients treated with coronary stenting.     

Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST-elevation acute coronary syndromes

OBJECTIVE: We sought to determine whether elevation of plasma creatine kinase muscle-brain fraction (CK-MB) would be useful to triage patients with acute coronary syndromes (ACS) to early angiography/revascularization. BACKGROUND: It is unknown whether the measurement of CK-MB is effective for triage to an aggressive management strategy. METHOD: Patients in the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy (TACTICS-TIMI) 18 study received aspirin, heparin, and tirofiban for treatment of ACS, were randomized to an invasive or a conservative strategy (angiography/revascularization between 4 and 48 h), and were followed up for a composite end point of death, myocardial infarction, or rehospitalization for ACS.Of 2,220 patients, CK-MB was elevated in 826 (37%). Of the patients with negative CK-MB, troponin T was elevated in 361 (31.2%). Event rates at 30 and 180 days were twice as high in patients with elevated CK-MB than in patients without elevated CK-MB. Both groups had similar benefit from an invasive strategy; there was no evidence of interaction between CK-MB elevation and strategy on the composite end point at 30 or 180 days. When patients were stratified according to both CK-MB and troponin status, there was evidence of a benefit in the invasive strategy among patients who were CK-negative but troponin-positive (odds ratios [95% confidence interval]: 0.13 [0.04 to 0.39] at 30 days and 0.29 [0.16 to 0.52] at 180 days). CONCLUSION: Patients with minimal amounts of recent onset myonecrosis but elevated risk as indicated by CK-MB and troponin, respectively, benefit most from invasive management. Determination of troponin levels yielded significant information regarding triage to an invasive strategy, particularly in CK-MB-negative patients.     

The prevalence and prognosis of minimally elevated creatine kinase-myocardial band activity in elderly patients with syncope

Syncope in elderly patients is often the initial manifestation of myocardial infarction (MI). Small elevations in creatine kinase-myocardial band (CK-MB) activity following syncope may represent MI, transient myocardial hypoperfusion, or insignificant background activity. To determine the prevalence and prognostic significance of minimal CK-MB elevations in elderly patients with syncope, serial serum CK-MB activities and subsequent survival experiences were determined for elderly syncope patients with and without MI, and for age-matched nonsyncopal controls. While all syncope patients with MI by specific clinical criteria had one or more abnormal CK-MB levels (greater than 5 U/L) and died within 31 months, 10% of syncope patients without MI and 10% of controls had abnormal CK-MB with no impact on mortality. Using standard clinical laboratory techniques, minimal elevation in CK-MB was found in 10% of elderly subjects with and without syncope and probably had no prognostic significance.     

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)     

New diagnostic criteria for acute myocardial infarction and in-hospital mortality.

BACKGROUND: The recent introduction of new diagnostic criteria for acute myocardial infarction (AMI), with troponin measurement, has increased the number of patients admitted with this diagnosis. OBJECTIVE: To evaluate the epidemiologic and prognostic implications of the new diagnostic criteria for AMI. METHODS: This was a retrospective study of 586 patients admitted for acute coronary syndrome (ACS) to the coronary care unit of our hospital, between 2002 and 2003. Data were collected from RECIMA, the Madeira Ischemic Heart Disease Registry. The population was analyzed following two different definitions of ACS: 1 - old criteria (Group I): AMI with ST elevation (typical symptoms or ECG with ST-segment elevation and raised CK-MB >2x), AMI without ST elevation (typical symptoms or ECG without ST elevation and raised CK-MB >2x) and unstable angina (UA) (symptoms or ECG indicative of ischemia, with normal CK-MB, regardless of troponin status); 2 - new criteria (Group II): AMI with ST elevation (typical symptoms or ECG with segment ST elevation and raised CK-MB >2x or troponin), AMI without ST elevation (typical symptoms or ECG without ST-segment elevation and raised CK-MB >2x or troponin) and UA (symptoms or ECG indicative of ischemia, with normal enzymes). We evaluated whether this change in criteria had any influence on in-hospital mortality. RESULTS: The new criteria significantly (by 11.9 %) increased the total number of patients admitted with AMI. This was due to an increase in AMI without ST elevation (p < 0.001) and a decrease in patients with UA (p < 0.001), with no changes in AMI with ST elevation. In-hospital mortality was lower in patients with AMI diagnosed by the new criteria and in those with UA. CONCLUSION: The overall increase in AMI resulting from the new diagnostic classification was accompanied by a decrease, although not statistically significant, of in-hospital mortality, probably due to the lower risk of the population analyzed.     

Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain.

AIMS: To determine the prognostic value of baseline plasma adiponectin levels in patients with known or suspected coronary artery disease referred for coronary angiography. METHODS AND RESULTS: Adiponectin was measured in 325 male patients with stable angina, troponin-negative unstable angina, and non-ST-segment elevation myocardial infarction (MI) undergoing coronary angiography at a Veterans Administration Medical Center. The patients were then followed prospectively for the occurrence of all-cause mortality, cardiac mortality, and MI. Follow-up data at 24 months were available for 97% of the patients. Adiponectin was the only biomarker to independently predict the individual endpoints of all-cause mortality, cardiac mortality, and MI. The 24-month survival rates for patients in the lower (< or =4.431 mg/L), middle (>4.431 and < or =8.008 mg/L), and upper (>8.008 mg/L) tertiles of plasma adiponectin values were 95.0, 90.4, and 83.5%, respectively (P = 0.0232 by log-rank test). Furthermore, when patients with chest pain were risk-stratified into those with and without a non-ST-segment elevation acute coronary syndrome (NSTEACS), adiponectin remained an independent predictor of both all-cause mortality and cardiac mortality in the NSTEACS subgroup. CONCLUSION: In a cohort of male patients undergoing coronary angiography, a single baseline determination of plasma adiponectin is independently predictive of the subsequent risk of death and MI.     

Long-term clinical events following creatine kinase--myocardial band isoenzyme elevation after successful coronary stenting

OBJECTIVE: We sought to evaluate the impact of intermediate creatine kinase-myocardial band isoenzyme (CK-MB) elevation on late clinical outcomes in patients undergoing successful stent implantation in native coronary arteries. BACKGROUND: Elevations of CK-MB after percutaneous coronary interventions are frequent. An association between high level of CK-MB elevation (>5 times normal) and late mortality after balloon and new device angioplasty has been reported previously. However, significant controversy remains on the long-term clinical importance of lower CK-MB elevations (one to five times normal) after percutaneous coronary revascularization. Moreover, the incidence and prognostic importance of cardiac enzyme elevation after coronary stenting have not been well established. METHODS: Prospectively collected data from 900 consecutive patients (1,213 lesions) undergoing successful stenting in native vessels were analyzed. Based on the CK-MB levels after coronary stenting, patients were classified into three groups: normal group 1 (n = 585), elevation of >1 to 5 times normal group 2 (n = 238) and elevation of >5 times normal group 3 (n = 77). RESULTS: Patients in group 3 had more in-hospital recurrent ischemia (p = 0.001) and pulmonary edema (p = 0.01) than patients in groups 1 and 2. Long-term clinical end points were similar between groups 1 and 2. However, patients in group 3 had an increased incidence of late mortality compared with patients in groups 2 and 1 (6.9%, 1.2% and 1.7%, respectively, p = 0.01). Multivariate analysis showed that patients with CK-MB >5 times normal after coronary stenting had an increased risk of major adverse clinical events (relative risk: 1.70, p < 0.05) and death (relative risk: 3.25, p < 0.05) that was not observed in patients with lower CK-MB rise. CONCLUSIONS: Patients with CK-MB elevation >5 times normal had higher late mortality and more unfavorable event-free survival than those patients with normal or lower CK-MB rise after coronary stenting. While intermediate CK-MB elevation (>1 to 5 times normal) is frequent after coronary stenting (26%), this was not associated with an increased risk of late mortality or major adverse clinical events.     

Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain.

OBJECTIVES: This study was designed to determine the diagnostic value of adenosine cardiac magnetic resonance (CMR) in troponin-negative patients with chest pain. BACKGROUND: We hypothesized that adenosine CMR could determine which troponin-negative patients with chest pain in an emergency department have coronary artery disease (CAD) or future adverse cardiac events. METHODS: Adenosine stress CMR was performed on 135 patients who presented to the emergency department with chest pain and had acute myocardial infarction (MI) excluded by troponin-I. The main study outcome was detecting any evidence of significant CAD. Patients were contacted at one year to determine the incidence of significant CAD defined as coronary artery stenosis >50% on angiography, abnormal correlative stress test, new MI, or death. RESULTS: Adenosine perfusion abnormalities had 100% sensitivity and 93% specificity as the single most accurate component of the CMR examination. Both cardiac risk factors and CMR were significant in Kaplan-Meier analysis (log-rank test, p = 0.0006 and p < 0.0001, respectively). However, an abnormal CMR added significant prognostic value in predicting future diagnosis of CAD, MI, or death over clinical risk factors. In receiver operator curve analysis, adenosine CMR was a more accurate predictor than cardiac risk factors (p < 0.002). CONCLUSIONS: In patients with chest pain who had MI excluded by troponin-I and non-diagnostic electrocardiograms, an adenosine CMR examination predicted with high sensitivity and specificity which patients had significant CAD during one-year follow-up. Furthermore, no patients with a normal adenosine CMR study had a subsequent diagnosis of CAD or an adverse outcome.     

Correlation of postpercutaneous coronary intervention creatine kinase-MB and troponin I elevation in predicting mid-term mortality

Creatine kinase-MB (CK-MB) and troponin I elevations after successful percutaneous coronary intervention (PCI) are common, and different gradations have been correlated with mortality. To establish which of these 2 markers of myonecrosis, CK-MB and troponin I, accurately predicts mortality after successful PCI, we analyzed 2,873 patients without acute myocardial infarction who underwent PCI for in-hospital events and mid-term mortality. Patients were stratified into 4 groups based on peak post-PCI cardiac markers values: group I: normal CK-MB (<16 U/L) or troponin I (<2 ng/ml); group II: CK-MB or troponin I levels 1 to 3 times normal; group III: >3 to 5 times normal; and group IV: >5 times normal. CK-MB elevation occurred in 16.1% of patients, with 12.2%, 2.3%, and 1.6% in groups II to IV, respectively. Troponin I elevation was detected in 38.9% of patients, with 16.4%, 8.4%, and 14.1% in groups II to IV, respectively. There was poor correlation between postprocedural CK-MB and troponin I values (r = 0.10) and in their individual subgroups. Kaplan-Meier estimates of death for postprocedure CK-MB were 2.1%, 2.7%, 1.7%, and 10.3% (p = 0.002) for groups I to IV, respectively; for troponin I, these estimates were 2.2%, 2.3%, 2.9%, and 2.1% for groups I to IV, respectively (p = 0.58). A Cox proportional hazards model showed that CK-MB >5 times normal was the strongest predictor of mortality (hazard ratio 6.7, 95% confidence interval 1.9 to 22.9; p = 0.002), although heart failure, peripheral vascular disease, pre-PCI digoxin therapy, and post-PCI renal failure also predicted mortality. However, neither troponin I peak elevation nor any subgroup predicted mortality. Troponin I is frequently elevated after PCI, but does not predict mortality. Periprocedural CK-MB elevation >5 times normal remains an independent predictor of mid-term mortality and a valuable marker for PCI prognosis in low-to-medium risk patients.     

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.)     

Prognostic value of recurrent episodes of creatine kinase-MB elevation following repeated catheter-based coronary interventions.

Creatine kinase-MB (CK-MB) enzyme elevations were shown to affect cardiac prognosis following percutaneous coronary interventions (PCIs). This study examined whether recurrent episodes of CK-MB elevation following repeated PCIs may be associated with a cumulative adverse prognostic risk. We studied 767 consecutive patients (age, 64 +/- 11 years; 69% male) who underwent two consecutive PCI procedures on two separate hospitalizations (mean interval, 121 +/- 110 days). Patients were stratified into four groups according to number of episodes of any (> 4 ng/ml) postinterventional CK-MB rise (no elevation, previously elevated, currently elevated, or elevated at the time of both procedures; n = 403, 107, 153, and 104 patients, respectively). In-hospital clinical outcomes (death, Q-MI, and repeat revascularization) and up to 1-year follow-up events were obtained. Recurrent episodes of CK-MB elevation were associated with increased in-hospital mortality (3.8% vs. 0.9% vs. 0% vs. 0%, P = 0.0003), increased cumulative mortality (18.9% vs. 5.9% vs. 4.3% vs. 4.3%, P = 0.0003) and cumulative Q wave MI (8.0% vs. 4.9% vs. 1.0% vs. 0.8%, P = 0.005) at 1 year, and lower overall cardiac event-free survival at follow-up (66.8% vs. 80.5% vs. 88.8% vs. 88.8%, P = 0.0001 for patients with twice, current, previous, and no CK-MB elevation, respectively). By multivariate analysis, CK-MB elevated at the time of both procedures, was the strongest independent predictor for cumulative mortality (OR 3.4, 95% CI 1.6-7.1, P = 0.001) or any adverse cardiac events (OR 2.6, 95% CI 1.6-4.3, P = 0.0002). We conclude that cumulative episodes of periprocedural CK-MB elevation are associated with an incremental adverse prognostic risk including mortality and Q-wave MI. Thus, measures aimed at reducing subsequent CK-MB rise may be warranted in particular among patients with a prior history of PCI related CK-MB elevation.     

Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy

OBJECTIVES: We sought to evaluate cardiac troponin I (cTnI) for predicting early clinical outcomes and the efficacy of enoxaparin among patients with non-ST segment elevation acute coronary syndrome (ACS) and negative creatine kinase, MB fraction (CK-MB) levels. BACKGROUND: Cardiac TnI identifies patients with unstable angina who are at higher risk of death or myocardial infarction (MI) by 30 days. The utility of cTnI for predicting very early clinical events, including recurrent ischemia, and the efficacy of enoxaparin are not yet established. METHODS: At baseline and 12 h to 24 h after enrollment in the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, samples were collected for cTnI determination. RESULTS: Among 359 patients with negative serial CK-MB values, 50.1% had a cTnI result > or =0.1 ng/ml within the first 24 h. Patients with elevated cTnI were at higher risk of death or MI at 48 h (3.9 vs. 0%, p = 0.01) and 14 days (13.9 vs. 2.2%, p<0.0001). Elevated cTnI also correlated with higher risk of recurrent ischemia requiring urgent revascularization by 48 h (10.0 vs. 1.7%, p = 0.001) and 14 days (20.6 vs. 5.6%, p< or =0.0001). Enoxaparin had a greater benefit among patients with elevated vs. normal cTnI (p = 0.03), achieving a 47% reduction in the risk of death, MI or urgent revascularization by 14 days in cTnI-positive patients (p = 0.007). CONCLUSIONS: Elevation of cTnI among patients with non-ST segment elevation ACS and negative levels of CK-MB identifies those at higher risk for very early adverse outcomes, including severe recurrent ischemia. Treatment with enoxaparin reduces the risk associated with elevated cTnI.