Highly sensitive troponin T in patients with acute ischemic stroke.

BACKGROUND: Newly developed troponin assays have superior diagnostic and prognostic performance in acute coronary syndrome (ACS), when compared to conventional troponin assays; however, highly sensitive troponin has not been evaluated in patients with acute ischemic stroke. METHODS: Highly sensitive troponin T (hsTnT) was measured daily during the first 4 days in 193 consecutive patients with acute ischemic stroke without overt ACS or atrial fibrillation. The patients were previously tested normal with a fourth-generation TnT assay. The patients were followed for 47 months, with all-cause and cardiovascular mortality end-points. RESULTS: A total of 33.7% of the patients had hsTnT levels >14 ng/l following admission. Patients with increased hsTnT were older, had decreased hemoglobin levels and increased creatinine, NT-proBNP and CRP levels. hsTnT concentrations at admission were significantly higher in decedents than in survivors. After adjustment for stroke severity, C-reactive protein, age, NT-proBNP and prior heart and/or renal failure, hsTnT levels were not a significant predictor of long-term all-cause or cardiovascular mortality. CONCLUSION: Elevated levels of hsTnT are frequently present in patients with acute ischemic stroke previously tested normal with a fourth-generation TnT assay. hsTnT did not provide additional prognostic information in these subjects.

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers.

OBJECTIVE: Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. MATERIAL AND METHODS: We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H-FABP) in 23 patients admitted with acute ST-segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24 h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2 h after admission. RESULTS: From 30 min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H-FABP (p<0.05). CONCLUSIONS: The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.

Long term risk stratification of patients with acute coronary syndromes: characteristics of troponin T testing and continuous ST segment monitoring.

OBJECTIVE: To examine the long term prognostic characteristics of troponin T testing and continuous multi-lead ST segment monitoring in combination with clinical and 12 lead ECG risk indicators in patients with acute coronary syndromes (ACS). PATIENTS AND DESIGN: Patients with suspected ACS (n = 213) were studied. Troponin T was analysed in blood samples collected during the first 12 hours after admission. Continuous vectorcardiography ST segment monitoring was performed for 24 hours and the number of ST vector magnitude episodes was registered. Patients were followed up for a median of 28 months. The end point was a composite of cardiac death and acute myocardial infarction. RESULTS: Thirty eight (18%) patients reached the composite end point. The median (interquartile range) time from study inclusion to the time of the composite end point was longer for patients predicted to be at risk by troponin T testing (n = 27) than for those predicted to be at risk by ST segment monitoring (n = 20) (8.4 (0.2-15) months v 0.3 (0.1-4.3) months, p = 0.04). Significant univariate predictors of the composite end point were age > or = 65 years, diabetes, previous myocardial infarction, congestive heart failure, use of beta blockers or diuretics at admission, 12 lead ECG ST segment depression at admission, troponin T concentration > or = 0.10 microg/l, and > or = 1 ST vector magnitude episodes. Age > or = 65 years, previous myocardial infarction, and troponin T concentration > or = 0.10 microg/l provided independent prognostic information after multivariate analysis of potential risk variables. The prognostic value of transient ischaemic episodes in ACS seems to be confined to the short term. CONCLUSIONS: Both biochemical and continuous ECG markers reflect an increased risk for patients with ACS; however, the methods exhibit different temporal risk characteristics.

Cardiac troponin levels following monitored epileptic seizures.

Cardiac arrhythmia associated with myocardial injury is a proposed mechanism for sudden unexplained death in epilepsy. The authors measured serial cardiac troponin levels in 11 patients after monitored seizures. Using highly sensitive assays and criteria, no troponin elevations were seen, indicating that myocardial injury does not occur during uncomplicated seizures. An elevation in postictal troponin elevations should suggest the presence of cardiac injury secondary to neurocardiogenic mechanisms or primary cardiac factors, prompting further evaluation.

Admission risk assessment by cardiac troponin T in unstable coronary artery disease: additional prognostic information from continuous ST segment monitoring. TRIM study group. Thrombin Inhibition in Myocardial Ischemia.

OBJECTIVES: We investigated whether the addition of 24 h of continuous vectorcardiography ST segment monitoring (cVST) for an early (within 24 h of the latest episode of angina) determination of cardiac troponin T (cTnT) could provide additional prognostic information in patients with unstable coronary artery disease (UCAD), i.e., unstable angina and non-Q wave myocardial infarction. BACKGROUND: Determination of cTnT at admission and cVST are individually reported to be valuable techniques for the risk assessment of patients with UCAD. METHODS: Two hundred and thirty-two patients suspected of UCAD were studied. Patients were followed for 30 days, and the occurrence of cardiac death or acute myocardial infarction (AMI) were registered. RESULTS: One ST segment episode or more (relative risk [RR] 7.43, p = 0.012), a cTnT level > or = 0.20 microg/liter (RR 3.85, p = 0.036) or prestudy medication with calcium antagonists (RR 3.31, p = 0.041) were found to carry independent prognostic information after multivariate analysis of potential risk variables. By combining a cTnT determination and subsequent cVST for 24 h, subgroups of patients at high (25.8%) (n = 31), intermediate (3.1%) (n = 65) and low risk (1.7%) (n = 117) of death or AMI could be identified. CONCLUSIONS: Twenty-four hours of cVST provides additional prognostic information to that of an early cTnT determination in patients suspected of having UCAD. The combination of biochemical and electrocardiographic methods provides powerful and accurate risk stratification in UCAD.

Clinical application of two novel rapid bedside tests for the detection of cardiac troponin T and creatine kinase-MB mass/myoglobin in whole blood in acute myocardial infarction.

The objective of this study was to determine whether two novel rapid bedside assays for whole-blood detection of cardiac troponin T and creatine kinase (CK)-MB mass/myoglobin could rule out or rule in acute myocardial infarction in patients with acute chest pain. Ninety-two patients with chest pain <12 h prior to admission were investigated. No difference in the cumulative sensitivity of the TropT test and the CARDIAC STATus test (CK-MB mass and myoglobin in combination) was found 6 h after admission (94 vs. 97%). The cumulative positive predictive value of the TropT test and CARDIAC STATus test 6 h after admission was 97 and 76%, respectively. The negative predictive value was 97% for the TropT test and 98% for the CARDIAC STATus test at this time point. Our data show that the rapid assays provide diagnostic as well as prognostic information shortly after admission.

Creatine kinase isoenzyme MB mass, cardiac troponin T, and myosin light chain isotype 1 as serological markers of myocardial injury and their prognostic importance in acute coronary syndrome.

Acute coronary syndrome encompasses the entities acute MI, unstable AP and sudden cardiac death. The syndrome of unstable AP covers a very heterogenous group of patients. Recent pathological post-mortem investigations have revealed, that unstable AP leading to MI or sudden cardiac death is frequently preceded by microinfarctions. Despite the fact that thrombus formation is recognized as the major cause, the role of coronary artery spasm seems also important. Therefore, the pathological hallmark of ACS is at present thought to be caused by an active coronary plaque (the culprit lesion), which is often the site of intermittent occlusion and of thrombus formation, with or without vasospasm. The release of myocardial cell constituents in connection with these microinfarctions is to be expected. In order to detect these, diagnostic tools sensitive to myocardial injury and specific for myocardial tissue must be employed. According to WHO the criteria for the diagnosis of acute MI are based on clinical history, electrocardiographic changes, and enzymes in serum. Although these criteria are quite adequate in most cases, they are not present or easily discernible in all acute MI patients. The clinical symptoms are and will remain insensitive and nonspecific indicators of acute MI. Electrocardiographic alterations are carefully described, but sometimes less applicable due to non-interpretable ECG's. During the last decades, activity measurements of cardiac enzymes, and especially the isoenzymes of CK and LD, have become the final arbiters by which myocardial damage is diagnosed or excluded. However, they are not fully cardiospecific and have a low sensitivity to detect MMI, retaining a high specificity. Improved immunoassays have therefore been developed measuring the mass concentration of CK-MB instead of its catalytic activity, as well as immunoassays measuring structural proteins of the heart i.e., TnT, a tropomyosin-binding protein of the troponin regulatory complex located on the thin filament of the contractile apparatus of the myocyte; and MLC, a component of the thick filament of the contractile apparatus of the myocyte. We, and others, have shown that minor ischaemic myocardial injury can be detected by CK-MB mass immunoassays in around one-fourth to one-third of patients with unstable AP or in whom an acute MI has been ruled out. However, the prognostic significance of this identification has not been investigated. A priori, it is known that 5-20% of patients with unstable AP have a poor prognosis, with progression to acute MI or cardiac death within the first year. Additional, non-Q wave MI may also be considered a relatively unstable condition associated with a lower initial mortality but a higher risk of later MI/cardiac death. It is of further importance, that although the incidence of unrecognized MI is less than that of clinically apparent MI, the long-term prognosis for unrecognized MI appears to be similar to, and as serious as, that following detected MI. Therefore, in order to follow-up this subgroup identification based on CK-MB mass levels, we subsequently carried out a prognostic study. It demonstrated a significantly increased risk of cardiac events (i.e., non-fatal acute MI, cardiac death) in patients with significant fluctuations of CK-MB mass in serum. A similar observation has been supported by others using the rate of change in serial samples of CK-MB mass. Further, we demonstrated a good correlation between elevated CK-MB mass levels and a poor prognosis, when using a fixed discrimination limit. However, an increasing number of CK-MB mass immunoassays have been developed, and a standardization of CK-MB mass is urgently needed, as at present each laboratory determines its own reference levels and discriminatory values leading to the risk of diagnostic confusion. (ABSTRACT TRUNCATED)

Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial ischemia.

BACKGROUND: Studies have demonstrated that troponin T is a strong independent indicator of a poor prognosis in patients with unstable coronary artery disease. Up to the present, no study has compared the prognostic value of troponin T with that of troponin I in the same cohort of patients. METHODS AND RESULTS: Patients (n=516) suspected of having unstable coronary artery disease were investigated. Follow-up was done after 30 days, and the occurrences of cardiac death, acute myocardial infarction, refractory angina pectoris, and recurrent angina pectoris were registered. Elevated levels of troponin T (> or = 0.10 microg/L) were associated with an increased risk of cardiac death at 30 days compared with patients with normal levels, 3.2% versus 0.4% (P=.014). Troponin I values above the chosen cutoff (2.0 microg/L) were similarly found to be an indicator of increased risk of cardiac death, 3.2% versus 0.7% (P=.026). With regard to the composite end point of cardiac death/acute myocardial infarction, the troponins were strong independent indicators of adverse outcome. CONCLUSIONS: In patients suspected of having unstable coronary artery disease, both troponin T and troponin I provide independent prognostic information with regard to cardiac death and acute myocardial infarction.

Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of follow-up in 196 patients.

OBJECTIVES: We sought to determine the incidence and independent prognostic value of increased serum levels of sensitive serologic markers in patients in whom a conventionally diagnosed acute myocardial infarction had been ruled out. BACKGROUND: Increased serum levels of creatine kinase (CK) isoenzyme MB mass and cardiac troponin T in patients with unstable angina pectoris are associated with a poor prognosis. METHODS: We analyzed data from 196 consecutive patients with suspected acute myocardial infarction, which was later ruled out in 124. Increased serum levels of CK-MB mass, troponin T and myosin light chains were compared with clinical findings, ST-T wave abnormalities and presence of arrhythmias. RESULTS: Of the patients in the noninfarction group, 28% had serum CK-MB mass > or = 6 micrograms/liter, 20% had troponin T > or = 0.20 micrograms/liter, and 26% had myosin light chains > or = 0.4 micrograms/liter (discrimination limits). The cardiac event rate (cardiac death, nonfatal acute myocardial infarction) within 28 months was significantly higher in patients in the noninfarction group with elevated marker levels (range 22% to 24%) than in patients with values below these discriminators (range 3% to 5%) but was not significantly different from that in patients with a definite diagnosis of acute myocardial infarction (29%). Further, significant predictors of cardiac events were previous myocardial infarction; myocardial infarction or angina pectoris, or both; previous congestive heart failure; ST-T wave abnormalities on admission; a transient ST-T wave shift on serial electrocardiograms (ECGs); recurrent chest pain; and occurrence of supraventricular or ventricular tachycardia, or both, during the 1st 48 h after admission. It was found that all three biochemical markers, in the main, convey independent prognostic information with respect to clinical findings and presence of arrhythmias but not ST-T wave abnormalities on admission or a transient ST-T wave shift on serial ECGs. CONCLUSIONS: Increased serum levels of CK-MB mass, troponin T and myosin light chains all detect a subgroup of 25% of patients without acute myocardial infarction who have as poor a prognosis as that of patients with a definite diagnosis of acute myocardial infarction. All three biochemical markers provide similar important independent prognostic information with regard to clinical findings and arrhythmias but add no additional prognostic information once ECG ST-T wave changes are considered.

[Troponin T in acute myocardial infarction. Diagnosis and prognosis in patients admitted for suspected acute myocardial infarction]. / Troponin T ved akut myokardieinfarkt. Diagnostik og prognostik hos patienter indlagt til observation for akut myokardieinfarkt.

Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool for myocardial damage. A blinded prospective multicentre study representing 298 patients who on admission were suspected of acute myocardial infarction (AMI) to the coronary care units of six Scandinavian hospitals was undertaken to assess the diagnostic performance and prognostic efficacy of a new cardiospecific TnT immunoassay. We used a discriminator value of TnT of 0.20 micrograms/l. One hundred and fifty-five patients (52%) had definite AMI, based on WHO criteria (all had peak S-TnT values > or = 0.20 micrograms/l); 127 patients (43%) had ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all had peak S-TnT values < 0.20 micrograms/l). The 127 IHD-patients without definite AMI could be subdivided into a group of 44 patients with S-TnT peak values > or = 0.20 micrograms/l, and a group of 83 patients with TnT below this level. A follow-up study was able to define the clinical significance of these findings. The cumulative six months probability of suffering cardiac death or AMI was significantly higher in the subgroup with increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83)) (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the patients with definite AMI. We conclude that increased troponin T in serum can detect a subgroup of IHD-patients in whom AMI has been ruled out, but who still have a prognosis as serious as that of patients with definite AMI.

Ventricular arrhythmias in the acute and chronic phases after acute myocardial infarction. Effect of intervention with captopril.

BACKGROUND: Ventricular arrhythmias (VAs) are independent predictors of mortality in survivors of myocardial infarction (MI), and they are more likely to be induced in dilated hearts with increased wall stress. Angiotensin-converting enzyme (ACE) inhibitors have been shown to prevent progressive dilation of the left ventricle after MI. METHODS AND RESULTS: The effects of captopril were evaluated in 58 patients with left ventricular (LV) dysfunction after MI. Patients were randomized on day 7 to either placebo or captopril (50 mg daily) in a double-blind parallel study over a period of 6 months. Patients were followed up by means of ambulatory ECG monitoring and echocardiography. There was a significant increase in VA in the placebo group (P < .05) in contrast to a significant decrease in the captopril group (P < .05). As a consequence, there was a significant between-group difference after 6 months (P < .05). Furthermore, the number of patients without VA at baseline who presented with this at the completion of the study was 6% in the captopril group versus 38% in the placebo group (P < .05). At baseline as well as at the termination of the study, LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) were significantly increased among patients with VA (P < .01). On day 180, both myocardial ischemia and an increase in the LVEDVI were independent predictors of VA; however, progressive dilation of the left ventricle was confined to the placebo patients with significant increases in the LVEDVI compared with the captopril group: 17% versus 0%, respectively (P < .01). Furthermore, the duration of ambulatory ST-segment depression was significantly longer in this group compared with the captopril group (P < .01). CONCLUSIONS: Dilation of the left ventricle and myocardial ischemia predict VA during both the acute and chronic phases after MI. In post-MI patients with LV dysfunction, captopril has a beneficial effect on both the number of complex VAs as well as the number of patients who develop VA during the chronic phase. This is in all probability mediated through effects on both LV remodeling, LV function, and myocardial ischemia in patients who are exposed to an increased risk of undergoing progressive dilation of the left ventricle.

Exercise capacity in patients with left ventricular dysfunction following acute myocardial infarction: relation to systolic and diastolic function and intervention with captopril.

Patients with acute or chronic heart disease may have limited exercise capacity if they have reduced left ventricular function. Indexes of reduced left ventricular function during exercise are a predictor of subsequent survival although left ventricular ejection fraction is a poor predictor of physical endurance. We evaluated the effect of captopril on physical endurance in 48 males with left ventricular dysfunction following myocardial infarction. On the 7th day following myocardial infarction patients were randomized to either captopril 50 mg daily or corresponding placebo. Patients were followed up by means of serial echocardiography and exercise stress testing for a period of 180 days. Exercise capacity was significantly improved in the captopril group. Changes in exercise capacity were significantly correlated to changes in left ventricular (LV) volumes and compliance. The beneficial effect of captopril on exercise capacity was probably mediated via improvement in LV performance and compliance.

Therapeutic effects of captopril on ischemia and dysfunction of the left ventricle after Q-wave and non-Q-wave myocardial infarction.

Treatment with angiotensin-converting enzyme inhibitors has a beneficial effect on myocardial ischemia and left ventricular dysfunction after myocardial infarction. The effect of captopril on myocardial ischemia was evaluated in 58 patients with left ventricular dysfunction (ejection fraction < 45%) after Q-wave or non-Q-wave myocardial infarction in a placebo-controlled, parallel, double-blind study. Patients were randomized on day 7 to either placebo or captopril (50 mg daily) and monitoring for a period of 180 days by serial echocardiography and ambulatory ST-segment monitoring. There was a significant effect of captopril on the duration of ambulatory ST depression during the 180 days: The values per day were reduced from 28 +/- 5 min at baseline to 2 +/- 1 min on day 180 in the Q-wave group (p < 0.01) and from 39 +/- 10 min at baseline to 6 +/- 1 min on day 180 in the non-Q-wave group (p < 0.05). In the placebo group the duration of ST depression on day 180 were 21 +/- 8 min in the Q-wave group and 22 +/- 7 min in the non-Q-wave group, thus being significantly higher as compared with the corresponding captopril groups (p < 0.01 and p < 0.05, respectively). In the placebo Q-wave group there was a significant increase in left ventricular end-diastolic volume index from 74 +/- 3.5 to 89 +/- 4.5 ml/m2 (p < 0.01) during the study period, which was in contrast to unchanged values of 75.5 +/- 3.0 and 75.0 +/- 3.5 ml/m2 (not significant [NS]) in the captopril Q-wave group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris.

The incidence of cardiac troponin T (Tn-T) and creatine kinase (CK) isoenzyme MB mass release was studied in 23 patients with stable angina pectoris undergoing visually successful percutaneous transluminal coronary angioplasty (PTCA). Serial blood samples were drawn for measurement of serum Tn-T, CK-MB mass, total CK activity, CK-MB activity, and lactate dehydrogenase isoenzyme (LD-1). ST segment monitoring was carried out during PTCA and for the following 24 hours. None of the patients showed electrocardiographic (ECG) evidence of myocardial infarction. However, Tn-T was elevated in three patients (0.23 to 1.32 micrograms/L), and in these three and an additional three patients CK-MB mass was also elevated (7.0 to 27.5 micrograms/L). Total CK activity and LD-1 were only elevated in one of these six patients. None had elevated CK-MB activity. ST segment depression on ECG recording was not predictive of Tn-T or CK-MB mass release. Patients with elevated Tn-T or CK-MB mass did not differ with respect to demographic data, stenosis characteristics, or in the PTCA procedure. We conclude that CK-MB mass uncovers clinically and ambulatory electrocardiographically inapparent severe myocardial ischemia/minor myocardial damage (microembolization) in 26% (6 of 23) of patients after visually successful PTCA; 13% (3 of 23) had elevated Tn-T, indicating minor myocardial damage. The application of these markers in the future could be of considerable value for determining the efficacy of coronary angioplasty and atherectomy, as well as for drug therapy in connection with such procedures.

Human ventricular myosin light chain isotype 1 as a marker of myocardial injury.

A monoclonal enzyme immunoassay for measuring human ventricular myosin light chain isotype 1 (HVMLC1) in serum has been developed. To evaluate the method in patients with suspected myocardial injury, we studied 51 patients (16 acute myocardial infarction (AMI), 19 unstable angina pectoris (UAP), 9 stable angina pectoris, 3 nonischemic heart disease, 4 hip surgery patients), and 190 controls (blood donors). Serial blood-samples were drawn from patients; a single blood-sample from controls. The diagnostic value of the HVMLC1 assay was compared with total creatine kinase (CK), CKMB activity, CKMB mass concentration, lactate dehydrogenase isoenzyme 1 (LD1), troponin T (TnT) and mitochondrial-aspartate aminotransferase (m-ASAT). The detection limit of HVMLC1 was 0.4 microgram/l (linear range 0-20 micrograms/l). Sera from 190 reference persons did not contain detectable levels of HVMLC1 (< 0.4 microgram/l; 99% percentile). The coefficients of variation were 13% (1.0 microgram/l) and 3.1% (17.7 micrograms/l). Cross-reactivity with myosin from skeletal muscle was seen. Times to peak value were: CK 19.3 +/- 2.0, LD1 43.4 +/- 3.2, HVMLC1 72.9 +/- 7.0, and m-ASAT 67.3 +/- 5.6 h. Time-curves of HVMLC1 and m-ASAT were similar, whereas time-curves for HVMLC1 and TnT were quite different in most cases. Peak value of HVMLC1 was five times higher than CK peak value and eight times that of LD1. HVMLC1 appeared in the blood within hours after the onset of chest pain and in the majority remained for more than a week after AMI. Among patients with UAP 16% (3/19) had elevated HVMLC1 in serum, whereas elevated TnT was seen in 26% (5/19) and elevated CKMB mass in 26% (5/19). We conclude that the new HVMLC1 assay offers a sensitive diagnosis of myocardial injury. It is characterized by a wide diagnostic time window. The similarity of the HVMLC1 and m-ASAT curves indicates that it may be used to estimate the extent of myocardial necrosis.