Elevations of cardiac enzymes are commonly used to indicate myocardial ischemia, but they can be elevated due to other conditions. Different forms of Troponin (cTnT, sTnT, cTnI), can cause cross-reactivity in the Troponin T assay, leading to false positives. This report describes a patient with polymyositis who had elevated Troponin T, but no cardiac abnormalities. The purpose is to show that Troponin T, which is believed to be solely from cardiac muscle breakdown, can be seen in inflammatory muscle disease, so Troponin I should be used instead.
This is a case report of a 70-year-old woman with a history of diabetes, hypertension, gout and polymyositis, who presented with one-day history of lightheadedness and abdominal pain. To rule out myocardial ischemia, cardiac enzyme testing was ordered which showed elevated CK, CK-MB, and Troponin T. A full cardiac workup was performed which showed no signs of ischemia. Troponin I was <0.05 ng/mL, (normal).
In inflammatory myositis, there are elevations in many cardiac markers due to non-cardiac causes, which could be related to muscle regeneration and gene expression. This is not seen certain isoforms of Troponin I, specifically cardiac Troponin I.
In patients with history of diabetes and other comorbidities, silent myocardial ischemias should be ruled out. Non-cardiac elevations in Troponin T can be seen in patients with inflammatory, so Troponin I should be ordered to get an accurate interpretation. Patients with inflammatory myopathies can have elevations in CK, CK-MB, and Troponin T, but not Troponin I.
false positive Troponin T; Polymyositis; Troponin T; Troponin I
Objective—To investigate the intraoperative release of troponin T during uncomplicated coronary artery surgery and to determine its relation to ischaemic time and to recovery of left ventricular function and oxidative metabolism.
Design—A prospective observational study.
Setting—Cardiac surgical unit in a tertiary referral centre.
Methods—Troponin T, creatine kinase, and lactate were analysed from arterial and coronary sinus samples taken before operation, and 1, 4, 6, 10, 20, 35, and 45 minutes after cross clamp release. Net myocardial troponin T release and lactate extraction were derived from their respective arteriovenous differences. Haemodynamic measurements were made using a thermodilution pulmonary artery catheter.
Patients—45 patients, mean (SD) age 62 (9) years, with two or three vessel coronary artery disease and chronic stable angina undergoing routine coronary artery surgery.
Results—Before operation, troponin T concentrations were not raised, but within one minute of cross clamp release they increased progressively in both coronary sinus and arterial blood for the entire 45 minutes of reperfusion studied. Coronary sinus troponin T concentrations were consistently higher than arterial concentrations at all time points (p < 0.001), indicating net troponin T release by the myocardium. Peak net troponin T release and area under the curve of net troponin T release correlated closely with ischaemic time (r = 0.58 and r = 0.61, p < 0.0001 for both). Area under the curve of arterial troponin T concentration was also significantly correlated with ischaemic time (r = 0.44, p < 0.01). Patients with cross clamp times longer than 72 minutes (upper quartile for ischaemic time) had greater troponin T release, delayed reversion to lactate extraction, and lower left ventricular stroke work index three hours after surgery, compared with patients who had short (< 50 minutes, lower quartile) and intermediate (51-71 minutes, interquartile) cross clamp times. Peak net troponin T release and area under the curve of arterial troponin T concentration were inversely correlated with left ventricular stroke work index three hours after surgery (r = −0.57, r = −0.38, p < 0.01).
Conclusions—Troponin T concentrations increased in every patient after cross clamp release, and were consistently higher in coronary sinus blood than in arterial blood, indicating net myocardial release of troponin T during the period of reperfusion. Intraoperative net troponin T release has functional significance, as it is closely related to ischaemic time and reflects delayed recovery of left ventricular function and oxidative metabolism; therefore, its measurement may contribute to the perioperative assessment of myocardial injury sustained during coronary artery surgery.
Keywords: coronary artery surgery; troponin T; intraoperative assessment; myocardial injury
Laboratory infarction diagnostics are based on the detection of elevated serum activities of total Creatine Kinase (CK), Creatine Kinase isoensyme MB, (CKMB), Lactate dehydrogenase (LDH), isoenzyme forms of LDH and transaminases. Determination of these cardiac marker enzymes permits a highly sensitive diagnosis of transmural myocardial infarction. In such patients the diagnosis of acute myocardial infarction can be confirmed by the clinical, symptoms, and changes in the ECG in addition to the enzyme assays. The 50 AMI patients selected in the present study were those admitted to the ICCU of Shri Krishna Hospital, Karamsad. The blood samples were taken at the time of admission (ie. within four hours of the start of chest pain). The samples were analyzed for CK, CKMB, SGOT, (Serum glutamate oxaloactate transaminase) αHBDH α-hydroxybutyrate dehydrogenase and troponin T. The serum CKMB activity in AMI showed an increase only 5–6 hours after the commencement of chest pain. The elevation in SGOT and αHBDH was still delayed. At the same time we could observe that the cardiac Troponin T (cTnT) was elevated at the time of admission of the patient itself. This increase of cTnT in AMI patients was 20 times higher than the normal blood donors. The controls included 25 normal blood donors and 25 patients with polytraumatic injuries with no chest contusion. The study shows that cTnT estimation could serve in the early diagnosis of AMI. The increase of cardiac troponin T in AMI patients was 20 times higher than the normal blood donors in AMI patients at the time of admission. Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial cell injury than CKMB activity and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina as well. When the blood of normal blood donors or that of patients with polytraumatic injury was analysed the troponin T values were well within the normal range in both the above categories showing that cardiac troponin T is highly specific for heart tissue. Although CKMB and cardiac troponin T are released soon after the myocardial injury, the release of cardiac troponin T is much earlier than CKMB thereby invalidating the important role of cardiac troponin T in diagnosing AMI. Cardiac troponin T has been shown to be highly sensitive for cardiac injury and not elevated in any other trauma, heavy exercise or skeletal muscle injury. Cardiac troponin T is ordinarily undetectable in healthy individuals, and so its measurement can serve as a powerful tool in the diagnosis of AMI.
Cardiac Troponin T; alpha hydroxybutyrate dehydrogenase; Lactate dehydrogenase; myocardial infarction
Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.
The complex of tropomyosin and troponin binds to actin and inhibits activation of myosin ATPase activity and force production of striated muscles at low free Ca2+ concentrations. Ca2+ stimulates ATP activity, and at subsaturating actin concentrations, the binding of NEM-modified S1 to actin–tropomyosin–troponin increases the rate of ATP hydrolysis even further. We show here that the Δ14 mutation of troponin T, associated with familial hypertrophic cardiomyopathy, results in an increase in ATPase rate like that seen with wild-type troponin in the presence of NEM-S1. The enhanced ATPase activity was not due to a decreased incorporation of mutant troponin T with troponin I and troponin C to form an active troponin complex. The activating effect was more prominent with a hybrid troponin (skeletal TnI, TnC, and cardiac TnT) than with all cardiac troponin. Thus it appears that changes in the troponin–troponin contacts that result from mutations or from forming hybrids stabilize a more active state of regulated actin. An analysis of the effect of the Δ14 mutation on the equilibrium binding of S1-ADP to actin was consistent with stabilization of an active state of actin. This change in activation may be important in the development of cardiac disease.
To investigate the frequency, diagnosis and outcome of patients admitted to hospital with acute coronary syndrome (ACS) or other conditions associated with raised levels of cardiac troponin T.
A large university hospital.
Consecutive patients admitted over an 8‐week period who had a serum troponin T test as part of their clinical assessment were included. Patients were separated into those with raised (⩾0.01 μg/l) or normal (<0.01 μg/l) troponin T levels, and further categorised into those with or without a diagnosis of ACS.
Main outcome measures
In‐hospital mortality in all patients; and 6‐month hospital re‐admissions and all‐cause mortality in patients without or with ACS and raised levels of troponin T.
Of 1021 patients, 118 patients had no ACS but raised troponin T levels, 195 had ACS with raised troponin T, 80 had ACS with normal troponin T and 628 had no ACS with normal troponin T. Their in‐hospital all‐cause mortalities were 36%, 18%, 0% and 3%, respectively (p<0.001, highest mortality v other groups). 6‐month all‐cause mortality remained higher in patients without ACS and with raised levels of troponin T than in those with ACS and raised troponin T (42% v 29%; p = 0.020).
Patients without ACS but with raised levels of troponin T comprised 38% of all hospitalised patients found to have raised troponin T. These patients had worse in‐hospital and 6‐month outcome than those having ACS with raised levels of troponin T.
acute coronary syndrome; without acute coronary syndrome; raised troponin T; all‐cause mortality
Troponin T is a unique cardiac antigen which is continuously released from infarcting myocardium. Its cardiospecificity as a marker protein might be particularly useful in assessing myocardial cell damage in patients undergoing cardiac surgery. Therefore, circulating troponin T was measured in serial blood samples from 56 patients undergoing cardiac surgery and in two control groups--22 patients undergoing minor orthopaedic surgery and 12 patients undergoing lung surgery by median sternotomy. In both control groups no troponin T could be detected, whereas activities of creatine kinase were raised in all 12 lung surgery controls and activities of the MB isoenzyme were raised in five of the 12 patients in the lung surgery group and in four of the 22 patients in the orthopaedic surgery group, respectively. All the patients undergoing coronary artery bypass grafting (n = 47) and cardiac surgery for other reasons (n = 9) had detectable concentrations of troponin T. Five patients had perioperative myocardial infarction detected as new Q waves and R wave reductions. In these five patients troponin T release persisted and serum concentrations (5.5-23 micrograms/l) reached a peak on the fourth postoperative day. In the 51 patients without perioperative myocardial infarction serum concentrations and the release kinetics of troponin T depended on the duration of cardiac arrest. In patients in whom aortic cross clamping was short troponin T increased slightly on the first postoperative days; in patients with longer periods of aortic cross clamping troponin T concentrations were higher and remained so beyond the fifth postoperative day. In patients with non-specific changes on the electrocardiogram troponin T concentrations were significantly higher on days 1 and 4 after operation than in patients with normal postoperative electrocardiograms(11.2 (5) and 4.5 (2.6) v 8.2 (3.4) and 2.9 (1.6) 1microg/l). Serum concentrations of troponin T showed some myocardial cell damage in every patient undergoing cardiac surgery. The persistent increases that were more common in patients with longer periods of cardiac arrest must have been caused by damage to the contractile apparatus. These results suggest that perioperative myocardial cell necrosis may be more common than indicated by changes of the QRS complex on the electrocardiogram.
The role of the C-domain sites of cardiac troponin C in the modulation of the calcium signal remains unclear. In this study we investigated the effects of hypertrophic cardiomyopathy linked mutations A8V, E134D and D145E in cardiac troponin C on the properties of the C-domain sites. The A8V mutation had essentially no effect on the calcium or magnesium binding properties of the C-domain sites, while E134D mutation moderately decreased calcium and magnesium binding affinities. On the other hand, D145E mutation affected cooperative interactions between sites III and IV, significantly reducing calcium binding affinity of both sites. Binding of the anchoring region of cardiac troponin I (corresponding to residues 34-71) to cardiac troponin C with D145E mutation was not able to recover normal calcium binding to the C-domain. Experiments utilizing the fluorescent hydrophobic probe bis-ANS suggest that D145E mutation dramatically reduced the extent of calcium-induced hydrophobic exposure by the C-domain. At high non-physiological calcium concentration, A8V, E134D and D145E mutations minimally affected the affinity of cardiac troponin C for the regulatory region of cardiac troponin I (corresponding to residues 128-180). In contrast, at lower physiological calcium concentration, D145E mutation led to ~8-fold decrease in the affinity of cardiac troponin C for the regulatory region of cardiac troponin I. Our results suggest that calcium binding properties of the C-domain sites might be important for the proper regulatory function of cardiac troponin C.
OBJECTIVE—To compare cardiac troponin T release and lactate metabolism in coronary sinus and arterial blood during uncomplicated coronary grafting on the beating heart with conventional coronary grafting using cardiopulmonary bypass.
DESIGN—A prospective observational study with simultaneous sampling of coronary sinus and arterial blood: before and 1, 4, 10, and 20 minutes after reperfusion for analysis of cardiac troponin T and lactate. Cardiac troponin T was also analysed in venous samples taken 3, 6, 24, 48, and 72 hours after surgery.
SETTING—Cardiac surgical unit in a tertiary referral centre.
PATIENTS—18 patients undergoing coronary grafting on the beating heart (10 single vessel and eight two-vessel grafting) and eight undergoing two-vessel grafting with cardiopulmonary bypass.
RESULTS—Cardiac troponin T was detected in coronary sinus blood in all patients by 20 minutes after beating heart coronary artery surgery before arterial concentrations were consistently increased. Peak arterial and coronary sinus cardiac troponin T values on the beating heart during single (0.03 (0 to 0.05) and 0.09 (0.07 to 0.16 µg/l, respectively) and two-vessel grafting (0.1 (0.07 to 0.11) and 0.19 (0.14 to 0.25) µg/l) were lower than the values obtained during cardiopulmonary bypass (0.64 (0.52 to 0.72) and 1.4 (0.9 to 2.0) µg/l) (p < 0.05). The area under the curve of venous cardiac troponin T over 72 hours for two-vessel grafting on the beating heart was less than with cardiopulmonary bypass (13 (10 to 16) v 68 (26 to 102) µg.h/l) (p < 0.001). Lactate extraction began within one minute of snare release during beating heart coronary surgery while lactate was still being produced 20 minutes after cross clamp release following cardiopulmonary bypass.
CONCLUSIONS—Lower intraoperative and serial venous cardiac troponin T concentrations suggest a lesser degree of myocyte injury during beating heart coronary artery surgery than during cardiopulmonary bypass. Oxidative metabolism also recovers more rapidly with beating heart coronary artery surgery than with conventional coronary grafting. Coronary sinus cardiac troponin T concentrations increased earlier and were greater than arterial concentrations during beating heart surgery, suggesting that this may be a more sensitive method of intraoperative assessment of myocardial injury.
Keywords: beating heart coronary artery surgery; troponin T; cardiopulmonary bypass; intraoperative assessment; myocardial injury
Aims: To establish a practical postnatal reference range for cardiac troponin T in neonates and to investigate concentrations in neonates with respiratory distress.
Methods: Prospective investigation in a tertiary neonatal unit, recruiting infants with and without respiratory distress (sick and healthy infants respectively). Concentrations of cardiac troponin T were compared between sick and healthy infants, accounting for confounding variables.
Results: A total of 162 neonates (113 healthy and 49 sick infants) had samples taken. The median (interquartile range) cardiac troponin T concentration in the healthy infants was 0.025 (0.01–0.062) ng/ml, and the 95th centile was 0.153 ng/ml. There were no significant relations between cardiac troponin T and various variables. The median (interquartile range) cardiac troponin T concentration in the sick infants was 0.159 (0.075–0.308) ng/ml. This was significantly higher (p < 0.0001) than in the healthy infants. In a linear regression model, the use of inotropes and oxygen requirement were significant associations independent of other basic and clinical variables in explaining the variation in cardiac troponin T concentrations.
Conclusions: Cardiac troponin T is detectable in the blood of many healthy neonates, but no relation with important basic and clinical variables was found. Sick infants have significantly higher concentrations than healthy infants. The variations in cardiac troponin T concentration were significantly associated with oxygen requirement or the use of inotropic support in a regression model. Cardiac troponin T may be a useful marker of neonatal and cardiorespiratory morbidity.
The cardiac thin filament regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin and tropomyosin. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components. We propose a dynamic, complete model of the thin filament that encompasses known structures of cardiac troponin, tropomyosin and actin and show that it is able to capture key experimental findings. By performing molecular dynamics simulations in two conditions, one with calcium bound and the other without calcium bound to site II of cardiac troponin C (cTnC), we found that subtle changes in structure and protein contacts within cardiac troponin resulted in sweeping changes throughout the complex that alter tropomyosin (Tm) dynamics and cardiac troponin-actin interactions. Significant calcium-dependent changes in dynamics occur throughout the cardiac troponin complex resulting from the combination of: secondary structural changes in the N-lobe of cTnC at and adjacent to sites I and II and the link between them; secondary structural changes of the cardiac troponin I (cTnI) switch peptide, the mobile domain, and in the vicinity of residue 25 of the N-terminus; secondary structural changes in the cardiac troponin T (cTnT) linker and Tm-binding regions; and small changes in cTnC-cTnI and cTnT-Tm contacts. As a result of these changes, we observe large changes in the dynamics of the following regions: the N-lobe of cTnC; the mobile domain of cTnI; the I-T arm; the cTnT linker; and overlapping Tm. Our model demonstrates a comprehensive mechanism for calcium-activation of the cardiac thin filament consistent with previous, independent experimental findings. This model provides a valuable tool for research into the normal physiology of cardiac myofilaments and a template for studying cardiac thin filament mutations that cause human cardiomyopathies.
Stress-induced cardiomyopathy is usually associated with an increased level of cardiac enzymes, leading to difficulties in differentiating this condition from acute coronary syndrome. The final diagnosis is usually made based on angiographic findings revealing normal coronary arteries. It was hypothesized that maximal cardiac enzyme elevation in these patients should have an upper limit. In the present study, reported cases of stress cardiomyopathy were compared with documented cardiac enzyme levels to evaluate the upper cut-off point of troponin in this population.
All of the articles published in PubMed and MEDLINE from November 2007 to July 2008, on takotsubo or stress-induced cardiomyopathy, were identified. Only the cases that reported the absolute or mean level of cardiac enzymes were included. The level of various enzymes were correlated with cardiac function, and the upper limit of enzyme elevation was calculated in these patients.
A total of 114 patients (mean [± SD] age 63.5±14.5 years) were included in the study. Seventy-one per cent of the patients were older than 50 years of age and 86% were female. Mean values for troponin I, troponin T, creatine kinase (CK) and CK-MB were 6.5 ng/mL, 3.6 ng/mL, 556 U/L and 32.9 U/L, respectively. All of the patients with takotsubo cardiomyopathy had a troponin T level of 6 ng/mL or less and troponin I level of 15 ng/mL or less. Troponin T showed a significant inverse correlation with initial ejection fraction (R2=0.6), which was not seen with the levels of troponin I, CK and CK-MB. Takotsubo cardiomyopathy was classified as classic (66.7%), mid-cavitary (10%), reverse (23.3%) or local (0%).
Among patients with takotsubo cardiomyopathy, troponin T level correlated with initial ejection fraction. Furthermore, the diagnosis of takotsubo cardiomyopathy appears to be unlikely in patients with troponin T greater than 6 ng/mL or troponin I greater than 15 ng/mL.
Acute coronary syndrome; Cardiomyopathy; Correlation; Ejection fraction; Left ventricular ejection fraction; Myocardial infarction; Stress cardiomyopathy; Troponin I; Troponin T
Despite the widespread use of cardiac troponins as biomarkers for the diagnosis and quantitation of cardiac injury, the effect of troponin release and a possible autoimmune response to the troponins is unknown. Other investigators reported that programmed cell death – 1 (PD-1) – receptor deficient mice developed severe cardiomyopathy with autoantibodies to troponin I. We found that immunization of genetically susceptible mice with troponin I but not troponin T induced a robust autoimmune response leading to marked inflammation and fibrosis in the myocardium. At later times, antibodies to cardiac myosin were detected in troponin – immunized mice. The severity of inflammation correlated with expression of chemokines RANTES, MIP-2, IP-10 and MCD-1 in the myocardium. Prior immunization with troponin I increased the severity of experimental infarctions, indicating that an autoimmune response to troponin I aggravates acute cardiac damage. Cardiac inflammation, fibrosis and functional impairment were transferred from immunized to naive recipients by CD4+ T cells, and the cytokine profile suggested both a Th2 and Th17 profile in A/J mice. Finally we identified an 18-mer of troponin I containing an immuno-dominant epitope.
Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T), is an important gene for sarcomeric function. Four mutations (1 novel) were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE) was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases.
Elevated troponin levels indicate myocardial injury but may occur in critically ill patients without evidence of myocardial ischemia. An elevated troponin alone cannot establish a diagnosis of myocardial infarction (MI), yet the optimal methods for diagnosing MI in the intensive care unit (ICU) are not established. The study objective was to estimate the frequency of MI using troponin T measurements, 12-lead electrocardiograms (ECGs) and echocardiography, and to examine the association of elevated troponin and MI with ICU and hospital mortality and length of stay.
In this 2-month single centre prospective cohort study, all consecutive patients admitted to our medical-surgical ICU were classified in duplicate by two investigators as having MI or no MI based on troponin, ECGs and echocardiograms obtained during the ICU stay. The diagnosis of MI was based on an adaptation of the joint European Society of Cardiology/American College of Cardiology definition: a typical rise or fall of an elevated troponin measurement, in addition to ischemic symptoms, ischemic ECG changes, a coronary artery intervention, or a new cardiac wall motion abnormality.
We screened 117 ICU admissions and enrolled 115 predominantly medical patients. Of these, 93 (80.9%) had at least one ECG and one troponin; 44 of these 93 (47.3%) had at least one elevated troponin and 24 (25.8%) had an MI. Patients with MI had significantly higher mortality in the ICU (37.5% versus 17.6%; P = 0.050) and hospital (50.0% versus 22.0%; P = 0.010) than those without MI. After adjusting for Acute Physiology and Chronic Health Evaluation II score and need for inotropes or vasopressors, MI was an independent predictor of hospital mortality (odds ratio 3.22, 95% confidence interval 1.04–9.96). The presence of an elevated troponin (among those patients in whom troponin was measured) was not independently predictive of ICU or hospital mortality.
In this study, 47% of critically ill patients had an elevated troponin but only 26% of these met criteria for MI. An elevated troponin without ischemic ECG changes was not associated with adverse outcomes; however, MI in the ICU setting was an independent predictor of hospital mortality.
asphyxia is associated with cardiac dysfunction. This may be secondary
to myocardial ischaemia. Cardiac troponin T is the ideal marker for
myocardial necrosis. Elevated levels in cord blood may be associated
with intrauterine hypoxia and increased perinatal morbidity.
AIMS—To establish an
upper limit of normal for cardiac troponin T concentration in the cord
blood of infants. Relations between cardiac troponin T levels and other
variables were investigated.
samples were collected from 242 infants and analysed. Data on
gestation, birth weight, sex, Apgar scores, respiratory status, and
mode of delivery were recorded.
RESULTS—A total of 242 samples were collected, and 215 samples from infants without
respiratory distress were used to establish the 95th percentile of
0.050 ng/ml. The gestation of these infants ranged from 31 to 42 weeks
and birth weight ranged from 1.4 to 5 kg. There were no relations
between cardiac troponin T levels and the other variables in these
healthy infants. Twenty seven infants developed respiratory symptoms
requiring oxygen and/or ventilation. These infants had significantly
higher cord cardiac troponin T levels than their healthy counterparts
(median (interquartile range) 0.031 (0.010-0.084)
v 0.010 (0.010-0.014) ng/ml respectively; p < 0.001).
troponin T levels in the cord blood are unaffected by gestation, birth
weight, sex, or mode of delivery. Infants with respiratory distress had
significantly higher cord cardiac troponin T levels, suggesting that
cardiac troponin T may be a useful marker for myocardial damage in neonates.
In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown.
We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years.
With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 μg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 μg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there was a strong and graded increase in the cumulative incidence of cardiovascular death (adjusted hazard ratio per unit increase in the natural logarithm of the troponin T level, 2.09; 95% confidence interval [CI], 1.60 to 2.74; P<0.001) and of heart failure (adjusted hazard ratio, 2.20; 95% CI, 1.66 to 2.90; P<0.001) in this study group. Increased risk associated with higher levels of troponin T was evident well below the limit of detection of conventional cardiac troponin T assays and below the 99th percentile of values in a healthy population. There was no association between troponin T levels as measured with the highly sensitive assay and the incidence of myocardial infarction (adjusted hazard ratio, 1.16; 95% CI, 0.97 to 1.40; P = 0.11).
After adjustment for other independent prognostic indicators, cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated with the incidence of cardiovascular death and heart failure but not with myocardial infarction in patients with stable coronary artery disease.
BACKGROUND--The purpose of this study was to derive indices of reperfusion and non-reperfusion after acute myocardial infarction (AMI) from changes in serum concentrations of cardiac troponin T and to test the predictive value of these indices. METHODS--The indices were derived from a retrospective analysis of changes in serum troponin T concentration in 71 patients given thrombolytic treatment who had immediate and late angiography (group 1). These troponin T indices were first tested in a blinded and prospective study of 53 consecutive patients eligible for thrombolytic therapy (group 2). They were then used for the non-invasive assessment of reperfusion of AMI in 48 patients (group 3). RESULTS--In group 1 troponin T serum concentration curves were biphasic in patients who had reperfusion < or = 5.8 h after the onset of symptoms. Release of the cytosolic troponin T pool resulted in a peak at 14 h and ended at 38 h. The probability of reperfusion was > 95% when the ratio of peak cytosolic troponin T concentration to concentration at 38 h (PV1/38) exceeded 1.42 or the ratio of troponin T concentration at 14 h to that at 38 hours (14/38) exceeded 1.09. The probability of the presence of non-reperfused AMI was < 5% when troponin T PV1/38 and 14/38 ratios were < 0.99 and < 0.84 respectively. These discriminatory values of troponin T indices correctly classified (efficiency 96%) 48 of the 53 group 2 patients in whom immediate and late angiography were performed. When troponin T indices were used to classify 48 group 3 patients who were not studied by immediate angiography, thrombolytic therapy was deemed to have been successful in 82% of the treated patients, with spontaneous recanalisation in 11% and 23% of the non-treated patients assessed by PV1/38 and 14/38 respectively. CONCLUSION--The PV1/38 or 14/38 ratios of serum troponin T concentration indicated the effectiveness of thrombolytic therapy in achieving reperfusion of AMI.
The aim of this study was to use late gadolinium hyper‐enhancement cardiac magnetic resonance (LGE‐CMR) imaging to determine if a 72‐h troponin‐I measurement would provide a more accurate estimation of infarct size and microvascular obstruction (MVO) than serial creatine kinase (CK) or early troponin‐I values.
LGE‐CMR was performed 3.7±1.4 days after medical treatment for acute ST elevation or non‐ST elevation myocardial infarction. Infarct size and MVO were measured and correlated with serum troponin‐I concentrations, which were sampled 12 h and 72 h after admission, in addition to serial CK levels.
Ninety‐three patients, of whom 71 had received thrombolysis for ST elevation myocardial infarction, completed the CMR study. Peak CK, 12‐h troponin‐I, and 72‐h troponin‐I were related to infarct size by LGE‐CMR (r = 0.75, p<0.0001; r = 0.56, p = 0.0003; r = 0.62, p<0.0001 respectively). Serum biomarkers demonstrated higher values in the group with MVO compared with those without MVO (Peak CK 3085±1531 vs 1471±1135, p<0.001; 12‐h troponin‐I 58.3±46.9 vs 33.4±40.0, p = 0.13; 72‐h troponin‐I 11.5±9.9 vs 5.5±4.6, p<0.005). The correlation between the extent of MVO and 12‐h troponin‐I was not significant (r = 0.16), in contrast to the other serum biomarkers (peak CK r = 0.44, p<0.0001; 72‐h troponin‐I r = 0.46, p = 0.0002).
A single measurement of 72‐h troponin‐I is similar to serial CK measurements in the estimation of both myocardial infarct size and extent of MVO, and is superior to 12‐h troponin‐I measurements.
Ca2+ control of troponin-tropomyosin position on actin regulates cardiac muscle contraction. The inhibitory subunit of troponin, cardiac troponin I (cTnI) is primarily responsible for maintaining a tropomyosin conformation that prevents crossbridge cycling. Despite extensive characterization of cTnI, the precise role of its C-terminal domain (residues 193–210) is unclear. Mutations within this region are associated with restrictive cardiomyopathy, and C-terminal deletion of cTnI, in some species, has been associated with myocardial stunning.
We sought to investigate the effect of a cTnI deletion -removal of 17 amino acids from the C-terminus- on the structure of troponin-regulated tropomyosin bound to actin.
Methods and Results
A truncated form of human cTnI (cTnI1–192) was expressed and reconstituted with Troponin C and Troponin T to form a mutant troponin. Using electron microscopy and 3D-image reconstruction, we show that the mutant troponin perturbs the positional equilibrium dynamics of tropomyosin in the presence of Ca2+. Specifically, it biases tropomyosin position toward an “enhanced Cstate” that exposes more of the myosin-binding site on actin than found with wild-type troponin.
In addition to its well-established role of promoting the so-called “blocked-state” or “B-state”, cTnI participates in proper stabilization of tropomyosin in the “Ca2+-activated state” or “C-state”. The last 17 amino acids fulfill this stabilizing role. The data are consistent with a “fly-casting” model in which the mobile C-terminus of cTnI ensures proper conformational switching of troponin-tropomyosin. Loss of actin-sensing function within this domain, by pathological proteolysis or cardiomyopathic mutation, may be sufficient to perturb tropomyosin conformation.
troponin; thin filament; myocardial stunning; cardiomyopathy
The troponin complex plays an essential role in the thin filament regulation of striated muscle contraction. Of the three subunits of troponin, troponin I (TnI) is the actomyosin ATPase inhibitory subunit and its effect is released upon Ca2+-binding to troponin C. The exon 8-encoded COOH-terminal end segment represented by the last 24 amino acids of cardiac TnI is highly conserved and critical to the inhibitory function of troponin. Here we investigated the function and calcium regulation of the COOH-terminal end segment of TnI. A TnI model molecule was labeled with Alexa fluor 532 at a Cys engineered at the COOH-terminal end and used to reconstitute tertiary troponin complex. A Ca2+-regulated conformational change in the COOH terminus of TnI was shown by a sigmoid-shape fluorescence intensity titration curve similar to that of the circular dichroism calcium titration curve of troponin C. Such corresponding Ca2+-responses are consistent with the function of troponin as a coordinated molecular switch. Reconstituted troponin complex containing a mini-troponin T lacking its two tropomyosin-binding sites showed a saturable binding to tropomyosin at pCa 9 but not at pCa 4. This Ca2+-regulated binding was diminished when the COOH-terminal 19 amino acids of cardiac TnI were removed. These results provided novel evidence for suggesting that the COOH-terminal end segment of TnI participates in the Ca2+-regulation of muscle thin filament through an interaction with tropomyosin.
Troponin I; COOH-terminus; Tropomyosin; Calcium
Background: An early identification of the patients with the Acute Coronary Syndrome (ACS) is of prime importance, due to the associated very high mortality. Only about 22% of the patients who present at the emergency cardiology care centres with chest pain, have coronary disease. Ischaemia modified albumin has already been licensed by the US Food and Drug Administration for the diagnosis of suspected myocardial ischaemia.
Aim: The goal of the present study was to assess the diagnostic value of serum ischaemia modified albumin and to compare it with sensitive cardiac troponin I in patients with the acute coronary syndromes like unstable angina and acute myocardial infarction.
Methods: A diagnostic case control study was conducted on 102 patients who presented to the Emergency Department within 6 hrs of having acute chest pain and on 110 healthy age and sex matched volunteers who formed the control group. The serum Ischaemia Modified Albumin level was estimated by the albumin cobalt binding test by using a digital spectrophotometer, while Troponin I was measured by doing an immunofluroscence assay. A receiver operating characteristic curve was established for ischaemia modified albumin, to determine the cut-off point. The sensitivity and the specificity of ischaemia modified albumin and troponin I for the detection of acute coronary syndromes, were analyzed. The results of ischaemia modified albumin and troponin I alone and in combination, were correlated.
Results: The ischaemia modified albumin (p<0.05) and the troponin I (p<0.001) concentrations were significantly higher in acute myocardial infarction and in unstable angina than in the healthy controls. The sensitivity and the specificity of ischaemia modified albumin for the detection of acute coronary syndromes was 88% and 93% as compared to 87% and 75% respectively for troponin I. The combined use of ischaemia modified albumin and troponin I significantly enhanced the sensitivity to 96%. The area which was under the Receiver Operating Characteristic (ROC) curve of ischaemia modified albumin in acute coronary syndromes was 0.90.
Conclusion: Ischaemia modified albumin is a useful biochemical marker for the early diagnosis of acute coronary syndrome. The combined use of ischaemia modified albumin and cardiac troponin I enhances the sensitivity and specificity. Hence, a combination of ischaemia modified albumin and cardiac troponin I can be used as a more precise diagnostic marker for Acute Coronary Syndrome.
Acute Coronary Syndrome; Ischaemia modified albumin; Troponin I; Myocardial Ischaemia
The continuing advances in the biochemical research for the discovering an ideal biomarker for diagnosing myocardial injury have led to discovery cardiac Troponin, a biochemical gold standard for myocardial necrosis. Further with advances in the immunoassay techniques, the 99th percentile cutoff value of cardiac troponin required for the diagnosis of myocardial infarction decreased, with the latest available ultrasensitive cardiac troponin assay capable of measuring level as low as 0.005 ng/ml. Troponin have both diagnostic as well as prognostic significance in myocardial necrosis, but the cut off value by 99th percentile rule is useful only when applied to patients with a high pretest probability of Acute Coronary Syndrome(ACS) and also the results must be interpreted in the context of clinical history, ECG findings, and possibly cardiac imaging to establish the correct diagnosis. As cardiac troponins are also elevated in other cardiac conditions such as cardiomyopaties, the serial monitoring of the cardiac troponin level along with the absolute value would help to differentiate myocardial infarction from these many varied conditions, with the interval of serial assay being reduced to 3 hours. The aim of this review is to complement the advantages, to emphasize on proper interpretation of positive results, to appraise the challenges faced with the available cardiac troponin assays and need for further research to overcome them and build up the most ideal cardiac marker for diagnosing the myocardial infarction.
Acute coronary syndrome; cardiac troponin; myocardial infarction
Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.
This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.
We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).
Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.
Septic shock; myocardial ischemia; vasopressin; norepinephrine; troponin; electrocardiogram
Cerebral hypoperfusion during cardiopulmonary bypass surgery has been thought to be a factor in the aetiology of brain damage with evidence of post-operative neurological deficits. Cardiac-specific biomarkers such as troponin-I, troponin-T and CK-MB have been used extensively to predict myocardial injury and ischaemia. This prospective study investigateed the level of troponin-I release in both off-pump and CPB-technique CABG surgery, as well as postulated a relationship of troponin release and post-operative neurological outcome. A total of 44 adult patients undergoing coronary artery bypass graft (CABG) were enrolled into either an off-pump or on-pump groups, with 22 patients participating in each. Group A (on-pump) underwent myocardial revascularisation with CPB and cardioplegic arrest, while Group B (off pump) underwent beating heart surgery. The measurement of troponin-I is a 1-step enzyme immunoassay method, with specificity and sensitivity set at 0.4 ug/mL. Neurological assessment was done using the NIH Stroke Scale, and neuropsychologic assessment was assessed on cognitive function using modified Weschler Memory Scale, for which scores were standardized to achieve a composite measure of concentration. A set of statistical analysis was done to correlate troponin-I release with different surgical techniques of CPB and OPCAB. Although each independent technique showed a marked rise of troponin-I from baseline to 6 hours post-operatively, the difference in troponin release was not significant between the 2 groups at specified time intervals (p=0.124). There was however a significant correlation of troponin-I release with the number of grafts used in the surgery, irrespective of the type of grafts or surgical technique. None of the patients in either group showed any neurological or cognitive deficits presenting at day 3 and day 7 post-operatively. The findings of this study demonstrate that there is no significant short-term cognitive or neurological dysfunctions post-operatively, as indicated by troponin-I release in assessing the severity of myocardial injury.