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1.
High-Sensitivity Cardiac Troponin T Improves the Diagnosis of Perioperative MI.
Brown, JC, Samaha, E, Rao, S, Helwani, MA, Duma, A, Brown, F, Gage, BF, Miller, JP, Jaffe, AS, Apple, FS, et al
Anesthesia and analgesia. 2017;(5):1455-1462
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Abstract
BACKGROUND The diagnosis of myocardial infarction (MI) after noncardiac surgery has traditionally relied on using relatively insensitive contemporary cardiac troponin (cTn) assays. We hypothesized that using a recently introduced novel high-sensitivity cTnT (hscTnT) assay would increase the detection rate of perioperative MI. METHODS In this ancillary study of the Vitamins in Nitrous Oxide trial, readjudicated incidence rates of myocardial injury (new isolated cTn elevation) and MI were compared when diagnosed by contemporary cTnI versus hscTnT. We probed various relative (eg, >50%) or absolute (eg, +5 ng/L) hscTnT change metrics. Inclusion criteria for this ancillary study were the presence of a baseline and at least 1 postoperative hscTnT value. RESULTS Among 605 patients, 70 patients (12%) had electrocardiogram changes consistent with myocardial ischemia; 82 patients (14%) had myocardial injury diagnosed by contemporary cTnI, 31 (5.1%) of which had an adjudicated MI. After readjudication, 67 patients (11%) were diagnosed with MI when using hscTnT, a 2-fold increase. Incidence rates of postoperative myocardial injury ranged from 12% (n = 73) to 65% (n = 393) depending on the hscTnT metric used. Incidence rates of MI using various hscTnT change metrics and the presence of ischemic electrocardiogram changes, but without event adjudication, ranged from 3.6% (n = 22) to 12% (n = 74), a >3-fold difference. New postoperative hscTnT elevation, either by absolute or relative hscTnT change metric, was associated with an up to 5-fold increase in 6-month mortality. CONCLUSIONS The use of hscTnT compared to contemporary cTnI increases the detection rate of perioperative MI by a factor of 2. Using different absolute or relative hscTnT change metrics may lead to under- or overdiagnosis of perioperative MI.
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High-sensitivity cardiac troponin I and B-type natriuretic Peptide as predictors of vascular events in primary prevention: impact of statin therapy.
Everett, BM, Zeller, T, Glynn, RJ, Ridker, PM, Blankenberg, S
Circulation. 2015;(21):1851-60
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Abstract
BACKGROUND Cardiac troponin and B-type natriuretic peptide (BNP) concentrations are associated with adverse cardiovascular outcome in primary prevention populations. Whether statin therapy modifies this association is poorly understood. METHODS AND RESULTS We measured high-sensitivity cardiac troponin I (hsTnI) in 12 956 and BNP in 11 076 participants without cardiovascular disease in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial before randomization to rosuvastatin 20 mg/d or placebo. Nearly 92% of participants had detectable circulating hsTnI, and 2.9% of men and 4.1% of women had levels above proposed sex-specific reference limits of 36 and 15 ng/L, respectively. hsTnI concentrations in the highest tertile were associated with a first major cardiovascular event (adjusted hazard ratio [aHR], 2.19; 95% confidence interval, 1.56-3.06; P for trend <0.001). BNP levels in the highest tertile were also associated a first cardiovascular event (aHR, 1.94; 95% confidence interval, 1.41-2.68; P for trend <0.001). The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02). Rosuvastatin was equally effective in preventing a first cardiovascular event across categories of hsTnI (aHR range, 0.50-0.60) and BNP (aHR range, 0.42-0.67) with no statistically significant evidence of interaction (P for interaction=0.53 and 0.20, respectively). CONCLUSIONS In a contemporary primary prevention population, baseline cardiac troponin I and BNP were associated with the risk of vascular events and all-cause mortality. The benefits of rosuvastatin were substantial and consistent regardless of baseline hsTnI or BNP concentrations. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
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Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction.
Solecki, K, Dupuy, AM, Kuster, N, Leclercq, F, Gervasoni, R, Macia, JC, Cung, TT, Lattuca, B, Cransac, F, Cade, S, et al
Clinical chemistry and laboratory medicine. 2015;(5):707-14
Abstract
BACKGROUND Cardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI). METHODS We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines. RESULTS Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9-12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1-99.9) vs. cTnI by 86.8% (76.6-92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9-42.9) when compared with CK that fell by 79.5% (64.3-90.7). CONCLUSIONS Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.
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A comparison of markers of myocardial injury and their relation to nutritional parameters in hemodialysis patients.
Stosovic, MD, Stankovic, SDj, Stanojevic, MLj, Simic-Ogrizovic, SP, Jovanovic, DB, Naumovic, RT
Renal failure. 2014;(7):1060-6
Abstract
BACKGROUND Serum cardiac troponin T (cTnT) is a valuable marker of ischemic heart disease (IHD) and left ventricular hypertrophy, as well as a mortality predictor in hemodialysis populations. We compared the value of cTnT, creatinine kinase (CK)-MB mass and myoglobin as mortality predictors in our hemodialysis patients and evaluated their relation to nutritional status. METHODS A total of 118 hemodialysis patients were prospectively studied from January 2004 to April 2013. Clinical and laboratory evaluations during the 12-month baseline period included the history of IHD, signs of left ventricular hypertrophy (LVH), Kt/V and serum cardiac markers together with the percentage of body fat (%fat), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), triceps skinfold (TSF) and BMI. RESULTS Underweight patients had significantly higher cTnT values (Mann-Whitney, p<0.05). Correlation analysis (Spearman) showed an inverse association between cTnT and TSF (ρ=-0.22, p<0.05), as well as between CK-MB mass and TSF (ρ=-0.26, p<0.01). In men cTnT also correlated inversely with %fat (ρ=-0.27, p<0.05) and BMI (ρ=-0.33, p<0.05). In addition, myoglobin was correlated significantly with MAC, MAMC and albumin. Among cardiac markers cTnT was the only independent variable predicting mortality (Multivariate Cox regression, HR=1.04 CI (1.01-1.07); p<0.01; measurement units 0.01 μg/L). CONCLUSION Troponin T and CK-MB mass were significantly elevated in the underweight patient group. Troponin T was the only independent cardiac marker predictor of all cause mortality in our hemodialysis patients.
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Combined use of the novel biomarkers high-sensitivity troponin T and ST2 for heart failure risk stratification vs conventional assessment.
Lupón, J, de Antonio, M, Galán, A, Vila, J, Zamora, E, Urrutia, A, Bayes-Genis, A
Mayo Clinic proceedings. 2013;(3):234-43
Abstract
OBJECTIVE To assess an innovative multimarker strategy for risk stratification of death in a real-life ambulatory heart failure (HF) cohort. PATIENTS AND METHODS The study included 876 consecutive outpatients (median age, 70.3 years; left ventricular ejection fraction, 34%) between May 22, 2006, and July 7, 2010, prospectively followed up in a structured HF unit. A combination of biomarkers reflecting myocardial stretch (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), myocyte injury (high-sensitivity cardiac troponin T [hs-cTnT]), and ventricular fibrosis and remodeling (high-sensitivity ST2 [hs-ST2]) were added to an assessment based on established mortality risk factors (age, sex, left ventricular ejection fraction, New York Heart Association functional class, diabetes mellitus, estimated glomerular filtration rate, ischemic etiology, sodium level, hemoglobin level, and pharmacologic treatment). RESULTS During median follow-up of 41.4 months, 311 patients died. The combined addition of hs-cTnT and hs-ST2 to the model yielded good measurements of performance (C statistic, 0.789; Bayesian information criterion, 3611; integrated discrimination improvement, 4.1 [95% CI, 2.5-5.6]; and net reclassification index, 13.9% [95% CI, 6.2-21.6]). Reclassification did not significantly benefit after NT-proBNP addition into the full model; some indices even worsened with all 3 biomarkers. Separate addition of NT-proBNP provided prognostic discrimination only in the subgroup of patients with either hs-cTnT or hs-ST2 levels below the cutoff points (hazard ratio, 2.97; 95% CI, 2.24-9.39; P<.001). CONCLUSION A multimarker strategy seems useful for stratifying risk in chronic HF. However, NT-proBNP in addition to the new-generation biomarkers hs-cTnT and hs-ST2 had a limited effect on risk stratification.
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Myofibrillar Ca(2+) sensitivity is uncoupled from troponin I phosphorylation in hypertrophic obstructive cardiomyopathy due to abnormal troponin T.
Bayliss, CR, Jacques, AM, Leung, MC, Ward, DG, Redwood, CS, Gallon, CE, Copeland, O, McKenna, WJ, Dos Remedios, C, Marston, SB, et al
Cardiovascular research. 2013;(3):500-8
Abstract
AIMS: We studied the relationship between myofilament Ca(2+) sensitivity and troponin I (TnI) phosphorylation by protein kinase A at serines 22/23 in human heart troponin isolated from donor hearts and from myectomy samples from patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS AND RESULTS We used a quantitative in vitro motility assay. With donor heart troponin, Ca(2+) sensitivity is two- to three-fold higher when TnI is unphosphorylated. In the myectomy samples from patients with HOCM, the mean level of TnI phosphorylation was low: 0.38 ± 0.19 mol Pi/mol TnI compared with 1.60 ± 0.19 mol Pi/mol TnI in donor hearts, but no difference in myofilament Ca(2+) sensitivity was observed. Thus, troponin regulation of thin filament Ca(2+) sensitivity is abnormal in HOCM hearts. HOCM troponin (0.29 mol Pi/mol TnI) was treated with protein kinase A to increase the level of phosphorylation to 1.56 mol Pi/mol TnI. No difference in EC(50) was found in thin filaments containing high and low TnI phosphorylation levels. This indicates that Ca(2+) sensitivity is uncoupled from TnI phosphorylation in HOCM heart troponin. Coupling could be restored by replacing endogenous troponin T (TnT) with the recombinant TnT T3 isoform. No difference in Ca(2+) sensitivity was observed if TnI was exchanged into HOCM heart troponin or if TnT was exchanged into the highly phosphorylated donor heart troponin. Comparison of donor and HOCM heart troponin by mass spectrometry and with adduct-specific antibodies did not show any differences in TnT isoform expression, phosphorylation or any post-translational modifications. CONCLUSION An abnormality in TnT is responsible for uncoupling myofibrillar Ca(2+) sensitivity from TnI phosphorylation in the septum of HOCM patients.
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Use of troponin to diagnose periprocedural myocardial infarction: effect on composite endpoints in the British Bifurcation Coronary Study (BBC ONE).
Cockburn, J, Behan, M, de Belder, A, Clayton, T, Stables, R, Oldroyd, K, Curzen, N, Hildick-Smith, D
Heart (British Cardiac Society). 2012;(19):1431-5
Abstract
BACKGROUND Periprocedural myocardial infarction (PMI; ESC/ACC type 4a) is diagnosed on the basis of elevation of cardiac enzymes more than three times the 99th centile upper reference limit. Recent guidelines recommend the use of troponin instead of creatine kinase (CK) to diagnose PMI, but this assay increases diagnostic sensitivity, while the clinical significance of small increases in troponin remains undetermined. We examined the effects of using the new definition on the incidence of a composite endpoint (previously defined by CK) in a contemporary clinical randomised trial-the British Bifurcation Coronary Study (BBC ONE). METHODS The BBC ONE trial randomly allocated 500 patients with coronary bifurcation lesions to either a simple or complex stenting strategy. The composite primary endpoint (CPEP) included death, myocardial infarction (MI) (PMI plus subsequent MI) and target vessel failure, at 9 months. RESULTS In BBC ONE the CPEP occurred in 8% versus 15.2% in the simple and complex groups, respectively (HR 2.02, 95% CI 1.17 to 3.47, p=0.009). This difference was largely driven by PMI, which occurred in nine (3.6%) versus 28 (11.2%) patients (HR 3.24, 95% CI 1.53 to 6.86, p=0.001). Using troponin, PMI would have occurred in 71 (28.4%) versus 114 (45.6%) patients, respectively (HR 1.61, 95% CI 1.27 to 2.05, p=0.001), and the CPEP in 32% versus 48% of patients (HR 1.50, 95% CI 1.2 to 1.87, p=0.001). Use of troponin increased MI detection fivefold, from 7.4% to 37.0% overall. CONCLUSIONS Use of troponin would have led to a fivefold increase in diagnosis of PMI in the BBC ONE trial. Incorporation of PMI into a composite endpoint may no longer be justified in many interventional trials.
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Rapid detection of myocardial infarction with a sensitive troponin test.
Scharnhorst, V, Krasznai, K, van't Veer, M, Michels, R
American journal of clinical pathology. 2011;(3):424-8
Abstract
Rapid identification and treatment of patients with a myocardial infarction (MI) is mandatory. We studied the diagnostic capacities of a sensitive troponin assay for detection of MI in emergency department patients within 2 hours after arrival. The study included 157 patients suspected of having non-ST-elevation acute coronary syndrome. Blood was drawn on arrival (T0) and 2 (T2), 6, and 12 hours later. At T2, a troponin concentration above the MI cutoff is 87% sensitive and 100% specific for MI detection (positive predictive value [PPV], 100%; negative predictive value [NPV], 96%). If a difference of more than 30% between the troponin measurements at T0 and T2 in the absence of an absolute troponin increase above the 99th percentile of a reference population is also considered indicative of MI, the sensitivity increases to 100% and specificity decreases to 87% (PPV, 70%; NPV, 100%). Sensitivity and specificity of creatine kinase-MB and myoglobin are lower than those of troponin. By using a sensitive troponin assay and simple algorithms, the diagnosis of MI can be determined within 2 hours after arrival at the emergency department. Measurement of myoglobin and creatine kinase-MB has no added value.
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Association between fibroblast growth factor 23 and left ventricular hypertrophy in maintenance hemodialysis patients. Comparison with B-type natriuretic peptide and cardiac troponin T.
Negishi, K, Kobayashi, M, Ochiai, I, Yamazaki, Y, Hasegawa, H, Yamashita, T, Shimizu, T, Kasama, S, Kurabayashi, M
Circulation journal : official journal of the Japanese Circulation Society. 2010;(12):2734-40
Abstract
BACKGROUND Fibroblast growth factor 23 (FGF-23) is a novel bone-derived phosphate-regulating hormone, and serum FGF-23 levels are associated with mortality among hemodialysis (HD) patients. However, the pathophysiological role of FGF-23 in those patients remains unclear, so the association between serum FGF-23 levels and known cardiac biomarkers or echocardiographic measurements were investigated in long-term HD patients without cardiac symptoms. METHODS AND RESULTS The 87 consecutive patients treated in a single HD center (51 males, 36 females; mean age 64 years, mean HD duration 5.8 years) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. Serum FGF-23 levels in dialysis patients were 1,171±553pg/ml. In univariate analysis, serum phosphate (r=0.443, P<0.001) and calcium levels (r=0.256, P=0.04), left ventricular mass index (LVMI) (r=0.268, P=0.039) were significantly associated with FGF-23 levels. Neither the B-type natriuretic peptide (BNP) nor the cardiac troponin T level was correlated with FGF-23. In multivariate regression analysis, only LVMI (β=0.287, P=0.031, confidence interval (CI) 0.390-8.040) and phosphate levels (β=0.419, P=0.001, CI 57.12-207.7) and calcium levels (β=0.277, P=0.025, CI 24.95-360.1) remained significantly correlated with FGF-23. CONCLUSIONS Beside BNP, FGF-23 was identified as a factor that is significantly associated with LVMI. FGF-23 could be a novel biomarker of left ventricular overload, which is closely associated with the increased risk of death in HD patients.
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Comparison of Troponin T to creatine kinase and to radionuclide cardiac imaging infarct size in patients with ST-elevation myocardial infarction undergoing primary angioplasty.
Tzivoni, D, Koukoui, D, Guetta, V, Novack, L, Cowing, G, ,
The American journal of cardiology. 2008;(6):753-7
Abstract
Troponin is used mainly for detection of minor myocardial damage, whereas repeated measurements of creatine kinase (CK) and myocardial band (CK-MB) are used for assessing infarct size in patients with myocardial infarction. The purpose of this study was to correlate peak level and area under the curve (AUC) of troponin T to that of CK and CK-MB and with single-photon emission computed tomographic infarct size and left ventricular function in patients with ST elevation myocardial infarction. In this multicenter study (29 centers, 5 countries), we included 267 patients who underwent primary coronary intervention within 6 hours of onset of symptoms. All had repeated measurements of troponin T, CK, and CK-MB. Infarct size and left ventricular function were assessed by single-photon emission computed tomography performed on days 7 and 30. Mean infarct sizes were 14% on day 7 and 10% on day 30, and mean ejection fractions were 42% on day 7 and 45% on day 30 after the acute infarct. Very high correlation (r >0.85, Spearman correlation) was found between peak level and AUC of troponin T, CK, and CK-MB. Similar high correlation was found between peak level and AUC of troponin, CK, and CK-MB with single-photon emission computed tomographic infarct size (r >0.70). In conclusion, based on the results of this multicenter study, we suggest that peak levels and AUC of troponin are as accurate as CK and CK-MB in estimating myocardial infarct size.