Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review.

INTRODUCTION: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. METHODS: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection". RESULTS: Current literature data suggest adopting longer (≥10-14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45-50%), MDR (35%), XDR (15-20%), PDR (5.9-6.2%), and carbapenemases (CP)/metallo-ß-lactamases (MBL)-producing (12.5-20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5-7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum ß-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum ß-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. CONCLUSIONS: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.

Glycated Albumin for Glycemic Control in T2DM Population: A Multi-Dimensional Evaluation.

PURPOSE: To investigate the glycated albumin (GA) introduction implications, as an add-on strategy to traditional glycemic control (Hb1Ac and fasting plasma glucose - FPG) instruments, considering insulin-naïve individuals with type 2 diabetes mellitus (T2DM), treated with oral therapies. METHODS: A Health Technology Assessment was conducted in Italy, as a multi-dimensional approach useful to validate any innovative technology. The HTA dimensions, derived from the EUnetHTA Core Model, were deployed by means of literature evidence, health economics tools and qualitative questionnaires, filled-in by 15 professionals. RESULTS: Literature stated that the GA introduction could lead to a higher number of individuals achieving therapeutic success after 3 months of therapy (97.0% vs 71.6% without GA). From an economic point of view, considering a projection of 1,955,447 T2DM insulin-naïve individuals, potentially treated with oral therapy, GA introduction would imply fewer individuals requiring a therapy switch (-89.44%), with a 1.06% in costs reduction, on annual basis, thus being also the preferable solution from a cost-effectiveness perspective (cost-effectiveness value: 237.74 vs 325.53). According to experts opinions, lower perceptions on GA emerged with regard to equity aspects (0.13 vs 0.72, p-value>0.05), whereas it would improve both individuals (2.17 vs 1.33, p-value=0.000) and caregivers quality of life (1.50 vs 0.83, p-value=0.000). Even if in the short term, GA required additional investments in training courses (-0.80 vs 0.10, p-value = 0.036), in the long run, GA could become the preferable technology (0.30 vs 0.01, p-value=0.018) from an organisational perspective. CONCLUSION: Adding GA to traditional glycaemic control instruments could improve the clinical pathway of individuals with T2DM, leading to economic and organisational advantages for both hospitals and National Healthcare Systems.

Effortful speech with distortion of prosody following SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a 48-year-old Caucasian woman with SARS-CoV-2 infection followed by the onset of word finding difficulties, effortful speech along with prosody distortion, in the context of spared semantic and syntactic abilities. The clinical picture, perceived as foreign accent syndrome (FAS), was not associated with structural and functional imaging changes or neurophysiological assessment abnormalities. We suggest that FAS, herein perceived as a regional accent syndrome, should be considered a possible additional neurological manifestation of SARS-CoV-2.

Laboratory predictors of death from coronavirus disease 2019 (COVID-19) in the area of Valcamonica, Italy.

Background Comprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity. Methods The final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge). Results Compared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death. Conclusions The most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.

Glucose meters: What's the laboratory reference glucose?

BACKGROUND: The accuracy of glucose meters is evaluated by comparing their results with those from a reference laboratory glucose analyser. The main scientific societies recommend the use of a prompt glycolysis inhibitor such as citrate for an accurate glucose determination. In the present preliminary study, we discuss the bias between capillary and plasma glucose measured concentrations, determined in two Italian clinical laboratories, using tubes containing an NaF and citrate mixture in liquid and granular form. METHODS: 139 volunteers in whom 75 g OGTT was requested were recruited. Basal capillary glucose was determined using Abbott FreeStyle Precision Neo in Brescia (n=63), while clinical laboratory reference P-glucose was determined using tubes containing NaF/K3EDTA and liquid NaF/Na2EDTA/citrate. Basal capillary glucose was determined using a Roche Cobas Accu-Chek Inform II in Vicenza (n=76), while P-glucose was determined using tubes containing NaF/K2Ox and NaF/Na2EDTA/citrate in granulated form. Reference P-glucose was determined with a hexokinase method on Dimension Vista systems. Differences between capillary and reference P-glucose were evaluated according to ADA/ISO 15197:2013 specifications. RESULTS: 96.82% and 97.37% of capillary determinations were within specifications when liquid and granular citrate mixture tubes were used, respectively. Conversely, only 73.02% and 80.26% of determinations were within criteria using NaF. CONCLUSIONS: It's important to know what is the laboratory reference glucose in evaluating glucose meters' accuracy. The evaluation of glucometers' accuracy with respect to a reference laboratory may be wrong if tubes containing only NaF are used due to in vitro glycolysis. Only tubes containing citrate mixture permit the correct evaluation of glucose meters' accuracy.

Clinical impact of citrate-containing tubes on the detection of glucose abnormalities by the oral glucose tolerance test.

Background Plasma glucose levels provide the cornerstone of diabetes evaluation, and so it is crucial that clinical laboratories provide accurate and reliable plasma glucose results. To prevent in vitro glycolysis, citrate is used. Here, we present the first study on the 75-g oral glucose tolerance test (OGTT) using the currently available new citrate-containing tubes in liquid and granular forms and the previous sodium fluoride (NaF) for the diagnosis of carbohydrate metabolism disorders and gestational diabetes mellitus (GDM) according to the American Diabetes Association (ADA) guidelines. Methods The 75-g OGTT was performed in 147 volunteers, 83 of whom were pregnant women. Blood was collected in NaF/K3 ethylenediaminetetraacetic acid (EDTA) and NaF/Na2EDTA/citrate in liquid form in tubes in Brescia and in NaF/K2Ox and NaF/Na2EDTA/citrate in granular form in Vicenza. Glucose was measured within 3-4 h from the OGTT. The mean biases were calculated and compared with the desirable bias (<± 2.1%). Results OGTT glucose concentrations were higher in citrate tubes when compared to NaF-containing tubes. When citrate tubes were used, GDM increased to 12.5 and 11.7% in Brescia and Vicenza, respectively. Impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) increased to 36.7, 6.7 and 3.4%, respectively, in Brescia. In Vicenza, an increase of 47 and 1.9% in IFG and IGT, respectively, was found. Conclusions OGTT glucose measurement in citrate-containing tubes was shown to be more effective than those containing only NaF in diagnosing carbohydrate disorders. This new glycolysis inhibitor seems to be a necessary preanalytical tool for accurate and reliable plasma glucose results.

Effects of different anticoagulants on glycated albumin quantification.

INTRODUCTION: In the last 20 years glycated albumin (GA) measurement has been demonstrated to be a reliable glycation marker and recently as the most innovative one in western countries. Glycated albumin has been already adopted by some Asian countries due to its usefulness in diabetes screening. The aim of the present study was to investigate for the first time the effects of different anticoagulants on GA assay. MATERIALS AND METHODS: From each of 60 patients a serum tube and K3EDTA, Li-Heparin and NaF-EDTA containing tubes were collected. All tubes were from Sarstedt (Verona, Italy). Glycated albumin was measured in duplicate in each sample tube in a single analytical run with quantILab glycated albumin (Instrumentation Laboratory SpA - A Werfen Company, Milan, Italy) on Architect c8000 analyser (Abbott SRL, Rome, Italy). Comparison of GA% in evaluated tubes was made by paired Wilcoxon test. RESULTS: Median and interquartile range GA% concentrations were 15.4% (13.2 - 19.1) in serum, 15.7% (13.6 - 19.9) in K3EDTA, 15.6% (13.3 - 19.7) in Li-heparin and 15.5% (13.1 - 19.3) in NaF-EDTA samples, respectively. Glycated albumin mean relative bias respect to serum was within desirable bias derived from biological variation studies (± 2.9%) when K3EDTA (+ 2.8%), Li-heparin (+ 0.9%) or NaF-EDTA (+ 0.1%), were used as anticoagulants. CONCLUSIONS: Our results demonstrate that the GA% assay is not affected by relevant interferences when K3EDTA, Li-heparin or NaF-EDTA are used as anticoagulants, so they can be used interchangeably without a relevant impact on the clinical use of the test.

The new Greiner FC-Mix tubes equal the old Terumo ones and are useful as glucose stabilizer after prolonged storage of samples.

INTRODUCTION: The aim of our study is to compare new Greiner tubes containing granulated citrate buffer with the Terumo ones and to verify if they are suitable for glucose stabilization after prolonged storage. MATERIALS AND METHODS: In Study 1, blood was collected in two Terumo and two Greiner tubes from 40 healthy volunteers. Samples were stored at room temperature (RT) for 1 and 2 hours, respectively. Comparison was made by Deming regression. In Study 2, glucose was measured in a reference tube (N = 50), according to the ADA-NACB guidelines and in aliquots of Greiner samples maintained un-centrifuged at RT for 1, 2, 4 (N = 50) and 24, 48, 72 hours (N = 35). RESULTS: There were insignificant mixed biases between the Terumo and Greiner tubes. Compared to reference (5.3 mmol/L), glucose concentration in the new tubes was 5.4 (P < 0.05), 5.4 (P < 0.05), 5.3 (P = 0.265), 5.2 (P = 0.156), 5.3 (P < 0.05) and 5.2 (P < 0.05) mmol/L after 1, 2, 4, 24, 48 and 72 hours at RT, respectively. There was no biological difference between any of the time points up to 48 h (bias < ± 1.95%). CONCLUSIONS: The study shows that the new tubes perform equally well as the Terumo ones and ensure glucose stabilization up to 48 h as well as permit to create a link between the previous studies demonstrating the clinical utility of granulated citrate buffer and the future ones.

Multicenter evaluation of an enzymatic method for glycated albumin.

BACKGROUND: The use of glycated albumin (GA) has been proposed as an additional glycemic control marker particularly useful in intermediate-term monitoring and in situation when HbA1c test is not reliable. METHODS: We have performed the first multicenter evaluation of the analytical performance of the enzymatic method quantILab Glycated Albumin assay implemented on the most widely used clinical chemistry analyzers (i.e. Abbott Architect C8000, Beckman Coulter AU 480 and 680, Roche Cobas C6000, Siemens ADVIA 2400 and 2400 XPT). RESULTS: The repeatability of the GA measurement (expressed as CV, %) implemented in the participating centers ranged between 0.9% and 1.2%. The within-laboratory CVs ranged between 1.2% and 1.6%. A good alignment between laboratories was found, with correlation coefficients from 0.996 to 0.998. Linearity was confirmed in the range from 7.6 to 84.7%. CONCLUSION: The new enzymatic method for glycated albumin evaluated by our investigation is suitable for clinical use.

Effectiveness of citrate buffer-fluoride mixture in Terumo tubes as an inhibitor of in vitro glycolysis.

INTRODUCTION: Glycolysis affects glucose determination in vitro. The placement of sample tubes in ice-water slurry with plasma separation within 30 minutes is recommended, or alternatively the use of a glycolysis inhibitor. The aim of our two-steps study was to evaluate which Terumo tube is best for glucose determination in routine clinical setting. MATERIALS AND METHODS: In the first study, blood from 100 volunteers was collected into lithium heparin (LH), NaF/Na heparin (FH) and NaF/citrate buffer/Na2EDTA (FC-Mixture) tubes. LH sample was treated as recommended and considered as reference, while FH and FC-Mixture samples were aliquoted, maintained at room temperature (RT) for 1, 2 and 4 hours; centrifuged and plasma analysed in triplicate. In the second study, samples from 375 volunteers were collected in LH, FH and FC-Mixture tubes and held at RT before centrifugation from 10 to 340 minutes, depending on each laboratory practice. Samples were analysed in one analytical run. RESULTS: In the first study, FH glucose concentrations were 5.15 ± 0.66 mmol/L, 5.05 ± 0.65 mmol/L and 5.00 ± 0.65 mmol/L (P < 0.001) in tubes stored at RT for 1, 2 and 4 hours, respectively. Mean biases in all time points exceeded the analytical goal for desirable bias based on biological variation criteria. FC-Mixture glucose concentrations were 5.48 ± 0.65 mmol/L, 5.46 ± 0.6 mmol/L and 5.46 ± 0.64 mmol/L in tubes stored at RT for 1, 2 and 4 hours, respectively. Mean biases for FC-Mixture glucose in all time points reached optimal analytical goals. In the second study, the biases for LH and FH glucose compared to reference FC-Mixture glucose exceeded the preset analytical goals, regardless of the blood collection to centrifugation time interval. CONCLUSIONS: FC-mixture tubes glucose concentrations were preserved up to 4h storage at RT. We confirmed that NaF alone does not allow immediate glycolysis inhibition in real life pre-centrifugation storage conditions (up to 340 minutes). FC-Mixture should be used exclusively for glucose determination in laboratories unable to implement the recommended blood samples' treatment.

Which sample tube should be used for routine glucose determination?

BACKGROUND: Glucose is one of the most frequently requested analytes in clinical laboratory. Blood glucose analysis is affected from in vitro glycolysis. In order to determine the most suitable blood collection tube for this purpose we have compared different tubes: sodium fluoride, lithium heparin, sodium fluoride/citrate buffer containing tubes and serum with clot activator tube for the measurement of glucose when the tube has been kept at room temperature (RT) for up to 4h. METHODS: Venous blood was collected from 49 healthy volunteers into Sarstedt S-Monovettes for glucose analysis. Reference plasma glucose was determined in a lithium heparin tube and immediately placed in an ice/water slurry. Within 10min it was centrifuged at 4°C and plasma was separated from the blood cells. Samples have been preserved at RT for 1, 2 and 4h after drawing. Glucose has been determined using a hexokinase method. RESULTS: Glucose levels tested in a serum with clot activator tube, in lithium heparin and in sodium fluoride/sodium EDTA tubes when compared with lithium-heparin reference plasma did not meet the desirable bias for glucose (±1.8%) when kept at RT for up to 4h. GlucoEXACT tubes, when corrected by the Sarsted recommended factor of 1.16, showed a mean (95% CI) bias of +0.96% (0.45-1.47) at 1h, +1.40% (0.88-1.93) at 2h and +0.95% (0.44-1.46) at 4h, reaching the analytical goal for the desirable bias. CONCLUSIONS: Samples collected into GlucoEXACT tubes containing sodium fluoride/citrate buffer liquid mixture are equivalent to those collected in reference plasma tubes avoiding glycolysis completely and within a 4h delay in plasma separation.

Troponin T levels in patients with acute heart failure: clinical and prognostic significance of their detection and release during hospitalisation.

AIMS: Myocardial injury during an episode of acute heart failure (AHF) may be important for patents' outcome. We hypothesised that an increase of cardiac troponin levels (cTnT) during hospitalisation, in patients with undetectable levels on admission (cTnT release), may be a more specific marker of myocardial damage. With this aim, we assessed the clinical and prognostic significance of high serum cTnT levels at the time of admission and that of cTnT release in 198 consecutive patients admitted for AHF and with no signs of acute coronary syndrome. METHODS AND RESULTS: cTnT levels were serially measured at the time of admission, and after 6 and 12 h, in 198 consecutive patients admitted for AHF and with no signs of acute coronary syndrome. cTnT was detectable (>0.01 ng/mL) in 102 patients (52 %) and positive for myocardial necrosis (>0.03 ng/mL) in 78 patients (39 %). Negative cTnT at the time of admission became positive at 6 and/or 12 h in 36 (18 %) patients. Patients with increased cTnT levels were more likely to have coronary artery disease, hypertension, diabetes, and renal dysfunction. During a median follow-up duration of 247 days (IQR 96-480 days), the detection of increased cTnT levels was associated with a higher rate of all-cause deaths and, for cTnT release, all-cause death and cardiovascular rehospitalisation rate. CTnT release was an independent predictor of all-cause death and cardiovascular rehospitalisation, along with glomerular filtration rate, and the administration of inotropic agents during the initial hospitalisation. CONCLUSIONS: Increased cTnT levels are a frequent finding in patients with AHF. They are more likely to occur in patients with comorbidities and are associated with poorer outcomes. cTnT release is an independent predictor of poorer outcomes.

Measurement of troponin I 48 h after admission as a tool to rule out impaired left ventricular function in patients with a first myocardial infarction.

Few studies have evaluated cardiac troponin I (cTnI) as a marker for infarct size and left ventricular (LV) dysfunction. Here we investigated the ability of a single-point cTnI, measured with a second-generation assay (Access AccuTnI), to estimate infarct size and assess LV function in patients with a first myocardial infarction (AMI). cTnI measurements were performed 12 and 48 h after admission in 63 consecutive AMI patients. LV function was evaluated by gated single-photon emission computed tomography (SPECT) and infarct size was estimated by CK-MB peak and SPECT myocardial perfusion. LV function and infarct size were evaluated by SPECT before hospital discharge. SPECT was also repeated 3 months later. Significant correlations (p<0.001) were found between cTnI at 12 and 48 h and both the peak CK-MB (r=0.61 and r=0.82, respectively) and the perfusion defect size at SPECT (r=0.55 and r=0.61, respectively). cTnI at 12 and 48 h were inversely related (p<0.001) to LV ejection fraction (LVEF) assessed both early (r=-0.45 and r=-0.57, respectively) and 3 months after AMI (r=-0.51 and r=-0.69, respectively). cTnI >14.8 microg/L at 48 h predicted an LVEF <40% at 3 months with a sensitivity of 100% [95% confidence interval (CI) 73.5-100%], specificity of 65% (CI 49-79%), and a negative predictive value of 100%. Our findings demonstrate that a single cTnI measurement 48 h after admission is useful for ruling out impaired LV function in a routine clinical setting.

Rapid determination of brain natriuretic peptide in patients with acute myocardial infarction.

We evaluated a rapid brain natriuretic peptide (BNP) assay (Triage BNP, Biosite Diagnostics) as indicator of infarct size, left ventricular (LV) dysfunction, and longterm survival in patients with acute myocardial infarction (AMI) during the coronary care unit stay. We studied 64 AMI patients in whom infarct size was estimated by creatine kinase isoenzyme MB (CK-MB) peak concentrations and single-photon emission computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi, and LV function by gated SPECT imaging. Measurements of BNP and SPECT were performed approximately 3 days after admission. SPECT was also repeated 3 months later. We found a significant correlation between BNP and both the peak CK-MB concentrations (r = 0.40, p = 0.001) and the perfusion defect size at SPECT (r = 0.38, p = 0.002). BNP was weakly related to LV ejection fraction (LVEF) assessed both early and 3 months after AMI (r = -0.29, p = 0.02; and r = -0.27, p = 0.04, respectively). The sensitivity and specificity of BNP for predicting survival of patients over 1 year of follow-up was 100% and 43%, respectively, with a negative predictive value of 100%. The positive predictive power of BNP was very modest (12%). Considering our results, the measurement of BNP did not look nearly as promising when tested in the setting of our cardiological intensive care.

Single-point cardiac troponin T at coronary care unit discharge after myocardial infarction correlates with infarct size and ejection fraction.

BACKGROUND: One of the major concerns in replacing creatine kinase MB (CK-MB) with cardiac troponins is the lack of evidence of the ability of troponins to estimate the size of acute myocardial infarction (AMI). We investigated the ability of a single measurement of cardiac troponin T (cTnT) at coronary care unit (CCU) discharge to estimate infarct size and assess left ventricular (LV) function in AMI patients. METHODS: We studied 65 AMI patients in whom infarct size was estimated by CK-MB peak concentrations and gated single-photon emission computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi and LV function by SPECT imaging. Measurements of cTnT and SPECT were performed 72 h (median) after admission (range, 40-160 h). SPECT was also repeated 3 months later. RESULTS: We found a significant correlation between cTnT and both the peak CK-MB concentrations (r = 0.76; P <0.001) and the perfusion defect size at SPECT (r = 0.62; P <0.001). cTnT was inversely related to LV ejection fraction (LVEF) assessed both early (r = -0.56; P <0.001) and 3 months after AMI (r = -0.70; P <0.001). cTnT >2.98 micro g/L predicted a LVEF <40% at 3 months with a sensitivity of 86.7%, specificity of 81.4%, and a likelihood ratio for a positive test of 4.7 (95% confidence interval, 4.0-5.4). CONCLUSIONS: A single cTnT measurement at CCU discharge after AMI is useful as a noninvasive estimate of infarct size and for the assessment of LV function in routine clinical setting.

Evaluation of a sandwich enzyme-linked immunosorbent assay for the measurement of serum heart fatty acid-binding protein.

BACKGROUND: We evaluated the sandwich enzyme-linked immunosorbent assay (ELISA) MARKIT-M for the determination of heart fatty-acid-binding protein (H-FABP). RESULTS AND CONCLUSIONS: The between-run coefficient of variation of this assay was <3.9 and it showed good correlation with a previously established ELISA method. The upper reference limit in 30 healthy individuals was 6.1 microg/L. Admission serum H-FABP was evaluated against myoglobin in 41 patients with suspected myocardial infarction (onset of symptoms < or = 5 h). H-FABP showed the same diagnostic efficiency as myoglobin [area (standard error) under the receiver operating characteristic curve: 0.798 (0.079) for H-FABP, 0.771 (0.085) for myoglobin, P = 0.55]. However, using the upper reference limit as decision cut-off, the sensitivity for H-FABP [91%; 95% confidence interval (CI): 76-98%] was significantly (P = 0.019) higher than that of myoglobin (65%; 95% CI: 47-80%).

Coronary angiographic findings in patients with clinical unstable angina according to cardiac troponin I and T concentrations in serum.

CONTEXT: Elevated cardiac troponin levels have been reported to identify unstable angina patients at high risk. OBJECTIVE: To examine the relation of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels to findings of coronary angiography in these patients. METHODS: Samples for troponin estimation were taken every 4 hours throughout the first 48 hours after admission before angiography in 34 patients with primary unstable angina. Patients were considered to be troponin positive if the marker was increased (>0.04 microg/L for cTnT and >0.03 microg/L for cTnI) in at least one sample collected. RESULTS: An increased troponin (I or T) concentration was documented in 14 patients (41.2%). Twelve patients (35.3%) had elevations of both markers, whereas the remaining 2 patients had elevations of cTnI or cTnT alone. Patients with or without increased troponin levels did not differ with respect to degree of coronary disease at angiography. However, patients with elevated troponin concentrations had more complex lesion characteristics. In 69% of patients with increased cTnI levels and in 77% of patients with increased cTnT levels, type B2 or C lesions were documented with presence of ulcerated plaques and thrombus formation. In contrast, only 23% of the patients with elevated cTnI or cTnT levels had type A lesions compared with 71% of patients with negative troponin concentrations. CONCLUSIONS: Patients with unstable angina who have significant release of cTnI and/or cTnT have evidence of more complex lesions on coronary angiography, supporting the hypothesis that both troponins might be used without distinction as surrogate markers for microembolization from thrombus formation on a disrupted plaque.