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Franca Pagani

Publications and source records attributed to Franca Pagani.

18 recordsLinked to original sources
PubMed2005

Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.

Acute Disease↗
PubMed2005

Quality specifications for B-type natriuretic peptide assays.

BACKGROUND: The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. METHODS: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. RESULTS: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. CONCLUSIONS: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

Biomarkers↗
PubMed2005

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.

Adult↗
PubMed2004

Multicenter evaluation of analytical performance of the Liaison troponin I assay.

OBJECTIVES: This study evaluated the analytical characteristics of the Liaison immunoassay for cardiac troponin I (cTnI). DESIGN AND METHODS: The protocol consisted of eight sections: evaluation of antibody specificity, linearity, detection limit and imprecision, method comparison, evaluation of endogenous interferents, anticoagulant interference, sample stability, and reference values. RESULTS: The assay equally measured free and complexed cTnI. The minimum detectable cTnI concentration was 0.021 microg/l. The cTnI concentration corresponding to a total CV of 10% was 0.056 microg/l. Linearity of response was demonstrated along the entire dynamic range of the assay. Assay interferences were minimal. cTnI concentrations in serum and heparinized plasma were significantly different. Values in EDTA plasma were on average approximately 5% higher than in matched serum, but this difference was not significant. The 99th percentile cTnI value in healthy subjects was 0.036 microg/l. CONCLUSIONS: Being sensitive, specific, and precise, the Liaison cTnI assay meets current requirements to aid in the diagnosis of myocardial necrosis.

Adult↗
PubMed2004

External quality assessment for biochemical markers of myocardial damage: an Italian experience.

In 1999 the Centre of Biomedical Research (CRB) in co-operation with the Italian interdisciplinary and intersociety Working Group on Markers of Myocardial Damage proposed a national external quality assurance scheme that was granted in accordance with the UK Clinical Pathology Accreditation Standards in 2001. The scheme, which stresses the importance of educational aspects in quality assurance, was scientifically designed to ensure that it would provide an objective assessment of participants' performance and promote quality improvements to meet the needs of participants. The present paper reports on the data collected in EQA cycles conducted to evaluate improvements in the performance of participants and in related methods. The findings obtained demonstrate that during the 4-year experience the scheme provided opportunities to improve the performance of laboratories and promoted an efficient, more satisfactory approach to analytical aspects. The number of unacceptable performances decreased from 11.6% to 5.6% for troponin I, from 19.5% to 9.0% for myoglobin and from 13.2% to 4.3% for creatine kinase myocardial isoenzyme (CK-MB). During cycles in 2001 and 2002, inter-variability (coefficient of variation, CV%) data for all markers appeared satisfactory and showed a significant improvement (lower than 10%), in particular for procedures automated on Dade Behring Dimension and Beckman Access systems. However, reference values/decisional limits declared by laboratories and those suggested by the manufacturers are not comparable, even within the same diagnostic system. The findings demonstrate that participation in EQA schemes provided an opportunity for participating laboratories to continuously improve the quality of their services.

Biomarkers↗
PubMed2003

Evaluation of imprecision for cardiac troponin assays at low-range concentrations.

BACKGROUND: The European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction (MI) has recommended that an increased cardiac troponin should be defined as a measurement above the 99th percentile value of the reference group. A total imprecision (CV) at the decision limit of </=10% is recommended. However, peer-reviewed data on assay imprecision are lacking. The purpose of this study was to construct the clinically relevant imprecision profiles for each of the commercially available cardiac troponin assays. Pools of human sera containing cardiac troponin concentrations around the MI decision limit were assessed to identify the lowest concentration associated with a 10% CV. METHODS: Eight serum pools targeting different concentrations of cardiac troponin (I and T) were prepared and stored at -70 degrees C until usage. The cardiac troponin measurement protocol consisted of two replicates per specimen per run, and one run per day for 20 days, using two reagent lots and three calibrations. Manufacturers of each cardiac troponin assay directly performed the measurements. Data analysis for each assay was centralized and performed according to the NCCLS EP5-A guideline. RESULTS: The lowest concentrations (microg/L) providing a 10% CV were as follows: AxSYM, 1.22; ACS:180, 0.37; Centaur, 0.33; Immuno 1, 0.34; Access, 0.06; Vidas, 0.36; Liaison, 0.065; Dimension, 0.26; Opus, 0.90; Stratus CS, 0.10; Immulite, 0.32; Vitros ECi, 0.44; Elecsys, 0.04; AIA 21, 0.09. CONCLUSION: No cardiac troponin assay was able to achieve the 10% CV recommendation at the 99th percentile reference limit defined by the manufacturer.

Clinical Chemistry Tests↗
PubMed2003

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.

Adult↗
PubMed2002

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%).

Biomarkers↗
PubMed2002

Recommendations for the routine use of pancreatic amylase measurement instead of total amylase for the diagnosis and monitoring of pancreatic pathology.

This document reviews the scientific evidence expected to persuade clinical laboratories to substitute pancreatic amylase measurement for total amylase in cases of suspected pancreatic pathology. A substantial evidence is now available to support such change. The measurement of pancreatic amylase in serum is: 1. more sensitive and specific for the detection of pancreatic tissue damage than that of the total enzyme activity, 2. easy and quick to perform in emergency conditions, 3. analytically precise in relation to its clinical application, 4. suitable for easy transfer and comparison of results from different care delivery units, and 5. characterized by well-defined decision limits for the diagnosis of acute pancreatitis.

Acute Disease↗
PubMed2002

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.

Angina, Unstable↗
PubMed2002

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.

Adult↗