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Background: NT-proBNP measurements aid in the evaluation of patients with suspected heart failure (HF) and may facilitate risk stratification in patients with HF and acute coronary syndrome (ACS). Point-of-care (POC) assays may provide more timely results and potentially improve patient outcomes., Methods: We evaluated the analytical performance of the Response Biomedical Corporation whole blood RAMP amino-terminal pro-B type natriuretic peptide (NT-proBNP) POC assay compared to the Roche Elecsys proBNP (NT-proBNP) assay., Results: Intra-day and total imprecision (% CV) ranged from 5.5% to 10.3% at 140, 449 and 1675 ng/L. The lowest concentration that yields a 20% CV was 57 ng/L. The lower limit of detection was 18 ng/L. The upper limit of linearity was validated to 23,428 ng/L with an average recovery of 95%. Correlation by Passing and Bablok regression yielded RAMP=1.01 Elecsys+14.6, r=0.98 (n=540; range of Elecsys values <5 to >35,000). Concordance of RAMP versus Elecsys using cut-offs of 125 ng/L for subjects <75 years and 450 ng/L for subjects > or =75 was 92% (95% CI 89-94%) for a group consisting of 127 apparently healthy individuals and 208 non-healthy subjects without HF, and 99% (95% CI 97-100%) for patients with HF, using the New York Heart Association (NYHA) functional classification. Overall, 80%, 87%, 97% and 100% of the RAMP results and 77%, 85%, 96% and 100% of the Elecsys results were greater than the age appropriate cut-off for NYHA I, II, III or IV groups. For both the RAMP and Elecsys results, the median NT-proBNP value was statistically correlated (increasing) with NYHA I, II, III or IV groups, respectively (p<0.0001), with no significant difference between the two methods., Conclusions: The POC Response Biomedical RAMP NT-proBNP assay provides comparable results that measured on the FDA cleared Roche Elecsys central laboratory platform.

Background: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients presenting with symptoms of acute coronary syndrome., Methods: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We used the Modification of Diet in Renal Disease formula to calculate the estimated glomerular filtration rate (eGFR). Endpoints were cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cardiac death) and all-cause mortality. We estimated cumulative event rates over a 4-month period with the Kaplan-Meier method and relative risk (RR) with the Cox proportional hazards model., Results: Patients with increased PlGF, NT-proBNP, hsCRP, or cTnI or decreased eGFR had 11% to 20% higher all-cause mortality rates than patients with concentrations within reference intervals: 20.4% (eGFR), 16.0% (PlGF), 15.8% (hsCRP), 12.7% (NT-proBNP), and 11.3% (cTnI; all P < or = 0.03). No differences in mortality rates were observed between those with increased vs normal concentrations of MPO, CD40L, or MMP-9. Decreased eGFR (RR 3.4, P = 0.004) and increased NT-proBNP (RR 7.9, P = 0.04) were independently predictive of mortality, and PlGF (RR 2.0, P = 0.08) approached significance. Patients with increased NT-proBNP (12.3%) or cTnI (33.8%) had higher cardiac event rates (each P <0.02), with increased MPO (11.1%) showing a trend (P = 0.09). Patients in whom both cTnI and MPO were increased had a cardiac event rate of 43%., Conclusion: Multiple biomarkers that are likely indicative of different underlying pathophysiologic mechanisms are independently predictive of increased risk for adverse events in patients with acute coronary syndrome.

Cardiac troponin (cTn) assays were compared in 490 unselected patients with symptoms suggestive of acute coronary syndrome with varying renal functions for risk stratification. cTnI (Dade, Newark, NJ; Beckman, Chaska, MN; and Tosoh, South San Francisco, CA) and cTnT (Roche, Indianapolis, IN) measurements and estimated glomerular filtration rates (eGFRs) were obtained and classified along sex-derived cutoffs. The cTn levels were increased in 14% to 25% of patients. In 68%, the eGFR was 60 mL/min/1.73 m2 or more; in 17%, it was between 41 and 59; and in 15%, it was 40 or less. There were 36 deaths and 9 cardiac events. Risk stratification was significant at 30 days and 6 months (P < or = .05). Relative risks ranged from 3.1 to 3.7, and cumulative event rates ranged from 22.4% to 24.2% for an increased troponin level compared with 6.7% to 8.9% for a normal level. The 6-month event rate with an eGFR less than 60 mL/min/1.73 m2 and an increased troponin level ranged from 29.9% to 50.8% compared with 4.9% to 6.6% for a normal troponin level and an eGFR greater than 60 mL/min/1.73 m2 (P < .05). The eGFR in combination with an increased cTn level demonstrated the most powerful stratification.

Background: The need to rapidly evaluate patients presenting to emergency departments and cardiology services for ruling in and ruling out acute myocardial infarction (AMI) is widely recognized as a clinical challenge. We determined the impact of incorporating point-of-care (POC) cardiac troponin I (cTnI) testing into a cardiology service regarding assay turn around time (TAT), patient length of stay (LOS), financial matrixes and patient outcomes compared to central laboratory cTnI testing., Methods: Patients presenting with symptoms suggestive of acute coronary syndrome (ACS) were enrolled pre-POC (PreCS, n=271) and post-POC (PostCS, n=274). POC cTnI determinations were performed at the bedside on the Dade Behring Stratus CS by nursing staff. Routine cTnI determinations were performed in the central laboratory (Dade Behring Dimension) by laboratory staff. Data were collected and analyzed on each patient per hospital stay by review of electronic medical and financial records. In addition, risk stratification outcomes for all cause death were determined at 30 days and 1 y following baseline sampling based on the 99th percentile cutoff concentrations of <0.1 microg/l for both assays., Results: There was a decrease in time from blood draw to result to healthcare provider (PreCS mean 76 min; PostCS mean 19.5 min; p<0.001) as well as a decrease trend in charge per patient admission (4281 dollars savings) following implementation of POC testing. Total charges per patient admission decreased by 25% PostCS vs. PreCS (17,163 dollars vs. 12,882 dollars); a composite of lower charges for: boarding (-21%), other departments (-58%), pharmacy (-28%), labs (-22%), non-cardiac procedures (-28%), cardiac procedures (-14%). The mean LOS also decreased 8% (p=0.05) from PreCS (2.36 days) to PostCS (2.19 days). cTnI reagents charges to the laboratory were higher for the POC assay, 10.54 dollars, vs. the central lab assay, 3.83 dollars. One year survival was greater in the <0.1 microg/l patients (PreCS 96.2%, PostCS 97.2%) compared to the >0.1 microg/l patients (PreCS 77.7%, PostCS 75.5%); both p<0.001. Kaplan-Meier survival curves showed early separation by 30 days in each group., Conclusions: Our study demonstrates the cost effectiveness and clinical effectiveness of implementation of POC whole blood, cTnI testing for assisting clinicians with diagnostic and risk assessment of ACS patients.

Background: Few studies have investigated the role of cardiac troponin point-of-care (POC) testing for predicting adverse outcomes in acute coronary syndrome (ACS) patients. We investigated the use of a POC cTnI assay in ACS patients., Methods: We studied consecutive patients (n = 367) presenting with symptoms suggestive of ACS who were admitted through the emergency department. We measured plasma cTnI with the i-STAT assay. Patients were risk-stratified based on cTnI concentrations defined by the predetermined 99th percentile reference limit for plasma (0.04 microg/L). Patients were followed for 60 days. We computed survival and event curves with the Kaplan-Meier method and compared risk stratification groups with the log-rank test., Results: Acute myocardial infarction (MI) was diagnosed in 8.1% of patients. Odds ratios and 95% confidence intervals for all-cause death (ACD), MI or ACD, MI or cardiac death, and cardiac death at 60 days were all statistically significant after adjustment for age, diabetes, hypertension, and history of renal failure as follows: 2.54 (1.24-5.20), P = 0.009; 2.76 (1.37-5.58), P = 0.003; 5.98 (1.65-21.7), P = 0.008; and 2.54 (1.24-5.20), P = 0.009. Kaplan-Meier curves showed early separation between patients with increased vs. reference concentrations before 30 days for ACD, MI or ACD, and MI or cardiac death., Conclusion: The i-STAT POC cTnI assay can be added to the list of assays for risk stratification.

Background: This study determines the analytical characteristics of the i-STAT cardiac troponin I assay (cTnI; i-STAT, Princeton, NJ), a 10-min POC assay, designed to be performed at the bedside., Methods: Three different hospitals participated in a patient specimen and analytical validation study (n=186) for the i-STAT cTnI assay carried out in real time. A total of 186 whole blood specimens (lithium heparin) were collected from patients presenting with symptoms suggestive of acute coronary syndromes (ACS) for correlation studies as well as from 162 healthy subjects for reference interval determination. Factors studied included antibody specificity, detection limit, imprecision, linearity, assay specificity, sample type stability, interferences, reference limit determination and comparison vs. the Dade Stratus CS cTnI assay., Results: Total imprecision (CV) of 10% and 20% were seen at 0.09 and 0.07 microg/l, respectively. The detection limit was 0.02 microg/l. The 99th percentile reference limit was 0.08 microg/l. The assay was not affected by common interferents. An equimolar response within 5% was found for reduced and phosphorylated forms of TIC and IC complexes. Regression analysis for the i-STAT cTnI between whole blood and plasma specimens and for whole blood between the i-STAT and Stratus CS cTnI assays demonstrated slopes of 1.06 and 0.89, respectively., Conclusions: The i-STAT cTnI assay is a sensitive and precise monitor of cTnI, poised for point-of-care/near bedside clinical utilization for triage, diagnostics and risk management of acute coronary syndrome patients., (Copyright 2004 Elsevier B.V.)

Background: Creatine kinase (CK) exists as three cytosolic isoenzymes, CK-MM, CK-MB, and CK-BB, and one mitochondrial isoenzyme. Animal and human observations suggest that the CK-MB content of myocardium is dynamic and may increase in response to ischemia, but the response of the myocardial CK system to chronic coronary artery occlusion is not well-defined., Methods and Results: We measured serial changes in myocardial total CK, percent CK-MB, and percent CK-BB before and 3 weeks after coronary artery occlusion in 17 pentobarbital-anesthetized dogs. Tissue biopsies were obtained from the left anterior descending (LAD) coronary artery myocardium, the right coronary artery (RCA) myocardium, and the circumflex coronary artery myocardium at baseline and 3 weeks after LAD occlusion (n = 6), RCA occlusion (n = 5), and no coronary artery occlusion (n = 6). Tissue samples were assayed for total CK, percent CK-MB, and percent CK-BB. Samples were also examined by electron microscopy for evidence of ischemic myopathy. Total myocardial CK activity did not change over 3 weeks. Percent CK-MB increased significantly in the tissue supplied by the occluded artery (4.1-fold in dogs with LAD occlusion and 6.7-fold in dogs with RCA occlusion). Percent CK-BB did not change. Dogs with LAD occlusion had ultrastructural evidence of myopathic fibers interspersed with normal fibers in the LAD myocardium. Dogs with RCA occlusion had no ultrastructural evidence of myopathic fibers in the RCA myocardium., Conclusions: Chronic coronary artery occlusion causes a pronounced change in the canine myocardial CK system that is limited to the tissue supplied by the occluded coronary artery. These biochemical alterations do not correlate with any cellular ultrastructural changes. Myocardial CK-MB content is dynamic, varies geographically within the heart, and increases rapidly after coronary artery occlusion.