References

1

Goodacre S, Cross E, Arnold J, Capewell S, Nicholl J

The health care burden of acute chest pain Heart 2005;91:229-30

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2

Hamm CW et al ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).Eur Heart J. 2011 Dec;32(23):2999-3054

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3

J Am Coll Cardiol. 2011 Sep 20;58(13):1332-9. doi: 10.1016/j.jacc.2011.06.026.

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay.

Body R, Carley S, McDowell G, Jaffe AS, France M, Cruickshank K, Wibberley C, Nuttall M, Mackway-Jones K.

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Source

University of Manchester, Manchester, United Kingdom.

Abstract

OBJECTIVES:

This paper sought to evaluate whether high sensitivity troponin (hs-cTnT) can immediately exclude acute myocardial infarction (AMI) at a novel ‘rule out’ cut-off.

BACKGROUND:

Subgroup analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation.

METHODS:

In a cohort study, we prospectively enrolled patients with chest pain, evaluating them with standard troponin T and testing for hs-cTnT (Roche Diagnostics, Basel, Switzerland) at presentation. The primary outcome was a diagnosis of AMI. We also followed up patients for adverse events within 6 months. After subsequent clinical implementation of hs-cTnT, we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise.

RESULTS:

Of 703 patients in the cohort study, 130 (18.5%) had AMI, none of whom initially had undetectable hs-cTnT (sensitivity: 100.0%, 95% confidence interval [CI]: 95.1% to 100.0%, negative predictive value: 100.0%, 95% CI: 98.1% to 100.0%). This strategy would rule out AMI in 27.7% of patients, 2 (1.0%) of whom died or had AMI within 6 months (1 periprocedural AMI, 1 noncardiac death). We evaluated this approach in an additional 915 patients in clinical practice. Only 1 patient (0.6%) with initially undetectable hs-cTnT had subsequent elevation (to 17 ng/l), giving a sensitivity of 99.8% (95% CI: 99.1% to 100.0%) and a negative predictive value of 99.4% (95% CI: 96.6% to 100.0%).

CONCLUSIONS:

Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifying patients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.

4

Emerg Med J. 2007 Dec;24(12):811-4.

New methods for improved evaluation of patients with suspected acute coronary syndrome in the emergencydepartment.

Ekelund U, Forberg JL.

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Source

Division of Emergency Medicine, Lund University Hospital, SE-221 85 Lund, Sweden.

Abstract

This paper aims to identify and review new and unproven emergency department (ED) methods for improved evaluation in cases of suspected acute coronary syndrome (ACS). Systematic news coverage through PubMed from 2000 to 2006 identified papers on new methods for ED assessment ofpatients with suspected ACS. Articles found described decision support models, new ECG methods, new biomarkers and point-of-care testing, cardiac imaging, immediate exercise tests and the chest pain unit concept. None of these new methods is likely to be the perfect solution, and the best strategy today is therefore a combination of modern methods, where the optimal protocol depends on local resources and expertise. With a suitable combination of new methods, it is likely that more patients can be managed as outpatients, that length of stay can be shortened for those admitted, and that some patients with ACS can get earlier treatment.

5

N Engl J Med. 2000 Apr 20;342(16):1163-70.

Missed diagnoses of acute cardiac ischemia in the emergency department.

Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, Griffith JL, Selker HP.

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Source

Center for Cardiovascular Health Services Research, Department of Medicine, New England Medical Center, Boston, Mass 02111, USA.

Abstract

BACKGROUND:

Discharging patients with acute myocardial infarction or unstable angina from the emergency department because of missed diagnoses can have dire consequences. We studied the incidence of, factors related to, and clinical outcomes of failure to hospitalize patients withacute cardiac ischemia.

METHODS:

We analyzed clinical data from a multicenter, prospective clinical trial of all patients with chest pain or other symptoms suggesting acutecardiac ischemia who presented to the emergency departments of 10 U.S. hospitals.

RESULTS:

Of 10,689 patients, 17 percent ultimately met the criteria for acute cardiac ischemia (8 percent had acute myocardial infarction and 9 percent had unstable angina), 6 percent had stable angina, 21 percent had other cardiac problems, and 55 percent had noncardiac problems. Among the 889 patients with acute myocardial infarction, 19 (2.1 percent) were mistakenly discharged from the emergency department (95 percent confidence interval, 1.1 to 3.1 percent); among the 966 patients with unstable angina, 22 (2.3 percent) were mistakenly discharged (95 percent confidence interval, 1.3 to 3.2 percent). Multivariable analysis showed that patients who presented to the emergency department with acute cardiac ischemia were more likely not to be hospitalized if they were women less than 55 years old (odds ratio for discharge, 6.7; 95 percent confidence interval, 1.4 to 32.5), were nonwhite (odds ratio, 2.2; 1.1 to 4.3), reported shortness of breath as their chief symptom (odds ratio, 2.7; 1.1 to 6.5), or had a normal or nondiagnostic electrocardiogram (odds ratio, 3.3; 1.7 to 6.3). Patients with acute infarction were more likely not to be hospitalized if they were nonwhite (odds ratio for discharge, 4.5; 95 percent confidence interval, 1.8 to 11.8) or had a normal or nondiagnostic electrocardiogram (odds ratio, 7.7; 95 percent confidence interval, 2.9 to 20.2). For the patients with acute infarction, the risk-adjusted mortality ratio for those who were not hospitalized, as compared with those who were, was 1.9 (95 percent confidence interval, 0.7 to 5.2), and for the patients with unstable angina, it was 1.7 (95 percent confidence interval, 0.2 to 17.0).

CONCLUSIONS:

The percentage of patients who present to the emergency department with acute myocardial infarction or unstable angina who are not hospitalized is low, but the discharge of such patients is associated with increased mortality. Failure to hospitalize is related to race, sex, and the absence of typical features of cardiac ischemia. Continued efforts to reduce the number of missed diagnoses are warranted.

6

BMJ. 2000 Jun 24;320(7251):1702-5.

Prospective audit of incidence of prognostically important myocardial damage in patients discharged fromemergency department.

Collinson PO, Premachandram S, Hashemi K.

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Source

Department of Chemical Pathology, Mayday University Hospital, Croydon CR7 7YE.

Abstract

OBJECTIVE:

To assess the incidence of prognostically important myocardial damage in patients with chest pain discharged from the emergencydepartment.

DESIGN:

Prospective observational study.

SETTING:

District general hospital emergency department.

PARTICIPANTS:

110 patients presenting with chest pain of unknown cause who were subsequently discharged home after cardiac causes of chest pain were ruled out by clinical and electrocardiographic investigation.

INTERVENTIONS:

Patients were reviewed 12-48 hours after presentation by repeat electrocardiography and measurement of cardiac troponin T.

MAIN OUTCOME MEASURES:

Incidence of missed myocardial damage.

RESULTS:

Eight (7%) patients had detectable cardiac troponin T on review and seven had concentrations >/=0.1 microg/l. The repeat electrocardiogram showed no abnormality in any patient.

CONCLUSION:

6% of the patients discharged from the emergency department had missed prognostically important myocardial damage. Follow up measurement of cardiac troponin T allows convenient audit of clinical performance in the emergency department.

7

J Electrocardiol. 2011 Jul-Aug;44(4):432-8. doi: 10.1016/j.jelectrocard.2011.03.001. Epub 2011 Apr 29.

Heart fatty acid-binding protein in combination with the 80-lead body surface potential map improves early detection of acute myocardial infarction in patients who are cardiac troponin T-negative at presentation.

Daly MJ, McCann CJ, Owens CG, Harbinson MT, Adgey JA.

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Source

The Heart Centre, Royal Victoria Hospital, Belfast, Northern Ireland, UK.

Abstract

Of patients who present with ischemic-type chest pain and a negative cardiac troponin T (cTnT) at first medical contact, there are patients at a very early stage of infarction. The aim of this research was to assess heart fatty acid-binding protein (H-FABP), a novel marker of myocyte necrosis, in combination with the 80-lead body surface potential map (BSPM) in the early diagnosis of acute myocardial infarction (AMI).

METHODS:

In this prospective study, consecutive patients presenting with acute ischemic-type chest pain between 2003 and 2006 were enrolled. At first medical contact, blood was sampled for cTnT and H-FABP; in addition, a 12-lead electrocardiogram (ECG) and BSPM were recorded. A second cTnT was sampled 12 hours or more after presentation. Peak cTnT 0.03 μg/L or higher diagnosed AMI. Elevated H-FABP was 5 ng/mL or higher. A cardiologist blinded to both the clinical details and 12-lead ECG interpreted the BSPM.

RESULTS:

Enrolled were 407 patients (age 62 ± 13 years; 70% men). Of these 407, 180 had cTnT less than 0.03 μg/L at presentation. Acute myocardial infarction occurred in 52 (29%) of 180 patients. Of these 180 patients, 27 had ST-segment elevation (STE) on ECG, 104 had STE on BSPM (sensitivity, 88%; specificity, 55%), and 95 (53%) had H-FABP elevation. The proportion with elevated H-FABP was higher in the AMI group compared with non-AMI group (P < .001). Body surface potential map STE was significantly associated with H-FABP elevation (P < .001). Of those with initial cTnT less than 0.03 μg/L, the c-statistic for the receiver operating characteristic curve distinguishing AMI from non-AMI using H-FABP alone was 0.644 (95% confidence interval [CI], 0.521-0.771), using BSPM alone was 0.716 (95% CI, 0.638-0.793), and using the combination of BSPM and H-FABP was 0.812 (95% CI, 0.747-0.876; P < .001).

CONCLUSION:

In patients with acute ischemic-type chest pain who have a normal cTnT at presentation, the combination of H-FABP and BSPM at first assessment identifies those with early AMI (c-statistic, 0.812; P < .001), thus allowing earlier triage to reperfusion therapy and secondary prevention.

8

N Engl J Med. 2009 Aug 27;361(9):858-67. doi: 10.1056/NEJMoa0900428.

Early diagnosis of myocardial infarction with sensitive cardiac troponin assays.

Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, Noveanu M, Breidthardt T, Twerenbold R,Winkler K, Bingisser R, Mueller C.

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Source

Department of Internal Medicine, University Hospital, Basel, Switzerland.

Abstract

BACKGROUND:

The rapid and reliable diagnosis of acute myocardial infarction is a major unmet clinical need.

METHODS:

We conducted a multicenter study to examine the diagnostic accuracy of new, sensitive cardiac troponin assays performed on blood samples obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardialinfarction. Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays (Abbott-Architect Troponin I, Roche High-Sensitive Troponin T, Roche Troponin I, and Siemens Troponin I Ultra) and a standard assay (Roche Troponin T). The final diagnosis was adjudicated by two independent cardiologists.

RESULTS:

Acute myocardial infarction was the adjudicated final diagnosis in 123 patients (17%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly higher with the four sensitive cardiac troponin assays than with the standard assay (AUC for Abbott-Architect Troponin I, 0.96; 95% confidence interval [CI], 0.94 to 0.98; for Roche High-Sensitive Troponin T, 0.96; 95% CI, 0.94 to 0.98; for Roche Troponin I, 0.95; 95% CI, 0.92 to 0.97; and for Siemens Troponin I Ultra, 0.96; 95% CI, 0.94 to 0.98; vs. AUC for the standard assay, 0.90; 95% CI, 0.86 to 0.94). Among patients who presented within 3 hours after the onset of chest pain, the AUCs were 0.93 (95% CI, 0.88 to 0.99), 0.92 (95% CI, 0.87 to 0.97), 0.92 (95% CI, 0.86 to 0.99), and 0.94 (95% CI, 0.90 to 0.98) for the sensitive assays, respectively, and 0.76 (95% CI, 0.64 to 0.88) for the standard assay. We did not assess the effect of the sensitive troponin assays on clinical management.

CONCLUSIONS:

The diagnostic performance of sensitive cardiac troponin assays is excellent, and these assays can substantially improve the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain. (ClinicalTrials.gov number, NCT00470587.)

9

Hollander JE Highly sensitive troponins the answer or just more questions? J Am Coll Cardiol. 2009 Sep 22;54(13):1173-5

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10

Thygesen K et al Third universal definition of myocardial infarction Eur Heart J. 2012 Oct;33(20):2551-2567

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11

Clin Chem. 2012 Mar;58(3):628-37. doi: 10.1373/clinchem.2011.171496. Epub 2012 Jan 18.

Troponin T percentiles from a random population sample, emergency room patients and patients with myocardialinfarction.

Hammarsten O, Fu ML, Sigurjonsdottir R, Petzold M, Said L, Landin-Wilhelmsen K, Widgren B, Larsson M, Johanson P.

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Source

Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

BACKGROUND:

High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI.

METHODS:

cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non-ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI.

RESULTS:

The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%-67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival.

CONCLUSIONS:

Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.

12

Eur Heart J. 2008 Dec;29(23):2843-50. doi: 10.1093/eurheartj/ehn363. Epub 2008 Aug 5.

Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T.

McCann CJ, Glover BM, Menown IB, Moore MJ, McEneny J, Owens CG, Smith B, Sharpe PC, Young IS, Adgey JA.

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Source

The Heart Centre, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, Northern Ireland, UK.

Abstract

AIMS:

To evaluate the role of novel biomarkers in early detection of acute myocardial infarction (MI) in patients admitted with acute chest pain.

METHODS AND RESULTS:

A prospective study of 664 patients presenting to two coronary care units with chest pain was conducted over 3 years from 2003. Patients were assessed on admission: clinical characteristics, ECG (electrocardiogram), renal function, cardiac troponin T (cTnT), heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, NT-pro-brain natriuretic peptide, D-dimer, hsCRP (high sensitivity C-reactive protein), myeloperoxidase, matrix metalloproteinase-9, pregnancy associated plasma protein-A, soluble CD40 ligand. A > or = 12 h cTnT sample was also obtained. MI was defined as cTnT > or = 0.03 microg/L. In patients presenting <4 h of symptom onset, sensitivity of H-FABP for MI was significantly higher than admission cTnT (73 vs. 55%; P = 0.043). Specificity of H-FABP was 71%. None of the other biomarkers challenged cTnT. Combined use of H-FABP and cTnT (either one elevated initially) significantly improved the sensitivities of H-FABP or cTnT (85%; P < or = 0.004). This combined approach also improved the negative predictive value, negative likelihood ratio, and the risk ratio.

CONCLUSION:

Assessment of H-FABP within the first 4 h of symptoms is superior to cTnT for detection of MI, and is a useful additional biomarker for patients with acute chest pain.

13

Scand J Clin Lab Invest. 2013 Feb;73(1):48-53. doi: 10.3109/00365513.2012.734396. Epub 2012 Nov 1.

Clinical and analytical evaluation of an immunoturbidimetric heart-type fatty acid-binding protein assay.

Carless DR, Wnęk M, Knox C, Harrison KR, Calder N, Hall AS, Barth JH.

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Source

Blood Sciences, Leeds General Infirmary, Leeds, UK.

Abstract

BACKGROUND:

Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty acids in the myocardium. It is an early marker for ACS. We have evaluated the Randox Laboratories immunoturbidimetric assay on a Siemens Advia 1800 analyzer. The assay employs latex particles coated with mouse monoclonal anti-HFABP antibodies to generate turbidity.

METHODS:

We used redundant patient samples and pools to assess precision, functional sensitivity, limit of detection, linearity, recovery of recombinant H-FABP and interference. We evaluated the 99th centile values and compared H-FABP with troponin in samples routinely received from chest pain patient samples.

RESULTS:

Precision was typically < 10% and 12.5% at all concentrations for within and between batches. The functional sensitivity was 2.4 μg/L. The assay was linear on dilution over the range 2.76-115 μg/L. Recovery of recombinant H-FABP was approximately 20-25%. No interference was seen with haemoglobin concentrations <1.5 g/L, bilirubin < 250 μg/L and triacylglycerol < 5 mmol/L or rheumatoid factor. The 99th centile value in a reference population with eGFR > 60mL/min/1.73m(2) was 9.1 μg/L with no significant gender difference. H-FABP was measured in routine clinical samples (N = 1310) received for troponin I measurement. Using Siemens TnI > 50 ng/L as an indicator of myocardial damage, the ROC area under curve for H-FABP was 0.82.

CONCLUSIONS:

The immunoturbidimetric H-FABP assay is robustly designed and shows good analytical performance. It is therefore well suited for use in a routine clinical laboratory.

14

Eur Heart J. 2008 Dec;29(23):2843-50. doi: 10.1093/eurheartj/ehn363. Epub 2008 Aug 5.

Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T.

McCann CJ, Glover BM, Menown IB, Moore MJ, McEneny J, Owens CG, Smith B, Sharpe PC, Young IS, Adgey JA.

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Source

The Heart Centre, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, Northern Ireland, UK.

Abstract

AIMS:

To evaluate the role of novel biomarkers in early detection of acute myocardial infarction (MI) in patients admitted with acute chest pain.

METHODS AND RESULTS:

A prospective study of 664 patients presenting to two coronary care units with chest pain was conducted over 3 years from 2003. Patients were assessed on admission: clinical characteristics, ECG (electrocardiogram), renal function, cardiac troponin T (cTnT), heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, NT-pro-brain natriuretic peptide, D-dimer, hsCRP (high sensitivity C-reactive protein), myeloperoxidase, matrix metalloproteinase-9, pregnancy associated plasma protein-A, soluble CD40 ligand. A > or = 12 h cTnT sample was also obtained. MI was defined as cTnT > or = 0.03 microg/L. In patients presenting <4 h of symptom onset, sensitivity of H-FABP for MI was significantly higher than admission cTnT (73 vs. 55%; P = 0.043). Specificity of H-FABP was 71%. None of the other biomarkers challenged cTnT. Combined use of H-FABP and cTnT (either one elevated initially) significantly improved the sensitivities of H-FABP or cTnT (85%; P < or = 0.004). This combined approach also improved the negative predictive value, negative likelihood ratio, and the risk ratio.

CONCLUSION:

Assessment of H-FABP within the first 4 h of symptoms is superior to cTnT for detection of MI, and is a useful additional biomarker for patients with acute chest pain

15

Am J Emerg Med. 2012 Feb;30(2):267-74. doi: 10.1016/j.ajem.2010.11.022. Epub 2011 Jan 3.

Diagnostic accuracy of heart-type fatty acid-binding protein for the early diagnosis of acute myocardial infarction.

McMahon CG, Lamont JV, Curtin E, McConnell RI, Crockard M, Kurth MJ, Crean P, Fitzgerald SP.

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Source

Emergency Department and Chest Pain Assessment Unit, St. James’s Hospital, Dublin 8, Republic of Ireland.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the diagnostic efficacy of multiple tests-heart-type fatty acid-binding protein (H-FABP), cardiac troponin I (cTnI), creatine kinase-MB, and myoglobin-for the early detection of acute myocardial infarction among patients who present to the emergency department with chest pain.

METHODS:

A total of 1128 patients provided a total of 2924 venous blood samples. Patients with chest pain were nonselected and treated according to hospital guidelines. Additional cardiac biomarkers were assayed simultaneously at serial time points using the Cardiac Array (Randox Laboratories Ltd, Crumlin, United Kingdom).

RESULTS:

Heart-type fatty acid-binding protein had the greatest sensitivity at 0 to 3 hours (64.3%) and 3 to 6 hours (85.3%) after chest pain onset. The combination of cTnI measurement with H-FABP increased sensitivity to 71.4% at 3 to 6 hours and 88.2% at 3 to 6 hours. Receiver operating characteristic curves demonstrated that H-FABP had the greatest diagnostic ability with area under the curve at 0 to 3 hours of 0.841 and 3 to 6 hours of 0.894. The specificity was also high for the combination of H-FABP with cTnI at these time points. Heart-type fatty acid-binding protein had the highest negative predictive values of all the individual markers: 0 to 3 hours (93%) and 3 to 6 hours (97%). Again, the combined measurement of cTnI with H-FABP increased the negative predictive values to 94% at 0 to 3 hours, 98% at 3 to 6 hours, and 99% at 6 to 12 hours.

CONCLUSION:

Testing both H-FABP and cTnI using the Cardiac Array proved to be both a reliable diagnostic tool for the early diagnosis of myocardial infarction/acute coronary syndrome and also a valuable rule-out test for patients presenting at 3 to 6 hours after chest pain onset.

16

Resuscitation. 2011 Aug;82(8):1041-6. doi: 10.1016/j.resuscitation.2011.03.015. Epub 2011 Apr 2.

A FABP-ulous ‘rule out’ strategy? Heart fatty acid binding protein and troponin for rapid exclusion of acute myocardial infarction.

Body R, McDowell G, Carley S, Wibberley C, Ferguson J, Mackway-Jones K.

Cardiovascular Sciences Research Group, University of Manchester, Oxford Road, Manchester, M13 9WL, United Kingdom.

View Abstract

Abstract

OBJECTIVE:

Many Emergency Departments (EDs) utilise ‘triple marker’ testing with CK-MB, myoglobin and troponin I (cTnI) to exclude acute myocardial infarction (AMI) within hours of presentation. We evaluated the ability of 8 biomarkers to rapidly exclude AMI at the point of presentation and investigated whether ‘triple marker’ testing represents the optimal multimarker strategy.

METHODS:

We recruited patients who presented to the ED with suspected cardiac chest pain occurring within 24 h. Blood was drawn at the time of presentation. Diagnostic value was assessed by calculating the area under the ROC curve (AUC) and a multivariate model was constructed by logistic regression. The primary outcome was a diagnosis of AMI, established by ≥12-h troponin testing in all patients.

RESULTS:

705 included patients underwent venepuncture a median of 3.5 h after symptom onset. Heart fatty acid binding protein (H-FABP) had an AUC of 0.86 (95% CI 0.82-0.90), which was significantly higher than any other biomarker including cTnI. While no single biomarker could enable exclusion of AMI, multivariate analysis identified cTnI and H-FABP as the optimal biomarker combination. Combined with clinical risk stratification, this strategy had a sensitivity of 96.9%, specificity of 54.7%, PPV 32.4% and NPV 98.8%.

CONCLUSIONS:

We have derived an algorithm that would enable AMI to be immediately excluded in 315 (44.7%) patients at the cost of missing 6 AMIs per 1000 patients treated. While the risk is likely to be unacceptable for clinical implementation, we have highlighted an area for future development using serial testing and increasingly sensitive assays.

17

Circ J. 2011;75(12):2813-20. Epub 2011 Sep 21.

Heart fatty acid-binding protein offers similar diagnostic performance to high-sensitivity troponin T in emergencyroom patients presenting with chest pain.

Inoue K, Suwa S, Ohta H, Itoh S, Maruyama S, Masuda N, Sugita M, Daida H.

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Source

Department of Cardiology, Juntendo University Nerima Hospital, Tokyo, Japan.

Abstract

BACKGROUND:

The aim of the present study was to evaluate the diagnostic accuracy of high-sensitivity troponin T (hsTnT) in patients with suspected acute coronary syndrome (ACS) in comparison to heart fatty acid-binding protein (H-FABP), high-sensitivity C-reactive protein, myeloperoxidase (MPO), and pentraxin 3 (PTX3). METHODS AND REsults: Patients (n=432) with chest pain were recruited for the analysis. ACS was diagnosed in 298 patients (69%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver operating curve (AUC), was highest for hsTnT (AUC=0.82; 95% confidence interval [CI]: 0.78-0.87) and H-FABP (AUC=0.83; 95%CI: 0.78-0.87). Sensitivity (87.9%) and negative likelihood (LH; 0.2) for hsTnT were the highest and lowest, respectively, but H-FABP had the highest specificity (78.5%) and positive LH (3.6). Among patients who presented within 2h after the onset of chest pain, MPO had the highest AUC (0.82; 95%CI: 0.69-0.94). Combined use of H-FABP and MPO measurements yielded a sensitivity of 69.2%, specificity of 84.2%, positive LH of 4.4, and negative LH of 0.4.

CONCLUSIONS:

The hsTnT assay offers excellent diagnostic performance to rule out ACS, but it is prone to false-positive results. H-FABP offers similar overall diagnostic performance, while the combination of H-FABP and MPO assays may improve the diagnosis of ACS, particularly in patientswith recent onset of chest pain.

18

LO1630 – COMBINING HEART FATTY ACID BINDING PROTEIN AND HIGH SENSITIVITY TROPONIN IN THE EMERGENCY DEPARTMENT

R. Body1,2, S. Carley1, G. Burrows3, P. Pemberton4, K. Mackway-Jones1

1Emergency Department, Central Manchester NHS Foundation Trust; 2Cardiovascular Sciences Research Group, University of Manchester, Manchester; 3Biochemistry Department, Stockport NHS Foundation Trust, Stockport; 4Specialist Assay Laboratory, Central Manchester NHS Foundation Trust, Manchester, United Kingdom

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Source

Abstract

OBJECTIVES:

Recent evidence suggests that the combination of heart fatty acid binding protein (H-FABP) and troponin is more effective than established multi-marker strategies for early exclusion of acute myocardial infarction (AMI). It is not known whether H-FABP retains value when a high sensitivity troponin assay is used. We aimed to establish whether H-FABP and high sensitivity troponin T (hs-TnT) have independent value for diagnosing AMI and predicting major adverse cardiac events (MACE) in patients with chest pain.

METHODS:

For this analysis we pooled results from 2 similarly designed prospective cohort studies at 2 centres. We tested for H-FABP and hs-TnT on presentation to the emergency department (ED) in consenting adults with suspected cardiac chest pain at two centres. The primary outcome was a diagnosis of AMI, established following 12-hour troponin testing. We also evaluated the incidence of 30-day MACE.

RESULTS:

Among 1,171 participants, the C-statistic was 0.89 for H-FABP and 0.94 for hs-TnT. After adjusting for hs-TnT and ECG, H-FABP independently predicted both AMI (odds ratio 5.1, 95% CI 3.2-8.2) and MACE (odds ratio 2.8, 1.9-4.2). The combination of H-FABP, hs-TnT and ECG had a sensitivity of 99.1% (95% CI 96.6–99.9%), specificity 59.3% (56.2–62.5%), positive predictive value 35.0% (31.2–39.0%) and negative predictive value 99.7% (98.7–100.0%). This combination could exclude AMI in 48.8% of patients, while missing 0.95% AMIs.

CONCLUSION:

H-FABP, hs-TnT and ECG give independent diagnostic and prognostic information. In combination, they identify 99.1% of AMIs using a single blood test at presentation. Future work should investigate the added value of serial sampling and evaluate whether H-FABP can help to improve treatment decisions.

19

Lancet. 2011 Mar 26;377(9771):1077-84. doi: 10.1016/S0140-6736(11)60310-3.

A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study.

Than M, Cullen L, Reid CM, Lim SH, Aldous S, Ardagh MW, Peacock WF, Parsonage WA, Ho HF, Ko HF, Kasliwal RR, Bansal M, Soerianata S, Hu D, Ding R,Hua Q, Seok-Min K, Sritara P, Sae-Lee R, Chiu TF, Tsai KC, Chu FY, Chen WK, Chang WH, Flaws DF, George PM, Richards AM.

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Source

Christchurch Hospital, Christchurch, New Zealand.

Abstract

BACKGROUND:

Patients with chest pain contribute substantially to emergency department attendances, lengthy hospital stay, and inpatient admissions. A reliable, reproducible, and fast process to identify patients presenting with chest pain who have a low short-term risk of a major adverse cardiac event is needed to facilitate early discharge. We aimed to prospectively validate the safety of a predefined 2-h accelerated diagnostic protocol (ADP) to assess patients presenting to the emergency department with chest pain symptoms suggestive of acute coronary syndrome.

METHODS:

This observational study was undertaken in 14 emergency departments in nine countries in the Asia-Pacific region, in patients aged 18 years and older with at least 5 min of chest pain. The ADP included use of a structured pre-test probability scoring method (Thrombolysis in Myocardial Infarction [TIMI] score), electrocardiograph, and point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The primary endpoint was major adverse cardiac events within 30 days after initial presentation (including initial hospital attendance). This trial is registered with the Australia-New Zealand Clinical Trials Registry, number ACTRN12609000283279.

FINDINGS:

3582 consecutive patients were recruited and completed 30-day follow-up. 421 (11.8%) patients had a major adverse cardiac event. The ADP classified 352 (9.8%) patients as low risk and potentially suitable for early discharge. A major adverse cardiac event occurred in three (0.9%) of these patients, giving the ADP a sensitivity of 99.3% (95% CI 97.9-99.8), a negative predictive value of 99.1% (97.3-99.8), and a specificity of 11.0% (10.0-12.2).

INTERPRETATION:

This novel ADP identifies patients at very low risk of a short-term major adverse cardiac event who might be suitable for early discharge. Such an approach could be used to decrease the overall observation periods and admissions for chest pain. The components needed for the implementation of this strategy are widely available. The ADP has the potential to affect health-service delivery worldwide.

20

J Am Coll Cardiol. 2011 Sep 20;58(13):1332-9. doi: 10.1016/j.jacc.2011.06.026.

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivityassay.

Body R, Carley S, McDowell G, Jaffe AS, France M, Cruickshank K, Wibberley C, Nuttall M, Mackway-Jones K.

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Source

University of Manchester, Manchester, United Kingdom.

Erratum in

  • J Am Coll Cardiol. 2012 Sep 18;60(12):1122.

Abstract

OBJECTIVES:

This paper sought to evaluate whether high sensitivity troponin (hs-cTnT) can immediately exclude acute myocardial infarction (AMI) at a novel ‘rule out’ cut-off.

BACKGROUND:

Subgroup analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation.

METHODS:

In a cohort study, we prospectively enrolled patients with chest pain, evaluating them with standard troponin T and testing for hs-cTnT (Roche Diagnostics, Basel, Switzerland) at presentation. The primary outcome was a diagnosis of AMI. We also followed up patients for adverse events within 6 months. After subsequent clinical implementation of hs-cTnT, we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise.

RESULTS:

Of 703 patients in the cohort study, 130 (18.5%) had AMI, none of whom initially had undetectable hs-cTnT (sensitivity: 100.0%, 95% confidence interval [CI]: 95.1% to 100.0%, negative predictive value: 100.0%, 95% CI: 98.1% to 100.0%). This strategy would rule out AMI in 27.7% ofpatients, 2 (1.0%) of whom died or had AMI within 6 months (1 periprocedural AMI, 1 noncardiac death). We evaluated this approach in an additional 915 patients in clinical practice. Only 1 patient (0.6%) with initially undetectable hs-cTnT had subsequent elevation (to 17 ng/l), giving a sensitivity of 99.8% (95% CI: 99.1% to 100.0%) and a negative predictive value of 99.4% (95% CI: 96.6% to 100.0%).

CONCLUSIONS:

Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifyingpatients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.

21

J Am Coll Cardiol. 2007 Nov 20;50(21):2061-7. Epub 2007 Nov 5.

Heart-type fatty acid-binding protein predicts long-term mortality after acute coronary syndrome and identifieshigh-risk patients across the range of troponin values.

Kilcullen N, Viswanathan K, Das R, Morrell C, Farrin A, Barth JH, Hall AS; EMMACE-2 Investigators.

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Source

Coronary Artery Disease Clinical Research Network Group, Leeds Institute for Genetic, Health & Therapeutics, Leeds, United Kingdom.

Abstract

OBJECTIVES:

Our aim was to determine if a high-performance assay for heart-type fatty acid-binding protein (H-FABP) has a role in predicting all-cause mortality after acute coronary syndrome (ACS).

BACKGROUND:

Heart-type fatty acid-binding protein is released into the circulation following myocardial ischemia and necrosis and therefore may be of value to physicians when caring for patients admitted to hospital with a clinical diagnosis of ACS.

METHODS:

This was a prospective observational study with a follow-up of 12 months. The H-FABP was measured 12 to 24 h after onset of symptoms in 1,448 patients admitted to hospital with ACS. The main outcome measure was all-cause mortality 1 year after index hospital admission. Multivariable analyses were conducted using the well validated GRACE (Global Registry of Acute Coronary Events) variables together with troponin I and highly sensitive C-reactive protein (hs-CRP).

RESULTS:

After 12 months of follow-up, 296 patients had died. Multivariable analysis demonstrated that H-FABP quartiles were strongly predictive of outcome: Q1 hazard ratio (HR) 1.0; Q2 HR 2.32 (95% confidence interval [CI] 1.25 to 4.30; p = 0.007); Q3 HR 3.17 (95% CI 1.73 to 5.82; p < 0.001); Q4 HR 4.88 (95% CI 2.67 to 8.93; p < 0.001). The crude all-cause 1-year mortality for unstable angina patients with H-FABP <5.8 microg/l was 2.1% compared with 22.9% for patients above this cutoff. The adjusted all-cause mortality HR in this group was 11.35 (95% CI 2.00 to 64.34; p = 0.006).

CONCLUSIONS:

Heart-type fatty acid-binding protein predicts long-term mortality after ACS and identifies high-risk patients in a manner that is additive to the GRACE clinical risk factors, troponin, and hs-CRP, possibly as a result of identifying the occurrence of myocardial ischemia with or without necrosis.

22

Abstract 11374: In Acute Coronary Syndromes, Heart-type Fatty Acid Binding Protein is a More Accurate Predictor of Long Term Prognosis than Troponin.

Ian R Pearson; Alistair S Hall; Christopher P Gale; Mohan U Sivananthan; Karthik Viswanathan; Niamh Kilcullen; Julian H Barth

Leeds Teaching Hosps NHS Trust, Leeds, United Kingdom

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Abstract

INTRODUCTION:

We have previously shown that heart-type fatty acid binding protein (H-FABP) has a role in predicting all-cause mortality after acute coronary syndromes (ACS) and, after multivariable analysis, provides additional information to that gained from the GRACE clinical risk factor score, troponin and highly sensitive CRP. H-FABP is released into the circulation during myocardial ischaemia and after myocardial necrosis, in contrast to troponin which is released after myocardial necrosis only. We have also shown that there is a group of ACS patients who are at high risk of cardiac events and death despite normal troponin levels on admission. This group may benefit from an early invasive strategy.

HYPOTHESIS:

Plasma H-FABP level, taken between twelve and twenty-four hours after admission, can identify troponin negative ACS patients who are at a high long-term risk of death.

METHODS:

Six year mortality data is now available for patients enrolled in the FAB 1 study, for which one year mortality data was published in 2007. In this study, 1 448 unselected patients admitted to hospital with ACS had serum H-FABP level measured in addition to usual care. Mortality was tracked by the UK Office of National Statistics.

RESUTLS:

At six years overall all-cause mortality, available for 1421 patients (98.1%), was 43.5%. If troponin -ve/H-FABP -ve mortality was 20.9%; troponin -ve/H-FABP +ve 56.4%; troponin +ve/H-FABP -ve 20.2%; troponin +ve/H-FABP +ve 49.1%. Mortality rate was independent of troponin status but strongly related to H-FABP status.

CONCLUSION:

The current system of stratification of ACS patients for early invasive management if troponin positive will miss a cohort of patients who are at high risk of death despite being troponin negative, and who may benefit from invasive investigation. Conversely, it is likely that some ACS patients undergo angiography based on a false positive troponin level. The addition of H-FABP measurement to the management of ACS could avoid this.

23

J Am Coll Cardiol. 2010 Jun 8;55(23):2590-8. doi: 10.1016/j.jacc.2009.12.062.

Heart-type fatty acid-binding protein predicts long-term mortality and re-infarction in consecutive patients withsuspected acute coronary syndrome who are troponin-negative.

K, Kilcullen N, Morrell C, Thistlethwaite SJ, Sivananthan MU, Hassan TB, Barth JH, Hall AS.

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Source

C-NET Group, Multidisciplinary Cardiovascular Research Centre, The LIGHT Institute, University of Leeds, Leeds, United Kingdom.

Abstract

OBJECTIVES:

The purpose of this study was to establish the prognostic value of measuring heart fatty acid-binding protein (H-FABP) in patients withsuspected acute coronary syndrome (ACS) (in particular, low- to intermediate-risk patients), in addition to troponin measured with the latest third-generation troponin assay.

BACKGROUND:

We have previously shown that H-FABP is a useful prognostic marker in patients with proven ACS.

METHODS:

Patients (n = 1,080) consecutively admitted to the hospital with suspected ACS were recruited over 46 weeks. Siemens Advia Ultra-TnI (Siemens Healthcare Diagnostics, Newbury, United Kingdom) and Randox Evidence H-FABP (Randox Laboratories, Ltd., Co., Antrim, United Kingdom) were analyzed on samples collected 12 to 24 h from symptom onset. After exclusion of patients with ST-segment elevation and new left bundle branch block, 955 patients were included in the analysis.

RESULTS:

The primary outcome measure of death or readmission with myocardial infarction after a minimum follow-up period of 12 months (median 18 months) occurred in 96 of 955 patients (10.1%). The H-FABP concentration was an independent predictor of death or myocardial infarction, after multivariate adjustment. Patients with H-FABP concentrations >6.48 microg/l had significantly increased risk of adverse events (adjusted hazard ratio: 2.62, 95% confidence interval: 1.30 to 5.28, p = 0.007). Among troponin-negative patients (which constituted 79.2% of the cohort), the aforementioned cutoff of 6.48 microg/l identified patients at very high risk for adverse outcomes independent of patient age and serum creatinine.

CONCLUSIONS:

We have demonstrated that the prognostic value of elevated H-FABP is additive to troponin in low- and intermediate-risk patientswith suspected ACS. Other studies suggest that our observations reflect the value of H-FABP as a marker of myocardial ischemia, even in the absence of frank necrosis.

24

Body R, Dixon D, Burrows G, Cook G, Lewis PS. Economic evaluation of a heart fatty acid binding protein based protocol for rapid chest pain assessment. 14th International Conference on Emergency Medicine. Acad Emerg Med. 2012;19(6):746-747.

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25

Circulation. 2006 Aug 8;114(6):550-7. Epub 2006 Jul 31.

Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes.

O’Donoghue M, de Lemos JA, Morrow DA, Murphy SA, Buros JL, Cannon CP, Sabatine MS.

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Source

Cardiovascular Division, Brigham and Women’s Hospital, 350 Longwood Ave, First Floor, Boston, Mass 02115, USA.

Abstract

BACKGROUND:

Heart-type fatty acid binding protein (H-FABP) is a cytosolic protein that is released rapidly from the cardiomyocyte in response to myocardial injury. Although it has been investigated as an early marker of acute myocardial infarction, its prognostic utility in acute coronarysyndromes has not been established.

METHODS AND RESULTS:

We measured H-FABP in 2287 patients with acute coronary syndromes from the OPUS-TIMI 16 trial. H-FABP was elevated (> 8 ng/mL) in 332 patients (14.5%). Patients with an elevated H-FABP were more likely to suffer death (hazard ratio [HR], 4.1; 95% CI, 2.6 to 6.5), recurrent myocardial infarction (HR, 1.6; 95% CI, 1.0 to 2.5), congestive heart failure (HR, 4.5; 95% CI, 2.6 to 7.8), or the composite of these end points (HR, 2.6; 95% CI, 1.9 to 3.5) through the 10-month follow-up period. H-FABP predicted the risk of the composite end point both in patientswho were troponin I negative (HR, 2.1; 95% CI, 1.3 to 3.4) and in those who were troponin I positive (HR, 3.3; 95% CI, 2.0 to 5.3). In a Cox proportional-hazards model that adjusted for baseline variables, including demographics, clinical characteristics, creatinine clearance, ST deviation, index diagnosis, and troponin I, elevated H-FABP remained a significant predictor of the composite end point (HR, 1.9; 95% CI, 1.3 to 2.7), as well as the individual end points of death (HR, 2.7; 95% CI, 1.5 to 4.9) and CHF (HR, 2.4; 95% CI, 1.2 to 5.0). In a multimarker approach, H-FABP, troponin I, and B-type natriuretic peptide provided complementary information.

CONCLUSIONS:

Elevation of H-FABP is associated with an increased risk of death and major cardiac events in patients presenting across the spectrum of acute coronary syndromes and is independent of other established clinical risk predictors and biomarkers.

26

Eur Heart J. 2007 Jan;28(2):224-9. Epub 2006 Nov 24.

Heart-type fatty acid-binding protein permits early risk stratification of pulmonary embolism.

Puls M, Dellas C, Lankeit M, Olschewski M, Binder L, Geibel A, Reiner C, Schäfer K, Hasenfuss G, Konstantinides S.

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Source

Department of Cardiology and Pulmonology, University of Goettingen, Germany.

Abstract

AIMS:

We investigated the value of a novel early biomarker, heart-type fatty acid-binding protein (H-FABP), in risk stratification of patients with acutepulmonary embolism (PE).

METHODS AND RESULTS:

We prospectively included 107 consecutive patients with confirmed PE. The endpoints were (i) PE-related death or major complications and (ii) overall 30-day mortality. Overall, 29 patients (27%) had abnormal (>6 ng/mL) H-FABP levels at presentation. Of those, 12 (41%) had a complicated course, whereas all patients with normal baseline H-FABP had a favourable 30-day outcome (OR, 71.45; P<0.0001). At multivariable analysis, H-FABP (P<0.0001), but not cardiac troponin T (P=0.13) or N-terminal pro-brain natriuretic peptide (P=0.36), predicted an adverse outcome. Evaluation of a strategy combining biomarker testing with echocardiography revealed that patients with a negative H-FABP test had an excellent prognosis regardless of echocardiographic findings. In contrast, patients with a positive H-FABP test had a complication rate of 23.1% even in the presence of a normal echocardiogram, and this rose to 57.1% if echocardiography also demonstrated right ventricular dysfunction (OR vs. a negative H-FABP test, 5.6 and 81.4, respectively).

CONCLUSION:

H-FABP is a promising early indicator of right ventricular injury and dysfunction in acute PE. It may help optimize risk stratificationalgorithms and treatment strategies.

27

J Am Coll Cardiol. 2010 May 11;55(19):2150-7. doi: 10.1016/j.jacc.2009.10.078.

Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensivepatients with acute pulmonary embolism.

Dellas C, Puls M, Lankeit M, Schäfer K, Cuny M, Berner M, Hasenfuss G, Konstantinides S.

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Source

Department of Cardiology and Pulmonology, Georg August University of Goettingen, Goettingen, Germany.

Abstract

OBJECTIVES:

We assessed the predictive value of heart-type fatty acid-binding protein (H-FABP) in normotensive patients with acute pulmonary embolism (PE).

BACKGROUND:

Risk stratification of initially normotensive patients with PE on the basis of right ventricular dysfunction or injury remains controversial. Previous studies investigating biomarkers or imaging modalities included unselected patients, some of whom presented with cardiogenic shock.

METHODS:

We included 126 consecutive normotensive patients with confirmed PE. Complicated 30-day outcome was defined as death, resuscitation, intubation, or use of catecholamines. Long-term survival was assessed by follow-up clinical examination.

RESULTS:

During the first 30 days, 9 (7%) patients suffered complications. These patients had higher baseline H-FABP values (median, 11.2 ng/ml [interquartile range: 8.0 to 36.8 ng/ml]) compared with patients with an uncomplicated course (3.4 ng/ml [2.1 to 4.9 ng/ml]; p < 0.001). H-FABP values were above the calculated (by receiver operating characteristic curve analysis) cutoff value of 6 ng/ml in 29 patients. Eight (28%) of them suffered complications versus 1 of 97 patients with low H-FABP (negative predictive value, 99%; p < 0.001). By logistic regression, elevated (> or =6 ng/ml) H-FABP was associated with a 36.6-fold increase in the death or complication risk. The combination of H-FABP with tachycardia was a particularly useful prognostic indicator. H-FABP also predicted long-term mortality over 499 (interquartile range: 204 to 1,166) days (hazard ratio: 3.6; 95% confidence interval: 1.6 to 8.2; p = 0.003).

CONCLUSIONS:

The H-FABP might be a useful biomarker for risk stratification of normotensive patients with acute PE.

28

Anesth Analg. 2010 Nov;111(5):1101-9. doi: 10.1213/ANE.0b013e3181dd9516. Epub 2010 May 10.

Heart-type fatty acid binding protein is an independent predictor of death and ventricular dysfunction after coronary artery bypass graft surgery.

Muehlschlegel JD, Perry TE, Liu KY, Fox AA, Collard CD, Shernan SK, Body SC.

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Source

Department of Cardiology and Pulmonology, Georg August University of Goettingen, Goettingen, Germany.

Abstract

BACKGROUND:

Heart-type fatty acid binding protein (hFABP) functions as a myocardial fatty acid transporter and is released into the circulation early after myocardial injury. We hypothesized that hFABP is superior to conventional cardiac biomarkers for predicting early perioperative myocardial injury after coronary artery bypass graft (CABG) surgery.

METHODS:

A prospective cohort study of 1298 patients undergoing primary CABG with cardiopulmonary bypass (CPB) was performed at 2 institutions. Four plasma myocardial injury biomarkers (hFABP; cardiac troponin I [cTnI]; creatine kinase, MB [CK-MB] fraction; and myoglobin) were measured at 7 perioperative time points. The association among perioperative cardiac biomarkers and ventricular dysfunction, hospital length of stay (HLOS), and up to 5-year postoperative mortality (median 3.3 years) was assessed using Cox proportional hazard models. We defined in-hospital ventricular dysfunction as a new requirement for 2 or more inotropes, or new placement of an intraaortic balloon pump, or ventricular assist device either during the intraoperative period after the patient separated from CPB or postoperatively in the intensive care unit.

RESULTS:

The positive and negative predictive values of mortality for hFABP are 13% (95% confidence interval [CI], 9%-19%) and 95% (95% CI, 94%-96%), respectively, which is higher than for cTnI and CK-MB. After adjusting for clinical predictors, both postoperative day (POD) 1 and peak hFABP levels were independent predictors of ventricular dysfunction (P < 0.0001), HLOS (P < 0.05), and 5-year mortality (P < 0.0001) after CABG surgery. Furthermore, POD1 and peak hFABP levels were significantly superior to other evaluated biomarkers for predicting mortality. In a repeated-measures analysis, hFABP outperformed all other models of fit for HLOS. Patients with POD2 hFABP levels higher than post-CPB hFABP levels had an increased mortality compared with those patients whose POD2 hFABP levels decreased from their post-CPB level (hazard ratio, 10.9; 95% CI, 5.0-23.7; P = 7.2 × 10(-10)). Mortality in the 120 patients (10%) with a later hFABP peak was 18.3%, compared with 4.7% in those who did not peak later. Alternatively, for cTnI or CK-MB, no difference in mortality was detected.

CONCLUSION:

Compared with traditional markers of myocardial injury after CABG surgery, hFABP peaks earlier and is a superior independent predictor of postoperative mortality and ventricular dysfunction.


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