The value of signs, symptoms and plasma heart-type fatty acid-binding protein (H-FABP) in evaluating patients presenting with symptoms possibly matching acute coronary syndrome: background and methods of a diagnostic study in primary care

Robert T A Willemsen, Frank Buntinx, Bjorn Winkens, Jan F Glatz, Geert Jan Dinant, ‘RAPIDA’-study team, Robert T A Willemsen, Frank Buntinx, Bjorn Winkens, Jan F Glatz, Geert Jan Dinant, ‘RAPIDA’-study team

Abstract

Background: Chest complaints presented to a general practitioner (GP) are frequently caused by diseases which have advantageous outcomes. However, in some cases, acute coronary syndrome (ACS) is present (1.5-22% of cases). The patient's signs, symptoms and electrocardiography results are insufficient diagnostic tools to distinguish mild disease from ACS. Therefore, most patients presenting chest complaints are referred to secondary care facilities where ACS is then ruled out in a majority of patients (78%). Recently, a point of care test for heart-type fatty acid-binding protein (H-FABP) using a low cut-off value between positive and negative of 4 ng/ml has become available. We aim to study the role of this point of care device in triage of patients presenting chest complaints possibly due to ACS, in primary care. Our research protocol is presented in this article. Results are expected in 2015.

Methods/design: Participating GPs will register signs and symptoms in all patients presenting chest complaints possibly due to ACS. Point of care H-FABP testing will also be performed. Our study will be a derivation study to identify signs and symptoms that, combined with point of care H-FABP testing, can be part of an algorithm to either confirm or rule out ACS. The diagnostic value for ACS of this algorithm in general practice will be determined.

Discussion: A safe diagnostic elimination of ACS by application of the algorithm can be of significant clinical relevance. Improved triage and thus reduction of the number of patients with chest complaints without underlying ACS, that are referred to secondary care facilities, could lead to a substantial cost reduction.

Trial registration: ClinicalTrials.gov, NCT01826994, accepted April 8th 2013.

References

    1. Reimer KA, Jennings RB. The “wavefront phenomenon” of myocardial ischaemic cell death. II. Transmural progression of necrosis within the framework of ischaemic bed size (myocardium at risk) and collateral flow. Lab Invest. 1979;40:633–644.
    1. Gersh BJ, Stone GW, White HD, Holmes DR., Jr Pharmacological facilitation of primary percutaneous coronary intervention for acute myocardial infarction: is the slope of the curve the shape of the future? JAMA. 2005;293:979–986. doi: 10.1001/jama.293.8.979.
    1. Chambers J, Bass C. Atypical chest pain: looking beyond the heart. QJM. 1998;91:239–244. doi: 10.1093/qjmed/91.3.239.
    1. Goodacre S, Cross E, Arnold J, Angelini K, Capewell S, Nicholl J. The health care burden of acute chest pain. Heart. 2005;91:229–230. doi: 10.1136/hrt.2003.027599.
    1. Hocaoglu C, Gulec MY, Durmus I. Psychiatric comorbidity in patients with chest pain without a cardiac etiology. Isr J Psychiatry Relat Sci. 2008;45:49–54.
    1. Bruins Slot MHE, Rutten FH, Van der Heijden GJ, Geersing GJ, Glatz JF, Hoes AW. Diagnosing acute coronary syndrome in primary care: comparison of the physicians’ risk estimation and a clinical decision rule. Fam Pract. 2011;28:323–328. doi: 10.1093/fampra/cmq116.
    1. McConaghy JR, OZA RS. Outpatient diagnosis of acute chest pain in adults. Am Fam Physician. 2013;87:177–182.
    1. Willemsen RTA, Dinant GJ, Buntinx F, Glatz J, Grieten L, Van Severen E, Vandervoort P. Heart-type Fatty Acid-binding Protein compared to high-sensitive Troponin T for early exclusion of acute myocardial infarction. London: Abstractbook EPCCS; 2013.
    1. Body R, Carley S, Wibberley C, McDowell G, Ferguson J, Mackway-Jones K. The value of symptoms and signs in the emergentdiagnosis of acute coronary syndromes. Resuscitation. 2010;81:281–286. doi: 10.1016/j.resuscitation.2009.11.014.
    1. Rutten FH, Kessels AG, Willems FF, Hoes AW. Electrocardiography in primary care: is it useful? Int J Cardiol. 2000;74:199–205. doi: 10.1016/S0167-5273(00)00284-9.
    1. Swap CJ, Nagurney JT. Value and limitations of chest pain history in the evaluation of patients with suspected acute coronary syndromes. JAMA. 2005;294:2623–2629. doi: 10.1001/jama.294.20.2623.
    1. Hess EP, Thiruganasambandamoorthy V, Wells GA, Erwin P, Jaffe AS, Hollander JE, Montori VM, Stiell IG. Diagnostic accuracy of clinical prediction rules to exclude acute coronary syndrome in the emergency department setting: a systematic review. CJEM. 2008;10:373–382.
    1. Bruyninckx R, Aertgeerts B, Bruyninckx P, Buntinx F. Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis. Br J Gen Pract. 2008;58:105–111. doi: 10.3399/bjgp08X277014.
    1. Haasenritter J, Bösner S, Vaucher P, Herzig L, Heinzel-Gutenbrunner M, Baum E, Donner-Banzhoff N. Ruling out coronary heart disease in primary care: external validation of a clinical prediction rule. Br J Gen Pract. 2012;62:415–421. doi: 10.3399/bjgp12X649106.
    1. Hani MA, Keller H, Vandenesch J, Sönnichsen AC, Griffiths F, Donner-Banzhoff N. Different from what the textbooks say: how GPs diagnose coronary heart disease. Fam Pract. 2007;24:622–627. doi: 10.1093/fampra/cmm053.
    1. Bruyninckx R, Van den Bruel A, Hannes K, Buntinx F, Aertgeerts B. GPs’ reasons for referral of patients with chest pain: a qualitative study. BMC Fam Pract. 2009;10:55. doi: 10.1186/1471-2296-10-55.
    1. Buntinx F, Mant D, Van den Bruel A, Donner-Banzhof N, Dinant GJ. Dealing with low-incidence serious diseases in general practice. Br J Gen Pract. 2011;61:43–46. doi: 10.3399/bjgp11X548974.
    1. Grijseels EW, Deckers JW, Hoes AW, Boersma E, Hartman JAM, Van der Does E, Simoons ML. Implementation of a pre-hospital decision rule in general practice. Triage of patients with suspected myocardial infarction. Eur Heart J. 1996;17:89–95. doi: 10.1093/oxfordjournals.eurheartj.a014697.
    1. Graff LG, Dallara J, Ross MA, Joseph AJ, Itzcovitz J, Andelman RP, Emerman C, Turbiner S, Espinosa JA, Severance H. Impact on the Care of the Emergency Department Chest Pain Patient from the Chest Pain Evaluation Registry (CHEPER) Study. Am J Cardiol. 1997;80:563–568. doi: 10.1016/S0002-9149(97)00422-0.
    1. Bruins Slot MHE, Rutten FH, Heijden van der GJMG, Doevendans PA, Mast EG, Bredero AC, Van der Spoel OP, Glatz JFC, Hoes AW. Diagnostic value of a heart-type fatty acid-binding protein (H-FABP) bedside test in suspected acute coronary syndrome in primary care. Int J Cardiol. 2013;168:1485–1489. doi: 10.1016/j.ijcard.2012.12.050.
    1. Christenson J, Innes G, McKnight D, Boychuk B, Grafstein E, Thompson CR, Rosenberg F, Anis AH, Gin K, Tilley J, Wong H, Singer J. Safety and efficiency of emergency department assessment of chest discomfort. CMAJ. 2004;170:1803–1807. doi: 10.1503/cmaj.1031315.
    1. Cals JWL, Ament AJHA, Hood K, Butler CC, Hopstaken RM, Wassink GF, Dinant GJ. C-reactive protein point of care testing and physician communication skills training for lower respiratory tract infections in general practice: economic evaluation of a cluster randomized trial. J Eval Clin Pract. 2011;17:1059–1069. doi: 10.1111/j.1365-2753.2010.01472.x.
    1. Geersing GJ, Erkens PMG, Lucassen WAM, Büller HR, Ten Cate H, Hoes AW, Moons KGM, Prins MH, Oudega R, Van Weert HCPM, Stoffers HEJH. Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: prospective cohort study. BMJ. 2012;345:e6564. doi: 10.1136/bmj.e6564.
    1. Little P, Stuart B, Francis N, Douglas E, Tonkin-Crine S, Anthierens S, Cals JWL, Melbye H, Santer M, Moore M, Coenen S, Butler CC, Hood K, Kelly M, Godycki-Cwirko M, Mierzecki A, Torres A, Llor C, Davies M, Mullee M, O’Reilly G, Van der Velden A, Geraghty AWA, Goossens H, Verheij T, Yardley L. Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial. Lancet. 2013;382:1175–1182. doi: 10.1016/S0140-6736(13)60994-0.
    1. NICE Clinical Guideline 95. Chest pain of recent onset. National Clinical Guideline Centre for Acute and Chronic Conditions. 2010 []
    1. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D. 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;32:2999–3054. doi: 10.1093/eurheartj/ehr236.
    1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR. White HD: the writing group on behalf of the joint ESC/ACCF/AHA/WHF task force for the universal definition of myocardial infarction: third universal definition of myocardial infarction. Circulation. 2012;126:2020–2035. doi: 10.1161/CIR.0b013e31826e1058.
    1. Newby LK, Jesse RL, Babb JD, Christenson RH, De Fer TM, Diamond GA, Fesmire FM, Geraci SA, Gersh BJ, Larsen GC, Kaul S, McKay CR, Philippides GJ, Weintraub WS. ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: a report of the american college of cardiology foundation task force on clinical expert consensus documents. J Am Coll Cardiol. 2012;60:2427–2463. doi: 10.1016/j.jacc.2012.08.969.
    1. Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, Van’t Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC) Eur Heart J. 2012;33:2569–2619. doi: 10.1093/eurheartj/ehs289.
    1. Dekker MS, Mosterd A, van’t Hof AW, Hoes AW. Novel biochemical markers in suspected acute coronary syndrome: systematic review and critical appraisal. Heart. 2010;96:1001–1010. doi: 10.1136/hrt.2009.189886.
    1. McMahon CG, Lamont JV, Curtin E, McConnell RI, Crockard M, Kurth MJ, Crean P, Fitzgerald SP. Diagnostic accuracy of heart-type fatty acid-binding protein for the early diagnosis of acute myocardial infarction. Am J of Emergency Med. 2012;30:267–274. doi: 10.1016/j.ajem.2010.11.022.
    1. Ruff CT, Bonaca MP, Kosowsky JM, Conrad MJ, Murphy SA, Jarolim P, Donahoe SM, O’Donoghue ML, Morrow DA. Evaluation of the diagnostic performance of heart-type fatty acid-binding protein in the BWH-TIMI ED chest pain study. J Thromb Thrombolysis. 2013;36:361–367. doi: 10.1007/s11239-013-0870-7.
    1. Body R, McDowell G, Carley S, Wibberley C, Ferguson J, Mackway-Jones K. A FABP-ulous ‘rule out’ strategy? Heart fatty acid-binding protein and troponin for rapid exclusion of acute myocardial infarction. Resuscitation. 2011;82:1041–1046. doi: 10.1016/j.resuscitation.2011.03.015.
    1. Charpentier S, Maupas-Schwalm F, Cournot M, Elbaz M, Ducassé JL, Bottela JM, Lauque D. Diagnostic accuracy of quantitative heart-fatty acid-binding protein assays compared with Cardiodetect(®) in the early detection of acute coronary syndrome. Arch Cardiovasc Dis. 2011;104:524–529. doi: 10.1016/j.acvd.2011.07.002.
    1. Carroll C, Al Khalaf M, Stevens JW, Leaviss J, Goodacre S, OCollinson P, Wang J. Heart-type fatty acid-binding protein as an early marker for myocardial infarction: systematic review and meta-analysis. Emerg Med J. 2013;30:280–286. doi: 10.1136/emermed-2012-201174.
    1. Lippi G, Mattiuzzi C, Cervellin G. Critical review and meta-analysis on the combination of heart-type fatty acid-binding protein (H-FABP) and troponin for early diagnosis of acute myocardial infarction. Clin Biochem. 2013;46:26–30. doi: 10.1016/j.clinbiochem.2012.10.016.
    1. Bruins Slot MH, van der Heijden GJ, Stelpstra SD, Hoes AW, Rutten FH. Point-of-care tests in suspected acute myocardial infarction: a systematic review. Int J Cardiol. 2013;168:5355–5362. doi: 10.1016/j.ijcard.2013.08.002.
    1. 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 T, Tsai KC, Chu FY, Chen WK, Chang WH, Flaws DF, George PM, Richards AM. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011;377:1077–1084. doi: 10.1016/S0140-6736(11)60310-3.
    1. Tomonaga Y, Gutzwiller F, Lüscher TF, Riesen WF, Hug M, Diemand A, Schwenkglenks M, Szucs TD. Diagnostic accuracy of point-of-care testing for acute coronary syndromes, heart failure and thromboembolic events in primary care: a cluster-randomised controlled trial. BMC Fam Pract. 2011;12:12. doi: 10.1186/1471-2296-12-12.
    1. Reiter M, Twerenbold R, Reichlin T, Mueller M, Hoeller R, Moehring B, Haaf P, Wildi K, Merk S, Bernhard D, Zellweger Mueller C, Freese M, Freidank H, Campodarve Botet I, Mueller C. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction. Heart. 2013;99:708–714. doi: 10.1136/heartjnl-2012-303325.
    1. Glatz J, Mohren R. Plasma reference value of heart-type fatty acid-binding protein, the earliest available plasma biomarker of acute myocardial infarction. Health. 2013;5:1206–1209. doi: 10.4236/health.2013.58163.
    1. Stiell IG, Wells GA. Methodologic standards for the development of clinical decision rules in emergency medicine. Ann Emerg Med. 1999;33:437–447. doi: 10.1016/S0196-0644(99)70309-4.
    1. Rutten FH, Bakx C, Bruins Slot MHE, Van Casteren BCAM, Derks CJT, Rambharose VR, Burgers J, Wiersma T, Mensink PAJS, Bouma M. NHG-Standaard Acuut coronair syndroom (eerste herziening) Huisarts Wet. 2012;55:564–570.
    1. Knottnerus JA, Muris JW. Assessment of the accuracy of diagnostic tests: the cross-sectional study. J Clin Epidemiol. 2003;56:1118–1128. doi: 10.1016/S0895-4356(03)00206-3.
    1. Fox KA, Goodman SG, Klein W, Brieger D, Steg PG, Dabbous O, Avezum A. Management of acute coronary syndromes. Variations in practice and outcome, findings from the Global Registry of Acute Coronary Events (GRACE) Eur Heart J. 2002;23:1177–1189. doi: 10.1053/euhj.2001.3081.
    1. Hasdai D, Behar S, Wallentin L, Danchin N, Gitt AK, Boersma E, Fioretti PM, Simoons ML, Battler A. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS) Eur Heart J. 2002;23:1190–1201. doi: 10.1053/euhj.2002.3193.
    1. Knottnerus JA. Application of logistic regression to the analysis of data: exact modeling of a probability tree of multiple binary variables. Med Decis Making. 1992;12:93–108. doi: 10.1177/0272989X9201200202.
    1. Knottnerus JA, Muris JW. Assessment of the accuracy of diagnostic tests: the cross-sectional study. In: Knottnerus JA, Buntinx F, editors. The Evidence Base of Clinical Diagnosis: Theory and Methods of Diagnostic Research. 2. Oxford Hoboken NJ: BMJ Books, Wiley-Blackwell Publishing Ltd; 2008. pp. 42–63.
    1. Buntinx F, Aertgeerts B, Aerts M, Bruyninckx R, Knottnerus JA, Van Den Bruel A, Van Den Ende J. Multivariable Analysis in Diagnostic Accuracy Studies. What are the Possibilities? In: Knottnerus JA, Buntinx F, editors. The Evidence Base of Clinical Diagnosis: Theory and Methods of Diagnostic Research. 2. Oxford, Hoboken NJ: BMJ Books, Wiley-Blackwell Publishing Ltd; 2008. pp. 146–167.
    1. Breiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. New York: Chapman & Hall; 1984.
    1. Declaration of Helsinki for Ethical Principles for Medical Research Involving Human Subjects (first version June 1964, latest amend October 2013) at: .
    1. McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS. Users’guide to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-based medicine working group. JAMA. 2000;284:79–84. doi: 10.1001/jama.284.1.79.

Source: PubMed

3
Subscribe