Troponin als Herzinfarktmarker     Zurück 

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Das Wichtigste zum Troponin:

==> Wenn sich kein Troponin Anstieg nachweisen läßt , liegt auch kein akuter Herzinfarkt vor !

Die Troponinbestimmung liefert eine sehr gute Aussage , ob ein Herzmuskelschaden vorliegt oder nicht. Sie ist hochspezifisch  ( > 90 %) , aber nicht 100 % spezifisch. Troponin ist kein Schnelltest der schon einige Minuten nach Beginn des Infarktes positiv wird. Vernünftige Aussage sind erst nach ca 6 Stunden zu erwarten. Es ist kein klarer klinisch bedeutsamer Unterschied zwischen Trop I und Trop T erkennbar. Beide habe geringe Vor- und Nachteile . Es gibt noch keine sauber standardisierten Referenzwerte, die Hersteller- und Methoden übergreifend festgelegt sind.

Indikationen:

Keine Indikation:

Referenzbereich:

Troponin

Für diese Werte braucht man ein Röhrchen mit grüner Kappe ( Lithium -  Heparin )

Indikationen mit Fragestellung

Herzinfarkt

instabile Angina

-----------------------------------------------------------------------------------------------------------------------------------

Akutes Koronarsyndrom  

Sofortaussage: Anamnese , EKG , Echo, Puls und RR, klinischer Befund Lunge Atmung

Schnelle Aussage :   Myoglobin . Zweites EKG

Langsame sichere Aussage: Troponin

-----------------------------------------------------------------------------------------------

Sepsispatienten mit CPK Anstieg und auffälligem EKG

pulmonale Patienten mit EKG Veränderungen

Notaufnahme :

Myokarditis :

operierte Patienten mit postoperativ Angina

ungefähre Kosten

Blutentnahmezeiten (cTroponin)

Üblicherweise ...

Meßhäufigkeit:

Täglich in der Routine, als Notfallmessung auf oberärztliche Anordnung.

Wichtig: Es gibt herzspezifische oder herztypische Marker aber keine Koronarischämie- spezifischen Marker. Eine Freisetzung kardialer Marker ist bei jeder Art von Kardiomyozytenschädigung möglich (Ischämie, Entzündung, Trauma u.a.)

Differentialdiagnose kardialer Troponinerhöhungen nicht akuter koronarer Genese

Eine Troponinerhöhung hat möglicherweise prognostische Bedeutung bei folgenden Erkrankungen:

Bilder

Troponin I ist ein myofibrilläres Protein der Herzmuskulatur. Im Gegensatz zu CK-MB wird Troponin I im Skelettmuskel nicht exprimiert. Beim Herzinfarkt werden CK bzw. CK-MB und Troponin I in etwa zeitgleich freigesetzt (Anstieg nach 4 - 6 Stunden, Maximum nach 12 - 18 Stunden). Troponin I ist deutlich länger (mindestens 4 - 6 Tage lang) im Serum erhöht nachweisbar als CK-MB (Halbwertszeit 15 - 17 Stunden), da der Abbau des kontraktilen Apparates über einen lägeren Zeitraum vonstatten geht. Troponin I eignet sich auch zur Erkennung myokardialer Mikronekrosen bei instabiler Angina pectoris. Die Troponin I-Bestimmung scheint der CK-MB-Bestimmung aufgrund der längeren Persistenz für die Risikobeurteilung überlegen zu sein.

Prognose der Instabilen Angina pectoris

Troponin positiv schlechter als Troponin negativ

Troponine allgemein

Troponin ist zusammen mit Actin, Myosin, und Tropomyosin ein struktureller Bestandteil des kontraktilen Apparates der Muskeln. Das Troponin besteht aus drei Untereinheiten dem Troponin I, T und C. Seit ca. 10 Jahren ist bekannt, dass im Herz- und Skelettmuskel verschiedene Isoformen des Troponin I und T vorkommen. Die kardialen Isoformen, Troponin I (cTnI) und Troponin T (cTnT) werden bei einen Herzinfarkt und der damit verbundenen Nekrose von Herzmuskelzellen ins Blut abgegeben.

Diese Tatsache ist klinisch bedeutend, da die kardialen Isoformen über Immunoassays mit spezifischen Antikörpern nachgewiesen werden können und so die Schädigungen des Herzmuskels (Infarkt) zuverlässig diagnostiziert werden kann. Das cTnI wird ca. 3-8 Stunden nach dem Infarkt im Serum nachgewiesen, erreicht nach ca. 18-25 Stunden einen Peak und fällt innerhalb der nächsten 5-10 Tage wieder auf den Normalwert ab.

Troponinkomplex

95% gebunden  , 5% frei

TnI- und TnT- Isoformen von Herz und Skeletmuskel unterscheiden sich in ihrer Aminosäuresequenz.

Immunoassays: Spezifischer und sensitiver Nachweis der kardialen Isoformen cTnI und cTnT.

Die Verteilung dieser 3 Troponine variiert zwischen Skelett- und Herzmuskelzelle.

Durch cTnI und cTnT sind minimale kardiomyozytäre Nekrosen nachweisbar (ca. 1 g Gewebe) .

Methode

Dade Behring Dade, (TnID),   http://www.dadebehring.com

Stratus® CS Cardiac Troponin-I TestPak

Catalog number: CCTNI

Name: Stratus® CS Cardiac Troponin-I TestPak

Description:

The cardiac troponin-I method is an in vitro diagnostic test for the measurement of cardiac troponin-I in heparinized whole blood/plasma. Cardiac troponin-I measurements can be used as an aid in diagnosing acute myocardial infarction. It can also be used as an aid in the risk stratification of patients with acute coronary syndrome with respect to their relative risk of mortality.

This is a 2nd generation assay with analytical sensitivity of 0.03 ng/mL that meets National Academy of Clinical Biochemistry (NACB) and European Society of Cardiology (ESC)/American College of Cardiology (ACC) precision criteria of < 10% CV at the 99th percentile.

Availability: EU , US

Package Configuration:   100 single use TestPaks per box

Categories: Tests, Stratus®CS, Cardiac

abbott AxSym

Troponin I

Referenzbereich:

Einheit nanog / ml = mikrog/ l

Troponin I

Für diese Werte braucht man ein Röhrchen mit grüner Kappe

( Lithium -  Heparin )

Hersteller:

Roche

TROPT® sensitive Schnelltest

Qualitativer Schnelltest auf immunologischer Reaktionsbasis im Volblut als bedside-Test auf der Station und in der Arztpraxis.

Elecsys® Troponin-T

Quantitative Bestimmung aus Serum oder Plasma für den Einsatz im Labor an Elecsys Analysegeräten.

CARDIAC T quantitative (Cardiac reader)

Quantitative Bestimmung aus Vollblut für den Einsatz als bedside-Test auf der Station, in der Notaufnahme und in der Arztpraxis.

Fragen

Was ist besser Troponin I oder Troponin T ?

Steigt bei einer elektrischen Kardioversion das Troponin an ?

Steigt nach einer Herzdruckmassage das Troponin an ?

Wie hoch ist das Troponin bei einem kleinen HI ( max CPK < 200 ) ?

Wie hoch ist das Troponin bei einem mittleren HI ( max CPK 200 - 800 ) ?

Wie hoch ist das Troponin bei einem großen HI ( CPK > 800 ) ?

Ist bei erfolgreich lysierten Herzinfarkten der Tropninkurvenverlauf anders als bei nicht lysierten Infarkten ?

Wieso ist auch bei einer größeren Lungenembolie manchmal das Troponin erhöht ?

Kann man bei einem negativen Troponinwert eine Myokarditis ausschließen ?

Dtsch Med Wochenschr 1998 Apr 3;123(14):409-17

Related Articles, Books, LinkOut

Cardiac troponin T in the diagnosis and follow up of suspected myocarditis

Lauer B, Niederau C, Kuhl U, Schannwell M, Pauschinger M, Strauer BE, Schultheiss HP.

Herzzentrum Leipzig, Klinik fur Innere Medizin/Kardiologie, Universitat Leipzig.

E.und.B.Lauer@t-online.de

BACKGROUND AND OBJECTIVE: Results of routine laboratory tests for demonstrating myocardial damage in patients suspected of having myocarditis are often negative. This study was undertaken to ascertain (1) whether measuring Tropinin T (cTnT) in these patients can sensitively determine myocardial cell death, (2) to what extent this correlates with the findings of endomyocardial biopsy, and (3) whether measurement of cTnT can provide noninvasive assessment of the course of myocarditis. PATIENTS AND METHODS: 80 consecutive patients (52 men, 28 women) with clinically suspected myocarditis were investigated. The main clinical symptoms were heart failure (n = 45), angina pectoris (n = 25) or cardiac arrhythmias (n = 10). In most patients the symptoms had developed in temporal relation to a viral infection. Coronary heart disease was excluded in all by coronary angiography. Interventricular septal endomyocardial biopsies were examined histologically and immunohistologically. cTnT was measured with a highly sensitive sandwich-immunoassay. RESULTS: An increased level of cTnT (> 0.1 ng/ml) was demonstrated in 28 of the 80 patients (35%). Myocarditis was diagnosed histologically in only 5 patients, but immunohistologically in 26 of 28 (93%) with a raised cTnT level and in 23 of 52 (44%) with a normal cTnT level. The cTnT level was more frequently elevated in patients with a brief  rather than a long history of myocarditis. After 6 months the cTnT level was elevated in only 4 of 28 patients with myocarditis, but the myocardial biopsy showed persisting myocarditis in 14 patients.

CONCLUSION: Measurement of cTnT is a very sensitive way of demonstrating myocardial cell damage in patients clinically suspected of having myocarditis. Immunohistological analysis can often provide positive results even if the histological findings are unremarkable. The sensitivity in diagnosing of cTnT is greatest when the patient is tested shortly after the onset of symptoms.

PMID: 9581167 [PubMed - indexed for MEDLINE]

Literatur

Stichworte

Cardiac markers. Troponin I , Troponin T , cTI , cTT , cardiac damage  

myocardial cell damage, Cardiac troponins , acute coronary syndrome , diagnosis

Deutsche Literatur 3/2002

Stork T, Gareis R, Muller R, Hammerle M, Muller-Bardorff M, Braun R, Frohlich E, Koenig W,

Mockel M.

Related Articles

[Suspected acute coronary syndrome in patients without ST-elevation. Exclusion of infarction, early

clinical estimation and non-coronary diagnoses]

Dtsch Med Wochenschr. 2002 Feb 8;127(6):260-5. German.

PMID: 11832985 [PubMed - indexed for MEDLINE]

1: Dtsch Med Wochenschr 2002 Feb 8;127(6):260-5

Related Articles, Books, LinkOut

[Suspected acute coronary syndrome in patients without ST-elevation.

Exclusion of infarction, early clinical estimation and non-coronary

diagnoses]

[Article in German]

Stork T, Gareis R, Muller R, Hammerle M, Muller-Bardorff M, Braun R, Frohlich E,

Koenig W, Mockel M.

Kardiologie/Angiologie, Karl-Olga-Krankenhaus, Akad. Lehrkrankenhaus der Universitat Ulm,

Stuttgart. Thomas.Stoerk@t-online.de

BACKGROUND AND OBJECTIVE: Patients admitted to the hospital with suspected acute

coronary syndrome (ACS) represent a collective at high risk. The NOWIS substudy aimed at

evaluating 3 points: (1) Safe exclusion of myocardial infarction by history, symptoms, biochemical

markers and the ECG, (2) value of the first diagnosis by the physician in the emergency room, and

(3) prevalence and distribution of non-coronary leading diagnoses. PATIENTS AND METHODS:

In 164 patients admitted with suspected ACS without ST-segment elevation (73 % men, median

age 66 years) the cardiac markers myoglobin, troponin T and CK/CK-MB were assessed on

admission and 4 h later. In 2 of the NOWIS centers, the diagnosis on admission, derived from the

ECG, history and clinical symptoms, was compared with the leading diagnosis at discharge, based

on coronary angiography and, if negative, on additional esophago-gastroscopy. RESULTS: (1)

Myoglobin was the biochemical marker with the highest sensitivity 4 h after admission for acute

myocardial infarction (classic) definition by CK-MB elevation) with 90.4 %, followed by troponin T

with 84.6 %. Four h after admission, in 15.4 % of the infarction patients (prevalence 31.7 %)

troponin T was normal. (2) The admission diagnosis instable angina pectoris was confirmed in 46.7

% (57 of 122), suspected acute infarction in 76.2 % (32 of 42). On the other hand, 90.4 % (57 of

63) of the patients with instable angina as leading diagnosis at discharge were correctly diagnosed

on admission, but only 61.5 % (32 of 42) of the patients with infarction. (3) At discharge, 29.9 %

(49 of 164) of the patients had a non-coronary leading diagnosis. Here, the most common were

gastro-intestinal (55.1 %), costo-vertebral (18.4 %) and broncho-pulmonary (16.3 %).

CONCLUSIONS: (1) Troponin and myoglobin are helpful in patients without ST-segment

elevation; yet, 4 h after admission, a safe exclusion of myocardial infarction is not possible. (2) The

clinical diagnosis on admission is important. However, it corresponds with the leading diagnosis at

discharge, based on coronary angiography, in only 50 to 75 %. Patients admitted with suspected

ACS should be monitored for 24 h in the hospital (chest pain units or coronary care units). (3)

Nearly one third of the patients initially admitted with suspected ACS show a non-coronary leading

diagnosis, thus underlining the value of further investigations and of an interdisciplinary approach.

PMID: 11832985 [PubMed - indexed for MEDLINE]

2:

Kaiser ME, Birnbaum DE.

Related Articles

Kongressbd Dtsch Ges Chir Kongr. 2001;118:568-71. German.

PMID: 11824316 [PubMed - in process]

3:

Osterziel KJ, Scheffold T, Perrot A, Dietz R.

Related Articles

[Genetics of dilated cardiomyopathy]

Z Kardiol. 2001 Jul;90(7):461-9. Review. German.

PMID: 11515275 [PubMed - indexed for MEDLINE]

4:

Siaplaouras J, Thul J, Will JC, Bauer J, Kreuder J, Valeske K, Akinturk H, Schranz D.

Related Articles

[Cardiac troponin I after heart surgery corrective operation in infancy and childhood]

Z Kardiol. 2001 Jun;90(6):408-13. German.

PMID: 11486575 [PubMed - indexed for MEDLINE]

5:

Walter S, Carlsson J, Cuneo A, Tebbe U.

Related Articles

[Leading symptoms of chest pain in the emergency room. Using cardiac markers for risk

stratification]

Dtsch Med Wochenschr. 2001 Jul 6;126(27):771-8. German.

PMID: 11486476 [PubMed - indexed for MEDLINE]

Dtsch Med Wochenschr 2001 Jul 6;126(27):771-8

Related Articles, Books, LinkOut

[Leading symptoms of chest pain in the emergency room. Using cardiac

markers for risk stratification]

[Article in German]

Walter S, Carlsson J, Cuneo A, Tebbe U.

Medizinische Klinik II, Klinikum Lippe-Detmold.

BACKGROUND AND OBJECTIVE: The acute coronary syndrome (ACS)--acute infarction or

unstable angina pectoris--requires special monitoring and differentiated treatment. A prospective

trial was undertaken to determine (1) clinical characteristics of patients with chest pain; (2) value

of cardiac markers troponin T, myoglobin and CK-MB mass in differentiating cardiac and

noncardiac chest pain; (3) the proportion of patients with ACS in whom these markers provided

helpful additional information on admission and afterwards. PATIENTS AND METHODS: 233

consecutive patients (134 men, 99 women; aged 18-98 years), presenting in 1998 with nontraumatic

chest pain at the emergency unit of the Lippe-Detmold Hospital were prospectively enrolled in the

study. Levels of troponin T, myoglobin, CK-MB mass and activity and creatine kinase were

measured on admission and after 2, 4 and 12-24 hours. RESULTS: ACS was ultimately diagnosed

in 73 patients (31%). These were significantly older (p = 0.0015) and more often male (p = 0.046).

91% of patients with ACS but only 68% of those without described the chest pain as a sense of

pressure or stabbing (p = 0.0002). Measurement of troponin T and myoglobin on admission was

helpful in 39% of those with ACS, compared with 15% of those without. When the admission ECG

was normal or nonspecific in patients with ACS, troponin T was elevated in 16%, CK-MB mass in

24%. In patients with unstable angina no single marker was associated with an increased risk (high

rate of special supervision and intervention). CONCLUSION: In the assessment of patients with

acute chest pain clinical judgement plays the predominant role. In the mostly elderly and male

patients with ACS (31% of the cohort) feeling of pressure or stabbing chest pain were most

prominent (91%). Cardiac markers troponin T, CK-MB mass and myoglobin were helpful in the

differential diagnosis of chest pain, even when the ECG was unremarkable or nonspecific. At the

time of admission myoglobin was the most significant marker for acute myocardial infarction or

unstable angina.

PMID: 11486476 [PubMed - indexed for MEDLINE]

6:

Giannitsis E, Muller-Bardorff M, Katus HA.

[Acute heart infarct--new definition and diagnostic techniques]

Internist (Berl). 2001 May;42(5):641-2, 645-8. Review. German. No abstract available.

PMID: 11400571 [PubMed - indexed for MEDLINE]

7:

Goldmann BU, Hamm CW.

Related Articles

[Risk stratification in acute coronary syndrome]

Herz. 2001 Apr;26 Suppl 1:24-9. German.

PMID: 11349623 [PubMed - indexed for MEDLINE]

8:

Auer J, Berent R, Maurer E, Mayr H, Weber T, Eber B.

Related Articles

[Acute coronary syndromes: an update. I. Pathogenesis and drug therapy]

Herz. 2001 Mar;26(2):99-110. Review. German.

PMID: 11349620 [PubMed - indexed for MEDLINE]

9:

Auer J, Berent R, Maurer E, Mayr H, Weber T, Eber B.

Related Articles

[Acute coronary syndromes: an update. II. Coronary revascularization and risk stratification]

Herz. 2001 Mar;26(2):111-8. Review. German.

PMID: 11349613 [PubMed - indexed for MEDLINE]

Herz 2001 Mar;26(2):111-8

Related Articles, Books, LinkOut

[Acute coronary syndromes: an update. II. Coronary revascularization and

risk stratification]

[Article in German]

Auer J, Berent R, Maurer E, Mayr H, Weber T, Eber B.

II. Interne Abteilung mit Kardiologie und Internistischer Intensivmedizin, Allgemeines Offentliches

Krankenhaus der Barmherzigen Schwestern vom Heiligen Kreuz, Wels, Osterreich.

johann.auer@khwels.at

CORONARY REVASCULARIZATION: PTCA in patients with refractory unstable angina is

associated with a substantial risk of the following complications: death, myocardial infarction, need

for emergency surgery, and restenosis. The introduction of intracoronary stents, however, has

improved both short-term and long-term outcomes. The newer adjunctive pharmacologic therapies

enhance even further the benefits associated with the use of stents. The decision regarding the

specific revascularization procedure to be used (e.g., CABG, PTCA, stent placement, or

atherectomy) is based on the coronary anatomy, the left ventricular function, the experience of the

medical and surgical personnel, the presence or absence of coexisting illnesses, and the

preferences of both the patient and the physician. RISK STRATIFICATION: Among patients with

unstable angina or non-Q-wave myocardial infarction, there is an increased risk of death within 6

weeks in those with elevated troponin I levels and the risk of death continues to increase as the

troponin level increases. Reversible ST segment depression is associated with an increase by a

factor of 3-6 in the likelihood of death, myocardial infarction, ischemia at rest, or provocable

ischemia during a test to stratify risk. Exercise or pharmacologic stress testing provides important

information about a patient's risk. Although the conditions of the majority of patients with unstable

angina will stabilize with effective antiischemic medications, approximately 50-60% of such patients

will require coronary angiography and revascularization because of the "failure" of medical therapy.

High-risk patients are those who have had angina at rest, prolonged angina, or persistent angina

with dynamic ST segment changes or hemodynamic instability, and they urgently require

simultaneous invasive evaluation and treatment. Medical therapy should be adjusted rapidly to

relieve manifestations of ischemia and should include antiplatelet therapy (aspirin, or ticlopidine or

clopidogrel if aspirin is contraindicated), antithrombotic therapy (unfractionated heparin or

low-molecular-weight heparin), beta-blockers, nitrates, and possibly calcium-channel blockers.

Early administration of glycoprotein IIb/IIIa inhibitors may be particularly important, especially in

high-risk patients with positive troponin tests or those in whom implantation of coronary stents is

anticipated.

10:

Herrmann J, Volbracht L, Haude M, Eggebrecht H, Malyar N, Mann K, Erbel R.

Related Articles

[Biochemical markers of ischemic and non-ischemic myocardial damage]

Med Klin. 2001 Mar 15;96(3):144-56. Review. German.

PMID: 11315398 [PubMed - indexed for MEDLINE]

11:

Langenbach MR, Korbmacher B, Schulte H, Zirngibl H, Grabensee B, Plum J.

Related Articles

[Atrial natriuretic peptide as an indicator of mild postoperative cardiac dysfunction after

uncomplicated bypass surgery]

Z Kardiol. 2000 Dec;89(12):1133-40. German.

PMID: 11201029 [PubMed - indexed for MEDLINE]

12:

Mockel M, Heller G Jr, Muller C, Klefisch FR, Riehle M, Searle J, Frei U, Stork T.

Related Articles

[C-reactive protein as an independent marker of prognosis in acute coronary syndrome: comparison

with troponin T]

Z Kardiol. 2000 Aug;89(8):658-66. German.

PMID: 11013970 [PubMed - indexed for MEDLINE]

13:

Rautenstrauch J.

Related Articles

[Laboratory values in acute myocardial infarct. New markers improve diagnosis]

MMW Fortschr Med. 1999 Oct 14;141(41):18. German. No abstract available.

PMID: 10904632 [PubMed - indexed for MEDLINE]

14:

Beyer R.

Related Articles

[Coronary emergency--the best pathway for rapid diagnosis]

MMW Fortschr Med. 1999 Jul 22;141(28-29):26-9. German.

PMID: 10897938 [PubMed - indexed for MEDLINE]

15:

Ries MW, Rupprecht HJ, Dudsjak H, Hafner G, Meyer J.

Related Articles

[Release of troponin T following PTCA in patients with unstable and stable angina pectoris]

Z Kardiol. 1999 Nov;88(11):914-21. German.

PMID: 10643059 [PubMed - indexed for MEDLINE]

16:

Helm M, Hauke J, Weiss A, Lampl L.

Related Articles

[Cardiac troponin T as a biochemical marker of myocardial injury early after trauma. Diagnostic

value of a qualitative bedside test]

Chirurg. 1999 Nov;70(11):1347-52. German.

PMID: 10591777 [PubMed - indexed for MEDLINE]

17:

Walter S, Carlsson J, Schroder R, Neuhaus KL, Sorges E, Tebbe U.

Related Articles

[Enzymatic markers of reperfusion in acute myocardial infarct. With data from the ISAM study]

Herz. 1999 Oct;24(6):430-9. Review. German.

PMID: 10546147 [PubMed - indexed for MEDLINE]

18:

Frey N, Muller-Bardorff M, Katus HA.

Related Articles

[Value of laboratory parameters in risk assessment of patients with coronary heart disease and

chronic myocardial ischemia]

Z Kardiol. 1998;87 Suppl 2:100-5. Review. German.

PMID: 9827468 [PubMed - indexed for MEDLINE]

19:

Heeschen C, Hamm CW, Goldmann BU, Moeller RH, Meinertz T.

Related Articles

[Cost-effectiveness of a rapid test for troponin in emergency admissions]

Dtsch Med Wochenschr. 1998 Oct 16;123(42):1229-34. German.

PMID: 9809044 [PubMed - indexed for MEDLINE]

20:

Schmidt S.

Related Articles

[S100B: pathogenetic and pathophysiologic significance in neurology]

Nervenarzt. 1998 Aug;69(8):639-46. Review. German.

PMID: 9757414 [PubMed - indexed for MEDLINE]

Relative Messergebnisse von cTroponin I Assays verschiedener Hersteller bei Proben mit unterschiedlichen freien und komplexierten Troponin I - Isoformen

Wu A.H.B., Feng Y.J., Moore R. et al.: Characterization of cardiac troponin subunit release into serum after acute myocarial infarction and comparison of assays for troponin T and I.

Clin Chem 1998; 44:6, 1198-1208

American Heart Association. Blood tests for rapid detection of heart attack. Heart and Stroke Guide.   Available at: http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/bloodt.html.

Accessed on July 12, 2001.

Lancet 1998 May 16;351(9114):1513

Comment on:

Lancet. 1998 Feb 21;351(9102):537-9

Cardiac troponins.

Hillis G, Mangione A, Dalsey W.

Publication Types:

Comment

Letter

PMID: 9605830 [PubMed - indexed for MEDLINE]

Stubbs P, Collinson P.

Cardiac troponins in acute coronary syndromes.

N Engl J Med. 1997 Apr 24;336(17):1257-8; discussion 1258-9. No abstract available.

PMID: 9121526 [PubMed - indexed for MEDLINE]

1: Scand Cardiovasc J 2001 Sep;35(4):229-32

Detection of myocardial damage - are the troponins the ultimate solution?

Lindahl B.

Department of Cardiology, University Hospital, Uppsala, Sweden. bertil.lindahlcard.uas.lul.se

Biochemical markers of myocardial damage are together with the clinical history, the physical examination and the 12-lead ECG key elements in the clinical evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome (ACS). In this situation the detection of myocardial damage, even very minor, is of importance, not only for diagnosis, but also for risk assessment and selection of treatment. The new markers of myocardial damage. troponin T and I, have been shown to offer some advantages over the conventional markers in ACS and there is also an increasing interest for troponins in other clinical situations, e.g. after surgery and percutaneous coronary intervention. This paper will discuss the role of troponins in these different clinical situations.

Cardiac troponin T composition in normal and regenerating human skeletal muscle

Geza S. Bodor1,a, Libby Survant1, Ellen M. Voss2,

Stephen Smith2, Diane Porterfield1 and Fred S. Apple2

1 Department of Pathology, Vanderbilt University School of Medicine, 4605

TVC, Nashville, TN 37232-5310.

2 Department of Laboratory Medicine and Pathology, Hennepin County

Medical Center, University of Minnesota School of Medicine, Minneapolis,

MN 55415.

a Author for correspondence. Fax 615-343-8420; e-mail bodorgs@ctrvax.vanderbilt.edu.

Cardiac troponin T (cTnT), measurement of which has been recommended for diagnosing myocardial infarction, was initially believed to be specific for the heart. However, recent publications have reported cTnT in sera of patients without cardiac disease; therefore, we investigated whether cTnT could be found in human skeletal muscle tissues. Using immunohistochemistry, Western blot, and quantitative cTnT ELISA, we assayed human heart (n = 3), normal human skeletal muscle (n = 6), and diseased skeletal muscle samples from patients with polymyositis (PM, n = 13) and Duchenne muscular dystrophy (DMD, n = 6). All heart specimens contained cTnT, but the expression of cTnT in normal skeletal muscle samples varied widely, ranging from no expression (quadriceps femoris) to expression by up to 20% of the muscle fibers (diaphragm). Immunohistochemistry detected cTnT in skeletal muscle of 8 of the PM patients and all of the DMD patients. Mean myofibrillar cTnT concentrations (mg/g myofibrillar protein) were: cardiac = 10.0, normal skeletal = 0.8, PM skeletal = 0.7, and DMD skeletal = 4.37, confirming the results of immunohistochemistry. Western blot analysis also confirmed the expression of cTnT in muscle from DMD patients. These findings provide evidence that cTnT is not 100%  cardiac-specific but also is expressed in regenerating (PM and DMD) as well as in normal (nonregenerating) skeletal muscle.

Key Words: indexing terms: heart disease • polymyositis • muscular dystrophy • immunohistochemistry • Western blot • ELISA

Myocardial Infarction Redefined - A Consensus Document of The Joint European Society of Cardiology/ American College of Cardiology

• J- Am- Coll- Cardiol. 2000 Sep; 36( 3): 959- 69

• Eur- Heart- J. 2000 Sep; 21( 18): 1502- 13

Vorteile der Neudefinition

Nachteile

Links

http://www.chestpainperspectives.com/

http://www.dadebehring.com

http://www.dpc-biermann.de/immulite_turbo/i_turbo2.htm

http://www.zentrallabor.uni-wuerzburg.de/aktuell/rundschreiben/Rundschreiben1.htm

http://www.roche.de/diagnostics/labor/index.htm  

Experten

Dr. E. Spanuth, Roche Diagnostics

PD Dr. G. Hafner, Institut für klinische Chemie und Laboratoriumsmedizin, Universität Mainz,

Dr. M. Möckel, Campus Virchow Klinikum, Berlin

Professor W. Stein, Chemisches Laboratorium des Allgemeinen Krankenhauses St. Georg, Hamburg,

Orginaltexte

Wichtig: Es gibt herzspezifische oder herztypische Marker aber keine Koronarischämie- spezifischen Marker. Eine Freisetzung kardialer Marker ist bei jeder Art von Kardiomyozytenschädigung möglich (Ischämie, Entzündung, Trauma u.a.)

Differentialdiagnose kardialer Troponinerhöhungen nicht akuter koronarer Genese

Eine Troponinerhöhung hat möglicherweise prognostische Bedeutung bei folgenden Erkrankungen:

Gabl HM, Mair P, Mair J.

BMJ 2000;320:1502-1504 ( 3 June )

Papers

Relation between troponin T concentration and mortality in patients presenting with an acute stroke: observational study

P James, medical registrar, a C J Ellis, cardiologist, b R M L Whitlock,

clinical physiologist, c A R McNeil, clinical head, d J Henley, director of

general medicine, a N E Anderson, associate professor of neurology. b

a Department of General Medicine, Auckland Hospital, Grafton, Auckland 1000, New

Zealand, b Department of Medicine, Auckland Hospital, Grafton, c Department of

Physiology, Green Lane Hospital, Green Lane West, Auckland 1003, New Zealand,

d Department of Chemical Pathology, Auckland Hospital, Grafton

Correspondence to: C J Ellis, Department of Medicine, 4th Floor, Auckland Hospital, Grafton, Auckland 1001, New Zealand

cj.ellis@auckland.ac.nz

Objective: To assess whether a raised serum troponin T concentration would be an independent predictor of death in patients

with an acute ischaemic stroke.

Design: Observational study.

Setting: Auckland Hospital, Auckland, New Zealand.

Subjects: All 181 patients with an acute ischaemic stroke admitted over nine months in 1997-8, from a total of 8057 patients

admitted to the acute medical service.

Main outcome measures: Blood samples for measuring troponin T concentration were collected 12-72 hours after admission;

other variables previously associated with severity of stroke were also recorded and assessed as independent predictors of

inpatient mortality.

Results: Troponin T concentration was raised (>0.1 µg/l) in 17% (30) of patients admitted with an acute ischaemic stroke. Thirty one patients died in hospital (12/30 (40%) patients with a raised troponin T concentration v 19/151 (13%) patients with a normal concentration (relative risk 3.2 (95% confidence 1.7 to 5.8; P=0.0025)).

==> Of 17 possible predictors of death, assessed in a multivariate stepwise model, only a raised troponin T concentration (P=0.0002), age (P=0.0008), and an altered level of consciousness at presentation (P=0.0074) independently predicted an adverse outcome.

Conclusions: Serum troponin T concentration at hospital admission is a powerful predictor of mortality in patients admitted with an acute ischaemic stroke.

© BMJ 2000

This article has been cited by other articles:

Wong, C-K, White, H D (2002). Recognising ""painless"" heart attacks. Heart 87: 3-5 [Full text]

Boysen, G., Christensen, H. (2001). Early Stroke: A Dynamic Process. Stroke 32: 2423-2425 [Full text]

Sander, D., Winbeck, K., Klingelhofer, J., Etgen, T., Conrad, B. (2001). Prognostic relevance of pathological sympathetic

activation after acute thromboembolic stroke. Neurology 57: 833-838 [Abstract] [Full text]

Rapid Response responses to this article:

Read all Rapid Response responses

Myocardial Injury and Cardiac Troponin

Nilesh Parekh

bmj.com, 8 Jun 2000 [Response]

Troponin I in patients with supraventricular tachycardia

My Svensson

bmj.com, 22 May 2001 [Response]

Troponin ist kein Schnelltest

Anläßlich der 46. Jahrestagung des American College of Cardiology erinnerte Dr. Christopher deFillipi, University of Texas, in Anaheim an die oft verdrängte Tatsache, daß die Differentialdiagnose des Myokardinfarktes nach wie vor nicht immer ganz einfach ist.

DeFillipi nannte Zahlen, die diesen Umstand verdeutlichen: so werden beispielsweise in den USA pro Jahr etwa 4 Millionen Frauen und Männer aufgrund von Schmerzen in der Brust unter der Verdachtsdiagnose Herzinfarkt in eine Klinik eingewiesen. Im Verlauf der aufwendigen und teuren Diagnostik stellt sich dann heraus, daß von diesen Patienten nur etwa 32% tatsächlich einen Infarkt erlitten haben. Das Bild wird zusätzlich durch den Umstand getrübt, daß anderseits in jedem Jahr etwa 34.000 Patienten aus dem Krankenhaus entlassen werden, ohne daß ein tatsächlich vorhandener Herzinfarkt erkannt wurde.

Das Resultat dieser falsch positiven und negativen Diagnosen trägt mit dazu bei, daß in jedem Jahr etwa 500.000 Amerikaner an einem Infarkt sterben. Diese diagnostischen Unsicherheiten sind der Grund dafür, daß ein neuer von Boehringer Mannheim entwickelter Herzinfarkt-Schnelltest (TROP T-Test) von der Ärzteschaft sehr positiv aufgenommen wurde. Dieser Test beruht auf dem Nachweis des Eiweißes Troponin T. Da dieser hochempfindliche Test vorhanden ist stellt sich die Frage, zu welchem Zeitpunkt die Untersuchung sinnvollerweise durchgeführt werden sollte.

Da das ausschließlich im Myokard vorkommende kardiale Troponin T (TnT) ein sehr früher Marker für einen akuten Herzinfarkt ist, hat eine Arbeitsgruppe um Dr. Andreas Schuchert untersucht, wie frühzeitig der Test im klinischen Alltag medizinisch sinnvoll ist. Am Universitätskrankenhaus Hamburg Eppendorf stellten sich die Kardiologen und Notfallmediziner daher die Frage, ob es für die Patienten faßbare medizinische Vorteile hat, wenn der Schnelltest auf Troponin T (TROP T®) bei Verdacht auf einen akuten Herzinfarkt bereits im Notarztwagen durchgeführt wird.

An der Studie nahmen 158 Patienten teil. Bei allen wurde bereits auf dem Transport in die Klinik ein derartiger Schnelltest ausgewertet. Ein zweiter Test wurde innerhalb von drei Stunden nach der erfolgten Klinikaufnahme durchgeführt. Nach Auswertung aller Untersuchungsbefunde zeigte es sich, daß 40 der eingelieferten 158 Patienten tatsächlich einen Herzinfarkt hatten. Interessanterweise war der bereits im Notarztwagen durchgeführte Trop T Schnelltest jedoch nur bei sieben Infarktpatienten (18 Prozent) positiv - dies offenbar aufgrund der Tatsache, daß die ischämisch bedingte Schädigung der Myokardzellen noch zu frisch war, um ausreichend große Mengen Troponin-T freizusetzen. Da aber andererseits bereits sehr kleine Menge vorhandenen Troponin T nachgewiesen werden können, war der Test bei vier der 118 (3 Prozent) Nichtinfarkt-Patienten positiv. Daraus folgerten die Wissenschaftler, daß ein zu früh durchgeführter Schnelltest mit zu vielen falsch negativen bzw. positiven Ergebnissen belastet ist und daher diagnostisch nicht weiterhilft. Der später in der Klinik durchgeführte zweite Trop T Test war im Gegensatz dazu bei nahezu 100% der Herzinfarktpatienten (39 von 40) positiv. Bei den Nichtinfarkt-Patienten hatten 14 (12 Prozent) zur Überraschung der Untersucher ebenfalls einen positiven Test.  

Diese "falsch-positiven" Befunde der Nichtinfarkt-Patienten erwiesen sich aber im nachhinein als wertvolles Werkzeug der Prognostik. Von jenen 14 Patienten bekamen nämlich sieben (50 Prozent) innerhalb von nur sechs Monaten schwere kardiale Komplikationen - überwiegend Herzinfarkte. Bei den Patienten mit negativem zweiten Trop T-Schnelltest traf dies dagegen nur auf 16 Prozent zu.

Aus diesen Befunden lassen sich zwei Dinge ableiten: zum einen ist es nicht sinnvoll unmittelbar nach Auftreten der ersten Brustschmerzen einen Trop T- Test durchzuführen. Zu diesem frühen Zeitpunkt ist das TnT-Eiweiß selbst bei Vorliegen eines frischen Infarkts im Blut noch nicht nachweisbar. Außerdem verdeutlichen die Untersuchungsergebnisse der Hamburger Studie, daß ein positiver Trop T-Test auch bei fehlendem Infarktnachweis ein hohes Herz-Kreislaufrisiko anzeigt. In diesen Fällen sind wahrscheinlich ansonsten klinisch stumme Mikroinfarkte für die Freisetzung von Troponin T verantwortlich. Dieses Warnzeichen für einen drohenden Infarkt kann aber Anlaß für einen ansonsten unterlassenen frühen Therapiebeginn sein.

Quelle: ACC Kongreß 1997, Anaheim 16.-19.3.97

Die erhöhten Troponin T Werte bei Niereninsuffizienz und Hämodialyse zeigen ein erhöhtes kardiales Risiko an und dürfen nicht wie früher vermutet als Störeinflüsse der zu Grund liegenden Erkrankungen angesehen werden.

Probleme:

Das übertrieben positive Image des Troponin I ist so nicht länger berechtigt. Es konnte nämlich unter anderem nachgewiesen werden, daß bei der Bestimmung des Troponin I bei verschiedenen Testmethoden ganz unterschiedliche Fragmente dieses Proteins gemessen werden. Durch verschiedene Oxidations- und Phosphorylierungsprozesse kann es außerdem schwierig werden, die Troponin I Proteine überhaupt im Serum wiederzufinden. Außerdem fehlt bis heute jegliche Standardisierung. Sogar die cut–off- Werte schwanken daher bei den unterschiedlichen klinischen Studien von 0,1 - >3 ng/ml. Es kommt hinzu, daß die angebotenen Troponin I-Tests eine sehr unterschiedliche Qualität haben. Die Ergebnisse müssen daher mit Vorsicht interpretiert werden. Ein übergreifender Vergleich unterschiedlicher Testmethoden z.B. in Metaanalysen ist daher nicht möglich.

Auch Erkrankungen wie Leberzirrhose, Tumore und sogar die regelmäßige Teilnahme an Blutspendeaktionen sorgen für falsch erhöhte Troponin I-Werte und relativieren den klinischen Wert des überwiegend in den USA verwendeten Markers.

Die Kardiospezifität des Troponin T Bestimmungen der 3. Test-Generation hat sich beispielsweise bei Marathonläufern verbessert. Es werden keine erhöhten Werte mehr angezeigt, die auf eine  Überanstrengung der Skelettmuskulatur zurückzuführen sind. Es gibt auch keine ursächlichen Zusammenhänge zwischen einer Kreatininerhöhung und hohen Troponin T Werten. Obgleich die GUSTO Studie gezeigt hat, daß es bei instabiler Angina pectoris neben erhöhten Troponin T auch erhöhte Troponin I- Serumspiegel gibt, ist Troponin T laut der Ergebnisse der GUSTO- und FRISC-Studien bei der instabilen Angina pectoris besser für die Risikostratifizierung geeignet als das Troponin I.

Literatur:

Wichtige Basisarbeit:

(Hamm et el.: The prognostic value of serum troponin T in unstable angina. N Engl J Med 1992; 327: 146 – 50).

Sinnvoller Einsatz kardialer Marker

http://www.zentrallabor.uni-wuerzburg.de/sections/notfall/Kard.Marker.htm

Die neueren kardialen Marker werden, wie sich nach Rücksprache immer wieder herausstellt, oftmals unkritisch angefordert. Doch anders als Enzyme wie z.B. die Creatinkinase werden die neueren kardialen Marker (Troponin I und Myoglobin) mittels teurer Immunoassays bestimmt. Um kardiale Marker adäquat einsetzen zu können, ist das Wissen um die diagnostischen Zeitfenster und die Stör- und Einflußgrößen dieser Marker unerläßlich. Wir möchten deshalb in Form zweier Tabellen eine Zusammenschau über die alten und neuen kardialen Marker geben. Unsere Angaben beruhen insbesondere auf den Empfehlungen der DGLM+-Arbeitsgruppe "Standardisierung von Immunoassays - Schwerpunkt Herzdiagnostik", die sich aus klinisch tätigen Kollegen und Laborärzten zusammensetzt (J Lab Med 1997; 21: 402-8).

+ Deutsche Gesellschaft für Laboratoriumsmedizin

MARKER

DIAGN.ZEITFENSTER*

AUCH ERHÖHT BEI

Myoglobin

2 Std. bis 12 Std.

Niereninsuffizienz, Skelettmuskelschäden

CK-/CK-MB-Aktivität

5 Std. bis 24 Std.

Makro-CK (CK-MB-Anteil > 25%), Myopathien, Hypothyreose

Troponin I

4 Std. bis 5 Tage

Niereninsuffizienz (sehr selten!)

GOT heutzutage obsolet

LDH (HBDH) heutzutage obsolet

Das Diagnostische Zeitfenster ist definiert als der Zeitraum, in dem für die kardialen Marker eine Sensitivität (berechnet nach Symptombeginn) von mindestens 50% erreicht wird.

  

INDIKATION

MARKER

BLUTENTNAHME

(Zeitp.nach Klinikaufnahme in Std.)

Absicherung eines klinisch eindeutigen Myokardinfarkt.

CK-/ CK-MB-Akt.

ggf. Myoglobin

0, 4 und 12

Ausschluß fraglicher Myokardinfarkt

Troponin I

ggf. Myoglobin

0, ggf. 4 und 12

0, ggf. 4 und 8

Reperfusionskontrolle

Myoglobin

0, 1,5 (2) nach Beginn der Lyse

Verlaufsbeurteilung

CK-/CK-MB-Akt.

evt. Troponin I

0, 8, 16, 24, 36, 48, 72

0, 72

Risikostratefizierung bei instab. Angina pectoris

Troponin I

0, ggf. 4 und 12

http://www.zentrallabor.uni-wuerzburg.de/aktuell/rundschreiben/Rundschreiben1.htm

Troponine: "To T or Not to T, That Is the Question"

So überschrieb Collinson 1997 sein Editorial in der Fachzeitschrift "Clinical Chemistry". Vor dieser Frage standen auch wir, nachdem unser Notfallgerät analytische Probleme aufwarf. Bei heparinisierten Patienten kam es im Gerät zu einem "Nachgerinnen" und somit vereinzelt zu falsch-positiven Troponin I-Werten. Troponin I galt, verglichen mit T, lange Zeit als der kardiospezifischere Assay. Chronische Skelettmuskelschäden konnten ebenso falsch-positive Troponin T-Befunde erzeugen wie Niereninsuffizienz. In dieser Hinsicht hatte die Herstellerfirma des Troponin T-Assays in der Zwischenzeit einige Verbesserungen eingebracht.

Vor diesem Hintergrund entschlossen wir uns zu einem Wechsel des Troponin-Assays. Der Troponin T-Assay (der mittlerweile 3. Generation) besticht zudem, verglichen mit dem bisher eingesetztem Analysensystem, durch einfachere Handhabung und schnellere Laufzeit. Ab 4. Februar 2000, 19 Uhr messen wir nicht mehr Troponin I, sondern T.

Was ändert sich für Sie ?

Der alte Troponin I-Assay hat eine Nachweisgrenze von 0,5 ng/ml. Die Nachweisgrenze entsprach dem Grenzwert, da bei Gesunden kein Troponin nachweisbar sein sollte. Werte über 2,0 ng/ml wiesen mit hoher Sicherheit auf einen Myokardinfarkt hin.

Werte dazwischen waren mit kardialen Ischämien wie einer instabilen Angina pectoris vereinbar.

Die Nachweisgrenze des Troponin T-Wertes liegt nun bei 0,03 ng/ml (das ist der Wert, der von Lauf zu Lauf noch mit 20% Abweichung gemessen werden kann). Wir geben für den neuen Test einen Grenzwert an, der nicht mehr mit der Nachweisgrenze identisch ist, sondern einen Wert, oberhalb dessen überhaupt von einer kardialen Ischämie ausgegangen werden kann. Ein "infarktspezifischer Grenzwert" existiert nicht.

Es ändert sich, verglichen mit dem etablierten Troponin-Assay, beträchtlich die Wertlage des neuen Troponin-Assays. Troponin T-Werte sind vergleichsweise um einen Faktor 10 und mehr geringer als Troponin I-Werte. Dieser krasse Unterschied ändert aber

nichts an der diagnostischen Sensitivität.

3. Chronische Niereninsuffizienz (insbesondere bei Hämodialyse) dürfte immer noch falsch-positive Troponin T-Werte hervorbringen. Während der alte Troponin T-Assay in diesen Fällen zu 37% erhöhte Werte lieferte, wiesen mittels des neuen Troponin-T-Test immer noch 20% der langfristig hämodialysierten Patienten erhöhte Werte auf (Clin Chem 1997;43:1877-84). Die Herstellerfirma weist darauf hin, daß es sich hierbei ebenso um kardiale Ischämien handeln würde. Absolut überzeugend war diese Behauptung bisher nicht zu belegen (Eur Heart J 1998;19,suppl N:N34-7). Dem stehen Studien gegenüber, die keinerlei kardiales Ereignis bei chron. niereninsuffizienten Patienten mit erhöhtem Troponin T beobachten konnten (Clin Chem Lab Med 1998;36:87-92, Clin Biochem 1999;32:125-30). Troponin T war dabei meist nur gering erhöht (überwiegend Werte bis 0,4 ng/ml). Vereinzelt bot im übrigen auch der Troponin I-Assay erhöhte Werte bei chron. niereninsuffizienten Patienten, wenngleich nicht in dem Ausmaß wie der Troponin T-Test. Von Skelettmuskelschäden ist im klinischen Alltag heute kein falsch-positives Troponin T mehr zu erwarten.

Haben Sie bei einem chron. niereninsuffizienten Patienten Zweifel, ob ein erhöhter Wert kardialen Ursprungs ist, empfiehlt sich die erneute Blutentnahme: Ändert sich der Wert kaum, spricht dies eher gegen eine kardiale Genese der erhöhten Troponin T-Konzentration.

4. Zur Indikationsstellung: Zusammengefaßt eignen sich Troponine zum Ausschluß eines fraglichen Herzinfarktes, nicht jedoch zur Frühdiagnose eines akuten Myokardinfarktes (siehe Myoglobin). Weitaus eher als Troponin I zeigt das Troponin T einen biphasischen Verlauf: Es gibt ein Maximum am 1. (Freisetzung des zytoplasmatischen Pools) und am 4. Tag (Freisetzung des strukturgebundenen Pools). Ein wichtiges Feld ist die Risikostratefizierung bei instabiler Angina pectoris. Neuerdings werden Troponin T wie I propagiert, um Hochrisikopatienten zu identifizieren, die von einer Therapie mit Glycoprotein IIb/IIIa-Antagonisten profitieren könnten (Lancet 1999;354:1757-62). Abciximab reduzierte die Rate kardialer Ereignisse bei Patienten mit refraktärer instabiler Angina pectoris eindrucksvoll, sofern Troponin T anfänglich erhöht war. Patienten mit unauffälligem Troponin T profitierten nicht von Abciximab (CAPTURE Studie, N Engl J Med 1999;340:1623-9). Die Autoren gaben dabei zu bedenken,daß bei Aufnahme eine einzige Bestimmung nicht ausreichend ist. Bei negativem Befund sollte die Bestimmung binnen (z. B. 4) Stunden wiederholt werden.

(Clinical Chemistry. 1997;43:421-423.)

© 1997 American Association for Clinical Chemistry, Inc.

Editorials

To T or Not to T, That Is the Question

Paul O. Collinson

Consultant Chemical Pathologist, Mayday University Hospital, London

Rd., Thornton Heath, Surrey CR7 7YE, UK

The quest for a test that is absolutely disease- and tissue-specific could be considered the Holy Grail of the clinical chemist, dreamt of but seldom achieved. Initial reports on measurement of the cardiac troponins, cardiac troponin T (cTnT) and cardiac troponin I (cTnI), for diagnosis of myocardial infarction suggested that these markers would become the "gold standard," replacing all other existing tests.

Questions have been raised as to the specificity of cTnT for cardiac damage in patients with extreme rhabdomyolysis, renal failure, polymyositis, and muscular dystrophy. This problem is addressed by the papers of Bodor et al. (1) and Müller-Bardorff et al. (2) in this issue of Clinical Chemistry. This is therefore a reasonable time to review what we know at the basic science level and how this relates to both papers and current clinical practice.  

Cardiac and skeletal muscle cells are closely related but arise from different embryonic lineages and express distinctive gene sets when terminally differentiated. During embryonic development, both muscle types cross-express several genes. There are three troponin T genes, corresponding to slow skeletal, fast skeletal, and cardiac troponin. During early embryonic development, the cTnT gene is activated and transcribed at relatively low levels in both cardiac and skeletal muscles until mid-fetal development, when expression is divergently regulated. In cardiac cells, transcription of the cTnT gene is sharply up-regulated, whereas in the skeletal cells it is repressed (3)(4)(5). Similarly, three isoforms of troponin I exist, also the products of three separate genes: fast skeletal muscle, slow skeletal muscle, and cardiac muscle troponin I. During fetal development, slow skeletal muscle troponin I is the predominant isoform in the heart. After birth, the slow skeletal isoform is lost such that, by 9 months of postnatal development, the cardiac isoform is the only detectable isoform (6)(7).

Multiple isoforms of cTnT with different amino acid sequences have been described, arising from alternative splicings of mRNA. The nomenclature used for these isoforms varies slightly between authors (8)(9)(10)(11). The sequences corresponding to the different isoforms have been characterized (9)(11)(12), as have the sequences for fast skeletal (13) and slow skeletal troponin T (14). The protein isoform expressed in embryonic cardiac and skeletal muscle cells is unique to this developmental stage (5). Multiple isoforms of cTnT are expressed in the fetal heart. In the adult heart, a single isoform of cTnT is present, referred to as cTnT2 (9) or cTnT3 (10). In fetal skeletal muscle, the adult cTnT isoform is detectable but at a very low amount. A second isoform, corresponding to a fetal cardiac isoform, is also detectable. This isoform is present in relatively greater abundance than the adult cTnT isoform. In both cases, these isoforms are present in low abundance relative to the skeletal isoforms (7)(10). No isoforms of cTnT can be detected in normal adult skeletal muscle, either by Western blot (10) or by reverse transcriptase polymerase chain reaction (RT-PCR) (9). Reexpression of a fetal isoform of cTnT in cardiac failure has been described by some (9)(10)(11) but not all (12) workers. Theoretically, because cTnT isoforms are expressed in fetal skeletal muscle during development and then suppressed, whereas cTnI is expressed only in the adult heart, cTnT might be reexpressed in damaged or regenerating skeletal muscle (10), but cTnI is unlikely to be found in noncardiac muscle. Reexpression, therefore, might result in detectable cTnT in the serum.

The data presented by Bodor and Müller-Bardorff must now be analyzed against these findings. Bodor et al. (1) approached the questions of specificity by investigating tissue immunohistochemistry. Their previously published studies on cTnI (15) convincingly demonstrated that this isoform is not present in normal or pathological skeletal muscle from adults, findings entirely compatible with the molecular biology described above. In their studies of cTnI, they used the same antibody in the immunohistochemistry as was used in the serum assay. The current study (1) does not; instead, the antibody used is directed at residues 3–15 of the N-terminal sequence of cardiac troponin T. This sequence is found in all of the isoforms of cTnT so far described, including fetal isoforms (9). The study of Müller-Bardorff et al. (2) uses a more conventional approach. The anti-cTnT monoclonal antibodies used in the original and reformulated assay of Müller-Bardorff et al. recognize a sequence specific for cTnT but not found near the N-terminus. The two antibodies in the reformulated assay recognize epitopes 6 amino acid residues apart. In evaluating the data presented, these differences must be kept in mind.

The Western blot data for normal skeletal muscle presented by Bodor et al. is entirely compatible with the molecular biology data summarized above. The lack of cross-reaction of skeletal muscle from psoas, diaphragm, and quadriceps presented by Müller-Bardorff et al. is similarly consistent. The measurement of tissue extracts in a system not optimized for such analyses may account for the positive values seen, as may the possibility of cross-reaction; it is difficult to be certain that these are not complicating factors. The immunohistochemical data are more interesting. The majority of skeletal muscle studied by Bodor et al. did not show staining, but ~20% of the muscle fibers from the diaphragm did. The finding of cTnT in normal skeletal muscle is not consistent with any of the previously cited studies or with the Western blot data presented by Bodor et al.

I can suggest three possible explanations for their findings. The antibody used may cross-react with skeletal troponin T. Indeed, the published sequences for fast skeletal troponin T, slow skeletal troponin T, and cTnT show a complete match for a pentapeptide within residues 3–15 of cTnT (the epitope recognized by the antibody used). Some cross-reaction might occur because of the polyclonal nature of the detection antibody used. Either of these might yield some low-intensity staining. Although the authors (1) demonstrated by competition assay that they could block the binding of antibody by using recombinant cTnT, they did not demonstrate that skeletal troponin T did not interfere. A third, and much more intriguing, possibility exists: Because fetal and adult isoforms of cTnT share a common N-terminal sequence, including residues 3–15, expression of any cardiac isoform in skeletal muscle will be recognized. The dominant isoform of cTnT expressed in fetal skeletal muscle is not the adult isoform but instead resembles that reexpressed in heart failure (9)(10)(11). Any fetal isoform present might therefore be identified by the immunohistochemical technique. The finding of immunostained tissue seems to be confined to the diaphragm. However, it is possible that fetal cTnT isoform is present in some of these skeletal muscle fibers. If so, the amounts appear to be very low and to not cross-react in the reformulated assay of Müller-Bardorff et al.

This information must now be put into its clinical context. At the analytical cutoff values quoted for the current commercially available assays, cTnT and cTnI are not detected in serum from normal reference groups. Studies on exertional rhabdomyolysis have not found cTnT in serum, despite evidence of skeletal muscle trauma and release of creatine kinase (16)(17)(18). Only when a large-scale release of skeletal troponin T occurs with nonspecific binding to the assay tube wall will a problem appear, because of detection of this isoform by the second antibody (19). This has been resolved by the reformulation of the assay. The study by Müller-Bardorff et al. shows that small increases found in the first-generation ELISA were abolished in the second-generation test. We may therefore conclude that, even if cTnT is present in normal skeletal muscle, it does not pose a problem in routine clinical practice.

The data for muscular dystrophy are more suggestive. Reexpression of cTnT would be most likely in this group. The immunohistochemistry data show clear staining of some but not all fibers, although the staining is less intense than that seen in fetal skeletal muscle or fetal cardiac muscle. Again, which one of the isoforms is being expressed is unknown; the data are compatible with a fetal or an adult isoform of cTnT. The Western blot data show multiple bands but the positions of the bands differ from that of the dominant cardiac isoform. Müller-Bardorff et al. show a decrease in the cTnT detected with the reformulated assay. Perhaps the first-generation ELISA shows cross-reaction with a reexpressed isoform or a skeletal isoform. Until histochemistry and Western blot analysis are performed with an antibody specific for the dominant adult isoform of cTnT—ideally, the antibodies used by Müller-Bardorff et al.—the questions raised by these studies remain unresolved.

The differential diagnosis of cardiac damage in patients with muscular dystrophy is interesting but is not a frequent problem in routine clinical practice. Much of the discussion on the relative merits of cTnT and cTnI comes from studies in patients with renal failure. One of the problems is that early reports used high cutoff values for cTnI (19). Reformulation of the cTnT ELISA reduces but does not abolish the number of patients with renal failure in whom cTnT is detectable. Conversely, cTnI clearly is also detectable in some patients with renal dysfunction (20). The relative proportion of patients with detectable cTnT exceeds that of cTnI in all reports (21)(22)(23)(24) and in my experience. The question of the origin of the excess of detectable cTnT in this group remains unexplained. Does the greater proportion of patients with renal dysfunction in whom cTnT is detected rather than cTnI mean that cTnT is more sensitive to minor cardiac damage in this patient group? The possibility of reexpression remains to be definitively confirmed or excluded. However, a single, properly timed measurement of cTnT or cTnI will be sufficient only to exclude rather than confirm cardiac damage. A positive result will require sequential measurements. The clinical significance of increases of cTnT and cTnI in patients with renal failure is unknown and will require outcome studies.

It is important to maintain a sense of perspective. The role of cardiac troponins is to detect myocardial injury in patients in whom acute coronary syndromes are suspected. Unlike with other markers, investigators have made a direct attempt to link measurement with outcomes. The ability of cTnT to predict short- and long-term prognosis has been unequivocally demonstrated in several studies in patients with unstable angina (25)(26)(27)(28) and myocardial infarction, both with and without ECG changes on admission (29)(30), and there is a developing body of literature (although not as extensive) for cTnI, at least for short-term prognosis (31)(32). Use of either marker is recommended by the American Heart Association (33). Direct comparison of cTnT and cTnI has demonstrated either a similar prognostic efficiency (34) or superior prognostic efficiency for cTnT (35), depending on methodology. The suggestion has been made that cTnT and cTnI may recognize different subpopulations in unstable angina patients (36) and that cTnT may be more sensitive to minor degrees of damage (37). The improved version of the cTnT ELISA seems to have overcome the problems of the first-generation assay in the presence of extensive muscle damage, leaving both cTnT and cTnI superior to CK-MB for differential diagnosis in patients with acute chest pain with or without skeletal muscle trauma.

Is there reexpression of a fetal (or adult) isoform of cTnT that gives rise to false-positive values in certain patient populations? If so, is this of clinical diagnostic and prognostic significance? Both papers address these questions. It appears possible that cTnT is reexpressed in certain patient groups. This may cause diagnostic difficulty or may provide a convenient marker for a generalized myopathy that includes a cardiomyopathy. Neither paper provides complete answers. One cannot categorically claim superiority of one troponin over another, and we may indeed find that cTnT and cTnI measurements are not exactly equivalent. The current

data suggest that more studies, both methodological and clinical outcome studies, are needed before any final statement can be made.

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BMJ 2000;320:1702-1705 ( 24 June )

Prospective audit of incidence of prognostically important myocardial damage in patients discharged from emergency department Commentary: Time for improved diagnosis and management of patients presenting with acute chest pain

Prospective audit of incidence of prognostically important myocardial damage in patients discharged from emergency department

P O Collinson, consultant chemical pathologist a, S Premachandram, specialist registrar b, K Hashemi, consultant in accident and emergency medicine b.

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

b Department of Accident and Emergency Medicine, Mayday University Hospital

Correspondence to: P O Collinson, Department of Clinical Biochemistry, 2nd Floor, Jenner Wing, St George's Hospital, London SW17 0QT

poctrop@poctrop.demon.co.uk

Abstract

Objective: To assess the incidence of prognostically important myocardial damage in patients with chest pain discharged from the emergency department.  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 µg/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.

Introduction

Patients presenting to the emergency department with chest pain of unknown cause are a management challenge. Clinical history and examination are imperfect tools for diagnosis. Electrocardiography is the first test, but rigorous comparison based on postmortem diagnosis shows that its diagnostic sensitivity is only 41-61%. 1 2 The admission electrocardiogram, although excellent for selecting patients for thrombolysis,3 has a diagnostic sensitivity for acute myocardial infarction of 55-75%. 4 5

Measurement of cardiac troponin T and cardiac troponin I concentrations has greatly improved diagnosis of patients presenting with suspected acute coronary syndromes. The diagnostic time window of these markers is wide, being up to 72 hours; the markers have 100% sensitivity for diagnosing acute myocardial infarction 12 hours after presentation to hospital, and concentrations remain raised for as long as 10 days.6 Raised concentrations of cardiac troponin T and cardiac troponin I are completely cardiac specific, unlike increases in concentrations of creatine kinase or its MB isoenzyme, which can be due to non-cardiac sources.7 Detection is diagnostic of myocardial damage in patients admitted with suspected acute coronary syndromes and indicates an unfavourable outcome. 8 9

We measured cardiac troponin T to assess the incidence of missed myocardial damage in patients presenting with chest pain and suspected acute coronary syndromes discharged from a hospital emergency department.

Participants and methods

We studied patients sequentially attending the emergency department over four months with chest pain. All patients had a full history and clinical examination, a 12 lead electrocardiogram recorded, and an initial blood sample taken for measurement of urea, electrolytes, blood glucose, and creatine kinase concentrations. Cardiac troponin T was not measured at presentation as its diagnostic sensitivity for acute myocardial infarction is equivalent to that of creatine kinase on first presentation with chest pain. Patients were then divided into the following categories: those with definite acute myocardial infarction requiring thrombolysis and admission to the cardiac care unit; those with suspected acute coronary syndromes on clinical or electrocardiographic grounds or with a raised creatine kinase concentration and who required medical referral and possible hospital admission; those in whom acute coronary syndromes were ruled out on clinical and electrocardiographic criteria and who could be discharged from the emergency department; and patients with a definite source of non-cardiac chest pain (obvious musculoskeletal trauma, migraine, chest pain relieved by antacids).

All patients in whom suspected acute coronary syndromes were ruled out and who would not otherwise have been medically reviewed were invited to reattend at 0900 the next working day (if this was 12 to 48 hours after first presentation to the emergency department) for a follow up assessment by a member of the emergency department staff (SP). All patients who accepted were examined again, and a follow up 12 lead electrocardiogram was recorded. A single blood sample was taken by using a 4 ml serum separator gel containing Vacutainer (Becton-Dickinson, Oxford) and sent to the laboratory for measurement of cardiac troponin T concentration. The sample was allowed to clot before spinning, and the serum was then separated and stored at 4°C. Serum was analysed for cardiac troponin T by enzyme linked immunoabsorbent assay (ELISA, Roche Diagnostics, Lewes) as previously described.6

Results

During the study 676 patients attended the emergency department with a presenting complaint of chest pain of unknown cause. A total of 268 (40%) patients were admitted for exclusion of acute myocardial infarction and 408 (60%) were discharged. Of the patients discharged, 122 (30%) were found to have definite non-cardiac chest pain (musculoskeletal injury, chest trauma, or gastrointestinal symptoms) or did not have chest pain on review (migraine, head injury, or upper body laceration). Seventy one (10.5%) were known to have ischaemic heart disease and referred for urgent outpatient medical follow up.

Two hundred and fifteen patients (53%) had a discharge diagnosis of chest pain of unknown cause. Fifty five of these patients were referred for subsequent medical assessment as an outpatient, and 160 were discharged without planned follow up. Of these 160, 110 patients (75 men, 35 women, age range 22.6-88.7 years, median 50.4, interquartile range 41.7 to 63.2) agreed to participate in the study. Fifty patients either declined review or could not be seen within 48 hours of initial presentation.

Initial electrocardiography and creatine kinase measurement gave normal results in all 110 cases. The patients had no further symptoms after discharge, and the repeat electrocardiograms all showed no abnormality. Cardiac troponin T was detected in eight (7%) patients at follow up (table 1). In seven the cardiac troponin T concentration was 0.1 µg/l, the level which indicates myocardial infarction. All patients with raised cardiac troponin T concentrations were subsequently referred for cardiac assessment and enrolled in the cardiac secondary prevention programme.

View this table:

Table 1. Cardiac troponin concentrations in patients discharged from emergency department

Discussion

We found missed myocardial damage of prognostic importance in 6% of patients sent home from

the emergency department. The ability of raised cardiac troponin T concentration to predict risk

of subsequent cardiac events has been well documented. 8 9 The size of the risk depends on how

high the troponin T concentration is, 10 11 but in patients without electrocardiographic changes a

cut-off of 0.1 µg/l is the optimal predictor of death. Some of the seven patients may have been

considered to have unstable angina rather than non-Q wave myocardial infarction by conventional

criteria. However, four patients had cardiac troponin concentrations above 0.5 µg/l, which has a 95% specificity for non-Q wave

myocardial infarction. The risk of subsequent cardiac events in non-Q wave acute myocardial infarction is the same as that seen

in patients with a cardiac troponin concentration above 0.1 µg/l.

Rates of missed acute myocardial infarction have usually been estimated by detailed review of case notes or by using follow up

with a questionnaire or interview.12-14 The measurement of cardiac troponin T to detect cardiac damage is a valuable addition to

the range of tests for audit and quality assurance or for follow up clinics.

The incidence of missed acute myocardial infarction was estimated at 11.8% in a detailed audit of patients discharged from the

emergency department,12 although the figure usually quoted is 6-8%. 13 14 We studied 69% (110/160) of the total eligible

population, and our audit is unlikely to have seriously underestimated or overestimated the number of patients missed (6%). Data

frequently presented for the United States show that of 6.0 million patients attending the emergency department each year with

chest pain, 5.7 million have non-diagnostic electrocardiograms; 4.1 million are sent home, of whom 75 000 (0.18%) have

undiagnosed acute myocardial infarction. However, a recent study which measured cardiac troponin T and cardiac troponin I

showed an incidence of prognostically important myocardial damage of 6% in patients without a diagnostic electrocardiogram on

presentation.15

Patients with missed myocardial infarction or high risk unstable angina who are sent home have a high risk of subsequent cardiac

events. Medical litigation for missed acute coronary syndromes in the United States accounts for 21-22% of malpractice claims,16

with an estimated total cost of $1.8bn-$15bn (£1bn-£9bn) annually.17 Medical litigation is also rising in the United Kingdom. More

importantly, however, these patients are deprived of the opportunity to enter cardiac secondary prevention programmes, which will

substantially improve their subsequent survival.

We have shown that measurement of cardiac troponin T can be used to assess the incidence of prognostically important

myocardial damage in patients discharged from the emergency department. The test can be used to determine the effectiveness of

other interventions to reduce misdiagnosis of chest pain, such as computer aided decision making protocols or serial biochemical

testing.18-24 In addition, measurement of cardiac troponin T at follow up is an easy and convenient method of risk assessment.

What is already known on this topic

Diagnosis is difficult in patients presenting with chest pain of unknown cause

Measurement of cardiac troponin T can reliably detect heart damage within 1-2 days after infarction

What this study adds

6% of patients discharged from the emergency department had troponin T concentrations suggesting important cardiac

damage on review after 12-48 hours

Repeat electrocardiography on these patients showed no abnormality

Measurement of cardiac troponin T is a convenient diagnostic and audit tool for monitoring performance in emergency

departments

Acknowledgments

Contributors: POC organised, planned, and directed the study; collated and analysed the data; wrote the paper; and acts as

guarantor. SP performed the clinical follow up and collected the clinical data. KH supervised the clinical work and edited the

paper.

Footnotes

Funding: Audit funding to the departments of chemical pathology and accident and emergency medicine.

Competing interests: None declared.

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(Accepted 15 March 2000)

Commentary: Time for improved diagnosis and management of patients

presenting with acute chest pain

R Lee Kennedy, professor.

Department of Medicine, Sunderland Royal Hospital, Sunderland SR4 7TP

lee.kennedy@sunderland.ac.uk

Cardiac troponins T and I are highly sensitive and specific markers for myocardial damage. Troponins are not detectable in

normal serum, and modern immunoassays make diagnosis of minor degrees of cardiac damage possible. Cardiac troponins are

detectable in all patients who have had a myocardial infarction within 12 hours of the onset of symptoms. They are also detectable

in around 30% of patients with unstable angina. Those with higher troponin concentrations are at increased risk of a cardiac

event over the ensuing weeks, and measurement of troponins can be used to guide acute treatment. 1 2 The conclusion of

Collinson et al that detection of troponin T in patients discharged from the emergency department reflects missed diagnosis of

acute coronary syndromes must be correct. The paper provides further evidence that our management of patients presenting with

acute chest pain is far from perfect.

Most people presenting to emergency departments have medical conditions, and chest pain is by far the commonest. It is

surprising, therefore, how few systematic data are available. Collinson et al's study is a welcome addition to the literature, but

some aspects should be interpreted with caution. The 6% rate of missed myocardial infarction refers to a subgroup of patients in

the study and not to the total number of patients presenting with suspected or confirmed myocardial infarction. Our study

suggested that the rate of missed infarction was much lower.3 The concentrations of troponin T reported certainly reflect

myocardial damage but may not indicate acute myocardial infarction by currently agreed criteria. It is not clear whether the

patients were divided prospectively into the four groups. There was no follow up of patients thought to have a non-cardiac

problem, yet accurate diagnosis of these patients is notoriously difficultfor example, not all patients whose pain improves after

antacid have gastrointestinal disease. Also, a third of the patients in the high risk group who were discharged were not followed

up. The long half life of circulating troponin T means that the marker may have been positive at presentation in some of the

patients, and it is a pity that it was not measured at presentation. The electrocardiogram appears abnormal in a large proportion of

patients with unstable coronary syndromes but was not found to have prognostic value in this study. It is not clear whether the

electrocardiograms were independently reviewed, and it is surprising that none of eight patients with supposed missed infarction

developed abnormal electrocardiographic traces.

How, then, can we improve chest pain management? Even though markers of cardiac damage cannot accurately diagnose

myocardial damage in the first few hours after presentation,4 logical combination of biochemical, clinical, and electrocardiographic

data may improve early diagnosis.5 The clinical situation is evolving, and it may be justified to admit patients to a low dependency

observation area for serial electrocardiography and biochemical tests. 6 7 Accurate diagnosis could be made within 12 hours in

most cases. Finally, urgent follow up of all discharged patients in whom cardiac disease was not fully excluded could be justified as

a routine. Measurement of troponin T or I, along with repeat electrocardiography, would certainly help to ensure that high risk

patients were not missed.

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effectiveness of alternatives to coronary care unit admission. N Engl J Med 1984; 310: 1301-1307[Abstract].

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Gibler BW, Runyon JP, Levy RC, Sayre MR, Kacich R, Hattemer CR, et al. A rapid diagnostic and treatment center for

patients with chest pain in the emergency department. Ann Emerg Med 1995; 25: 1-8[Medline].

Footnotes

This article has been cited by other articles:

Dougan, J.P., Mathew, T.P., Riddell, J.W., Spence, M.S., McGlinchey, P.G.,

Nesbitt, G.S., Smye, M., Menown, I.B.A., Adgey, A.A.J. (2001). Suspected

angina pectoris: a rapid-access chest pain clinic. QJ Med 94: 679-686

[Abstract] [Full text]

Herren, K R, Mackway-Jones, K, Richards, C R, Seneviratne, C J, France,

M W, Cotter, L (2001). Is it possible to exclude a diagnosis of myocardial

damage within six hours of admission to an emergency department?

Diagnostic cohort study. BMJ 323: 372-372 [Abstract] [Full text]

Capewell, S., Quinney, D. (2001). What future for chest pain observation

units?. Emerg Med J 18: 3-4 [Full text]

Herren, K R, Mackway-Jones, K (2001). Emergency management of

cardiac chest pain: a review. Emerg Med J 18: 6-10 [Full text]

Wyatt, J., Saeed, M. (2001). Journal scan. Emerg Med J 18: 71-73

[Full text]

Goodacre, S., Morris, F., Capewell, S. (2000). Randomised controlled trial of

chest pain units is needed. BMJ 321: 896-896 [Full text]

Rapid Response responses to this article:

Read all Rapid Response responses

Chest Pain Rapid Rule Out is already here

Steve Meek

bmj.com, 30 Jun 2000 [Response]

Prospective audit of incidence of prognostically important myocardial damage in

Victor A Inyang

bmj.com, 17 Jul 2000 [Response]

Are Chest Pain Observation Units the solution?

Steve Goodacre

bmj.com, 18 Jul 2000 [Response]

Troponin in patients discharged with chest pain from the emergency department.

Fiona Rae

bmj.com, 19 Jul 2000 [Response]

Related letters in BMJ:

Randomised controlled trial of chest pain units is needed

Steve Goodacre, Francis Morris, and Simon Capewell

BMJ 2000 321: 896. [Letter]

an D Watson,

Consultant Biochemist

Dept Clinical Biochemistry , University

Hospital Aintree, LIVERPOOL L9 7AL

Send response to journal:

Re: Care in use of Troponin measurements

Email Ian D Watson:

ian.watson@aht.nwest.nhs.uk

Troponin I or Troponin T are far preferable to CK measurement. However Troponin I is not as standardised as Troponin T and different cut- offs apply to different methods for the former. As pointed out by Dr Kilpatrick it is unlikely that the current assays are reaching sufficient sensitivity reliably enough to enable "rule-out".

Bedside reading of Troponins sounds good but these tend to have poorer sensitivity, cost more and require an agreed policy with the laboratory prior to introduction to ensure analytical comparability with the laboratory assay.

At no point in the article is it made clear that a 12 hour wait from admission is recommended before testing; though some advocate 12 hours since onset of pain, this is subject to more variability and requires validation.

Finally we have found occaisional spuriously elevated Troponin I values. Troponins are a better index of MI but care in their use is still required.

Carel W le Roux,

Specialist Registrar

Department of Metablic Medicine,

Hammersmith Hospital Trust, London W6

8RF,

Bernie Croal

Send response to journal:

Re: Was it a heart attack, is the wrong question

Email Carel W le Roux, et al.:

c.leroux@ic.ac.uk

EDITOR- If the wrong question is asked, don't expect the correct answer! The recent editorial by McKenna and colleagues1 does well to focus on a major problem facing diagnostics as applied to patients presenting with suspected acute coronary syndromes. In many ways, part of the problem has been our insistence over the years to try too hard to place patients into convenient diagnostic boxes such as MI, non-Q wave MI, unstable angina, etc. Such allocations although clinically valid are open to significant subjective interpretation and are not so competent in terms of identifying  risk and management strategy with a high degree of sensitivity and specificity. A new approach, made possible with the advent of troponins, is best focused around the realisation that we are not dealing with distinct clinical and pathological diagnoses, but a wide, risk-graded spectrum of ischaemic myocardial damage encompassed by the acute coronary syndrome. The challenge and the questions have therefore moved on from one of simple diagnosis allocation to an overall assessment of each patient in terms of:

a) Is there myocardial damage? b) What is this patient's current

and subsequent risk? c) What can we do to reduce this risk?

In recent years it has been accepted that troponin measurement

can detect myocardial damage with a very high degree of

sensitivity and specificity, and that such troponin positivity, signals

both short and long term risk and indeed clinical response to costly

treatments thus allowing more efficient targeting to the patient

group likely to benefit. Many hospitals in the UK are however

struggling to fund a new troponin service, while those who have

managed are mostly offering a very limited minimalist testing

protocol aimed at reducing laboratory costs rather than optimising

patient care. Rigid bureaucratic barriers appear to have led to this

situation with the entire extra cost of troponin testing being dumped

on the relatively small but definable laboratory budget, despite the

individual cost per patient being relatively small. Troponin testing

throughout the UK therefore remains inequitably patchy, with

diagnostic availability being defined by postcode.

Troponin measurement presents itself as a low cost but extremely

high yield diagnostic test. If cost is to be an issue, then this should

be centered around the impact on bed space usage, triage, targeting

of expensive treatments and long-term implications of new

diagnostic criteria. Is it any wonder that our North American and

European colleagues look on our struggle to introduce troponin

testing with disbelief. Again it would appear that we have been

asking the wrong question - not 'should we introduce troponin

testing?', but 'how should we use troponin testing to efficiently (both

clinically and financially) manage patients presenting with suspected

acute coronary syndromes'.

Carel le Roux, Specialist Registrar, Metabolic Medicine,

Hammersmith Hospital Trust, London W6 8RF

Bernie Croal, Clinical Senior Lecturer, The Health Services

Research Unit, University of Aberdeen, AB25 2ZD.

References

1. McKenna CJ, Forfar JC. Was it a heart attack? BMJ 2002;

324:377-8 (16 February.)

Agreement on Troponin cut off levels

18 February 2002

Richard W Neale,

Clinical Audit (Cardiology)

Wythenshawe Hospital Manchester,

M23 9LT

Send response to journal:

Re: Agreement on Troponin cut off levels

Email Richard W Neale, et al.:

richard.neale@smuht.nwest.nhs.uk

McKenna and Forfar are rightly concerned about confusion among clinicians, epidemiologists and patients. To this short list should be added public health strategists, health economists, researchers and clinical auditors (MINAP). While endorsing the recent ESC/ACC redefinition they carefully avoid indicating what the cut off Troponin T or I level should be in order to make the diagnosis of an MI. In our hospital we use a Troponin T value of 0.1, but this is quite arbitrary and not evidence based. Until a consensus is achieved and promulgated, confusion will reign, not least in the current MINAP study.  

Troponin measurement is not without its problems

18 February 2002

Eric S. Kilpatrick,

Consultant in Chemical Pathology

Hull Royal Infirmary, Anlaby Rd, Hull HU3

2JZ

Send response to journal:

Re: Troponin measurement is not without its

problems

Email Eric S. Kilpatrick:

eric_kilpatrick@hotmail.com

In their editorial, McKenna and Forfar describe how the proposed

redefinition of myocardial infarction (MI) has made the

measurement of cardiac –specific troponin central to its diagnosis

(1). In a patient presenting with chest pain, a troponin level above

the 99th percentile of normal is now sufficient to diagnose MI,

irrespsective of any electrocardiographic (ECG) changes.

Previously, as stated by the editorial authors, a patient had to

demonstrate the development of Q waves on the ECG and/or an

increase in creatinine (sic) kinase activity to greater than twice the

upper reference limit before this judgement was made.

While the widespread introduction of troponin T and troponin I

measurement is an undoubted improvement over creatine kinase in

detecting myocardial damage, limitations exist with the troponin

assays which most clinicians are unaware of and which may give

rise to diagnostic difficulties.

One issue concerns the use of the 99th percentile of normal as the

troponin cut-off for MI. Most assays are currently not sensitive

enough to measure values as low as this. For example, the 99th

percentile for troponin T (Roche Diagnostics, Lewes, UK) is

approximately 0.01ug/L, but the laboratory assay in routine use is

unable to reliably measure below 0.03ug/L. This means that

patients with troponin T concentrations between 0.01 and 0.03ug/L,

who would be defined by the new criteria as having had an MI, are

currently being missed and included in the ‘low risk’ category.

McKenna and Forfar mention the use of bedside as opposed to laboratory troponin measurement, but these near patient tests are less sensitive again, with the troponin T example only being suitable for measurement down to 0.1ug/L.

A second issue regards the fact that troponin measurement involves immunoassay analytical techniques as opposed to the more robust enzymatic methods used with traditional cardiac markers such as creatine kinase. As amply demonstrated by Ismail and Barth’s recent editorial (2), immunoassay methods can unpredictably lead to wrong results in some individuals which, in the context of troponins, are likely to be difficult to identify and could either be falsely reassuring or cause inappropriate diagnoses and treatment.

These and other limitations in troponin assays should not detract from the value they provide in the vast majority of patients tested. However, they do raise concerns if these tests are being used as the sole means of diagnosing MI in patient presenting with chest pain.

References

1. McKenna CJ, Forfar JC. BMJ 2002;324:377-378 (16 February)

2. Ismail AAA, Barth JH. Wrong biochemistry results. BMJ 2001;

323: 705-706 (29 September)

Dr. Eric S. Kilpatrick

Consultant in Chemical Pathology

Hull Royal Infirmary, Anlaby Rd, Hull HU3 2JZ

eric_kilpatrick@hotmail.com

Troponin I in patients with supraventricular tachycardia

22 May 2001

My Svensson,

Registrar

Department of

Cardiology, Aalborg

University Hospital,

Aalborg, Denmark

Send response to journal:

Re: Troponin I in patients

with supraventricular

tachycardia

Email My Svensson:

My_Svensson@hotmail.com

EDITOR - We have read the article by James et al. (1) regarding the relation between troponin T concentration and mortality in patients with an acute stroke with great interest. Seventeen per cent of the patients had an elevated troponin T value; this was later related to a poor prognosis. No reference is made to the occurrence of atrial fibrillation in patients included in the study. It is assumed that 15-20% of all strokes are of cardio-embolic origin and there could be significant overlap between the groups.

We have observed that there can be elevations of troponin I(TnI) in patients admitted with a recent onset of supraventricular tachycardia (<7 days). The medical records of 72 consecutive patients admitted with such were evaluated retrospectively. All patients had ECG documented tachycardia at admission. Atrial fibrillation/ flutter, was seen in 64 patients of whom 17 had an elevated TnI ( Axsym, Abbott diagnostics, TnI normal value 0.0-0.4 ug/l). Re-entry tachycardia was observed in 8 patients, three had an elevated TnI. The patients with elevated TnI were generally older(69.6+/-11.6 vs 62.4+/-13.6 years respectively, p<0.05, t-test), suffered a higher frequency of angina(75% vs 37%, respectively, p<0.01, chi-square test), as well as a higher frequency of significant ST-depression in ECG (55% vs 27%, respectively, p<0.05, t-test).

These results indicate that elevation of TnI is a common phenomenon (28%) in cases of supraventricular tachycardia. It might be of prognostic value as troponin I and T are sensitive and specific markers of myocardial injury and it has been demonstrated that these are of prognostic importance in unstable angina (2), severe heart failure (3), pulmonary embolism (4), renal failure (5) and ischaemic stroke (1). Further prospective studies are therefore necessary to determine the role of cardiac markers in patients suffering from tachycardia.

My Svensson 1

Kristian K. Thomsen 2

Jan Ravkilde 1

Egon Toft 1

1. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

2. Department of Cardiology, Esbjerg Central Hospital, Esbjerg, Denmark.

1. James P, Ellis C, Whitlock RM, Mc Neil AR, Henley J, Anderson NE. Relation

between troponin T concentration and mortality in patients presenting with an acute

stroke: observational study. BMJ 2000; 320: 1502- 04.

2. Ravkilde J. Creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light

chain isotype 1 as serological markers of myocardial injury and their prognostic

importace in acute coronary syndrome. Dan Med Bull 1998 Feb; 45 (1): 34-50.

3. La Vecchia L, Mezzena G, Zanolla L et al. Cardiac troponin I as diagnostic and

prognostic marker in severe heart failure. J Heart Lung Transplant 2000; 19: 644-652.

4. Giannitsis E, Muller-Bardoff M , Kurowski et al. Independent prognostic value of

troponin T in patients with confirmed pulmonary embolism. Circulation 2000; 102:

211-217.

5. Ooi D, Veinot J, Wells G, House A. Increased mortality in hemodialyzed patients

with elevated troponin T; a one-year outcome study. Clin Biochemistry 1999; 32:

647-652.

Tests can measure the level of other cardiac muscle proteins called troponins , specifically troponin T (cTnT) and troponin I (cTnI). These proteins control the interactions between actin and myosin, which contracts or squeezes the heart muscle. Troponins specific to heart muscle have been found, allowing the development of blood tests (assays) that can detect heart muscle injury with great sensitivity and specificity. Normally the level of cTnT and cTnI in the blood is very low. It increases substantially within several hours (on average four to six hours) of muscle damage. It peaks at 10 to 24 hours and can be detected for a week or more after.

AHA Recommendation

Several studies have identified a measurable relationship between cardiac troponin levels and long-term outcome after an episode of chest discomfort. They suggest that these tests may be particularly useful to evaluate levels of risk. In other words, it's possible that the results of a troponin test could identify people at either low risk or high risk for later, serious heart problems. It remains to be proven whether more cost-effective methods of treatment and, eventually, a better outcome will result from routine troponin testing.

Roche Satelliten-Symposium:

"Diagnostische Marker und therapeutische Strategien

zur Kardio- und Nephroprotektion - ein Update"

Mannheim, den 28.4. 2000

66. Jahrestagung der Deutschen Gesellschaft für Kardiologie- Herz-

und Kreislaufforschung

Volltext

Diagnostische Marker und therapeutische Strategien zur Kardio- und

Nephroprotektion

– ein Update

von Dr. med. Jochen Kubitschek

Privatdozent Dr. Meinrad Gawaz, München, betonte in Mannheim

anlässlich eines von Hoffmann-La Roche ausgerichteten Symposiums, dass

der Begriff des akuten Koronarsyndroms ein klinisches Spektrum akuter

oder rasch fortschreitender Symptome einer myokardialen Ischämie umfasst

, das von der instabilen Angina pectoris bis zum akuten Myokardinfarkt

reicht. In den letzten Jahren hat sich die Therapie des akuten

oronarsyndroms entscheidend verbessert. Hier haben sich in Kombination

mit der Acetylsalizylsäure (ASS) weitere antithrombotisch wirkende

Substanzen durchgesetzt.

Zu den neuen Medikamenten zählen neben den niedermolekularen

Heparinen auch die Fibrinogenrezeptorblocker und der

ADP-Rezeptor-Blocker Clopidogrel. Die Kombinationstherapie, bestehend

aus niedermolekularen Heparinen (Enoxaparin) und ASS, hat sich der

konventionellen antithrombotischen Therapie mit Standardheparinen als

überlegen erwiesen. Ebenso zeigte der kombinierte Einsatz von

Fibrinogenrezeptorantagonisten (Abciximab, Integrelin, Aggrastat) und ASS

(im Vergleich zur Standard- Heparintherapie) bei Patienten mit akutem

Koronarsyndrom eine bessere Wirksamkeit zur Verringerung von

Myokardinfarkt, Tod und refraktärer Ischämie. Diese gute Wirkung war bei

Patienten mit erhöhten Troponinwerten besonders ausgeprägt.

Professor Hugo Katus, Lübeck, bestätigte dies und wies darauf hin, dass

erhöhte Troponin T-Spiegel selbst bei einem Drittel aller Patienten mit

Ruheangina gefunden werden. Diese Troponin T-positiven Patienten haben

eine um das 2-3fach erhöhte kardiale Ereignisrate sowohl akut als auch über

6 Monate und 3 Jahre.

Koronarangiographisch kann bei diesen Troponin T-positiven Patienten

nicht nur eine schwerere koronare Herzkrankheit sondern auch eine höhere

Inzidenz von Thromben nachgewiesen werden. Die Höhe des Troponin

T-Spiegels im Blut ist direkt mit der Häufigkeit des Thrombennachweises

korreliert. Es kann somit das kardiale Troponin T im Blut als Surrogatmarker

für die Thrombuslast betrachtet werden.

In der FRISC 1-Studie konnte erstmalig gezeigt werden, dass nur die

Troponin T-positiven Patienten von der Therapie mit

niedermolekularem Heparin profitieren. In der retrospektiven Analyse

der CAPTURE-Studie war auch Abciximab nur bei den Troponin

T-positiven Patienten wirksam.

Diese Daten sind auch deshalb besonders interessant, da in der FRISC II

–Studie gezeigt werden konnte, dass die kardiale Ereignisrate bei den

Troponin T-positiven Patienten hoch signifikant durch die frühe perkutane

Koronarintervention reduziert werden konnte, wäh­rend dieser Effekt bei

den Troponin T-negativen Patienten nicht nachweisbar war. Somit ist gut

belegt, dass Patienten mit Mikronekrosen und Troponin T-Erhöhungen ein

Hochrisikokollektiv darstellen. Diese Patienten profitieren von einer

aggressiven antithrombotischen Therapie mit

Glycoprotein-IIb/llla-Rezeptorantagonisten und sollten deshalb bei

interventioneller Behandlung von Koronarstenosen im Rahmen eines akuten

Koronarsyndroms mit diesen Substanzen behandelt werden.

Privatdozent Dr. Markus Haass, Heidelberg, kam auf ein spezielles

Problem zu sprechen, das die Therapie der Herzinsuffizienz besonders in der

Praxis erschwert: bei diesem Leiden gibt es bislang keine für den

Praxisalltag geeigneten laboranalytischen Befunde die eine Identifikation

herzinsuffizienter Patienten, eine Objektivierung des Schweregrades der

Insuffizienz, eine Kontrolle des Krankheitsverlaufes sowie eine

Risikostratifizierung erlauben. Dieses Defizit könnte nach Meinung von

Haass bald durch die Bestimmung von NT-proBNP beseitigt werden.

Das zur Familie der natriuretischen Peptide zählende BNP (brain natriuretic

peptide) hat gegenüber anderen potentiellen ”Herzinsuffizienz-Markern” den

Vorteil einer hohen Spezifität, da es - in Abhängigkeit von der

Wandspannung - nahezu ausschließlich aus der linken Herzkammer in die

Blutbahn freigesetzt wird. Das zunächst als Prohormon (proBNP)

synthetisierte Peptid wird bei der Freisetzung in das biologisch aktive BNP

und in das biologisch inaktive N-terminale Fragment (NT-proBNP)

gespalten. NT-proBNP weist keine circadiane Rhythmik auf und ist in

EDTA-Vollblut bei Raumtemperatur über mehrere Tage stabil.

Es konnte gezeigt werden, dass die Plasmakonzentrationen von

NT-proBNP bei Patienten mit einer Herzinsuffizienz mit dem Schweregrad

(NYHA-Stadium) der Erkrankung zunehmen. NT-proBNP stellt jedoch

weit mehr als nur einen laboranalytischen Indikator des NYHA-Stadiums

dar: Innerhalb eines NYHA- Stadiums findet sich eine große Bandbreite der

NT-proBNP- Konzentrationen, wobei die Patienten mit den höchsten

Werten auch die höchste Hospitalisierungsrate und Sterblichkeit aufweisen.

NT-proBNP eignet sich somit nicht nur zur Objektivierung des

Schweregrades einer Herzinsuffizienz, sondern auch zur Risikostratifizierung

und damit zukünftig möglicherweise auch zur Optimierung der

Indikationsstellung sowie Terminierung einer Herztransplantation. Aufgrund

der unkomplizierten Präanalytik bietet sich NT-proBNP daher als ein

vielversprechender "Herzinsuffizienz-Marker" für den Praxisalltag an.

Professor Erland Erdmann, Köln, begrüßte die sich abzeichnenden

Fortschritte in der Diagnostik und wies darauf hin, dass sich glücklicherweise

auch bei der Therapie der Herzinsuffizienz einiges tut. Für drei Beta-Blocker,

Carvedilol, Bisoprolol und Metoprolol, gilt heute, dass sie zusätzlich zu

Diuretika, Digitalis und ACE Hemmern eingesetzt, die Letalität der

Herzinsuffizienz um 30 % bis 65% unter Carvedilol reduzieren, die Zahl der

Fälle von akutem Herztod um über 40 % senken und die Lebensqualität der

Patienten deutlich verbessern. Aus einer strengen Kontraindikation ist somit

eine eindeutige Indikation geworden.

Allerdings - so Erdmann - muss man den verwendeten Beta-Blocker initial

sehr niedrig dosieren. Eine Steigerung der Dosierung sollte danach sehr

langsam erfolgen. Wenn diese beiden Regeln beachtet werden, kommt es

nicht zu den anfangs beim Einsatz von Beta-Blockern gefürchteten

ausgeprägten Hypotonien oder Bradycardien. Zumindest für Carvedilol

existieren Daten, die zeigen, daß Carvedilol bereits ab einer Dosis von 2x

täglich 6,25 mg signifikant wirksam ist. Optimale Resulte lassen sich mit einer

Zieldosis von 2x täglich 25 mg erzielen und sollten daher auch angestrebt

werden. Erdmann wies darauf hin, dass man heute noch keine Empfehlung

für eine “optimale Therapie” geben kann.

“Man wird sich an die Dosierungen halten müssen, die in den großen Studien

gewählt wurden”, meinte er abschließend und betonte, dass es beim Einsatz

der Beta-Blocker erstaunlich wenige Nebenwirkungen gibt - teilweise

weniger als in der Plazebo-Gruppe. Daher ist die Beta-Blocker-Therapie

der chronischen symptomatischen Linksherzinsuffizienz heute immer dann

indiziert, wenn keine Kontraindikationen vorliegen.

Professor Michael Zeiher, Frankfurt am Main, ging schließlich auf die

Frage ein, ob es den “besseren Beta-Blocker” gibt – einen Wirkstoff also,

den man bei der Therapie der Herzinsuffizienz den anderen Beta-Blockern

vorziehen sollte. Hier herrscht derzeit noch große Unsicherheit, da die zur

Zeit laufenden Vergleichsstudien - bei denen beispielsweise der reine

Beta1-Blocker Metoprolol mit Carvedilol verglichen wird – noch nicht

abgeschlossen sind.

Da der Beta-Blocker der dritten Generation (Zeiher) Carvedilol sowohl die

beiden wichtigen Beta-Reptoren blockiert, als auch die Alpha-Rezeptoren,

ist der denkbare Unterschied der erreichbaren Therapieeffekte bei diesen

beiden Substanzen besonders groß. “Aufgrund der bisher vorliegenden

Untersuchungsbefunde haben wir Anlaß zu der Annahme, dass es einen

eindeutigen Vorteil darstellt, dass Carvedilol die drei relevanten Rezeptoren

blockiert”, bezog Zeiher Stellung und verwies auch auf die Tatsache, dass

Carvedilol - im Gegensatz zu anderen Substanzen - zusätzlich eine

antioxydative Eigenschaften hat und im Vergleich zu konventionellen

Betablockern stoffwechselneutral ist.

Professor Teut Risler, Tübingen, gab seinem Vorredner recht und

ergänzte, dass die Frage der Nephroprotektion derzeit bei der

Zusammenstellung einer medikamentösen Therapie eine große praktische

Rolle spielt. Für den Typ I-Diabetes gilt als gesichert, dass die

ACE-Hemmer bei der Verhinderung der diabetischen Nephropathie und

deren Fortschreiten das Medikament der ersten Wahl darstellen. Dies nahm

man bisher auch für Patienten mit einem Typ II-Diabetes an, bis die in

England durchgeführte UKPDS-Studie zeigte, dass eine Blutdrucksenkung

mit ACE-Hemmern oder Beta-Blockern gleich effektiv ist.

Es gibt heute Hinweise darauf – so Risler abschließend – dass es weniger

auf das einzelne verwendete Medikament ankommt wenn man die Nieren

schützen will, sondern vielmehr auf die möglichst optimale Blutdrucksenkung.

Diese wird aber in der Praxis oft erst durch die Kombination mehrerer

blutdrucksenkender Medikamente erreicht – also beispielsweise durch die

Kombination eines ACE-Hemmers mit einem Beta-Blocker, wie sie sich

immer mehr auch bei der Therapie der Herzinsuffizienz durchsetzt.

Myoglobin

Myoglobin ist der Sauerstoffspeicher der primär aerob arbeitenden Muskeln, zu denen auch der Herzmuskel gehört. Bei einer Herzmuskelschädigung (Infarkt) ist das Myoglobin nach etwa 2 Stunden im Serum nachzuweisen und erreicht ca. 12-24 Stunden nach Infarkt wieder den Normalbereich. Das Myoglobin ist der frühe Infarktmarker und ermöglicht das Erkennen eines Reinfarktes.

Nachteil der Myoglobinmessung ist die geringe Spezifität, da auch die Skelettmuskelformen zu 100% mitbestimmt werden. Zur Zeit gibt es aber keine Alternative zum Myoglobin als frühen Marker des Infarktes.

Myoglobin ist vor allem ein kardialer Marker, mit dessen Hilfe frühzeitig ein akuter Myokardinfarkt diagnostiziert werden kann. Er ist der beste biochemische Marker zur Erfolgskontrolle einer Reperfusion. Myoglobin ist aber nicht kardiospezifisch!

PRÄANALYTIK UND ANALYTIK

Methode Elektrochemilumineszenzimmunoassay

(Roche Diagnostics)

BEWERTUNG

Referenzbereich (ng/ml)   Männer: 23-72     Frauen: 19-51

Einflußgrößen : Niereninsuffizienz, Skelettmuskelschäden

CRP und Herz

Z Kardiol 2000 Aug;89(8):658-66

Related Articles, Books, LinkOut

[C-reactive protein as an independent marker of prognosis in acute

coronary syndrome: comparison with troponin T]

[Article in German]

Mockel M, Heller G Jr, Muller C, Klefisch FR, Riehle M, Searle J, Frei U, Stork T.

Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin,

Universitatsklinikum Charite, Medizinische Fakultat der Humboldt-Universitat, Berlin.

BACKGROUND: It has been suggested that inflammatory processes play a role in the pathogenesis of acute coronary syndromes (ACS). C-reactive protein (CRP) is a classic acute phase protein. It is yet unclear whether, in addition to established markers as troponin T (TnT), determination of CRP in patients admitted for ACS contributes significantly to the diagnosis and prognosis of ACS. PATIENTS AND METHODS: We investigated 50 patients with ACS (59.4 SD 13.9 years) in the first hour after admission and 4-24 h later with respect to TnT (Elecsys, Roche Diagnostics) and CRP (biokit, modified Quantex CRP plus, analytical sensitivity 0.02 mg/dL). Fifty percent of the patients were classified as having unstable angina retrospectively. All patients were followed in the 6 weeks post discharge regarding death and recurrent ACS.

RESULTS: The cumulative event rate at 6 weeks after discharge was

62.5% for patients being CRP and TnT positive compared to

35.3% in TnT positive and CRP negative patients.

In TnT negative patients a positive CRP test predicted 33.3% of events and

28.8% of patients negative for CRP and TnT had events at 42 days post discharge. Logistic regression analysis regarding the primary endpoint including TnT and CRP (4-24 h values), age, gender and diagnosis resulted in independent prediction of ACS or death by TnT (cutoff 0.1 microgram/L, p = 0.048, odds ratio = 7.5) and CRP (cutoff 0.862 mg/dL, p = 0.026, odds ratio = 5.3). Sensitivity/specificity for AMI diagnosis were 69.6%/75% for TnT and 12%/72% for CRP in the first hour and 91.3%/68.2% for TnT and 68%/72% for CRP 4-24 h later.

CONCLUSIONS: Besides TnT, high sensitivity CRP determination has no additional value for early AMI diagnosis.

The prognosis of these patients during the first 24 hours is significantly and independently predicted by CRP measurements in addition to troponin T.

PMID: 11013970 [PubMed - indexed for MEDLINE]

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