Cardiac Biomarkers and Acute Myocardial Infarction Troponin Beyond

March 2011

Cardiac Biomarkers and Acute Myocardial Infarction Troponin Beyond

Search Strategy: .Using PUBMED Clinical Queries (Diagnosis/broad) you conduct a search for “acute myocardial infarction” [20694 citations] and combine that search with “troponin” [13375 citations] and “early diagnosis” [186458 citations] to yield a manageable 374 citations including the selections below (http://tinyurl.com/4ql4lqe).

Mr. K is a 62 year old Turkish gentleman who presented to the emergency department because of chest pain which developed while he was eating dinner with his family. He had just recently immigrated to this country and his brother, who provided part of his history, said that he was having anxiety which his family attributed to his adjusting to a different culture, as well as to being dependent on his brother who is younger than he. He described the pain as “tight or aching” and as being located in the parasternal area. Initially, he had had some associated neck stiffness, but this had resolved. He had been treated for hypertension in Turkey, but the medication had been stopped before his transcontinental move because his BP’s had been low normal. There was no history of any prior chest pain or cardiac symptoms and he had never had a stress test or angiogram. His health was said to be good. He moved to the United States because he thought the employment opportunities would be better here. On physical exam, he had a furrowed brow and appeared uneasy. Otherwise his exam was unremarkable. His initial ECG was normal and there was no old tracing for comparison. Sublingual nitro and nitro paste relieved his pain completely, but he communicated that he still felt apprehensive. The first troponin was unfortunately clotted and a second was drawn about 1.5 hours after his ED arrival. It was 7.0. A repeat ECG was also normal. He was taken to the cardiac catheterization lab where he was found to have a 95% occlusion of the LAD. This was stented and recovered uneventfully. What does an elevated troponin tell us in NSTEMI ACS patients? Perhaps more importantly, what does a non-elevated troponin tell us in chest pain patients with potential ACS patients with a non-diagnostic ECG? How would we have diagnosed AMI in Mr. K without troponin and what does the future hold for cardiac biomarkers?


PICO Question

Population: Adult emergency department patients with potential ACS

Intervention: Measurement of troponin (or newer ultrasensitive troponin)

Comparison: Other cardiac biomarkers (or no biomarkers)

Outcome: Prognostic and diagnostic accuracy (sensitivity, specificity, likelihood ratio) for short-term cardiovascular death, myocardial infarction, or congestive heart failure.


Years

First years: Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes, NEJM 1996; 335: 1342-1349. (http://pmid.us/8857017)

Second years: Quantitative troponin and death, cardiogenic shock, cardiac arrest and new heart failure in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS): Insights from the Global Registry of Acute Coronary Events, Heart 2011; 97: 197-202. (http://pmid.us/21076124)

Third years: Sensitive troponin I assay in early diagnosis of acute myocardial infarction, NEJM 2009; 361: 868-877. (http://pmid.us/19710485)

Fourth years: Early diagnosis of myocardial infarction with sensitive cardiac troponin assays, NEJM 2009; 361: 858-867. (http://pmid.us/19710484)

Extra Materials #1: Early laboratory indicators of acute myocardial infarction, Emerg Med Clin North Am 1998; 16: 519-539. [obtaining PDF from Becker Library] (http://pmid.us/9739773)

Extra Materials #2: A personal history of markers of myocyte injury [myocardial infarction], Clin Chim Acta 2007; 381: 3-8. (http://pmid.us/17451663)


Articles

Article 1: Troponin ACS Mortality_NEJM 1996
ANSWER KEY

Article 2: Troponin & Risk of ACS Sequelae in NSTEMI_Heart 2011
ANSWER KEY

Article 3: ESensitive Troponin Early Dx AMI_NEJM 2009
ANSWER KEY

Article 4: Early Dx MI with Sensitive Trop I_NEJM 2009
ANSWER KEY


Bottom Line

Troponin-I should replace CK-MB as a diagnostic and prognostic marker to distinguish unstable angina from non-Q-wave myocardial infarction. In both forms of ACS (USA and NSTEMI), increasing levels of troponin are significantly associated with an increased 42-day mortality. Future studies are needed to assess the independent prognostic power of troponin when adjusted for the full spectrum of confounding baseline and interventional variables. Since biomarker elevation is part of the definition distinguishing USA from non-Q-wave MI, an RCT design allocating physicians to be aware or not aware of troponin-I levels will probably never occur so the additive benefit of the biomarker above EKG and clinical gestalt will remain unknown.

The extent of elevation of troponin is an independent predictor of mortality and in-hospital development of new CHF, cardiogenic shock or cardiac arrest in patients following NSTE ACS. Since the overall (unadjusted) 14 day mortality rate is 2.6% (with in-hospital death rates of 14% in those with troponin ratio >1000), future interventional trials are needed to identify effective management mechanisms incorporating the prognostic information provided by the degree of troponin elevation.

A single sensitive troponin I at the time of admission substantially improves diagnostic accuracy for AMI compared with conventional troponin T. In fact, measurement of sensitive troponin I within 3 hours of admission detected 100% of MI’s with increasing false-positive rates. Future diagnostic-interventional trials are needed to determine whether earlier detection improves patient-oriented outcomes in MI.

Multiple sensitive troponin assays can increase the diagnostic accuracy for acute MI in ED chest pain patients, particularly within the first 3º of symptom onset. However, these rapid troponin assays do not increase post-test probability to 100% or decrease it to 0% and they cannot be used to distinguish USA from other forms of non-cardiac chest pain. Furthermore, other conditions like myocarditis and heart failure also increase troponin levels so clinical evaluations will still be required.

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