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Three Part Question

In [patients who present with chest pain in the ED] are [sensitive troponin assays] able to [detect AMI faster then standard troponin assays]?

Clinical Scenario

A 55 year old male with no cardiac history presents for chest pressure with onset of about 2 hrs ago, now resolved. You question if new sensitive troponin assays will be able to more accurately rule in or rule out an acute myocardial infarction when compared with standard troponin assays.

Search Strategy

Medline 1966 – 5/10 using OVID interface, PubMed clinical queries, Cochrane Library (2010)
[(Exp troponin) AND (Exp myocardial infarction) AND (sensitive.mp)]. LIMIT to human AND English.

Search Outcome

179 studies were found of which 3 were relevant to the three part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Apple FS, Pearce LA, Smith SW, Kaczmarek JM, Murakami MM 2009 USA	Leftover plasma specimens were prospectively collected from 397 pts who presented with ACS symptoms through an ED in MN.	Single-center, prospective, clinical trial	cTnI >0.034ug/L (99th %) at presentation	69.2% sens 46.2% spec	It is impossible to define a gold-standard MI definition without the use of cTn. It is difficult to get accurate time of onset of symptoms from patients. 6 hour assays varied in time due to clinical environment. cTnI were ran based on the availability of leftover specimen. Patients might have had infarcts that were undetectable except by Sensitive Cardiac Troponin.
			cTnI >0.012ug/L (LoD) at presentation	90.4% sens 46.2% spec
			cTnI >0.034ug/L at 6 hrs	94.2% sens 81.2% spec
			cTnI>0.012ug/L at 6 hrs	98.1% sens 55.3% spec
Reichlin T et al 2009 Switzerland	718 consecutive patients who presented with symptoms suggestive of acute myocardial infarction at 6 EDs	Prospective, international, multicenter, and blinded study of 4 sensitive and one standard troponin assays.	Sensitive troponin sensitivity at presentation	99th%=84, 86, 89, 95%, LoD= 89, 92, 94, 100%	Cannot quantify the clinical effect associated with early diagnosis. Study did not include patients on dialysis. Patients might have had myocardial infarctions that were undetectable except by Sensitive Cardiac Troponin.
			Standard troponin sensitivity at presentation	99th%=83%
			AUC at 2hrs of presentation of sensitive troponin	0.92, 0.91, 0.9, 0.94
			AUC at 2 hrs of presentation of standard troponin	0.71
			AUC at 10 hrs of presentation of standard troponin	0.85
Keller T et al. 2009 Germany	1818 consecutive patients presenting with new onset chest pain at three chest pain units.	prospective, blinded, multicenter, clinical trial	Sensitive troponin at presentation	AUC 0.96 Sens 90.7% Spec 90.2%	Cannot quantify the clinical effect associated with early diagnosis. Patients might have had myocardial infarctions that were undetectable except by Sensitive Cardiac Troponin.
			Standard troponin at presentation	AUC 0.85 Sens 72.7% Spec 94.1%
			Sensitive troponin at <3hr presentation	AUC 0.95 Sens 84% Spec 93.2%
			Serial sensitive troponin at presentation and 3 hrs	Sens 100%

Comment(s)

The studies were robust and designs had relatively few weaknesses. All of them showed the superior diagnostic abilities of the sensitive troponin assays. This included higher sensitivity and greater area under the curve. The sensitivity of the sensitive troponin with one lab draw was still not high enough to allow for one marker to rule out an acute myocardial infarction with the range being 69.2 to 90.7%. Keller et al. does suggest however that obtaining two sets of sensitive troponin assays, one at presentation and another at greater then three hours, can be used to rule out an acute myocardial infarction with Keller showing a sensitivity of 100%.

Clinical Bottom Line

Sensitive troponin assays are more sensitive at all time intervals. This is most pronounced if presentation is less then 3 hours. There is a slight decrease in the specificity. Overall the sensitive troponin assays are more accurate with the area under the curve being significantly larger then standard troponin assays.

References

1. Apple FS, Pearce LA, Smith SW, Kaczmarek JM, Murakami MM Role of Monitoring Changes in Sensitive Cardiac Troponin I Assay Results for Early Diagnosis of Myocardial Infarction and Prediction of Risk of Adverse Events Clinical Chemistry 55:5 (2009) 930-937
2. Reichlin T et al Early Diagnosis of Myocardial Infarction with Sensitive Cardiac Troponin Assays New England Journal of Medicine 2009;361:858-67
3. Till Keller, M.D., Tanja Zeller, Ph.D., Dirk Peetz, M.D., Stergios Tzikas, M.D., Alexander Roth, Ph.D., Ewa Czyz, M.D., Christoph Bickel, M.D., Stephan Baldus, M.D., Ascan Warnholtz, M.D., Meike Fröhl Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial Infarction New England Journal of Medicine 8.27.2990; 361:868-877