In September (2007) the Clinical Laboratories of John Muir Health introduced a new assay for cTnI and implemented reporting practice guidelines published in the laboratory literature and endorsed by all major cardiology organizations (including ACC and AHA). A significant guideline for cTnI was the decision-limit for myocardial injury/myocardial-cell necrosis being set at the 99th percentile of a population of normal, healthy individuals without a known history of heart disease (>0.06 ng/mL with our new cTnI assay). Although these guidelines have been discussed in the literature for a few years, and updated in April 2007, their introduction locally has induced a "firestorm" of controversy.
Much of the controversy surrounds the high sensitivity of the decision-limit and the desire to have a cTnI value that is reasonably predictive of acute myocardial infarction (AMI) due to thrombotic coronary artery disease, regardless of the pretest probability of having it. To this end, it is determined that with our new assay, a cTnI value >0.50 ng/mL has a 96% clinical sensitivity and 94% clinical specificity for AMI. This information will be included in our laboratory reports.
Contemporary cTnI assays are quite sensitive and can detect very small episodes of myocardial necrosis (<1 g). In patients with a high pretest probability or clinical suspicion of acute coronary syndrome (ACS), the diagnostic and prognostic value of cTnI is well known. Even small increases above normal (i.e. >99th percentile decision-limit) in these patients have clinical significance. The available data from over 25 studies indicate an ~4 fold higher risk of death and recurrent MI among patients presenting with suspected non-ST elevation acute coronary syndrome (NSTEACS; which encompasses both unstable angina and non-ST elevation myocardial infarction [NSTEMI]) and an increased cTnI compared to patients with a cTnI that is within normal limits.
However, cTnI testing is also being used as a screening tool in patients with a low pretest probability of thrombotic coronary artery disease. Thus given the high sensitivity of cTnI for detecting even minimal myocardial-cell necrosis, cTnI may become "positive" even in the absence of thrombotic acute coronary syndromes, hence the "firestorm". The causes of cTnI elevations that are unrelated to coronary thrombosis is the subject of an excellent review article from cardiologists from the Beth Israel Deaconess Medical Center and Harvard Medical School (Ann Intern Med. 2005;142:786-91).
Finally, the optimal timing of sample acquisition is relevant for the diagnosis of AMI. It derives from cTnI kinetics (begins to rise within 3-4 hours, peaks at 12-24 hours, and can remain increased for up to 4-7 days) and patient-related factors (timing and duration of symptoms relative to presentation, and overall probability of ACS). Given the good analytical performance of contemporary cTnI assays, testing on presentation and up to 6 9 hours after presentation is expected to deliver optimal sensitivity in most patients. A significant rise in cTnI over this time period is indicative of AMI and unexpected in causes that are unrelated to coronary thrombosis. Repeat testing at 12-24 hours should be considered in patients for whom these initial cTnI values are negative and there is an intermediate or high clinical index of suspicion, or in whom plausibly ischemic symptoms have recurred.