Preparing the United States for High-Sensitivity Cardiac Troponin Assays

Editor’s Note: This article is based on Korley FK, Jaffe AS. Preparing the United States for High-Sensitivity Cardiac Troponin Assays. J Am Coll Cardiol 2013;Feb 6:[Epub ahead of print].

There is a need to develop a universal nomenclature for troponin assays.
Numerous terms have been used to refer to cardiac troponin (cTn) assays. To distinguish these assays using objective criteria, the preferred term, “high-sensitivity cardiac troponin assays” (hs-cTn) has been suggested to be used for cTn assays that measure cTn values in at least 50% of a reference population.

There is a need for uniform criteria for selecting reference populations.
Gender, age, race, renal function, heart failure, and structural heart disease (such as left ventricular mass) are associated with increased cTn concentrations, and thus will affect the determination of the 99th percentile value. Determination of the 99th percentile value should ideally be based on subjects whose blood pressure, serum glucose, creatinine and natriuretic peptide values are normal, who take no cardiac medications, and whose imaging (e.g., echocardiography, cardiac magnetic resonance imaging) documents no structural heart disease.

The optimal delta criteria for distinguishing between acute and chronic cardiac remain unclear and are likely to be assay-specific.
At elevated values, a change of 20% usually ensures that a given change is not caused by analytical variation alone. At values near the 99th percentile URL, change values >20% are necessary and absolute changes may be more appropriate. Choice of any specific change value will depend on what sensitivity and specificity are desired (i.e., the choice will vary depending on the trade-off of identifying more MI patients versus those with cTn elevations from structural abnormalities).

Distinguishing between type 1 and type 2 AMI is challenging, and more type 2 AMIs will be detected with hsTn assays.
As assay sensitivity increases, it is likely that the frequency of type 2 AMI will be increased. Both conditions result in an acute increase in cTn values, and thus are unlikely to be useful in differentiating the two types of MI.

Factors affecting the analytical precision of troponin assays (including how we collect samples) will become more important with the use of hs-cTn assays.
Because of the increased sensitivity, all analytical problems will be more critical with hs-cTn assays. Quantification of hs-cTn can be influenced by interference between reagent antibodies or the presence of autoantibodies, which can lead to false-positive or negative results. Use of blocking reagents, assay redesign, and use of antibody fragments can reduce but not completely eliminate interference. Other factors, such as the specimen type (serum versus heparinized plasma versus EDTA plasma) or hemolysis may also affect the accuracy of hs-cTn measurement.

The optimal duration for ruling out AMI remains unclear; novel approaches to this issue are being developed.
Although hs-cTn allows earlier diagnosis of MI, sampling out to 6-8 hours still may be required to identify all MI patients, especially those that present early after MI onset. More data is needed to confirm the accuracy of shorter MI exclusion protocols.

Elevated hs-cTn, regardless of the cause, has important prognostic implications and deserves additional evaluation; many cases of chronic elevations can be evaluated in an outpatient setting.
Elevated cTn values (including hs-cTn assays) are associated with a two-fold higher risk for longer-term all-cause mortality and cardiovascular death when compared to negative troponin values. This association is dependent on the degree of elevation. If values are rising, they are indicative of acute cardiac injury. For values that are stable, risk is increased over the long term, and further evaluation is warranted, although it can usually be performed on an out-patient basis.

Hs-cTn can be used to risk-stratify patients with non-ACS cardiovascular comorbidities.
Patients who have a rising pattern of values have a higher risk of mortality than those with negative values regardless of the cause. These include pulmonary embolism, congestive heart failure, sepsis, hypertensive emergency, and chronic obstructive pulmonary disease. Studies are needed to evaluate the incremental prognostic benefit of hs-cTn in these sub-groups and demonstrate how this may improve patient management strategies.

Keywords: Troponin, Troponin T, United States

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