Clinical Use of High-sensitivity Cardiac Troponin in Patients With Suspected Myocardial Infarction

Raphael Twerenbold, MD; Jasper Boeddinghaus, MD; Thomas Nestelberger, MD; Karin Wildi, MD; Maria Rubini Gimenez, MD; Patrick Badertscher, MD; Christian Mueller, MD


J Am Coll Cardiol. 2017;70(8):996-1012. 

In This Article

True and False False-positive hs-cTn Measurements

In the absence of overt myocardial ischemia, elevated cTn levels are often labeled as "false-positive" hs-cTn results, which is a misleading term. Most of these unexpected hs-cTn elevations are "true positive" for myocardial injury (rather than MI) and reflect previously undetected or underestimated cardiac disease including valvular heart disease, heart failure, hypertensive heart disease, and chronic coronary artery disease (CAD). Many primarily cardiac disorders as well as noncardiac disorders with cardiac involvement may lead to substantial amounts of cardiomyocyte injury and thereby hs-cTn elevations (Table 1).[10,27] It is important to note that cTn elevations universally portend a worse prognosis than otherwise similar patients without a cTn elevation. This is true regardless of whether the patient has heart failure, renal dysfunction, gastrointestinal bleeding, sepsis, respiratory disease, pulmonary embolism, subarachnoid hemorrhage, or stroke, or whether the patient is asymptomatic without known cardiovascular disease.[43] Obviously, the medical consequences of cardiomyocyte injury as quantified by cTn elevations will be highly individualized and different from that in patients with MI.

Nevertheless, there are some rare circumstances when high or even very high cTn concentrations are observed in the absence of myocardial injury, for example due to analytical assay interferences with heterophilic antibodies. In cases of striking discordance between cTn measurements and clinical presentation, analytical "false-positive" test results (e.g., due to heterophilic antibodies) must be considered. The following 2-step approach may facilitate further clinical workup: First, cTn retesting using the same cTn assay should be performed. In case of a relevant change, acute myocardial injury must be excluded by imaging or invasive strategy. If no cause of myocardial injury can be detected by imaging and further serial cTn measurements remain in the normal range, the cTn result suspected to be false positive can most probably be explained to be a nonrepeatable outlier. Second, if no cTn change after retesting can be observed, cTn should be measured using an alternative cTn assay (if available). In case of a cTn mismatch, contact the laboratory for ruling out analytical interferences resulting in real, but very rare, "false-positive" cTn measurements (e.g., heterophilic or troponin autoantibodies affecting cTnI or skeletal muscle disease affecting cTnT). In case of a match, chronic myocardial injury must be suspected and should be further elaborated with imaging techniques.[44]