Clinical Significance

The troponins (I, C, and T) are members of a complex of proteins that modulate the calcium-mediated interaction between actin and myosin within muscle cells. The nomenclature of these distinct proteins of the troponin complex is derived from their respective function in muscle contraction. Troponin T anchors the troponin complex to tropomyosin of the thin filament, whereas troponin I inhibits actomyosin ATPase, and troponin C is a calcium-binding subunit. Three isotypes of troponin I (TnI) have been identified: one associated with fast-twitch skeletal muscle, one with slow-twitch skeletal muscle, and one with cardiac muscle. The slow and fast-twitch isoforms have a similar molecular weight of approximately 20,000 dalton (Da) each. The cardiac-specific TnI (cTnI) isoform has a molecular weight of approximately 24,000 Da and contains a post-translational tail of 31 amino acids on the N-terminus of the molecule. This sequence and the 42% and 45% dissimilarity with the sequences of the other two isoforms have mad possible the generation of highly specific monoclonal antibodies without cross-reactivity with other non-cardiac TnI forms. As a result of its high tissue specificity cTnI is a cardio-specific, highly sensitive marker for myocardial damage. The Access AccuTnI+3 assay uses monoclonal antibodies specifically directed against human cardiac troponin I.

In myocardial infarction (MI), cTnI levels rise in the hours after the onset of cardiac symptoms, reaching a peak at 12-16 hours and can remain elevated for 4-9 days post MI.  Numerous pathologies can potentially cause troponin elevations without overt ischemic heart disease. These pathologies include, but are not limited to, congestive heart failure, acute and chronic trauma, electrical cardioversion, hypertension, hypotension, arrhythmias, pulmonary embolism, severe asthma, sepsis, critical illness, myocarditis, stroke, non-cardiac surgery, extreme exercise, drug toxicity (adriamycin, 5-fluorouracil, herceptin, snake venoms), end stage renal disease, and rhabdomyolysis with cardiac injury. Importantly, these other etiologies rarely demonstrate the classic rising and falling pattern experienced with a MI, which highlights the importance of serial monitoring when the clinical scenario is confusing.

_{Source: DxI Troponin IFU #A98264, 2/22/16}