Modern cardiac troponin T (cTnT) tests are highly sensitive in diagnosing AMI and myocardial
damage. Atrial fibrillation and many non-cardiac conditions and even strenuous exercise are
associated with elevated cTnT levels which are problematic to clinicians and may lead to
redundant use of diagnostic coronary angiography or "overdiagnosis" of ACS in the emergency
room workup.
The cardiac troponin (cTn) complex is part of the thin filaments of myocardium. Small part
(approximately 5% of total content) of troponins are cytosolic. These smaller cytosolic
fragments may more easily traverse across cell membranes that have become leaky for some
reason but not irreversibly damaged. Only cytoplasmic forms of troponin are contained in the
subcellular blebs which lyse upon early cTn release into the circulation. Bleb formation may
explain how troponin can appear in blood in the absence of cell necrosis. Still many aspects
of their intramyocardial degradation, their tissue release, and their degradation within and
elimination from the human circulation are still incompletely understood.
In the early hours of AMI, troponin is found in its full-size complex, but the complexed cTnT
degrades in a time-dependent pattern after the first hours. Small molecular weight troponin
fragments originating from the cytoplasm may traverse across leaky cell membranes not
completely damaged in various conditions without irreversible myocardial cell necrosis.
Commercial cTnT test detects all these fragments and may thus lead to false diagnosis of AMI.
At present, there is limited information based on small studies using complicated gel
filtration chromatography and Western blotting showing cTnT fragmentation in later phases of
AMI and in renal failure. These time-consuming analytical methods are, however, not suitable
for clinical purposes in the emergency room.
ANALYTICAL METHODS In this study we test a novel sensitive time-resolved immunofluorometric
assay, which has been developed at the biotechnology unit of the Department Biochemistry,
University of Turku, which enables us to measure cTnT from blood samples in its intact or
only slightly fragmented form. Thus, we can exclude the highly fragmented short forms of cTnT
from the analysis. This selectivity can be achieved with specific capture and tracer
antibodies that bind to carefully chosen epitopes located closer to the opposite ends of the
cTnT molecule. In the assay one of the antibodies is attached to a surface and acts as an
antigen capturing antibody. The capture-antigen pair can be detected with tracer antibody,
thus forming capture-antigen-tracer complex. In our case this tracer antibody has been
labeled with europium chelates which provide sensitive detection by time-resolved
fluorometry.
The aim of Tropo-Fragment study is to use the described preliminary assay format in the
clinical studies to evaluate:
TnT fragmentation and its time course in STEMI and NSTEMI
TnT fragmentation in renal failure, sepsis, strenuous exercise, stroke, atrial
fibrillation, takotsubo, myocarditis and healthy subjects