A Review of Cardiac and Non-Cardiac Causes of Troponin Elevation and Clinical Relevance Part I: Cardiac Causes

Abstract

IntroductionCardiac troponin T (cTnT) and troponin I (cTnI) are cardiac regulatory proteins that control the calcium mediated interaction between actin and myosin [1]. The troponin complex consists of three subunits: troponin C, troponin I, and troponin T. This complex is located on the myofibrillar thin (actin) filament of striated (skeletal and cardiac) muscle. The cardiac isoforms troponin T and I are only expressed in cardiac muscle [1].In the year 2007 a consensus statement from the Joint European Society of Cardiology and The American College of Cardiology committees redefined myocardial infarction (MI) as an elevation of cTnT or cTnI in conjunction with clinical evidence of myocardial ischemia [2]. They recommended highsensitivity cardiac troponin assays to rule out MI using a 3-hour pathway based on the 99 th percentile of the normal reference range [2]. Cardiac troponins are detected in the serum by the use of monoclonal antibodies to epitopes of cTnI and cTnT. These antibodies are highly specific for cardiac troponin but do not react with skeletal muscle troponins [3,4]. Troponin assays are quite sensitive and can detect <1 g of myocardial necrosis; therefore, the diagnosis of myocardial infarction requires that cTn must be above the 99 th percentile upper reference limit for the specific assay being used [5]. Some studies have reported that the 99 th percentile reference limit differs between men and women when measured with high-sensitivity assays for cardiac troponin [6].An elevation of cTn indicates the presence of, but not the underlying reason for, myocardial injury. Elevated troponins have been noted in several clinical conditions in addition to acute myocardial infarction (AMI). These conditions include pulmonary embolism, sepsis, heart failure, myocarditis, myocardial contusion, critical illness, cardio-toxic chemo, defibrillator shocks, atrial fibrillation, and end stage renal disease. Elevated cTnT and cTnI almost always imply a poor prognosis regardless of the mechanism by which troponins were released from cardiac myocytes into circulation. Ottani et al. found that the odds ratio for death and MI was 3.44-fold at 30 days in the cTnT-positive group compared to patients with unstable angina who did not have elevated troponins [7].The aim of this article is to highlight different conditions in which elevated troponins have been commonly noted, and to discuss the suggested mechanisms for elevated troponins in these patients. It is still unclear how to manage troponin elevation in clinical conditions other than AMI, but it is important to note the differential diagnosis for elevated troponins and the clinical significance of troponin elevation in each setting. Troponin elevation reflects acute or chronic myocardial damage but is not exclusive for ACS, thus causing some problems with interpretation of results. Differentiating elevated troponins due to non-coronary diseases is challenging; however, this differentiation is paramount in order to provide timely and appropriate treatment. This is a t...

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“…The mechanics of carbon monoxide (CO) poisoning are yet unknown. Proposed processes include CO-induced hypoxia producing cardiomyocyte necrosis [ 34 , 35 ], oxidative stress activating proteases [ 36 , 37 ], and apoptosis inducing membrane blebs with cTn release [ 38 – 40 ]. The degree of exposure, length of time, underlying heart condition, and measurement time all affect troponin elevation patterns [ 17 , 21 , 41 ].…”

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“…[ROC] analysis). [56] 4. Therefore, it makes sense to hypothesize that the initial measurement of cardiac damage biomarkers immediately after hospitalization for SARS-CoV-2 infection, as well as long-term monitoring during the hospital stay, may help identify a subset of patients with potential cardiac injury and thereby forecast the progression of COVID-19 toward a worse clinical picture.…”

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“…The rise of cTn serum levels in patients who succumb to SARS-CoV-2 infection shows a particular pattern as compared to the concentration dynamics that characterize acute coronary syndromes (ACS). In COVID-19, there is a steady upward trend of cTn serum levels while ACS is generally observed as a very typical abrupt rise [ 98 ]. Nevertheless, a cTn elevation can also be detected in certain non-cardiac conditions, such as systemic inflammatory response syndrome, sepsis, pulmonary embolism, critical illness, or end-stage renal disease [ 99 ].…”

“…In terms of prognosis, several meta-analyses reported that high serum levels of this biomarker are significantly correlated with increased mortality risk [ 10 , 98 ]. The ability of cTn concentration at admission to predict in-hospital mortality was outlined by an area under a curve greater than 0.90 (ROC analysis) [ 3 , 98 , 100 ].…”

“…In terms of prognosis, several meta-analyses reported that high serum levels of this biomarker are significantly correlated with increased mortality risk [ 10 , 98 ]. The ability of cTn concentration at admission to predict in-hospital mortality was outlined by an area under a curve greater than 0.90 (ROC analysis) [ 3 , 98 , 100 ]. In addition to being directly associated with major cardiovascular events, elevated cTn levels are also related to an increased risk of respiratory, hepatic, and renal impairment [ 101 ].…”