**4. Cardiac troponin and high sensitivity troponin**

Cardiac troponin (cTn) is a well-studied and commonly used marker of cardiovascular disease. Troponin is a calcium-regulatory protein for the calcium regulation of contractile function in skeletal and cardiac muscles. Troponin is a complex of three different subunits, troponins C, I, and T, which share characteristic functions of troponin, such as the binding of Ca2+ (troponin C), the inhibition of actomyosin interaction (troponin I), and the binding to tropomyosin (troponin T). Troponin is nearly undetectable in unaffected muscle, but troponin levels rise several hours after the onset of myocardial injury. Elevated levels of troponin have been used as a widely accepted marker of cardiac injury. It is detectable up to 10 days after the onset of injury. The degree of elevation of troponin also gives prognostic information on the subsequent outcome as seen in **Figure 3**. Cardiac troponin I levels of 1.0 μg/L or higher or cardiac troponin T levels of 0.1 μg/L or higher are considered elevated. Circulating cTn is a marker of myocardial injury, including

**Figure 3.** *Relationship of troponin T and expected probability of death.*

#### *COVID-19 and Cardiac Enzymes DOI: http://dx.doi.org/10.5772/intechopen.101402*

but not limited to myocardial infarction or myocarditis. There has been growing evidence of higher mortality rates among patients among those patients with underlying cardiovascular disease. The values of cardiac troponin and its elevations above normal concentrations in a patient with COVID-19 should be seen as the combination of the presence or extent of pre-existing cardiac disease and the acute myocardial injury related to COVID-19 and its complications. It further acts as a quantitative marker of this injury. It has been proposed that there are three phases of troponin elevation: first, when cardiac troponin increases mostly reflect ongoing comorbidities, commonly seen at the time of are admission; second, with a critical illness like ARDS; third, specific COVID-19 complications such as pulmonary embolism, stroke, endothelitis and myocarditis. Patients with COVID-19 admitted to the hospital, at 30-day follow up with higher cTn (concentrations greater than ≥21 ng/L) have been associated independently with a higher risk of all-cause mortality. Cardiac troponin elevations, even in small amounts (≥21 ng/L) provide a better prediction of 30-day all-cause mortally and severe course of the disease than other commonly used biomarkers for inflammation including C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer. Furthermore, greater elevations (cTn > 90 ng/L) correlate with higher risk of death than small concentrations (cTn > 30–90 ng/L). Patients with cTn concentrations in the third centile had about six times the all-cause mortality as well as cardiovascular mortality as compared to patients in the first tertile. Higher troponin concentrations are also related to a higher risk of death within 30 days as well as 2 years. Concentrations remained in the normal range in the majority of survivors. High sensitivity troponin I (hs-TnI) is a newer, more sensitive marker of disease progression and mortality in patients with cardiac disease [5]. It was established to be a better marker than those used to determine generalized inflammation including D-dimer and lymphocyte count. Raised hc-TnI in patients admitted with COVID-19 has also been showed to correlate with increased requirements of invasive as well as non-invasive ventilation, development of acute respiratory distress syndrome (ARDS) as well as acute kidney injury (AKI). Studies revealed that the elevated hs-TnI levels were closely correlated with the prognosis and mortality risk of COVID-19 patients. Specifically, the mortality risk increased by 20.8% when the hs-TnI level increased by 1 unit in one such study. However, it is noteworthy to remember that elevated levels are common in hospitalized patients, and are most commonly in the setting of type 2 myocardial infarction (myocardial oxygen supply-demand imbalance) or non-ischemic causes of myocardial injury. Marked elevations of cardiac troponin in patients without critical illnesses such as ARDS, may indicate the presence of takotsubo syndrome, myocarditis, or type 1 AMI triggered by COVID-19. In the absence of symptoms or electrocardiographic changes suggestive of type 1 acute myocardial injury, imaging studies including echocardiography and/cardiac magnetic resonance should be considered to detect left ventricular systolic dysfunction as a new and treatable condition. Patients with symptoms suggestive of type 1 AMI should be treated according to European Society of Cardiology (ESC) guidelines irrespective of COVID-19 diagnosis or suspicion. These patients should undergo rapid coronary angiography under specific catheter personnel. Patients with COVID-19 or other pneumonia who are critically ill with septic shock or ARDS, even marked cardiac troponin elevations are much more likely the consequence of critical illness. The recognition of myocardial injury with elevated cardiac troponin and hs-TnI, given its sensitivity as an early and precise marker of end-organ dysfunction, can prompt timely triage to a critical care unit and informs the measures to improve tissue oxygenation and perfusion with the use of inotropes and vasopressors. Further research is required to elucidate the value of cardiac troponin and high sensitivity troponin I in COVID-19.
