key: cord-0710645-jbjn89jc authors: Sandoval, Yader; Januzzi, James L.; Jaffe, Allan S. title: Cardiac Troponin for Assessment of Myocardial Injury in COVID-19: JACC Review Topic of the Week date: 2020-09-08 journal: J Am Coll Cardiol DOI: 10.1016/j.jacc.2020.06.068 sha: 5d7d0212296ebada579ce4bfa51c0ab0468dca82 doc_id: 710645 cord_uid: jbjn89jc Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death. These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations. The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients. Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury. The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients. assays, for which sex-specific thresholds are recommended (7) . Several studies ( Table 1 ) have defined the frequency of myocardial injury in COVID-19 (1) (2) (3) (4) (5) (6) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) . However, as in many cTn studies, how myocardial injury was defined and which cTn assay, thresholds, and sampling intervals were used are often not well defined. Because many studies have not used hs-cTn assays and only used early single time point measurements, the data likely underestimate the frequency and magnitude of myocardial injury in COVID- 19 . Anticipating more studies addressing this issue, Supplemental Table 1 provides a template for what they should include to make research more interpretable and comparable. It should also be noted that many studies have used nonguideline definitions of myocardial injury based on electrocardiographic (ECG) or echocardiographic abnormalities (1, 2, 4) or use thresholds other than the 99th percentile (11) . The frequency of myocardial injury in COVID-19 varies widely (Table 1, Figure 1 ), in part because of variations in definitions, populations studied, timing of sampling, and cTn assays/thresholds. There is a continuum in the relationship between myocardial injury and illness severity, with a higher frequency of myocardial injury in critically ill patients and nonsurvivors. The range of myocardial injury in COVID-19, however, is wide (1) (2) (3) (4) , with cTn concentrations often considerably lower than often observed for acute MI, including in severe COVID-19 cases (19) . Non-COVID studies have demonstrated that myocardial injury is more likely to occur in critically ill older patients and in those with comorbidities (20) . Previous data demonstrated that cTn increases are frequent (42% using fourth-generation cTnT, median 0.2 ng/ml ¼ 200 ng/l with fifthgeneration cTnT) and prognostic in those with acute respiratory disease (21) . Increases occur in SARS-CoV-1, MERS-CoV, and influenza (22, 23) . Except for rare analytical confounds, cTn increases >99th percentile URL are indicative of myocardial injury (7) . Although these increases are cardiospecific, there are a myriad of conditions that can cause them. Despite reports of myocarditis with COVID- 19 (24,25) , which can cause increases in cTn, elevations in COVID-19 patients should not always be considered to be due to myocarditis or direct severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) injury. The etiology of all cTn increases, including those in COVID-19, depends on clinical context and collaborating information, and not cTn alone. The risk for acute myocardial injury, ischemia, and infarction following acute infection (viral or bacterial) is well established and is thought to be related to the increased inflammatory, prothrombotic, and procoagulant state (26) . Laboratory data from COVID-19 studies confirm the relationship between illness severity, an increased inflammatory and prothrombotic state, and myocardial injury. Patients with more severe COVID-19 presentations have greater increases in inflammatory markers such as C-reactive protein (3, 5, 6, 15) , ferritin (2, 3, 15) , interleukin-6 (2,3,15), tumor necrosis factor-a (1,3), and HIGHLIGHTS Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19. Increases can be due to chronic injury, acute nonischemic injury, or acute MI. Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification. Cardiac Troponin in the Age of COVID Continued on the next page thrombotic markers such as D-dimer (1) (2) (3) (4) (5) . In some (3,5,6) but not all (1,2) studies, procalcitonin is also increased. It is challenging, however, to discern whether inflammation is always a cause or a response of acute myocardial injury. Although SARS-CoV-2 appears to have renal tropism (28) and COVID-19 patients with increased cTn concentrations have higher rates of kidney injury (5), it is important to note that at high concentrations, cTn is mainly cleared through extrarenal mechanisms (29) . There appears to be a small component related to renal clearance at low concentrations (29) Pulmonary embolism is another consideration in COVID-19, given data that procoagulant activity is increased (34) (35) (36) 100% Cardiac Troponin in the Age of COVID Increases in cTn should be categorized as chronic myocardial injury, acute nonischemic myocardial injury, or acute myocardial infarction. For several conditions, there is a spectrum and the most common category is indicated, but can present in other ways. CKD ¼ chronic kidney disease; COVID-19 ¼ coronavirus disease-2019; CRP ¼ C-reactive protein; cTn ¼ cardiac troponin; ESRD ¼ end-stage renal disease; NT-proBNP ¼ N-terminal pro-B-type natriuretic peptide; URL ¼ upper reference limit. There are limited cardiac pathological data (25, 36, (47) (48) (49) . The viral proteome has been detected in the myocardium using polymerase chain reaction (28). This indicates the presence of SARS-CoV-2 but not necessarily active infection. In an autopsy series, Fox Patients with myocardial injury (blue bars) have a higher risk of death, arrhythmias, ARDS, and mechanical ventilation as compared with those without injury (red bars). ARDS ¼ acute respiratory distress syndrome; VF ¼ ventricular fibrillation; VT ¼ ventricular tachycardia. Data from Shi et al. (6) showing that the higher the cardiac troponin (cTn), the worse the outcome, and vice versa. Abbreviations as in Detection of myocardial injury. Absence of a clear actionable response to such elevations. Identification of patients at higher risk for adverse cardiovascular outcomes that may warrant further evaluation, e.g., those with marked cTn increases and/or large deltas. Potential unnecessary increased in downstream testing and consultations unless the principles for using cTn measurements are understood. Improved prognostication as cTn facilitates the detection of patients at risk for arrhythmias, ARDS, and death. Potential increases in infection exposure if cTn increases lead to downstream testing that exposes health care personnel to COVID-19-positive patients. Improved resource utilization as those with very low hs-cTn concentrations may require less-intensive care and/or evaluation compared with those with marked increases/deltas in whom more aggressive care, monitoring, and/or evaluation may be needed. Potential inappropriate use of acute coronary syndrome therapies/ strategies in patients unlikely to have atherothrombosis. Facilitate the understanding of cardiac involvement and myocardial injury phenotypes/stages in patients with COVID-19. Based on the presence/absence of myocardial injury that portends a higher risk for malignant arrhythmias, inform the use of agents that might have effects on the QTc interval. ARDS ¼ acute respiratory distress syndrome; other abbreviations as in Table 1 . May not require hospital admission. Close outpatient follow-up. Consider further evaluation, for example cardiac imaging, if it will provide benefit and impact management exists between myocardial injury and adverse outcomes, including a higher risk for death and arrhythmias ( Figure 3) . Second, there is a continuous relationship between cTn concentrations and outcomes, with data from Shi et al. (6) showing that mortality rates increase with higher hs-cTn concentrations ( Figure 4) . Third, patients with chronic cardiovascular conditions diagnosed with COVID-19 are not only at higher risk for developing acute myocardial injury, but are at a higher mortality risk (5) . 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Available at Highsensitivity cardiac troponin can be an ally in the fight against COVID-19 COVID-19 illness in native and immunosuppressed states: a clinicaltherapeutic staging proposal KEY WORDS cardiac troponin, coronavirus disease 2019, myocardial injury, type 2 myocardial infarction APPENDIX For a supplemental table, please see the online version of this paper.