TROPONIN MYOCARDIAL INJURY MARKER AND OUTCOME IN COVID-19: SCOPING REVIEW

A scoping review was adopted, in the Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online and Virtual Health Library bases, from May to July 2022. Using as descriptors: Troponin; COVID-19; Cardiovascular System.

Results:

23 studies revealed cardiac alterations in hospitalized patients with COVID-19 by examining the cardio specific biomarker troponin, in addition to relating it to high mortality rates. Studies have shown a great relationship between acute myocardial injury, evidenced by elevated troponin, and a worse outcome during hospitalization.

Conclusion:

Cardiovascular changes were mapped in patients hospitalized with COVID -19 who progressed to severe cases of the disease. This study can contribute to care planning through protocols aimed at clinical management, specific for patients with the disease, both in the acute phase and in the post- COVID -19 phase.

DESCRIPTORS:
Troponin; Cardiovascular System; COVID -19; Nursing.

Database	Search strategy
PUBMED	Troponin AND COVID-19 AND Cardiovascular System
MEDLINE	Troponin AND COVID-19 AND Cardiovascular System
SCIELO	Troponin AND COVID-19 AND Cardiovascular System

Authors/Country/ Year	Title	Journal	Design / Sample / Change in troponin and clinical outcome
Alieva, et al⁶6 Alieva AAM, Reznik REV, Teplova TNV, Batov MBMA, Shnahova SLM, Arakelyan ARA, et al. Predictive value of cardiac troponins in COVID-19. Therapy. [Internet]. 2022 [cited in 2022 July 14]; (3):91-100. Available in: https://doi.org/10.18565/THERAPY.2022.3.91-100. https://doi.org/10.18565/THERAPY.2022.3.... . Russia 2022	Prognostic value of cardiac troponins in case of COVID-19.	Therapy	Retrospective Study 48,510 medical records Elevated serum troponin levels were correlated with deteriorating health and increased mortality in patients with and without heart disease. Troponin elevation was associated with death, mechanical ventilation, and intensive care.
Almeida, et al⁷7 Almeida Junior GLG de, Braga F, Jorge JK, Nobre GF, Kalichsztein M, Faria P de MP de, et al. Prognostic value of troponin-T and B-Type natriuretic peptide in patients hospitalized for COVID-19. Arq Bras Cardiol. [Internet]. 2020 [cited in 2022 May 28]; 115(4):660-66. Available in: https://doi.org/10.36660/abc.20200385. https://doi.org/10.36660/abc.20200385... . Brazil 2020	Prognostic Value of Troponin-T and B-Type Natriuretic Peptide in Patients Hospitalized for COVID-19	Arquivos Brasileiros de Cardiologia	Cohort study with convenience sample 183 patients First study in Brazil to identify TnT as an independent predictor of worse prognosis in patients with COVID-19. Troponin elevation was associated with the combined outcome of death or need for mechanical ventilation, with more than half of patients with troponin > 0.03 ng/dl having an unfavorable outcome.
Azevedo, et al⁸8 Azevedo RB, Botelho BG, Hollanda JVG de, Ferreira LVL, Andrade LZJ de, Oei SSML, et al. Practical Approach to acute coronary syndrome in patients with COVID-19. Int J Cardiovasc Sci. [Internet]. 2021 [cited in 2022 June 18]; 34(1):89-98. Available in: https://doi.org/10.36660/ijcs.20200150. https://doi.org/10.36660/ijcs.20200150... . Brazil 2021	Practical Approach to Acute Coronary Syndrome in Patients with COVID-19	International Journal of Cardiovascular Sciences	Scoping review 59 studies Acute myocardial injury is significantly associated with in-hospital mortality, with troponin being a marker of worse prognosis in SARS-CoV-2 infected patients. Several studies have shown that myocardial injury, diagnosed by increased troponin levels, is associated with higher mortality in patients with COVID-19.
Bavish, et al⁹9 Bavishi C, Bonow RO, Trivedi V, Abbott JD, Messerli FH, Bhatt DL. Special article - acute myocardial injury in patients hospitalized with COVID-19 infection: a review. Prog Cardiovasc Dis. [Internet]. 2020 [cited in 2022 May 14]; 63(5):682-89. Available in: https://doi.org/10.1016/j.pcad.2020.05.013. https://doi.org/10.1016/j.pcad.2020.05.0... . United States 2020	Acute myocardial injury in patients hospitalized with Covid-19 infection: A review.	Progress in Cardiovascular Diseases	Review study 26 articles (11,685 patients) Elevation of cardiac biomarkers was found to be common in patients with Covid-19 infection. In this review, the overall prevalence of acute myocardial injury ranged from 5% to 38%. Elevation of cardiac biomarkers, particularly high-sensitivity cardiac troponin (hs-troponin) was considered an important myocardial injury marker for diagnosis and risk stratification.
Cao, et al¹⁰10 Cao J, Zheng Y, Luo Z, Mei Z, Yao Y, Liu Z, et al. Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19 patients with no prior cardiovascular disease. Theranostics. [Internet]. 2020 [cited in 2022 June 06]; 10(21):9663-73. Available in: https://doi.org/10.7150/thno.47980. https://doi.org/10.7150/thno.47980... . China 2020	Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19.	Theragnostic	Review study 26 articles (11,685 patients) Elevation of cardiac biomarkers was found to be common in patients with Covid-19 infection. In this review, the overall prevalence of acute myocardial injury ranged from 5% to 38%. Elevation of cardiac biomarkers, particularly high-sensitivity cardiac troponin (hs-troponin) was considered an important myocardial injury marker for diagnosis and risk stratification.
Carillo-Esper, et al¹1 Carrillo-Esper R, Melgar-Bieberach RE, Tapia-Salazar M, Jacinto-Flores SA, Campa-Mendoza AN, Pérez-Calatayud ÁA, et al. Extrapulmonary manifestations of SARS-CoV-2 infection. Cir Cir. [Internet]. 2020 [cited in 2022 May 12]; 88(5):654-63. Available in: https://doi.org/10.24875/CIRU.20000363. https://doi.org/10.24875/CIRU.20000363... . Mexico 2020	Manifestaciones extrapulmonares de la infección por SARS-CoV-2.	Cirugía Y Cirujanos	Theoretical study Cardiac biomarker studies suggest a high prevalence of cardiac injury in patients hospitalized for Covid-19, with myocardial injury being an important prognostic factor.
Case, et al¹¹11 Case BC, Yerasi C, Forrestal BJ, Shea C, Rappaport H, Medranda GA, et al. Clinical impact and predictors of troponin elevation in patients With COVID-19. Cardiovasc Revasc Med. [Internet]. 2021 [cited in 2022 June 26]; 33:41-4. Available in: https://doi.org/10.1016/j.carrev.2021.03.002. https://doi.org/10.1016/j.carrev.2021.03... . United States 2021	Clinical impact and predictors of troponin elevation in patients with Covid-19	Cardiovascular Revascularization Medicine	Cohort study 2,716 patients with Covid-19 Of the sample, 250 had troponin elevation, presenting a higher risk for mechanical ventilation. Hospital mortality was significantly higher (48.4%) in COVID-19 positive patients with troponin elevation than without troponin elevation (12.2%; p<0.001).
Chen, et al¹²12 Chen Q, Xu L, Dai Y, Ling Y, Mao J, Qian J, et al. Cardiovascular manifestations in severe and critical patients with COVID-19. Clin Cardiol. [Internet]. 2020 [cited in 2022 May 06]; 43(7):796-802. Available in: https://doi.org/10.1002/clc.23384. https://doi.org/10.1002/clc.23384... . . China 2020	Cardiovascular manifestations in severe and critical patients with COVID-19.	Clinical Cardiology	Incidence study 54 patients with COVID-19 Troponin elevation was observed in 23 (42.6%) patients, with three patients having highly elevated values (>3 times the upper reference limit), indicative of severe myocardial injury, and all being classified as critical cases.
Fan, et al¹³13 Fan Q, Zhu H, Zhao J, Zhuang L, Zhang H, Xie H, et al. Risk factors for myocardial injury in patients with coronavirus disease 2019 in China. ESC Heart Fail. [Internet]. 2020 [cited in 2022 July 21]; 7(6):4108-17. Available in: https://doi.org/10.1002/ehf2.13022. https://doi.org/10.1002/ehf2.13022... . China 2019	Risk factors for myocardial injury in patients with coronavirus disease 2019 in China.	Esc Heart Failure	Cohort study 353 patients with COVID-19 Of the sample, 79 patients had myocardial injury. High troponin levels were significantly associated with immune response, multiple organ dysfunction and poor outcomes.
Kaufmann, et al¹⁴14 Kaufmann CC, Ahmed A, Burger AL, Muthspiel M, Jäger B, Wojta J, et al. Biomarkers associated with cardiovascular disease in COVID-19. Cells. [Internet]. 2022 [cited in 2022 June 06]; 11(6):922. Available in: https://doi.org/10.3390/cells11060922. https://doi.org/10.3390/cells11060922... . Austria 2022	Biomarkers Associated with Cardiovascular Disease in COVID-19.	Cells	Theoretical study The prognostic value of troponin in COVID-19 patients has been consistently demonstrated in several different study populations worldwide and has been confirmed by data from several meta-analyses. In the case of myocardial injury, a clear correlation with symptoms and signs of myocardial ischemia (chest pain, ECG, and echocardiogram) is necessary to adequately guide management decisions.
Kavsak, et al¹⁵15 Kavsak PA, Hammarsten O, Worster A, Smith SW, Apple FS. Cardiac troponin testing in patients with COVID-19: a strategy for testing and reporting results. Clin Chem. [Internet]. 2021 [cited in 2022 July 06]; 67(1):107-13. Available in: https://doi.org/10.1093/clinchem/hvaa225. https://doi.org/10.1093/clinchem/hvaa225... . Canada 2021	Cardiac Troponin Testing in Patients with COVID-19.	Clinical Chemistry	Theoretical study After respiratory complications, cardiac complications were the most prevalent finding in COVID-19 patients. Increased troponin (based on a threshold of 28 ng/L) at hospital admission may have a greater association with death.
Lala, et al¹⁶16 Lala A, Johnson KW, Januzzi JL, Russak AJ, Paranjpe I, Richter F, et al. Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection. J Am Coll Cardiol. [Internet]. 2020 [cited in 2022 June 06]; 76(5):533-46. Available in: https://doi.org/10.1016/j.jacc.2020.06.007. https://doi.org/10.1016/j.jacc.2020.06.0... . United States 2020	Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection	Journal of the American college of cardiology	Cohort study 3,069 patients hospitalized with Covid-19 Myocardial injury reflected by troponin concentrations above the upper reference limit of 0.03 ng/ml was present in 36% of patients hospitalized with COVID-19. Troponin levels among patients were generally <1.0 ng/ml. Even small amounts of myocardial injury (for example) troponin I >0.09 ng/dl, n = 530 [19.4%]) were associated with a more pronounced risk of death.
Luchian, et al¹⁷17 Luchian ML, Motoc AI, Lochy S, Magne J, Roosens B, Belsack D, et al. Troponin T in COVID-19 hospitalized patients: kinetics matter. Cardiol J. [Internet]. 2021 [cited in 2022 June 06]; 28(6):807-15. Available in: https://doi.org/10.5603/CJ.a2021.0104. https://doi.org/10.5603/CJ.a2021.0104... . Bélgica 2021	Troponin T in COVID-19 hospitalized patients: Kinetics matter	Cardiology Journal	Prospective study 202 patients Elevated cardiac troponin T on admission was associated with increased in-hospital mortality, whereas patients with troponin levels within the standards had less cardiovascular changes. The study emphasizes the additional role of cTnT testing in COVID-19 patients for risk stratification and improved diagnostic and management pathway.
Majure, et al¹⁸18 Majure DT, Gruberg L, Saba SG, Kvasnovsky C, Hirsch JS, Jauhar R. Northwell health COVID-19 research consortium. usefulness of elevated troponin to predict death in patients With COVID-19 and myocardial injury. Am J Cardiol. [Internet]. 2021 [cited in June 06]; 138:100-6. Available in: https://doi.org/10.1016/j.amjcard.2020.09.060. https://doi.org/10.1016/j.amjcard.2020.0... . United States 2021	Usefulness of Elevated Troponin to Predict Death in Patients With COVID-19 and Myocardial Injury	The American Journal of Cardiology	Analytical study 6,247 hospitalized patients with Covid-19 Of the sample, 4426 (71%) patients had normal troponin result, 919 (15%) mildly elevated and 902 (14%) had severely elevated troponin. Patients hospitalized with COVID-19 and elevated troponin had markedly increased mortality compared with patients with normal troponin levels. This risk was independent of cardiovascular comorbidities and elevated markers of inflammation.
Marzo, et al¹⁹19 Marzo V de, Di Biagio A, Bona RD, Vena A, Arboscello E, Emirjona H, et al. Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19. J Geriatr Cardiol. [Internet]. 2021 [cited in 2022 July 14]; 18(5):338-45. Available in: https://doi.org/10.11909/j.issn.1671-5411.2021.05.004. https://doi.org/10.11909/j.issn.1671-541... . Italia 2021	Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19.	Journal of Geriatric Cardiology	Retrospective study 343 patients Of the sample, 88 (25.7%) had troponin results above the upper reference limit (0.046 μg/L). Patients with elevated troponin had more comorbidities, greater impaired respiratory exchange, and higher inflammatory markers on admission than those with troponin levels within standards. In addition, they died more (73.9% vs. 37.3%, P < 0.001) over 15 (6-25) days of hospitalization.
Nascimento, et al²⁰20 Nascimento JHP, Gomes BFO, Oliveira GMM. Troponina cardíaca como preditor de injúria miocárdica e mortalidade por COVID-19. Arq Bras Cardiol [Internet]. 2020 [cited in 2022 July 14]; 115(4). Available in: https://doi.org/10.36660/abc.20200862. https://doi.org/10.36660/abc.20200862... . Brazil 2020	Troponina Cardíaca como Preditor de Injúria Miocárdica e Mortalidade por COVID-19	Arquivos Brasileiros de Cardiologia	Editorial. Myocardial injury is not uncommon in patients with COVID-19, and elevated cardiac troponin is a predictor of in-hospital mortality. The measurement of cTnI throughout hospitalization can facilitate the risk classification of these patients, with the advantage of being an easily reproducible method.
Rezabakhsh, et al²¹21 Rezabakhsh A, Sadat-Ebrahimi SR, Ala A, Nabavi SM, Banach M, Ghaffari S. A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system. J Cell Mol Med. [Internet]. 2022 [cited in 2022 July 23]; 26(2):274-86. Available in: https://doi.org/10.1111/jcmm.17122. https://doi.org/10.1111/jcmm.17122... . Iran 2022	A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system.	Journal of Cellular Molecular Medicine	Theoretical study Some evidence has suggested that a significantly high rate of cTnI induced by cardiac dysfunction could be considered an independent predictor of mortality from Covid-19. Troponin results could be applied for risk stratification on admission and assessment of disease progression in hospitalized patients.
Sahranavard, et al²²22 Sahranavard M, Rezayat AA, Bidary MZ, Omranzadeh A, Rohani F, Farahani RH, et al. Cardiac complications in COVID-19: a systematic review and meta-analysis. Arch Iran Med. [Internet]. 2021 [cited in 2022 May 23]; 24(2):152-63. Available in: https://doi.org/10.34172/AIM.2021.24. https://doi.org/10.34172/AIM.2021.24... . Iran 2021	Cardiac Complications in COVID-19: A Systematic Review and Meta-analysis	Archives of Iranian Medicine	Systematic review 22 articles included Comparisons of troponin levels between survivors and patients who died were performed in four studies, and the results showed that patients who died had higher troponin levels compared to survivors.
Shafi, et al²³23 Shafi AMA, Shaikh SA, Shirke MM, Iddawela S, Harky A. Cardiac manifestations in COVID-19 patients-A systematic review. J Card Surg. [Internet]. 2020 [cited in 2022 May 23]; 35(8):1988-2008. Available in: https://doi.org/10.1111/jocs.14808. https://doi.org/10.1111/jocs.14808... . England 2020	Cardiac manifestations in COVID-19 patients - A systematic review	Journal of Cardiac Surgery	Systematic review 61 articles included A wide range of cardiac manifestations are associated with the interaction between Covid-19 and the cardiovascular system. Specific cardiac biomarkers, such as troponin, provide a useful prognostic tool to help identify patients with severe disease early and allow timely treatment escalation.
Shah, et al²⁴24 Shah P, Doshi R, Chenna A, Owens R, Cobb A, Ivey H, et al. Prognostic value of elevated cardiac troponin I in hospitalized Covid-19 patients. Am J Cardiol. [Internet]. 2020 [cited in 2022 May 12]; 15(135):150-53. Available in: https://doi.org/10.1016/j.amjcard.2020.08.041. https://doi.org/10.1016/j.amjcard.2020.0... . United States 2020	Prognostic Value of Elevated Cardiac Troponin I in Hospitalized Covid-19 Patients	American Journal of Cardiology	Retrospective study 635 medical records of patients with Covid-19 In 309 patients, troponin I was measured at least once during hospitalization. Of these patients, 116 (37.5%) had elevated troponin I, and were found to have a higher need for intubation, dialysis, and ICU transfer. In addition, overall mortality was significantly higher among patients with elevated cTnI.
Sharma, et al²⁵25 Sharma YP, Agstam S, Yadav A, Gupta A, Gupta A. Cardiovascular manifestations of COVID-19: an evidence-based narrative review. Indian J Med Res. [Internet]. 2021 [cited in 2022 June 21]; 153(1 & 2):7-16. Available in: https://doi.org/10.4103/ijmr.IJMR_2450_20. https://doi.org/10.4103/ijmr.IJMR_2450_2... . India 2021	Cardiovascular manifestations of COVID-19: An evidence-based narrative review	Indian Journal of Medical Research	Theoretical study Troponin elevation is associated with increased incidence of malignant arrhythmias and mortality from Covid-19. In the initial report from Wuhan, China, up to 27.8% of Covid-19 patients had an elevated troponin level, indicating myocardial damage during hospitalization.
Tersalvi, et al²⁶26 Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated troponin in patients with Coronavirus disease 2019: possible mechanisms. J Card Fail. [Internet]. 2020 [cited in 2022 June 11]; 26(6):470-75. Available in: https://doi.org/10.1016/j.cardfail.2020.04.009. https://doi.org/10.1016/j.cardfail.2020.... . Switzerland 2020	Elevated Troponin in Patients with Coronavirus Disease 2019: Possible Mechanisms	Journal of Cardiac Failure	Theoretical study Elevated troponin levels are frequent in Covid-19 patients and significantly associated with fatal outcomes. Several mechanisms may explain this phenomenon: viral myocarditis, cytokine-induced myocardial injury, microangiopathy and unmasked coronary artery disease.
Tuo, et al³3 Tuo H, Li W, Tang L, He B, Yao B, Mao P, et al. Cardiac biomarker abnormalities are closely related to prognosis in patients with COVID-19. Int Heart J. [Internet]. 2021 [cited in 2022 May 20]; 62(1):148-52. Available in: https://doi.org/10.1536/ihj.20-180. https://doi.org/10.1536/ihj.20-180... . China 2021	Cardiac Biomarker Abnormalities Are Closely Related to Prognosis in Patients with COVID-19	International Hearth Journal	Observational study 148 patients The incidence of cardiovascular complications happened in 19 patients (12.8%). Five of them were survivors (5.2%) and 14 of them were non-survivors (26.9%). Compared to survivors, non-survivors had higher levels of high-sensitivity cardiac troponin I.

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[1] Associate editor: Dra. Luciana Kalinke