Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance

Tushar Kotecha, Daniel S Knight, Yousuf Razvi, Kartik Kumar, Kavitha Vimalesvaran, George Thornton, Rishi Patel, Liza Chacko, James T Brown, Clare Coyle, Donald Leith, Abhishek Shetye, Ben Ariff, Robert Bell, Gabriella Captur, Meg Coleman, James Goldring, Deepa Gopalan, Melissa Heightman, Toby Hillman, Luke Howard, Michael Jacobs, Paramjit S Jeetley, Prapa Kanagaratnam, Onn Min Kon, Lucy E Lamb, Charlotte H Manisty, Palmira Mathurdas, Jamil Mayet, Rupert Negus, Niket Patel, Iain Pierce, Georgina Russell, Anthony Wolff, Hui Xue, Peter Kellman, James C Moon, Thomas A Treibel, Graham D Cole, Marianna Fontana, Tushar Kotecha, Daniel S Knight, Yousuf Razvi, Kartik Kumar, Kavitha Vimalesvaran, George Thornton, Rishi Patel, Liza Chacko, James T Brown, Clare Coyle, Donald Leith, Abhishek Shetye, Ben Ariff, Robert Bell, Gabriella Captur, Meg Coleman, James Goldring, Deepa Gopalan, Melissa Heightman, Toby Hillman, Luke Howard, Michael Jacobs, Paramjit S Jeetley, Prapa Kanagaratnam, Onn Min Kon, Lucy E Lamb, Charlotte H Manisty, Palmira Mathurdas, Jamil Mayet, Rupert Negus, Niket Patel, Iain Pierce, Georgina Russell, Anthony Wolff, Hui Xue, Peter Kellman, James C Moon, Thomas A Treibel, Graham D Cole, Marianna Fontana

Abstract

Background: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.

Methods and results: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).

Conclusions: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Keywords: COVID-19; Cardiovascular magnetic resonance; Myocardial infarction; Myocardial oedema; Myocarditis; SARS-CoV-2.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Consort diagram. CMR, cardiovascular magnetic resonance.
Figure 2
Figure 2
Patterns of myocardial scar and cardiovascular magnetic resonance diagnoses. CMR, cardiovascular magnetic resonance; LGE, late gadolinium enhancement; MI, myocardial infarction.
Figure 3
Figure 3
Example of patient with a myocarditis-pattern late gadolinium enhancement and evidence of active inflammation. Native T1 and myocardial T2 were elevated in the inferolateral wall (T1 1261 ms, T2 56 ms) and normal in the basal inferoseptum (T1 983 ms, T2 50 ms). Late gadolinium enhancement imaging shows patchy areas of subepicardial enhancement in the lateral wall and basal inferior wall, and mid-wall enhancement in the distal septum and distal anterior wall (white arrows).
Figure 4
Figure 4
Example of patient admitted with COVID-19 infection and associated troponin rise. Late gadolinium enhancement (bright blood left two panels and dark blood third panel) shows a lateral infarct (white arrows). Coronary angiography (right panel) showed an occluded obtuse marginal branch (black arrow).
Figure 5
Figure 5
Example of patient admitted with COVID-19 infection and associated troponin rise. Cardiovascular magnetic resonance with adenosine stress perfusion mapping showed inducible ischaemia in the inferior wall, basal inferoseptum, anterior, and anterolateral walls. Coronary angiography showed occluded right coronary artery and severe disease in proximal-mid LAD (black arrows).
Figure 6
Figure 6
Example of patient with dual pathology. Late gadolinium enhancement showed mid-wall late gadolinium enhancement in the basal inferolateral wall (myocarditis-pattern, red arrow) and sub-endocardial late gadolinium enhancement in the mid-anterior and part of the distal lateral wall (myocardial infarction pattern, white arrows). Native T1 and T2 were normal within the area of myocarditis-pattern late gadolinium enhancement (T1 1061 ms, T2 52 ms).
Figure 7
Figure 7
Native T1 (left panel) and myocardial T2 (right panel) measured in the remote myocardium. There was no significant difference in native T1 or T2 in the remote myocardium between COVID-19 patients and controls.

References

    1. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020;20:533–534.
    1. Liu PP, Blet A, Smyth D, Li H. The science underlying COVID-19: implications for the cardiovascular system. Circulation 2020;142:68–78.
    1. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020;368:473–474.
    1. Long B, Long DA, Tannenbaum L, Koyfman A. An emergency medicine approach to troponin elevation due to causes other than occlusion myocardial infarction. Am J Emerg Med 2019;38:998–1006.
    1. Vestjens SMT, Spoorenberg SMC, Rijkers GT, Grutters JC, Ten Berg JM, Noordzij PG, Van de Garde EMW, Bos WJW, the Ovidius Study Group. High-sensitivity cardiac troponin T predicts mortality after hospitalization for community-acquired pneumonia. Respirology 2017;22:1000–1006.
    1. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, Wang H, Wan J, Wang X, Lu Z. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811.
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506.
    1. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B, Huang C. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020;5:802.
    1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061.
    1. Wei JF, Huang FY, Xiong TY, Liu Q, Chen H, Wang H, Huang H, Luo YC, Zhou X, Liu ZY, Peng Y, Xu YN, Wang B, Yang YY, Liang ZA, Lei XZ, Ge Y, Yang M, Zhang L, Zeng MQ, Yu H, Liu K, Jia YH, Prendergast BD, Li WM, Chen M. Acute myocardial injury is common in patients with covid-19 and impairs their prognosis. Heart 2020;106:1154–1159.
    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–1062.
    1. Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G, Merson L, Lee J, Plotkin D, Sigfrid L, Halpin S, Jackson C, Gamble C, Horby PW, Nguyen-Van-Tam JS, Dunning J, Openshaw PJM, Baillie JK, Semple MG. Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. 2020. The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. COVID-19-Guidance (accessed 10 June 2020).
    1. European Society of Cardiology. ESC guidance for the diagnosis and management of CV disease during the COVID-19 pandemic. . (10 June 2020).
    1. Bhatia S, Anstine C, Jaffe AS, Gersh BJ, Chandrasekaran K, Foley TA, Hodge D, Anavekar NS. Cardiac magnetic resonance in patients with elevated troponin and normal coronary angiography. Heart 2019;105:1231–1236.
    1. Dastidar AG, Baritussio A, De Garate E, Drobni Z, Biglino G, Singhal P, Milano EG, Angelini GD, Dorman S, Strange J, Johnson T, Bucciarelli-Ducci C. Prognostic role of CMR and conventional risk factors in myocardial infarction with nonobstructed coronary arteries. JACC Cardiovasc Imaging 2019;12:1973–1982.
    1. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De CR, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P, Pharmacotherapy WC. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J 2017;38:143–153.
    1. Knight DS, Kotecha T, Razvi Y, Chacko L, Brown JT, Jeetley PS, Goldring J, Jacobs M, Lamb LE, Negus R, Wolff A, Moon JC, Xue H, Kellman P, Patel N, Fontana M. COVID-19: myocardial injury in survivors. Circulation 2020;142:1120–1122.
    1. Han Y, Chen T, Bryant J, Bucciarelli-Ducci C, Dyke C, Elliott MD, Ferrari VA, Friedrich MG, Lawton C, Manning WJ, Ordovas K, Plein S, Powell AJ, Raman SV, Carr J. Society for Cardiovascular Magnetic Resonance (SCMR) guidance for the practice of cardiovascular magnetic resonance during the COVID-19 pandemic. J Cardiovasc Magn Reson 2020;22:26.
    1. Kellman P, Hansen MS. T1-mapping in the heart: accuracy and precision. J Cardiovasc Magn Reson 2014;16:2.
    1. Giri S, Chung YC, Merchant A, Mihai G, Rajagopalan S, Raman SV, Simonetti OP. T2 quantification for improved detection of myocardial edema. J Cardiovasc Magn Reson 2009;11:56.
    1. Kellman P, Arai AE. Cardiac imaging techniques for physicians: late enhancement. J Magn Reson Imaging 2012;36:529–542.
    1. Kotecha T, Martinez-Naharro A, Boldrini M, Knight D, Hawkins P, Kalra S, Patel D, Coghlan G, Moon J, Plein S, Lockie T, Rakhit R, Patel N, Xue H, Kellman P, Fontana M. Automated pixel-wise quantitative myocardial perfusion mapping by CMR to detect obstructive coronary artery disease and coronary microvascular dysfunction: validation against invasive coronary physiology. JACC Cardiovasc Imaging 2019;12:1958–1969.
    1. Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations. J Am Coll Cardiol 2018;72:3158–3176.
    1. von Knobelsdorff-Brenkenhoff F, Schüler J, Dogangüzel S, Dieringer MA, Rudolph A, Greiser A, Kellman P, Schulz-Menger J. Detection and monitoring of acute myocarditis applying quantitative cardiovascular magnetic resonance. Circ Cardiovasc Imaging 2017;10:e005242.
    1. Captur G, Gatehouse P, Keenan KE, Heslinga FG, Bruehl R, Prothmann M, Graves MJ, Eames RJ, Torlasco C, Benedetti G, Donovan J, Ittermann B, Boubertakh R, Bathgate A, Royet C, Pang W, Nezafat R, Salerno M, Kellman P, Moon JC. A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance-the T1 mapping and ECV standardization in cardiovascular magnetic resonance (T1MES) program. J Cardiovasc Magn Reson 2016;18:58.
    1. Captur G, Bhandari A, Brühl R, Ittermann B, Keenan KE, Yang Y, Eames RJ, Benedetti G, Torlasco C, Ricketts L, Boubertakh R, Fatih N, Greenwood JP, Paulis LEM, Lawton CB, Bucciarelli-Ducci C, Lamb HJ, Steeds R, Leung SW, Berry C, Valentin S, Flett A, de Lange C, DeCobelli F, Viallon M, Croisille P, Higgins DM, Greiser A, Pang W, Hamilton-Craig C, Strugnell WE, Dresselaers T, Barison A, Dawson D, Taylor AJ, Mongeon FP, Plein S, Messroghli D, Al-Mallah M, Grieve SM, Lombardi M, Jang J, Salerno M, Chaturvedi N, Kellman P, Bluemke DA, Nezafat R, Gatehouse P, Moon JC, TIMES Consortium. T1 mapping performance and measurement repeatability: results from the multi-national T 1 mapping standardization phantom program (T1MES). J Cardiovasc Magn Reson 2020;22:31.
    1. Heymans S, Eriksson U, Lehtonen J, Cooper LT Jr. The quest for new approaches in myocarditis and inflammatory cardiomyopathy. J Am Coll Cardiol 2016;68:2348–2364.
    1. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Bondi-Zoccai G, Brown TS, Nigoghossian C, Zidar DA, Haythe J, Brodie D, Beckman JA, Kirtane AJ, Stone GW, Krumholz HM, Parikh SA. Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic. J Am Coll Cardiol 2020;75:2352–2371.
    1. Halushka MK, Vander Heide RS. Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations. Cardiovasc Pathol 2021;50:107300.
    1. Rajpal S, Tong MS, Borchers J, Zareba KM, Obarski TP, Simonetti OP, Daniels CJ. Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol 2021;6:116–118.
    1. Aquaro GD, Ghebru Habtemicael Y, Camastra G, Monti L, Dellegrottaglie S, Moro C, Lanzillo C, Scatteia A, Di Roma M, Pontone G, Perazzolo Marra M, Barison A, Di Bella G. Prognostic value of repeating cardiac magnetic resonance in patients with acute myocarditis. J Am Coll Cardiol 2019;74:2439–2448.
    1. Schultheiss HP, Fairweather D, Caforio ALP, Escher F, Hershberger RE, Lipshultz SE, Liu PP, Matsumori A, Mazzanti A, McMurray J, Priori SG. Dilated cardiomyopathy. Nat Rev Dis Primers 2019;5:32.
    1. Verdonschot JAJ, Merlo M, Dominguez F, Wang P, Henkens MTHM, Adriaens ME, Hazebroek MR, Masè M, Escobar LE, Cobas-Paz R, Derks KWJ, van den Wijngaard A, Krapels IPC, Brunner HG, Sinagra G, Garcia-Pavia P, Heymans SRB. Phenotypic clustering of dilated cardiomyopathy patients highlights important pathophysiological differences. Eur Heart J 2021;42:162–174.
    1. Becker MAJ, Cornel JH, van de Ven PM, van Rossum AC, Allaart CP, Germans T. The prognostic value of late gadolinium-enhanced cardiac magnetic resonance imaging in nonischemic dilated cardiomyopathy: a review and meta-analysis. JACC Cardiovasc Imaging 2018;11:1274–1284.
    1. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP, the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052–2059.
    1. Atkins JL, Masoli JAH, Delgado J, Pilling LC, Kuo CL, Kuchel GA, Melzer D. Preexisting comorbidities predicting COVID-19 and mortality in the UK Biobank Community cohort. J Gerontol A Biol Sci Med Sci 2020;75:2224–2230.
    1. Turkbey EB, Nacif MS, Guo M, McClelland RL, Teixeira PB, Bild DE, Barr RG, Shea S, Post W, Burke G, Budoff MJ, Folsom AR, Liu CY, Lima JA, Bluemke DA. Prevalence and correlates of myocardial scar in a US cohort. JAMA 2015;314:1945–1954.
    1. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, Shchendrygina A, Escher F, Vasa-Nicotera M, Zeiher AM, Vehreschild M, Nagel E. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:1265.
    1. Tschöpe C, Ammirati E, Bozkurt B, Caforio ALP, Cooper LT, Felix SB, Hare JM, Heidecker B, Heymans S, Hübner N, Kelle S, Klingel K, Maatz H, Parwani AS, Spillmann F, Starling RC, Tsutsui H, Seferovic P, Van Linthout S. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat Rev Cardiol 2020;.
    1. Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M, Gatehouse PD, Arai AE, Friedrich MG, Neubauer S, Schulz-Menger J, Schelbert EB, Society for Cardiovascular Magnetic Resonance Imaging; Cardiovascular Magnetic Resonance Working Group of the European Society of Cardiology. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013;15:92.

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