Long-Lasting Myocardial and Skeletal Muscle Damage Evidenced by Serial CMR During the First Year in COVID-19 Patients From the First Wave

Laura Filippetti, Nathalie Pace, Jean-Sebastien Louis, Damien Mandry, François Goehringer, Maria-Soledad Rocher, Nicolas Jay, Christine Selton-Suty, Gabriela Hossu, Olivier Huttin, Pierre-Yves Marie, Laura Filippetti, Nathalie Pace, Jean-Sebastien Louis, Damien Mandry, François Goehringer, Maria-Soledad Rocher, Nicolas Jay, Christine Selton-Suty, Gabriela Hossu, Olivier Huttin, Pierre-Yves Marie

Abstract

Introduction: This observational CMR study aims to characterize left-ventricular (LV) damage, which may be specifically attributed to COVID-19 and is distant in time from the acute phase, through serial CMR performed during the first year in patients with no prior cardiac disease.

Methods: This study included consecutive patients without any prior history of cardiac disease but with a peak troponin-Ic > 50 ng/ml at the time of the first COVID-wave. All had a CMR in the first months after the acute phase, and some had an additional CMR at the end of the first year to monitor LV function, remodeling, and abnormalities evocative of myositis and myocarditis - i.e., increased T1/T2 relaxation times, increased extracellular volume (ECV), and delayed contrast enhancement.

Results: Nineteen consecutively admitted COVID-19 patients (17 men, median age 66 [57-71] years) were included. Eight (42%) had hypertension, six (32%) were obese, and 16 (84%) had suffered an acute respiratory distress syndrome. The 1st CMR, recorded at a median 3.2 [interquartile range: 2.6-3.9] months from the troponin peak, showed (1) LV concentric remodeling in 12 patients (63%), (2) myocardial tissue abnormalities in 11 (58%), including 9 increased myocardial ECVs, and (3) 14 (74%) increased ECVs from shoulder skeletal muscles. The 2nd CMR, obtained at 11.1 [11.0-11.7] months from the troponin peak in 13 patients, showed unchanged LV function and remodeling but a return to normal or below the normal range for all ECVs of the myocardium and skeletal muscles.

Conclusion: Many patients with no history of cardiac disease but for whom an increase in blood troponin-Ic ascertained COVID-19 induced myocardial damage exhibited signs of persistent extracellular edema at a median 3-months from the troponin peak, affecting the myocardium and skeletal muscles, which resolved within a one-year time frame. Associations with long-COVID symptoms need to be investigated on a larger scale now.

Clinical trial registration: NCT04753762 on the ClinicalTrials.gov site.

Keywords: COVID-19; cardiovascular magnetic resonance imaging; edema; myocarditis; skeletal muscle.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Filippetti, Pace, Louis, Mandry, Goehringer, Rocher, Jay, Selton-Suty, Hossu, Huttin and Marie.

Figures

Figure 1
Figure 1
Pre-contrast T1 map showing regions-of-interest (ROIs) drawn to determine ECV and relaxation times on the myocardium (blue) and shoulders skeletal muscle (red).
Figure 2
Figure 2
Individual variations between the 1st and 2nd CMR for the ECV from the myocardium and skeletal muscles, as well as for the LV mass/volume ratio, which was used to assess LV concentric remodeling and normalized to male values (i.e., with the values in women increased by 0.21 to compensate for the difference in the normal upper limits between women (0.90) and men (1.11)). The dashed lines represent the normal upper limits.
Figure 3
Figure 3
Schematic representation of the progressive decrease during the first year of the myocardial ECV, presumably in line with a delayed resolution of the interstitial edema.

References

    1. Maccio U, Zinkernagel AS, Shambat SM, Zeng X, Cathomas G, Ruschitzka F, et al. . SARS-CoV-2 leads to a small vessel endotheliitis in the heart. EBioMedicine. (202) 63:103182. 10.1016/j.ebiom.2020.103182
    1. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. . Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. (2020) 5:1265-73. 10.1001/jamacardio.2020.3557
    1. Filippetti L, Pace N, Marie PY. Cardiac Involvement After Recovering From COVID-19. JAMA Cardiol. (2021) 6:243–4. 10.1001/jamacardio.2020.5279
    1. Freaney PM, Shah SJ, Khan SS. COVID-19 and Heart Failure With Preserved Ejection Fraction. JAMA. (2020) 324:1499–500. 10.1001/jama.2020.17445
    1. Chen BH, Shi NN, Wu CW, An DA, Shi YX, Wesemann LD, et al. . Early cardiac involvement in patients with acute COVID-19 infection identified by multiparametric cardiovascular magnetic resonance imaging. Eur Heart J Cardiovasc Imaging. (2021) 22:844–51. 10.1093/ehjci/jeab042
    1. Huang L, Zhao P, Tang D, Zhu T, Han R, Zhan C, et al. . Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging. JACC Cardiovasc Imaging. (2020) 13:2330–9. 10.1016/j.jcmg.2020.05.004
    1. Doeblin P, Kelle S. Going after COVID-19 myocarditis. Eur Heart J Cardiovasc Imaging. (2021) 22:852–4. 10.1093/ehjci/jeab097
    1. Ramani SL, Samet J, Franz CK, Hsieh C, Nguyen CV, Horbinski C, et al. . Musculoskeletal involvement of COVID-19: review of imaging. Skeletal Radiol. (2021) 50:1763–73. 10.1007/s00256-021-03734-7
    1. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. . Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. (2015) 28:1–39. 10.1016/j.echo.2014.10.003
    1. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, 3rd, Dokainish H, Edvardsen T, et al. . Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. (2016) 17:1321–60. 10.1093/ehjci/jew082
    1. Vincenti G, Monney P, Chaptinel J, Rutz T, Coppo S, Zenge MO, et al. . Compressed sensing single-breath-hold CMR for fast quantification of LV function, volumes, and mass. JACC Cardiovasc Imaging. (2014) 7:882–92. 10.1016/j.jcmg.2014.04.016
    1. Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, et al. . Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations. J Am Coll Cardiol. (2018) 72:3158–76. 10.1016/j.jacc.2018.09.072
    1. Muehlberg F, Arnhold K, Fritschi S, Funk S, Prothmann M, Kermer J, et al. . Comparison of fast multi-slice and standard segmented techniques for detection of late gadolinium enhancement in ischemic and non-ischemic cardiomyopathy - a prospective clinical cardiovascular magnetic resonance trial. J Cardiovasc Magn Reson. (2018) 20:13. 10.1186/s12968-018-0434-2
    1. Marie PY, Mandry D, Huttin O, Micard E, Bonnemains L, Girerd N, et al. . Comprehensive monitoring of cardiac remodeling with aortic stroke volume values provided by a phase-contrast CMR sequence. J Hypertens. (2016) 34:967–73. 10.1097/HJH.0000000000000889
    1. Tsao CW, Gona PN, Salton CJ, Chuang ML, Levy D, Manning WJ, et al. . Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study. J Am Heart Assoc. (2015) 4:e002188. 10.1161/JAHA.115.002188
    1. Bluemke DA, Kronmal RA, Lima JA, Liu K, Olson J, Burke GL, et al. . The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. (2008) 52:2148–55. 10.1016/j.jacc.2008.09.014
    1. Huber AT, Bravetti M, Lamy J, Bacoyannis T, Roux C, de Cesare A, et al. . Non-invasive differentiation of idiopathic inflammatory myopathy with cardiac involvement from acute viral myocarditis using cardiovascular magnetic resonance imaging T1 and T2 mapping. J Cardiovasc Magn Reason. (2018) 20:11. 10.1186/s12968-018-0430-6
    1. Aquaro GD, Camastra G, Monti L, Lombardi M, Pepe A, Castelletti S, et al. . Reference values of cardiac volumes, dimensions, and new functional parameters by MR: A multicenter, multivendor study. J Magn Reson Imaging. (2017) 45:1055–67. 10.1002/jmri.25450
    1. Chuang ML, Gona P, Hautvast GL, Salton CJ, Breeuwer M, O'Donnell CJ, et al. . CMR reference values for left ventricular volumes, mass, and ejection fraction using computer-aided analysis: the Framingham Heart Study. J Magn Reson Imaging. (2014) 39:895–900. 10.1002/jmri.24239
    1. Eng J, McClelland RL, Gomes AS, Hundley WG, Cheng S, Wu CO, et al. . Adverse Left Ventricular Remodeling and Age Assessed with Cardiac MR Imaging: The Multi-Ethnic Study of Atherosclerosis. Radiology. (2016) 278:714–22. 10.1148/radiol.2015150982
    1. Constant Dit Beaufils AL, Huttin O, Jobbe-Duval A, Senage T, Filippetti L, Piriou N, et al. . Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse: Relation to Mitral Regurgitation, Ventricular Remodeling, and Arrhythmia. Circulation. (2021) 143:1763–74. 10.1161/CIRCULATIONAHA.120.050214
    1. Wang X, Joseph AA, Kalentev O, Merboldt KD, Voit D, Roeloffs VB, et al. . High-resolution myocardial T1 mapping using single-shot inversion-recovery fast low-angle shot CMR with radial undersampling and iterative reconstruction. Br J Radiol. (2016) 89:20160255. 10.1259/bjr.20160255
    1. Thavendiranathan P, Zhang L, Zafar A, Drobni ZD, Mahmood SS, Cabral M, et al. . Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis. J Am Coll Cardiol. (2021) 77:1503–16. 10.1016/j.jacc.2021.01.050
    1. van Heeswijk RB, Feliciano H, Bongard C, Bonanno G, Coppo S, Lauriers N, et al. . Free-breathing 3 T magnetic resonance T2-mapping of the heart. JACC Cardiovasc Imaging. (2012) 5:1231–9. 10.1016/j.jcmg.2012.06.010
    1. Soler R, Méndez C, Rodríguez E, Barriales R, Ochoa JP, Monserrat L. Phenotypes of hypertrophic cardiomyopathy. An illustrative review of CMR findings. Insights Imaging. (2018) 9:1007–20. 10.1007/s13244-018-0656-8
    1. Haslbauer JD, Tzankov A, Mertz KD, Schwab N, Nienhold R, Twerenbold R, et al. . Characterisation of cardiac pathology in 23 autopsies of lethal COVID-19. J Pathol Clin Res. (2021) 7:326–37. 10.1002/cjp2.212
    1. Mondello C, Roccuzzo S, Malfa O, Sapienza D, Gualniera P, Ventura Spagnolo E, et al. . Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis A Systematic Review. Front Pharmacol. (2021) 12:614586. 10.3389/fphar.2021.614586
    1. Files DC, Sanchez MA, Morris PE. A conceptual framework: the early and late phases of skeletal muscle dysfunction in the acute respiratory distress syndrome. Crit Care. (2015) 19:266. 10.1186/s13054-015-0979-5
    1. Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. . Acute respiratory distress syndrome. Nat Rev Dis Primers. (2019) 5:18. 10.1038/s41572-019-0069-0
    1. Yan Z, Yang M, Lai CL. Long COVID-19 Syndrome: A Comprehensive Review of Its Effect on Various Organ Systems and Recommendation on Rehabilitation Plans. Biomedicines. (2021) 9:966. 10.3390/biomedicines9080966

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