[Skip to Navigation]
Sign In
Comment & Response
October 28, 2020

Cardiac Involvement After Recovering From COVID-19—Reply

Author Affiliations
  • 1Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, University Hospital Frankfurt, Frankfurt am Main, Germany
JAMA Cardiol. 2021;6(2):244-245. doi:10.1001/jamacardio.2020.5285

In Reply As the awareness about the numerous late effects of coronavirus disease 2019 (COVID-19) infection is taking hold, there is a growing understanding that cardiac involvement constitutes an important part of early and late stages of the COVID-19 illness. We recently demonstrated high prevalence of cardiac inflammation by cardiac magnetic resonance imaging in patients recovered from COVID-19 illness, with no trend of abating with the time passed from the acute COVID-19 illness.1 We emphasized the absence of longitudinal studies and hard outcome data, precluding any speculation on the long-term effects of these findings and indicated the need for more research. Yet in some parts of the press and by Filippetti et al, our findings have been described as “alarmist.” Filippetti et al suggest that the results of myocardial biopsies did not meet the criteria for true myocarditis, as used by Lindner et al.2 Notably, Lindner et al2 and our article1 both used the established pathological definitions by the World Health Organization and International Society and Federation of Cardiology.3 Whereas there was evidence of acute lymphocytic infiltration in myocardial biopsies months after the infection in our study,1 this was not the feature in patients who died during the acute illness.2 In our view, these findings are informative and complementary; cardiovascular damage and heart failure during the acute COVID-19 illness may result from exertion through febrile status, tachycardias, and general hypoxia, especially in those with preexisting cardiovascular conditions. However, later stages reveal intrinsic inflammatory myocardial involvement, accompanied by clinical manifestation of chronic fatigue and palpitations, thus explaining the different patterns in myocardial biopsies.

The definition of myocarditis remains a subject of considerable discussion. Classically, it relies on the results of myocardial biopsies, which is rarely used prior to considerable structural heart impairment. The biopsy criteria have been changing over time and include “other immunohistochemical criteria.”3 Similarly, cardiac magnetic resonance–based criteria were expanded to accommodate for novel parameters by various combinations of techniques and findings to be regarded as positive, as suggested by Małek. We observe that none of these proposed criteria are underpinned by strong outcome studies to serve as a diagnostic criterion standard,4 necessitating imminent further research. The modern definitions must include the early changes, such as myocardial water and diffuse fibrosis, as demonstrated in patients with COVID-19 in our study1 and also in other autoimmune models of myocarditis, and which occur prior to development of structural heart disease.

Małek also further refers to the technical issues with T1 mapping and the difficulty in transferring between different vendors and techniques. Importantly, we did not use the vendor products. We established our own T1 mapping MOLLI variant forming the basis of the Goethe CVI Approaches, first on Philips (version 4) and later transferred onto Siemens by harmonizing all parameters (well beyond solely the inversion scheme). We undertook extensive validation work in phantoms, histological correlations, disease models, and outcome data as well as intraindividual comparisons between the vendor platforms. We thank the authors of the letters for their interest and discussion.

Back to top
Article Information

Corresponding Author: Valentina Puntmann, MD, PhD, Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany (vppapers@icloud.com).

Published Online: October 28, 2020. doi:10.1001/jamacardio.2020.5285

Conflict of Interest Disclosures: Dr Nagel has received grants and personal fees from Bayer and grants from NeoSoft, German Centre for Cardiovascular Research, and Deutsche Herzstiftung. No other disclosures were reported.

Puntmann  VO, Carerj  ML, Wieters  I,  et al.  Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19).   JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557PubMedGoogle Scholar
Lindner  D, Fitzek  A, Bräuninger  H,  et al.  Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases.   JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3551PubMedGoogle Scholar
Caforio  AL, Pankuweit  S, Arbustini  E,  et al; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.  Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.   Eur Heart J. 2013;34(33):2636-2648, 2648a-2648d. doi:10.1093/eurheartj/eht210PubMedGoogle ScholarCrossref
Nagel  E, Kwong  RY, Chandrashekhar  YS.  CMR in nonischemic myocardial inflammation: solving the problem of diagnosing myocarditis or still diagnostic ambiguity?   JACC Cardiovasc Imaging. 2020;13(1, pt 1):163-166. doi:10.1016/j.jcmg.2019.10.023PubMedGoogle ScholarCrossref