Long-term cardiac pathology in individuals with mild initial COVID-19 illness

Valentina O Puntmann, Simon Martin, Anastasia Shchendrygina, Jedrzej Hoffmann, Mame Madjiguène Ka, Eleni Giokoglu, Byambasuren Vanchin, Niels Holm, Argyro Karyou, Gerald S Laux, Christophe Arendt, Philipp De Leuw, Kai Zacharowski, Yascha Khodamoradi, Maria J G T Vehreschild, Gernot Rohde, Andreas M Zeiher, Thomas J Vogl, Carsten Schwenke, Eike Nagel, Valentina O Puntmann, Simon Martin, Anastasia Shchendrygina, Jedrzej Hoffmann, Mame Madjiguène Ka, Eleni Giokoglu, Byambasuren Vanchin, Niels Holm, Argyro Karyou, Gerald S Laux, Christophe Arendt, Philipp De Leuw, Kai Zacharowski, Yascha Khodamoradi, Maria J G T Vehreschild, Gernot Rohde, Andreas M Zeiher, Thomas J Vogl, Carsten Schwenke, Eike Nagel

Abstract

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77-177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274-383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.

Conflict of interest statement

V.P. and E.N. have received speaker fees from Bayer AG and Siemens AG as well as educational grants from Bayer AG and NeoSoft. The other authors report no relevant conflicts of interest related to this research project.

© 2022. The Author(s).

Figures

Fig. 1. Study population flowchart.
Fig. 1. Study population flowchart.
Number of participants eligible for inclusion at baseline and follow-up assessments. CMR: cardiovascular magnetic resonance.
Extended Data Fig. 1. Representative magnetic resonance…
Extended Data Fig. 1. Representative magnetic resonance images of a symptomatic patient.
(a-f) Late gadolinium enhancement imaging (A, D-F) and Native T1 (B) and T2 (C) mapping measurements of a 57-year-old woman evaluated 201 days after COVID-19 infection. This individual reported dyspnea, palpitations, and chest pain, worsening on minimal exertion. Late gadolinium enhancement imaging allows to visualize regional accumulation of the gadolinium-based contrast agent along the outer rim of the myocardial free wall (red arrows), as well as within the thickened pericardial layers, separated by small amounts of pericardial effusion (blue arrows).

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