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What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?
In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.
These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.
To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.
Design, Setting, and Participants
In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.
Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract.
Main Outcomes and Measures
Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57).
Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology.
Conclusions and Relevance
In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: July 6, 2020.
Published Online: July 27, 2020. doi:10.1001/jamacardio.2020.3557
Correction: This article was corrected on August 25, 2020, to fix pervasive errors in statistical numbers and data in the Abstract, Methods and Results sections, Tables, and Figures 1 and 2.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Puntmann VO et al. JAMA Cardiology.
Corresponding Author: Eike Nagel, MD, Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany (firstname.lastname@example.org).
Author Contributions: Drs Puntmann and Nagel had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Puntmann, Shchendrygina, Vasa-Nicotera, Zeiher, Nagel.
Acquisition, analysis, or interpretation of data: Puntmann, Carerj, Wieters, Fahim, Arendt, Hoffmann, Escher, Vehreschild, Nagel.
Drafting of the manuscript: Puntmann, Shchendrygina, Nagel.
Critical revision of the manuscript for important intellectual content: Puntmann, Carerj, Wieters, Fahim, Arendt, Hoffmann, Escher, Vasa-Nicotera, Zeiher, Vehreschild, Nagel.
Statistical analysis: Puntmann, Nagel.
Obtained funding: Puntmann, Zeiher, Nagel.
Administrative, technical, or material support: Puntmann, Carerj, Wieters, Fahim, Arendt, Escher, Vehreschild, Nagel.
Study supervision: Puntmann, Wieters, Arendt, Vasa-Nicotera, Vehreschild, Nagel.
Conflict of Interest Disclosures: Dr Escher has received personal fees from Institut Kardiale Diagnostik und Therapie outside the submitted work. Dr Zeiher has received grants from the German Centre for Cardiovascular Research during the conduct of the study and personal fees from Sanofi, Amgen, Boehringer Ingelheim, and Novo Nordisk outside the submitted work. Dr Vehreschild has received grants from BioNTech and Takeda outside the submitted work. Dr Nagel has received grants from Bayer, the German Ministry for Education and Research, Deutsche Herzstiftung e.V., Neosoft Technologies, and Cardio-Pulmonary Institute and personal fees from Bayer. No other disclosures were reported.
Funding/Support: Drs Puntmann, Arendt, Escher, Vasa-Nicotera, Zeiher, and Nagel were supported by grants from the German Ministry of Education and Research via the German Centre for Cardiovascular Research (DZHK) partner site RheinMain, Deutsche Herzstiftung e.V., Bayer, and Cardio-Pulmonary Institute
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We acknowledge the dedicated support of clinical research support staff of the Institute of Experimental and Translational Cardiovascular Imaging, including Tammy Wolf, Thourier Azdad, Franziska Weis, Deniz Desik, BA, and Layla Laghchioua, MSc, as well as of the Department of Infectious Diseases, University Hospital Frankfurt. We are very grateful to our colleagues of the Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany, for treating all critically ill patients with COVID-19. Contributors were not compensated for their work.
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