Myocardial Injury and Quality of Life in Patients Recovered From the Pneumonia Associated With the Novel Coronavirus Infectious Disease COVID-19
Conditions: COVID-19, Myocardial Injury, Myocarditis Post Infection
Sponsor: Voronezh Regional Clinical Consultative and Diagnostic Center

 
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Evaluation of myocardial injury and quality of life of patients recovered from Coronavirus 
Infectious Disease 19 (COVID-19) 
Approval Number 145 by Ethical Board as of 09/16/2020. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Evaluation of myocardial injury and quality of life of patients recovered from Coronavirus 
Infectious Disease 19 (COVID-19) 
The novel coronavirus disease 19 (COVID-19) pandemic made us to have a different look 
at the problem of cardiovascular injury by this virus. In the patients with severe course of 
COVID-19 there is approximately a 7% prevalence of fulminant myocarditis. Moreover, this 
infectious process worsens the outcomes of ischemic heart disease by accelerating the 
formation of intravascular thrombi (including intracoronary) and destabilizes the patients with 
chronic heart failure (Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur 
J Heart Fail 2020; 22:911–915.; Clinical course and risk factors for mortality of adult inpatients 
with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395:1054–62; 
Cardiovascular Imaging in Evaluation of COVID-19 Complications. J Am Coll Cardiol 2020; 
76:1345–57; Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy 
Cases. JAMA Cardiol. doi:10.1001/jamacardio.2020.3551). 
The research conducted at the beginning of COVID-19 pandemic in China showed us 
that among patients with no known cardiovascular past medical history and persistent 
complaints of heart racing (palpitations) and chest pain after recovery there were pathological 
findings in 58% of participants confirmed by cardiac magnetic resonance (CMR). Furthermore, 
in 54% of cases there was swelling of myocardium and in 31% there were foci of fibrosis 
(Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic 
Resonance Imaging. J Am Coll Cardiol Img 2020. https://doi.org/10.1016/j.jcmg.2020.05.004). 
Recent studies conducted in Germany and published in July 2020 demonstrated 
increase in the level of high-sensitivity troponin T (hsTropT) in 71% of patients following 2-3 
months after recovery from COVID-19. Moreover, CMR imaging with contrast showed that in 
78% of participants there were signs of myocardial tissue injury alongside with 60% of patients 
having signs of continuing myocardial inflammation (Outcomes of Cardiovascular Magnetic 
Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). 
JAMA Cardiol. doi:10.1001/jamacardio.2020.3557).    
International multipurpose study conducted in 7 hospitals of Milano and New-York 
demonstrated that 62.6%  patients hospitalized with COVID – 19 had increased levels of cardiac 
troponins and 47,5% had structural heart abnormalities secondary to the infectious disease 
visualized on echocardiography (Characterization он Myocardial Injury via Patients With COVID-
19. J Ан Coll Cardiol 2020;76:2043–55). 
According to these data patients after recovery from COVID-19 may have signs of injury 
not only of lung tissues but also the heart. This makes the correct and early diagnosis of such 
conditions, choice of optimal therapeutic strategy and rehabilitation procedures very important 
nowadays (Description and Proposed Management of the Acute COVID-19 Cardiovascular 
Syndrome. Circulation. 2020;141:1903–1914; Medical rehabilitation during novel coronavirus 
infectious disease - 19 (COVID-19). Physical and rehabilitation medicine, medical rehabilitation. 
2020;2(2):140–189. 
DOI: 
https://doi.org/10.36425/rehab34231; 
Temporary 
methodical 
recommendations «Prophylaxis, diagnosis, and therapy of the novel coronavirus infection 
(COVID-19)», 9th edition, 10/26/2020). 
The main goal of this observational non-interventional study is the evaluation of 
prevalence of myocardial injury (heart injury) of the participants recovered from the novel 
coronavirus infectious disease (COVID-19). Participants with signs of myocarditis (pericarditis) 
and/or myocardial fibrosis, and with a threat of heart failure development and other outcomes 
are selected into this study. In this cohort the percentage of participants having myocardial 
injury based on the level of high-sensitivity troponin, echocardiography (decreased Left 
Ventricle Ejection Fraction, abnormalities of wall motion, Right Ventricle dysfunction, increased 

 
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size of heart chambers above referential values, presence of pericardial effusion), cardiac MRI 
with contrast enhancement (presence of edema on T2-weighted images, presence of early and 
late gadolinium enhancement phenomenon, local motion abnormalities, increased size of heart 
chambers above referential values, presence of pericardial effusion). At 6 months of the 
dynamic follow-up, MRI with contrast enhancement will be repeated in the participants with 
established myocardial injury at inclusion to assess the percentage of the participants having 
ongoing myocardial injury (Comparative investigation of informative yield of non-invasive 
diagnostics methods of inflammatory diseases of myocardium. Russian cardiology journal 2018, 
2 (154): 53–59; Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation. 
Expert Recommendations. Am Coll Cardiol 2018; 72: 3158–76.). 
The secondary goal of the study is evaluation of quality of life of the patients recovered 
from the novel coronavirus infectious disease (COVID-19) by the means of EQ-5D and/or DASI 
questionnaire using the descriptive system of 5 components of quality of life related to the 
wellbeing, and visual analogue scale (Life quality of the Russian population by the data from 
ESSE-RF study. Cardiovascular Therapy and Prevention, 2016; 15(5): 84–90; Health-related 
quality of life population indicators using EQ–5D questionnaire. Health Care of the Russian 
Federation, Russian journal. 2018; 62(6): 295-303.). 
All the received information during the study will be stored in a formalized form with the 
use of relational database developed based on Microsoft® Access. To be able to gain valid 
results of the study, quantitative variables will be presented as the mean arithmetical number 
with standard deviation and the median with the upper and lower quartiles. For nominal 
variables the absolute value of the sign and its proportion will be shown. Unrelated features 
will be compared using the Mann – Whitney test, and related ones using the Wilcoxon test. 
Comparison of quantitative variables will be conducted using Pearson's chi-squared test. 
Qualitative related variables will be analyzed using McNemar's test.  To analyze the relationship 
between quantitative characteristics, regardless of the type of their distribution, as well as 
between ordinal variables, the Spearman rank correlation coefficients will be calculated. At the 
comparison of groups, the null hypothesis will be rejected if significance level is less than 0.05. 
In case of multiple comparisons, Bonferroni correction will be considered. 
The study will be conducted under the circumstances of common clinical practice and 
with the use of diagnostic methods and treatment approaches according to the current clinical 
guidelines of professional societies and clinical recommendations (Schultz J.C. et al. Diagnosis 
and Treatment of Viral Myocarditis // Mayo Clin. 2736 Proc. 2009. Vol. 84, № 11. P. 1001–
1009.; International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. 
Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009; 
53: 1475–1487.; Current state of knowledge on aetiology, diagnosis, management, and therapy 
of myocarditis. European Heart Journal July 3, 2013.; 2016 ESC Guidelines For The Diagnosis 
And Treatment Of Acute And Chronic Heart Failure. European Heart Journal (2016), 37: 2129-
2200; 16. Guidelines for the management of myocarditis. Eurasian cardiology journal 2015; 3:5-
17; Clinical recommendations on myocarditis of the Healthcare Ministry of the Russian 
federation, 
http://www.consultant.ru/document/cons_doc_LAW_326148/8efd5f17af55cb35a770f7393759
0c642437b7eb/). 
 
Main inclusion criteria into the study are:  
i. 
Adult patients of age above 18 years with diagnosed SARS-CoV-2 infection based on the PCR 
(polymerase chain reaction) and/or quantitative tests of IgM and IgG antibodies in serum; 
ii. 
Pneumonia development confirmed by chest computed tomography;  

 
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iii. 
Negative PCR test for SARS-CoV-2 at the time of inclusion into the study; 
iv. 
Stable patient state allowing outpatient follow-up; 
v. 
Signed informed consent. 
Main exclusion criteria are: 
i. 
Absence of convincing data confirming SARS-CoV-2 infection of a participant at the time of 
inclusion; 
ii. 
Absence of medical records regarding previous treatment of COVID-19; 
iii. 
Low compliance and unwillingness to undergo defined examinations; 
iv. 
Absence of informed consent. 
In this observational study the general examination of all patients who meet the 
inclusion criteria will be performed. Following dynamic observation and follow-up will be 
conducted only for those patients in whom presence of myocardial injury is established 
according to the echocardiography and/or cardiac MRI with contrast enhancement. Follow-up 
visits are scheduled at 3, 6, 9, and 12 months from the time of inclusion with an acceptable 
variation of a visit date up to 4 weeks. 
 During the general medical check-up and following follow-up visits the participants’ 
complaints, vital signs, physical examination, quality of life (EQ-5D and DASI questionnaire) are 
being assessed. 
Common laboratory tests, cardio-specific enzymes, ECG, echocardiography, 24-hour 
Holter ECG may also be performed in case of complaints of cardiac rhythm abnormalities. All 
patients will undergo the cardiac MRI with contrast enhancement at the inclusion to the study. 
Patients with established myocardial injury will undergo the second cardiac MRI with contrast 
enhancement 6 months later. Based on the results, the multi-spiral CT of the thoracic internal 
organs, pulmonologist consultation, and/or other examinations may be performed. 
In the process of observation, development of these clinical events in the participants will 
be recorded based on the comprehensive medical records and other sources of information: 
i. 
Myocardial infarction – any type of impairment of coronary blood flow with a typical 
clinical presentation, ECG changes, increase of specific cardiac enzymes;  
ii. 
Atypical angina followed by hospitalization; 
iii. 
Acute brain perfusion impairment – any type of developed acute impairment of brain 
blood flow; 
iv. 
Pulmonary artery thromboembolism; 
v. 
Decompensation of a known heart failure; 
vi. 
Atrial fibrillation or quivering of atria – confirmation by ECG and/or 24-hour ECG 
monitoring of paroxysms longer than 30 seconds in duration; 
vii. 
Bleeding of any localization followed by seeking of medical care.  
Should a lethal outcome take place, the whole medical information will be requested 
including medical death certificates. Lethal outcomes will be divided into these categories: 
i. 
Sudden death – unexpected death of a stable participant within a few hours since first 
signs of a distress; 
ii. 
Cardiovascular death – the death associated with the development of previously 
diagnosed cardiovascular disease in a participant (acute myocardial infarction, stroke, 
massive pulmonary thromboembolism etc.); 
iii. 
Non-cardiovascular death – the death which is not linked to any of the categories 
mentioned above and is associated with other pathological processes (cancer, 
bleeding, trauma etc.). 
Summary of the study is shown below.  

 
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Summary of the study 
Data collection 
Inclusion into 
the study 1 
Follow-up visit 
at 3 months 
(±4weeks) 2 
Follow-up visit 
at 6 months 
(±4weeks) 
Follow-up visit 
at 9 months 
(±4weeks) 
Follow-up visit 
at 12 months 
(±4weeks) 
Past medical history, including evaluation of the 
diseases preceding the COVID-19 
+ 
 
 
 
 
Features of the COVID-19 course and treatment 
+ 
 
 
 
 
Complaints, physical examination 
+ 
+ 
+ 
+ 
+ 
Laboratory tests 
+ 
+ 3 
+ 
 
+ 
ECG 
+ 
 
+ 
 
+ 
Echocardiography 
+ 
 
 
 
+ 
24-hour ECG monitoring 4 
+ 
 
+ 
 
+ 
Multi-spiral CT of the thoracic internal organs5 
+ 
 
+ 
 
 
Cardiac MRI with contrast enhancement 
+ 
 
+ 
 
 
Evaluation of physical state and functional class, 
physical activity, level of shortness of breath 
+ 
+ 
+ 
+ 
+ 
Evaluation of quality of life with EQ-5D and/or DASI 
questionnaire 
+ 
+ 
+ 
 
+ 
Treatment and treatment correction 
+ 
+ 
+ 
+ 
+ 
Clinical outcomes evaluation 
+ 
+ 
+ 
+ 
+ 
 
1 Performed in all patients included into the study.  
2 Following observation and examinations are performed only in patients with established myocardial (heart) injury at the inclusion. 
3 Repeated laboratory tests are performed only in patients with revealed abnormalities at the inclusion into the study. 
4 Only in patients with established heart rhythm abnormalities at the inclusion. 
5 Based on the pulmonologist’s opinion for evaluation of residual changes. 

 
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References 
1. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 
2020;22:911–915. 
2. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, 
China: a retrospective cohort study. Lancet 2020; 395:1054–62. 
3. Cardiovascular Imaging in Evaluation of COVID-19 Complications. J Am Coll Cardiol 
2020;76:1345–57. 
4. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. 
JAMA Cardiol. doi:10.1001/jamacardio.2020.3551. 
5. Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic 
Resonance Imaging. J Am Coll Cardiol Img 2020. https://doi.org/10.1016/j.jcmg.2020.05.004. 
6. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered 
From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol.doi:10.1001/jamacardio.2020.3557. 
7. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. 
Circulation. 2020;141:1903–1914. DOI:10.1161/CIRCULATIONAHA.120.047349. 
8. Medical rehabilitation during the novel coronavirus 19 disease (COVID-19). Physical and 
rehabilitation medicine, medical rehabilitation. 2020;2(2):140–189. DOI: 
https://doi.org/10.36425/rehab34231. 
9. Temporary methodical recommendation «Prophylaxis, diagnosis, and treatment of the novel 
coronavirus 19 (COVID-19)», 9th Edition released on 10/26/2020 
10. Schultz J.C. et al. Diagnosis and Treatment of Viral Myocarditis // Mayo Clin. 2736 Proc. 2009. 
Vol. 84, № 11. P. 1001–1009. 
11. International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. 
Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 
2009;53:1475–1487. 
12. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation. Expert 
Recommendations. Am Coll Cardiol 2018;72:3158–76. 
13. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis. 
European Heart Journal July 3, 2013. doi:10.1093/eurheartj/eht210. 
14. Comparative investigation of informative yield of non-invasive diagnostics methods of 
inflammatory diseases of myocardium. Russian cardiology journal 2018, (154): 53–59. 
http://dx.doi.org/10.15829/1560-4071-2018-2-53-59. 
15. 2016 ESC Guidelines For The Diagnosis And Treatment Of Acute And Chronic Heart Failure. 
European Heart Journal (2016), 37: 2129-2200, doi:10.1093/eurheartj/ehw128. 
16. Guidelines for the management of myocarditis. Eurasian cardiology journal 2015;3:5-17. 
17. Clinical recommendations on myocarditis of the Healthcare Ministry of the Russian 
federation: 
http://www.consultant.ru/document/cons_doc_LAW_326148/8efd5f17af55cb35a770f73937
590c642437b7eb/). 
18. Characterization of Myocardial Injury in Patients With COVID-19. J Am Coll Cardiol 
2020;76:2043–55. 
19. Life quality of the Russian population by the data from ESSE-RF study. Cardiovascular Therapy 
and Prevention, 2016; 15(5): 84–90 http://dx.doi.org/10.15829/1728-8800-2016-5-84-90. 
20. Health-related 
quality 
of 
life 
population 
indicators 
using 
EQ–5D 
questionnaire. 
Zdravookhranenie Rossiiskoi Federatsii (Health Care of the Russian Federation, Russian 
journal). 2018; 62(6): 295-303. (In Russ.) DOI: http://dx.doi.org/10.18821/0044-197Х-2018-62-
6-295-303.