Aims COVID-19 can cause severe illness and multiorgan dysfunction. Acute myocardial damage has been detected in a significant portion of patients with COVID-19; therefore, several studies have reported that electrocardiographic findings could be used to evaluate the severalty of COVID-19. However, performing standard ECG for each patient hospitalised with COVID-19 can increase the level of exposure to COVID-19 among medical staff. Therefore, this study aimed to investigate the prognostic value of continuous electrocardiographic monitor findings in patients with COVID-19.
Methods Among 1612 consecutive patients with COVID-19 who were admitted to our hospital between August 2021 and May 2022, we identified 96 (76±4 years) patients who underwent electrocardiographic monitor during hospitalisation. All electrocardiographic monitors were analysed by two independent cardiologists blinded to the clinical data of the patients. The endpoint was defined as the occurrence of all-cause mortality related to COVID-19. The event data were retrospectively gathered from the patients’ medical records. A multivariate Cox model was used to assess whether these electrocardiographic monitor findings and clinical data were associated with in-hospital mortality.
Results During a mean hospitalisation period of 22.8±3.2 days, in-hospital mortality occurred in 17 (18%) patients. Atrial fibrillation (HR: 3.95, 95% CI: 1.39 to 11.21) and lung disease complications (HR: 2.91, 95% CI: 1.06 to 7.98) were significant prognostic factors for death in multivariate analysis. Compared with the non-complicated lung disease and non-atrial fibrillation group, the risk of mortality was significantly higher in the lung disease complication and atrial fibrillation group in the multivariate Cox proportional model (HR: 8.37, 95% CI: 1.69 to 41.30, p=0.009).
Conclusions The simple method of ECG monitor could adequately detect atrial fibrillation. This study demonstrated that atrial fibrillation complicated with lung disease, could have potential prognostic value among patients with COVID-19.
- atrial fibrillation
Data availability statement
Data are available upon reasonable request.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
ECG could be used frequently for evaluating the severalty of COVID-19. However, it needs extra time to perform and increases the chances of infection. It was essential to stratify the severity of COVID-19 with an effective method during the pandemic.
WHAT THIS STUDY ADDS
This study has shown that patients with COVID-19 with atrial fibrillation detected ECG monitor and complicated with lung disease could have poor prognosis.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The results of this study could aid physicians in identifying patients with high-risk COVID-19. This study could contribute to the management of COVID-19, and we hope to prevent the loss of many lives that could have been saved.
In the December 2019, a novel infection emerged in Wuhan, China, which spread worldwide within several weeks. The infection was subsequently termed COVID-19 and declared a pandemic by the World Health Organization by March 2020. COVID-19 causes viral pneumonia and severe illness, resulting in organ dysfunction including acute respiratory distress syndrome (ARDS), acute cardiac injury, and renal injury.1 2 There is also an increased incidence of arrhythmias, especially in patients requiring intensive care.3
ECG is one of the leading tools used to assess the extent of cardiac involvement in patients with COVID-19. The left bundle branch block, ST-segment deviation and atrial fibrillation may be associated with an increased mortality risk.4 However, there are few reports on the relationship between ECG monitor findings and mortality in patients with COVID-19. As the number of patients with COVID-19 increased, many hospital workers (doctors, nurses and comedicals) treating such patients were also infected with COVID-19.5 This led to a reduction in the number of workers in hospitals, which was one of the reasons for hospitals and other healthcare facilities becoming overcrowded and overwhelmed.6 Therefore, it is important to consider simple and effective routine examinations for in-hospital patients to protect health workers from COVID-19 infection. Installing an ECG monitor is simple and easy, and does not take much time compared with the standard ECG. This study investigated the prognostic value of ECG monitor findings in patients with COVID-19.
Among the 1612 consecutive patients with COVID-19 who were hospitalised in Tokyo Metropolitan Ebara Hospital between August 2021 and May 2022, we identified 96 (76±4 years) patients who had ECG monitor during hospitalisation. Patients who required ECG monitor were selected by the primary physician. Patients with severe COVID-19, arrythmia, ischaemic heart disease and heart failure in the past were considered as candidates for ECG monitor. Demographic characteristics, including sex, age, known hypertension, dyslipidaemia, diabetes mellitus and lung disease, were retrieved from medical records. Laboratory parameters, including C reactive protein (CRP) and D-dimer levels, were analysed from blood samples taken at the first admission. The institutional review board approved this retrospective study and the requirement to obtain informed consent was waived (0331).
ECG monitor findings
A three-lead admission ECG monitor was attached to each patient before any treatment was started. All standard three-lead ECG monitors were recorded on digitised three-lead ECG monitor recordings (Nihon Kohden, Tokyo, Japan). All electrocardiographic monitors were analysed by two independent cardiologists blinded to the clinical data of the patients. The QTc interval, PR interval, QRS duration, ST-segment depressions, ST elevation, T-wave inversion and atrial fibrillation were evaluated according to the following criteria. PR interval: normal range 120–200 ms, first-degree atrioventricular block was defined as a PR interval >200 ms; QRS duration: a QRS interval >120 ms was accepted as prolongation; Corrected QT interval (QTc) and QT interval: QTc was calculated using Bazett’s formula, Qtc=QT/(√RR)7; QTc clinical limits of >450 ms for men and >460 ms for women were accepted as prolonged; ST-segment depressions were considered to be seen at least ≥0.05 mV after J point; ST elevation was defined as ST-segment elevation ≥0.1 mV at the J point; T-wave inversion was detected as ≥0.1 mV and an R/S ratio >1; atrial fibrillation was defined as an irregular rate without visible P waves.
Assessment of clinical outcome
The endpoint was defined as the occurrence of all-cause mortality related to COVID-19, including severe grade of SARS-CoV-2, multiorgan dysfunction, cardiac death (death caused by heart failure, acute myocardial infarction, lethal ventricular arrhythmias, or other definitive cardiac disorders). Event data were retrospectively gathered from the patients’ medical records.
Data are expressed as average±SD of continuous variables. Continuous variables from patients with and without events were compared using the Mann-Whitney U test, and categorical data were analysed using the χ2 test. Age, sex and factors with a significance level of p value <0.05 were included in a univariate Cox regression model. Thereafter, variables that were significant probable values were included in multivariate Cox regression models to determine whether the future occurrence of event was associated with the clinical parameters including ECG. A p value <0.05 was considered statistically significant. All statistical analyses were performed using STATA (V.17.0; StataCorp LLC, College Station, Texas, USA) for Windows.
The patient characteristics are presented in table 1. History of chronic kidney disease (48%), hypertension (39%) and heart failure (27%) were common (table 1). There were nine patients who had atrial fibrillation in the past. The average of COVID-19 severity was mild to moderate (O2 requirement). During hospitalisation, 22 (23%) did not require O2 supply, 56 (58%) needed O2 supply by mask, 9 (9%) required O2 supply by nasal high flow and 9 (9%) required O2 supply by ventilator (table 1).
Overall, 17 (18%) patients experienced death during 22.8±3.2 days of median hospitalisation. The cause of death was exacerbation of COVID-19 pneumonia in 17 patients. Table 1 shows that age, COVID-19 severity, lung disease complication ratio, CRP, atrial fibrillation ratio, premature ventricular contraction ratio, heart rate, tachycardia ratio, respiratory rate and National Early Waring Score were significantly higher in patients who died than in those who did not. In the univariate analysis, lung disease, atrial fibrillation and premature ventricular contraction were found to be significant risk factors for death (table 2). Lung disease and atrial fibrillation were determined to be the significant prognostic factors of death in each model in multivariate analysis after adjusting for age (table 3, models 1, 2). In the multivariate Cox proportional model, as compared with the group without either lung disease or atrial fibrillation, mortality risk was significantly the highest in the lung disease and atrial fibrillation group, followed by the group without lung disease but with atrial fibrillation, and the group with lung disease and no atrial fibrillation after adjusting for age (table 3, model 3).
In the present study of patients with COVID-19, our findings demonstrated that atrial fibrillation detected using an ECG monitor were associated with mortality. The combination of atrial fibrillation and lung disease had a predictive value for identifying future mortality in patients with COVID-19.
Prognostic value of complicated with lung disease in patients with COVID-19
In this study, lung disease complications were associated with mortality. In accordance with previous studies, chronic respiratory disease was a risk factors for worse severity during hospitalisation.8 Fang et al reported that chronic obstructive pulmonary disease was a predominant indicator of disease severity and prognosis of COVID-19. In that study, chronic obstructive pulmonary disease contributed most to intensive care unit (ICU) admissions and invasive ventilation for COVID-19.9 Wang et al reported that a meta-analysis of retrospective studies10–13 confirmed that chronic obstructive pulmonary disease is associated with a dramatically increased risk of aggravation in patients with COVID-19.14 Patients with COVID-19 and chronic obstructive pulmonary disease have a 5.9-fold higher risk of progression than patients without chronic obstructive pulmonary disease.14 Several underlying mechanisms for relationship between COVID-19 and chronic obstructive pulmonary disease could be considered. In the immune response, macrophages present SARS-CoV-2 antigens to T cells, which activate, differentiate and release chemokines and cytokines including interleukin (IL)-1, IL-6, IL-8, IL-21, tumour necrosis factor-β and monocyte chemotactic protein-1, causing the cytokine storm.15 16 Cytokine storm causes acute inflammatory lung injury and stimulates the production of profibrotic growth factors and profibrotic cytokine transcripts, leading to the collapse or closure of alveoli and loss of lung compliance.17 18 In the patients with chronic obstructive pulmonary disease, lung function could be more limited than in those without chronic obstructive pulmonary disease. Therefore, in this study, lung disease-related complications could be the risk factor and associated with mortality.
Prognostic value of atrial fibrillation in patients with COVID-19
In the current study, multivariate analyses showed that atrial fibrillation was significantly associated with mortality. Previous reports have shown that among patients with COVID-19, atrial fibrillation was detected in 19%–21% of all cases.19 20 The Task Force of Italian National Institute of Health showed that 24.5% of 355 non-surviving patients with COVID-19 presented with atrial fibrillation before SARS-CoV-2 infection.21 Some reports have shown that new-onset atrial fibrillation in patients with COVID-19 is related to worse outcome after SARS-CoV-2 infection.22 23 Several underlying mechanisms have been proposed. First, a reduction in ACE2 receptor availability promotes cardiac hypertrophy, vasoconstriction, tissue fibrosis and oxidative stress, potentially increasing the susceptibility to atrial fibrillation.24 Second, CD147 and sialic acid-spike protein interaction depends on upregulating the expression of cytokines including IL-18 which correlates with atrial fibrillation development,25 and biding to N-acetylneuraminic acid, which plays a key role in cardiac fibrosis and contributes to atrial fibrillation pathophysiology.26 Third, a cytokine storm might trigger a violent immune system response to ARDS and hypoxaemia, which indirectly damages myocardial cells.10 27 Additionally, some cytokines might induce atrial electrical and structural remodelling, leading to atrial fibrillation. There is a causal link between activation of the Nod-like receptor family pyrin domains containing three inflammasome in atrial cardiomyocyte and atrial fibrillation development.28 Forth, galactin-3 involved in extracellular matrix formation contributes to the progression of atrial fibrillation.29 Elevated levels of galectin-3 correlate with worse outcomes in patients with atrial fibrillation and COVID-19 severity.30 31 Fifth, COVID-19 causes the activation of the sympathetic nervous system that elevates the frequency of spontaneous diastolic Ca2+ release via ryanodine receptor with subsequent generation of delayed after depolarisations and action potentials, that cause atrial fibrillation.32 33 These theories do not contradict our results. Therefore, in this study, atrial fibrillation detected using monitor ECG could be an indicator of severity of COVID-19 and have a predictive value associated with mortality.
Comparison with National Early Warning Score to predict the occurrence of critical illness
The increasing number of COVID-19 cases has challenged healthcare systems worldwide. In this context of overwhelming demand for medical assessment and triage in emergency departments, the National Early Warning Score (NEWS) could be useful because of its accuracy in predicting the risk of ICU admission and death.34 However, in this study, NEWS was not a significant factor in the univariate Cox regression analysis for occurrence of death. The factors of chronic respiratory disease and atrial fibrillation could have a more powerful predictive value than the NEWS in patients with COVID-19.
This study has some limitations. The number of included patients was relatively small, which limited the statistical reliability of the study. The main reason for the small number of participants in the study was because the number of ECG monitors was quite few compared with the number of inpatients with COVID-19 during the pandemic, and many severe inpatients with COVID-19 were put on ECG monitor for a long time during hospitalisation. However, our results demonstrated that chronic respiratory disease and atrial fibrillation were significantly correlated with death. Future prospective studies with large populations are needed to confirm the prognostic value of chronic respiratory disease and atrial fibrillation detected using monitor ECG in patients with COVID-19.
This study demonstrated that atrial fibrillation detected using monitor ECG in addition to lung disease complication, could have potential prognostic value among patients with COVID-19.
Data availability statement
Data are available upon reasonable request.
Patient consent for publication
We are grateful to all the staff concerned with the medical treatment for COVID-19 patients in Tokyo Metropolitan Ebara Hospital.
Contributors All authors contributed to the study’s conception and design. Data collection and analysis were performed by HH, YH, TK, HS and MT. HH performed the statistical analyses and drafted the manuscript. YH and MT reviewed and edited the manuscript draft. HH was responsible for the overall content as the guarantor. All authors read and approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.