key: cord-352288-zr96k6p1
authors: Zou, Fengwei; Qian, Zhiyong; Wang, Yao; Zhao, Yang; Bai, Jianling
title: Cardiac Injury and COVID-19: A Systematic Review and Meta-Analysis
date: 2020-06-23
journal: CJC Open
DOI: 10.1016/j.cjco.2020.06.010
sha: 
doc_id: 352288
cord_uid: zr96k6p1

BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, a link between acute cardiac injury and COVID-19 infection has been observed. There is currently no consensus on the incidence of cardiac injury, its relationship to prognosis, or its possible cause. This article provides a comprehensive review and meta-analysis of the incidence, comorbidities, outcomes and possible mechanisms of acute cardiac injury in COVID-19 patients. METHODS: We searched PubMed and Embase for studies that evaluated cardiac injury in hospitalized COVID-19 patients. Demographic information, co-morbidities, and relevant laboratory values were extracted and a meta-analysis was performed. RESULTS: Sixteen studies from China, Italy and the US with 2224 patients were included in this meta-analysis. The incidence of cardiac injury was 24.4% (542/2224 patients) in hospitalized COVID-19 patients. The all-cause mortality in patients with cardiac injury was 72.6% (OR=17.32, 95% CI 9.21-32.57) compared to those without cardiac injury (14.5%). In subgroup analyses, factors associated with increased risk of developing cardiac injury were older age and history of hypertension (HTN), and chronic obstructive respiratory disease (COPD). CONCLUSION: Cardiac injury is common in hospitalized COVID-19 patients and is significantly associated with mortality. Patients who were older with HTN and COPD were prone to develop cardiac injury. Early screening, triage and cardiac monitoring are recommended for these patients.

China and subsequently a global pandemic involving 212 countries, areas or territories. 60 Approximately 3.5 million cases and 250,000 deaths were recorded worldwide as of May 2020 1 .

Increasing experience with this disease has led to the understanding that it is not just an illness of 62 the respiratory system, but that there are significant cardiovascular effects. Recent works by biomarkers such as troponin), but that those who developed cardiac injury had a significantly 66 higher mortality than those without. Moreover, a multivariable analysis of 416 patients found 67 that cardiac injury was independently associated with an increased risk of mortality in patients 68 with COVID-19 4 . Therefore, the purpose of this study was to present a systematic review and 69 meta-analysis of literature to investigate the incidence of cardiac injury, its correlations with co-70 morbidities and outcomes, and its possible mechanisms in the global COVID-19 population. 74 We performed a systematic literature search in PubMed and Embase. We used the following 75 search terms: ("coronavirus") AND ("cardiac injury" OR "myocardial injury" OR "myocarditis" 76 OR "troponin"). The search was limited to Chinese and English and all articles from Jan 1, 2020 77 to May 30, 2020 were reviewed. 

Original studies that reported cardiac injury as elevated troponin levels were included. Review 81 articles, meta-analysis and case reports were excluded. An aggregate data meta-analysis was 82 performed. The extracted data included the number of patients enrolled in each study, age, The primary outcome was defined as all-cause mortality. If mortality in patients with or without 90 cardiac injury was not directly reported, the mortality rate of patients with cardiac injury was 91 calculated as the ratio of deceased patients with cardiac injury to the overall number of patients 92 with reported cardiac injury. The secondary outcome was defined as any one of death, ICU 93 admission, respiratory failure in need of mechanical ventilation or shock 5 . odds ratio. P value of less than 0.05 was considered statistically significant. Statistical 102 heterogeneity was evaluated using the I 2 statistic. Publication bias was evaluated using funnel 103 plots. Sensitivity analyses were performed to identify potential heterogeneity by leaving out each 104 study. Table 1 .

Cardiac injury was defined as elevated serum troponin levels. Due to differences in the types of 115 troponin tested at each center and sensitivity of testing, specific troponin cut-off criteria for each 116 included study was also outlined in Table 1 . Table S1 compiles the incidence of cardiac injury in hospitalized COVID-19 patients. The primary outcome of all-cause mortality in hospitalized COVID-19 patients with cardiac 125 injury was 72.6% (307/423 patients) compared to a mortality rate of 14.5% (171/1181 patients) 126 in patients without cardiac injury (OR=17.32, 95% CI 9.21-32.57, I 2 =66%, Z=8.85, P<0.00001) 127 as shown in Figure 2A . 169 Since the outbreak, cardiac injury in COVID-19 patients who needed inpatient care has been 170 described. Cardiac injury in the form of myopericarditis were reported from China and Europe 7, 8 .

These case reports should ring a bell on the potential involvement of the cardiovascular system 172 in a wider range of COVID-19 patients worldwide. More than a dozen studies have reported 173 incidence of cardiac injury in hospitalized COVID-19 patients, ranging from 7% to 44% 2-4, [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] . 174 However, no consensus was reached on the overall incidence of cardiac injury in these patients. 175 Li et al 22 performed a meta-analysis and attempted to determine the incidence of cardiac injury. 176 However, only two studies (179 patients) were analyzed and the overall incidence of cardiac 177 injury was 8% (15/179). Although two other studies with more patients were included, only 178 elevated creatine kinase levels were reported, which was not specific for cardiac injury and could 179 not represent true incidence. In this analysis, 14 studies were integrated to look into how cardiac injury affected outcomes in 239 hospitalized COVID-19 patients. It was discovered that hospitalized COVID-19 patients with 240 cardiac injury had a significantly increased mortality rate compared to those without, with an OR 241 of 17.32. The mortality rate of hospitalized COVID-19 patients with cardiac injury was found to 242 be 72.6% . This mortality rate was significantly higher than any mortality rates reported so far. to note that these high rates of mortality were only associated with COVID-19 patients who were 258 hospitalized and could not be applied to those who did not require hospitalization. range. In order to analyze some of these continuous variables, conversion to median with 303 standard deviation was necessary, which might introduce bias in our results. Our meta-analysis revealed that cardiac injury was common in hospitalized COVID-19 patients 307 and its incidence was similar between the Chinese and the Western population. The overall 308 mortality of patients with cardiac injury was alarmingly high. Cardiac injury was significantly 309 associated with older age and co-morbidities including HTN and COPD. Early screening, triage 310 and support is warranted to help reduce the incidence of cardiac injury in hospitalized COVID-311 19 and its associated mortality. 

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