Cardiac biomarkers, cardiac injury, and comorbidities associated with severe illness and mortality in coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

Abstract Background Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in the intensive care unit. Biochemical markers of cardiac dysfunction are associated with high mortality in many respiratory conditions. The aim of this systematic review is to examine the link between elevated biomarkers of cardiac dysfunction in ARDS and mortality. Methods A systematic review of MEDLINE, EMBASE, Web of Science and CENTRAL databases was performed. We included studies of adult intensive care patients with ARDS that reported the risk of death in relation to a measured biomarker of cardiac dysfunction. The primary outcome of interest was mortality up to 60 days. A random-effects model was used for pooled estimates. Funnel-plot inspection was done to evaluate publication bias; Cochrane chi-square tests and I2 tests were used to assess heterogeneity. Results Twenty-two studies were included in the systematic review and 18 in the meta-analysis. Biomarkers of cardiac stretch included NT-ProBNP (nine studies) and BNP (six studies). Biomarkers of cardiac injury included Troponin-T (two studies), Troponin-I (one study) and High-Sensitivity-Troponin-I (three studies). Three studies assessed multiple cardiac biomarkers. High levels of NT-proBNP and BNP were associated with a higher risk of death up to 60 days (unadjusted OR 8.98; CI 4.15-19.43; p<0.00001). This association persisted after adjustment for age and illness severity. Biomarkers of cardiac injury were also associated with higher mortality, but this association was not statistically significant (unadjusted OR 2.21; CI 0.94-5.16; p= 0.07). Conclusion Biomarkers of cardiac stretch are associated with increased mortality in ARDS.

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The Predictive Value of Myoglobin for COVID-19-Related Adverse Outcomes: A Systematic Review and Meta-Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.757799 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chaoqun Ma ◽

Dingyuan Tu ◽

Jiawei Gu ◽

Qiang Xu ◽

Pan Hou ◽

...

Keyword(s):

Troponin I ◽

Meta Analysis ◽

Severe Disease ◽

Cardiac Injury ◽

Case Fatality ◽

Adverse Outcomes ◽

Cardiac Biomarkers ◽

Severe Illness ◽

Poor Outcomes ◽

Meta Analyses

Objective: Cardiac injury is detected in numerous patients with coronavirus disease 2019 (COVID-19) and has been demonstrated to be closely related to poor outcomes. However, an optimal cardiac biomarker for predicting COVID-19 prognosis has not been identified.Methods: The PubMed, Web of Science, and Embase databases were searched for published articles between December 1, 2019 and September 8, 2021. Eligible studies that examined the anomalies of different cardiac biomarkers in patients with COVID-19 were included. The prevalence and odds ratios (ORs) were extracted. Summary estimates and the corresponding 95% confidence intervals (95% CIs) were obtained through meta-analyses.Results: A total of 63 studies, with 64,319 patients with COVID-19, were enrolled in this meta-analysis. The prevalence of elevated cardiac troponin I (cTnI) and myoglobin (Mb) in the general population with COVID-19 was 22.9 (19–27%) and 13.5% (10.6–16.4%), respectively. However, the presence of elevated Mb was more common than elevated cTnI in patients with severe COVID-19 [37.7 (23.3–52.1%) vs.30.7% (24.7–37.1%)]. Moreover, compared with cTnI, the elevation of Mb also demonstrated tendency of higher correlation with case-severity rate (Mb, r = 13.9 vs. cTnI, r = 3.93) and case-fatality rate (Mb, r = 15.42 vs. cTnI, r = 3.04). Notably, elevated Mb level was also associated with higher odds of severe illness [Mb, OR = 13.75 (10.2–18.54) vs. cTnI, OR = 7.06 (3.94–12.65)] and mortality [Mb, OR = 13.49 (9.3–19.58) vs. cTnI, OR = 7.75 (4.4–13.66)] than cTnI.Conclusions: Patients with COVID-19 and elevated Mb levels are at significantly higher risk of severe disease and mortality. Elevation of Mb may serve as a marker for predicting COVID-19-related adverse outcomes.Prospero Registration Number:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020175133, CRD42020175133.

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Acute Cardiac Injury in COVID-19: A Systematic Review and Meta-analysis

Archives of Iranian Medicine ◽

10.34172/aim.2020.107 ◽

2020 ◽

Vol 23 (11) ◽

pp. 801-812

Author(s):

Mehrbod Vakhshoori ◽

Maryam Heidarpour ◽

Davood Shafie ◽

Marzieh Taheri ◽

Nima Rezaei ◽

...

Keyword(s):

Systematic Review ◽

Myocardial Injury ◽

Meta Analysis ◽

Clinical Status ◽

Cardiac Injury ◽

Cardiac Biomarkers ◽

Cardiac Complications ◽

The Mean ◽

Cardiac Manifestations

Background: Coronavirus disease 2019 (COVID-19) has been widespread since late December 2019, with several symptoms related to the upper and lower respiratory system. However, its cardiac manifestations are less frequently studied. We aimed to analyze the available COVID-19 data on acute cardiac injury, using troponin and brain natriuretic peptide (BNP) levels. Methods: We performed a systematic review on Medline/PubMed, Scopus, and Google Scholar databases until March 25, 2020. Relevant records reporting the incidence of acute cardiac injury as well as troponin and BNP levels were collected from published peer-reviewed articles with further analysis according to the clinical status of the patients (severe, non-severe, and death). Results: Eleven records of 1394 individuals were included. The mean age of patients with acute cardiac injury was 56.6 ± 33.4 years (males: 54.3%). The incidence of acute cardiac injury was 15% (95% CI: 11, 20%). Further analysis revealed that dead or severe patients had significantly higher percentages of myocardial injury, compared to non-severe ones (peer-reviewed: 44%, 95% CI: 16, 74% vs. 24%, 95% CI: 15, 34% vs. 5%, 95% CI: 1, 12%, respectively). Mean total troponin was 10.23 pg/mL (95% CI: 5.98, 14.47), while 13% (95% CI: 8%, 18%) of patients had elevated levels. Mean BNP was 216.74 pg/mL (95% CI: 3.27, 430.20). Conclusion: Acute cardiac injury in COVID-19 patients is more frequent than what was expected at the beginning of the outbreak. Meanwhile, further studies are needed to investigate the utility of cardiac biomarkers as diagnostic and prognostic tools for long-term cardiac complications of this infection.

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Red Blood Cell Distribution Width, Disease Severity, and Mortality in Hospitalized Patients with SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10020286 ◽

2021 ◽

Vol 10 (2) ◽

pp. 286

Author(s):

Angelo Zinellu ◽

Arduino A. Mangoni

Keyword(s):

Systematic Review ◽

Blood Cell ◽

Disease Severity ◽

Red Blood Cell ◽

Effect Size ◽

Meta Analysis ◽

Severe Illness ◽

Cell Distribution ◽

Distribution Width ◽

Red Blood Cell Distribution

The identification of biomarkers predicting disease severity and outcomes is the focus of intense research in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection). Ideally, such biomarkers should be easily derivable from routine tests. We conducted a systematic review and meta-analysis of the predictive role of the red blood cell distribution width (RDW), a routine hematological test, in patients with SARS-CoV-2 infection. We searched the electronic databases PubMed, Web of Science and Scopus, from January 2020 to November 2020, for studies reporting data on the RDW and coronavirus disease 2019 (COVID-19) severity, defined as severe illness or admission to the intensive care unit (ICU), and mortality. Eleven studies in 4901 COVID-19 patients were selected for the meta-analysis. Pooled results showed that the RDW values were significantly higher in patients with severe disease and non-survivors (standard mean difference, SMD = 0.56, 95% CI 0.31 to 0.81, p < 0.001). Heterogeneity between studies was extreme (I2 = 80.6%; p < 0.001). In sensitivity analysis, the effect size was not modified when each study was in turn removed (effect size range, between 0.47 and 0.63). The Begg’s (p = 0.53) and Egger’s tests (p = 0.52) showed no evidence of publication bias. No significant correlations were observed between SMD and age, gender, whole blood count, end point, study geographic area, or design. Our meta-analysis showed that higher RDW values are significantly associated with COVID-19 severity and mortality. This routine parameter might assist with early risk stratification in patients with SARS-CoV-2 infection.

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Cardiovascular Diseases and COVID-19 Mortality and Intensive Care Unit Admission: A Systematic Review and Meta-analysis

10.1101/2020.04.12.20062869 ◽

2020 ◽

Cited By ~ 3

Author(s):

Amir Shamshirian ◽

Keyvan Heydari ◽

Reza Alizadeh-Navaei ◽

Mahmood Moosazadeh ◽

Saeed Abrotan ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Cardiovascular Disease ◽

Intensive Care Unit ◽

Intensive Care ◽

Cardiovascular Diseases ◽

Meta Analysis ◽

Cardiac Injury ◽

Icu Admission ◽

The World

AbstractImportanceOn 11th March, the World Health Organization declared a pandemic of COVID-19. There are over 1 million cases around the world with this disease and it continues to raise. Studies on COVID-19 patients have reported high rate of cardiovascular disease (CVD) among them and patients with CVD had higher mortality rate.ObjectivesSince there were controversies between different studies about CVD burden in COVID-19 patients, we aimed to study cardiovascular disease burden among COVID-19 patients using a systematic review and meta-analysis.Data SourcesWe have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar.Study SelectionStudies reported cardiovascular disease among hospitalized adult COVID-19 patients with mortality or ICU admission (primary outcomes) were included into meta-analysis. In addition, all of studies which reported any cardiovascular implication were included for descriptive meta-analysis. Cohort studies, case-control, cross-sectional, case-cohort and case series studies included into the study. Finally, 16 studies met the inclusion criteria for primary outcome and 59 studies for descriptive outcome.Data Extraction and SynthesisTwo investigators have independently evaluated quality of publications and extracted data from included papers. In case of disagreement a supervisor solved the issue and made the final decision. Quality assessment of studies was done using Newcastle-Ottawa Scale tool. Heterogeneity was assessed using I-squared test and in case of high heterogeneity (>%50) random effect model was used.Main Outcomes and MeasuresMeta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs and Standardized Mean Difference (SMD) was calculated for Cardiac Troponin I. We have also performed a descriptive meta-analysis on different CVDs.ResultsSixteen papers including 3473 patients entered into meta-analysis for ICU admission and mortality outcome and fifty-nine papers including 9509 patients for descriptive outcomes. Results of meta-analysis indicated that acute cardiac injury, (OR: 15.94, 95% CI 2.31-110.14), hypertension (OR: 1.92, 95% CI 1.92-2.74), heart Failure (OR: 11.73, 95% CI 5.17-26.60), other cardiovascular disease (OR: 1.95, 95% CI 1.17-3.24) and overall CVDs (OR: 3.37, 95% CI 2.06-5.52) were significantly associated with mortality in COVID-19 patients. Arrhythmia (OR: 22.17, 95%CI 4.47-110.04), acute cardiac injury (OR: 19.83, 95%CI 7.85-50.13), coronary heart disease (OR: 4.19, 95%CI 1.27-13.80), cardiovascular disease (OR: 4.17, 95%CI 2.52-6.88) and hypertension (OR: 2.69, 95%CI 1.55-4.67) were also significantly associated with ICU admission in COVID-19 patients.ConclusionOur findings showed a high burden of CVDs among COVID-19 patients which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.Key PointsQuestionAre cardiovascular disease associated with mortality and Intensive Care Unit admission (ICU) of COVID-19 patients?FindingsIn this systematic review and meta-analysis, acute cardiac injury, hypertension, heart failure and overall cardiovascular diseases were significantly associated with mortality in COVID-19 patients. Arrhythmia, coronary heart disease, hypertension, acute cardiac injury and other cardiovascular disease were significantly associated with ICU admission of COVID-19 patients.MeaningCardiovascular diseases have significant role in mortality and disease severity of COVID-19 patients. COVID-19 patients need to be carefully monitored for cardiovascular diseases and managed properly in case of acute cardiac conditions.

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Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis

Heart ◽

10.1136/heartjnl-2020-317062 ◽

2020 ◽

Vol 106 (15) ◽

pp. 1142-1147 ◽

Cited By ~ 25

Author(s):

Xintao Li ◽

Bo Guan ◽

Tong Su ◽

Wei Liu ◽

Mengyao Chen ◽

...

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Hospital Mortality ◽

Mortality Risk ◽

Meta Analysis ◽

Cardiac Injury ◽

Sensitivity Analyses ◽

Future Research ◽

Cardiovascular Comorbidities ◽

The Impact

BackgroundCoronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk.MethodsPubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity.ResultsA total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I2=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I2=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I2=71%).ConclusionCOVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.

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Acute Cardiac Injury and COVID-19 – A Systematic Review and Meta-analysis

10.21203/rs.3.rs-37704/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Husam M Salah ◽

Angel Lopez Candales

Keyword(s):

Systematic Review ◽

Mortality Rate ◽

Meta Analysis ◽

Cardiac Injury ◽

Case Series ◽

Common Finding ◽

Full Spectrum ◽

Global Pandemic ◽

Current Prevalence ◽

Case Series Study

Abstract Introduction:The ongoing global pandemic, coronavirus disease 2019 (COVID-19), an illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ranged from an asymptomatic state to unprecedented number of deaths worldwide. In symptomatic patients, a viral pneumonia can unrelentingly progress to multi-system failure with preferential cardiac tropism. Although the full spectrum of COVID-19 cardiac manifestations is still not clear; acute cardiac injury (ACI) remains a common finding. The goal of our study, not only is to examine the current prevalence of ACI among COVID-19 infected patients but also, the reported mortality.Method:After thoroughly searching the literature for appropriate studies, a systematic review and meta-analysis were performed. Inclusion criteria were 1) Cohort study, case-control study, or case series study. 2) The study population included individuals with COVID-19 3) The presence or absence of cardiac injury was reported in the study 4) Mortality among patients with cardiac injury is reported or can be calculated.Results:Ten studies were included with a total of 1664 patients. The prevalence of ACI was 30.8%. The mortality rate among patients with concurrent COVID-19 and ACI was 53%.Conclusion:ACI can occur in one third of patients with COVID-19. Concurrent COVID-19 and ACI entails a high mortality rate. Serum troponin level can be a good prognostic tool in COVID-19.

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Case fatality rate in COVID-19: a systematic review and meta-analysis

10.1101/2020.04.01.20050476 ◽

2020 ◽

Cited By ~ 2

Author(s):

Chanaka Kahathuduwa ◽

Chathurika Dhanasekara ◽

Shao-Hua Chin

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Critical Illness ◽

Publication Bias ◽

Case Fatality Rate ◽

Meta Analysis ◽

Case Fatality ◽

Severe Illness ◽

Fatality Rate ◽

Meta Regression

AbstractBackgroundEstimating the prevalence of severe or critical illness and case fatality of COVID-19 outbreak in December, 2019 remains a challenge due to biases associated with surveillance, data synthesis and reporting. We aimed to address this limitation in a systematic review and meta-analysis and to examine the clinical, biochemical and radiological risk factors in a meta-regression.MethodsPRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords on March 07, 2020. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Numerators and denominators to compute the prevalence rates and risk factors were extracted. Random-effects meta-analyses were performed. Results were corrected for publication bias. Meta-regression analyses examined the moderator effects of potential risk factors.ResultsThe meta-analysis included 29 studies representing 2,090 individuals. Pooled rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. Adjusting for potential underreporting and publication bias, increased these estimates to 26%, 16% and 7.4% respectively. Increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity.ConclusionsRisk factors that emerged in our analyses predicting severity and case fatality should inform clinicians to define endophenotypes possessing a greater risk. Estimated case fatality rate of 7.4% after correcting for publication bias underscores the importance of strict adherence to preventive measures, case detection, surveillance and reporting.

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Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: a meta-analysis and systematic review

Critical Care ◽

10.1186/s13054-020-03183-z ◽

2020 ◽

Vol 24 (1) ◽

Cited By ~ 7

Author(s):

Xinye Li ◽

Xiandu Pan ◽

Yanda Li ◽

Na An ◽

Yanfen Xing ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Severe Disease ◽

Cardiac Injury ◽

Hospitalized Patients ◽

Icu Admission

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Brain–Heart Axis and Biomarkers of Cardiac Damage and Dysfunction after Stroke: A Systematic Review and Meta-Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms21072347 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2347

Author(s):

Chengyang Xu ◽

Ang Zheng ◽

Tianyi He ◽

Zhipeng Cao

Keyword(s):

Systematic Review ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Meta Analysis ◽

Cardiac Biomarkers ◽

Cochrane Library ◽

Cardiac Complications ◽

Brain Hemorrhage ◽

Cardiac Damage ◽

The Brain

Background: Cardiac complications after a stroke are the second leading cause of death worldwide, affecting the treatment and outcomes of stroke patients. Cardiac biomarkers such as cardiac troponin (cTn), brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been frequently reported in patients undergoing a stroke. The aim of the present study is to meta-analyze the relationship between changes in such cardiac biomarkers and stroke and to present a systematic review of the previous literature, so as to explore the brain–heart axis. Methods: We searched four online databases pertinent to the literature, including PubMed, Embase, the Cochrane Library, and the Web of Science. Then, we performed a meta-analysis to investigate changes in cTn, BNP, and NT-proBNP associated with different types of stroke. Results and Conclusions: A significant increase in cTnI concentration was found in patients exhibiting a brain hemorrhage. BNP increased in cases of brain infarction, while the NT-proBNP concentration was significantly elevated in patients suffering an acute ischemic stroke and brain hemorrhage, indicating cardiac damage and dysfunction after a stroke. Our analysis suggests that several potential mechanisms may be involved in the brain–heart axis. Finally, clinicians should pay careful attention to monitoring cardiac function in the treatment of cerebrovascular diseases in order to provide a timely and more accurate treatment.

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