key: cord-0739790-a5dudcwk
authors: Thakker, Ravi A.; Elbadawi, Ayman; Chatila, Khaled F.; Goel, Sachin S.; Reynoso, David; Berbarie, Rafic F.; Gilani, Syed; Rangasetty, Umamahesh; Khalife, Wissam
title: Comparison of Coronary Artery Involvement and Mortality in STEMI Patients With and Without SARS-CoV-2 During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis
date: 2021-10-28
journal: Curr Probl Cardiol
DOI: 10.1016/j.cpcardiol.2021.101032
sha: 4729503f0637bdf41257e7916d7e3426d77e107d
doc_id: 739790
cord_uid: a5dudcwk

INTRODUCTION: : Cardiovascular injury with SARS-CoV-2 infection is well known. Several studies have outlined baseline characteristics in patients presenting with STEMI and SARS-CoV-2. Paucity in data exists in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. METHODS: : A systematic search and meta-analysis of studies meeting the inclusion and exclusion criteria obtained from MEDLINE, Scopus, and Cochrane databases was performed utilizing PRISMA criteria. The main outcome was likelihood of coronary artery involvement among patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2. The primary adverse outcome measured was in-hospital mortality. RESULTS: : The final analysis included 5 observational studies with a total of 2, 266 patients. There was no statistical significance in LM (OR 1.40; 95% CI: 0.68, 2.90), LAD (OR 1.09; 95% CI 0.83, 1.43), LCX (OR 1.17; 95% CI: 0.75, 1.85), or RCA (OR 0.59; 95% Confidence Interval 0.30, 1.17) disease among the two groups. LAD disease was the most prevalent coronary involvement among patients with STEMI and SARS-CoV-2 (49.6%). Higher in-hospital mortality was observed in the STEMI and SARS-CoV-2 group (OR 5.24; 95% Confidence Interval 3.63, 7.56). DISCUSSION: : Our analysis demonstrated no statistical significance in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. The higher mortality among patients with SARS-CoV-2 and STEMI has been noted in prior studies with concerns being late presentation due to fear of infection, delayed care time, and poor resource allocation. Focus should be placed on identifying and managing comorbidities to reduce mortality.

The first reported cases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was in December 2019 in Wuhan, China 1 . Since then, as of August 26 th , 2021 there are over 213 million confirmed cases worldwide, increasing our knowledge of the coronavirus disease 2019 (COVID-19) pandemic 2 . The interplay between prior cardiovascular disease and severity of SARS-CoV-2 infection, as well as myocardial injury from the virus has been described 3 . Most notably, the hypercoagulable nature of the virus has been of growing interest with particular focus on the prothrombotic effects on vasculature 4 . Aside from the biological interplay of the disease, appreciation in the decline of hospital admissions for acute coronary syndrome during the COVID-19 pandemic has been well noted 5 . There have been several studies evaluating baseline characteristics and outcomes of patients presenting with ST segment elevation myocardial infarction (STEMI) during the pandemic in comparison to pre-pandemic times 6-9 . To better understand the presentation of STEMI patients who have SARS-CoV-2, our study sought to address the paucity in data that exists in outcomes of selective coronary involvement in patients presenting with STEMI and SARS-CoV-2 in comparison to those without SARS-CoV-2 during the COVID-19 pandemic.

We utilized the Medline, Scopus, and Cochrane databases to perform a systematic search adhering as closely as possible to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 10 ( Table 1) . Keywords utilized in the search were -STEMI‖ AND -COVID-19.‖ We included studies that evaluated patients presenting with acute STEMI and were positive for SARS-CoV-2. Studies should have reported clinical presentation, coronary involvement, and outcomes of patients with versus without SARS-CoV-2 during the COVID-19 pandemic. We included all studies irrespective of their design. We only included studies in the English language. Studies excluded were those which lacked details of coronary artery involvement, did not assess in-hospital mortality, or that compared populations that were pre-COVID-19 pandemic. The main outcome of our study was likelihood of coronary artery involvement among patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2. The primary adverse outcome measured was in-hospital mortality. Heterogeneity was presumed and bias was not assessed due to observational nature of the studies. This study was not registered, and review protocol was not created.

The statistical methods implemented for our analysis was the Cochran-Mantel-Haenszel test with the random effect analysis model. Odds ratio (OR) was used as the effect measure. To perform statistical analysis, we utilized the RevMan 5.0 software (Cochrane Collaboration, Oxford, United Kingdom).

Our search initially resulted in a total of 734 results. After implementation of our analysis criteria, 5 studies were included 11-15 (Figure 1 ). All studies were observational in nature. In total, there were 2,266 patients with 266 patients with STEMI and SARS-CoV-2 and 2,000 patients with STEMI but without SARS-CoV-2. Baseline characteristics of studies included can be found in Table 1 (Table 2) There was a total of 57 deaths (22.1%) in STEMI patients with SARS-CoV02 and 110 (5.8%) deaths in patients without SARS-CoV-2. There was a statistical significance in in-hospital mortality in patients with STEMI with SARS-CoV-2 versus without (OR 5.24; 95% Confidence Interval 3.63, 7.56) (Figure 2) [11] [12] [13] [14] [15] .

In this systematic review and meta-analysis of 5 observational studies evaluating 2,266 patients we aimed to compare coronary involvement and in-hospital mortality in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. Our findings were: 1) There was no statistical significance between LM, LAD, LCX, or RCA involvement in patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2; 2) There was a numerical trend towards LAD disease involvement in patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2 (49.6% versus 44.9%); 3) Higher in-hospital mortality of statistical significance was observed in patients with STEMI and SARS-CoV-2 vs without SARS-CoV-2 (22.1% versus 5.8%, OR 5.24; 95% Confidence Interval 3.63, 7.56).

The mechanism(s) behind coronary vasculature involvement in patients with SARS-CoV-2 is not fully understood, but multiple ongoing theories exist. One potential mechanism for Type 1 myocardial injury in SARS-CoV-2 infection has been attributed to pathogen-associated molecular patterns of the virus causing activation of immune receptors on pre-existing atherosclerotic plaques increasing the likelihood of plaque dislodgement. Another proposed mechanism related to pathogen associated molecular patterns is the activation of cytokines resulting in dysfunction with resultant vasoconstriction and thrombosis of coronary artery endothelium 16 . Intravascular coagulopathy associated with the so called -seeding‖ of microthrombi has been postulated secondary to initial pulmonary microvascular injury with subsequent systemic spread of a proinflammatory state with continued microvascular injury and thrombosis 4 .

A major potential cause of higher in-hospital mortality among patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic is the concern for late presentation of these critically ill patients and safety measures. Tam This analysis has several limitations. Given the observational nature of the studies heterogeneity in data exists such as sample size, population location, operator experience, hospital accommodations, and hospital resources. In addition, given the observational nature, although statistical significance in in-hospital morality was appreciated, causation is difficult to imply.

The findings of our systematic review and meta-analysis were notable for higher inhospital mortality among patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic but without statistical significance in selective coronary involvement among the two groups.

Modifiable risk factors such as those seen in our patient population [11] [12] [13] [14] [15] which included but are not limited to prior coronary artery disease (CAD), diabetes mellitus, hypertension, hyperlipidemia, and smoking should be addressed to prevent possible accelerated CAD and eventual STEMI. There was a numerical trend in LAD involvement, which is a finding that warrants further investigation and caution among patients presenting with STEMI and SARS-CoV-2.

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: 

Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect. 10b List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. Effect measures 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results.

Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)). 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.

Not Applicable 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. Page 4 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software Page 4 Section and Topic

Location where item is reported package(s) used.

13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression).

Not Applicable 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.

Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).

Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.

16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. Page 4 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.

Study characteristics 17 Cite each included study and present its characteristics. Page 4 Risk of bias in studies 18 Present assessments of risk of bias for each included study. Page 4 Results of individual studies

19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots.

Results of syntheses 20a For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies. Page 4 20b Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g. confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. Page 6 20c Present results of all investigations of possible causes of heterogeneity among study results. Page 4 20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.

Reporting biases 21 Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed.

Certainty of evidence 22 Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed.

23a Provide a general interpretation of the results in the context of other evidence. Page 6 23b Discuss any limitations of the evidence included in the review. Page 7 23c Discuss any limitations of the review processes used. Page 7 23d Discuss implications of the results for practice, policy, and future research. Page 7-8

Registration and protocol 24a Provide registration information for the review, including register name and registration number, or state that the review was not registered. Page 4 24b Indicate where the review protocol can be accessed, or state that a protocol was not prepared. Page 4 

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