key: cord-0941802-p1brjoti
authors: Garcia, Santiago; Dehghani, Payam; Stanberry, Larissa; Grines, Cindy; Patel, Rajan A.G.; Nayak, Keshav R.; Singh, Avneet; Htun, Wah Wah; Kabour, Ameer; Ghasemzadeh, Nima; Sanina, Cristina; Aragon, Joseph; Alraies, Chandi; Benziger, Catherine; Okeson, Brynn; Garberich, Ross; Welt, Frederick G.; Davidson, Laura; Hafiz, Abdul Moiz; Acharya, Deepak; Stone, Jay; Mehra, Aditya; Amlani, Shy; Mahmud, Ehtisham; Giri, Jay; Yildiz, Mehmet; Henry, Timothy D.
title: Trends in Clinical Characteristics, Management Strategies and Outcomes of STEMI Patients with COVID-19
date: 2022-04-04
journal: J Am Coll Cardiol
DOI: 10.1016/j.jacc.2022.03.345
sha: bb602c6d9d73afb754cedcb66462bca539d11d37
doc_id: 941802
cord_uid: p1brjoti

Background We previously reported high in-hospital mortality for STEMI patients with COVID-19 treated in the early phase of the pandemic. Objectives To describe trends of COVID-19 patients with STEMI during the course of the pandemic. Methods The N orth A merican C OVID-19 STE MI (NACMI) registry is a prospective, investigator initiated, multi-center, observational registry of hospitalized STEMI patients with confirmed or suspected COVID-19 infection in North America. We compared trends in clinical characteristics, management and outcomes of patients treated in the first year of the pandemic (1/2020 to 12/2020) versus those treated in the second year (1/2021 to 12/2021). Results A total of 586 COVID positive (+) patients with STEMI were included in the present analysis; 227 treated in Y2020 and 359 treated in Y2021. Patients’ characteristics changed over time. Relative to Y2020, the proportion of Caucasian patients was higher (58% vs. 39%, p<0.001), patients presented more frequently with typical ischemic symptoms (59% vs 51%, p=0.04), were less likely to have shock pre-PCI (13% vs 18%, p=0.07) or pulmonary manifestations (33% vs. 47%, p=0.001) in Y2021. In-hospital mortality decreased from 33% (Y2020) to 23% (Y2021) (p=0.008). In Y2021, none of the 22 vaccinated patients expired in hospital, whereas in-hospital death was recorded in 37 (22%) of unvaccinated patients (p=0.009). Conclusions Significant changes have occurred in the clinical characteristics and outcomes of STEMI patients with COVID-19 infection during the course of the pandemic.

The coronavirus disease-19 infection significantly increases the risk for both arterial and venous thromboembolic complications (1) . The risk of myocardial infarction (MI) doubles within a week of receiving a COVID-19 diagnosis and is associated with higher odds of mortality (2, 3) . Patients presenting with ST-segment elevation myocardial infarction (STEMI) and COVID-19 constitute a high-risk subset with distinct clinical features including preponderance of minority ethnicity, in-hospital presentation, cardiogenic shock and very high in-hospital mortality (4) (5) (6) (7) .

Despite increased number of COVID-19 cases worldwide, significant progress has been made in both disease prevention and management during the course of the pandemic, which has contributed to a marked reduction in mortality in selected countries (8) (9) (10) . We previously reported very high (33%) in-hospital mortality for patients with STEMI and COVID-19 treated in North America during the early phase of the pandemic (4).

The aim of this investigation is to examine trends in clinical characteristics, treatments and outcomes of STEMI patients with COVID-19 infection using data from the North American COVID-19 Myocardial Infarction Registry (NACMI).

NACMI is a prospective, investigator-initiated, multi-center, observational registry of hospitalized STEMI patients with confirmed or suspected COVID-19 infection in North America. A detailed description of the study design has been previously published (4, 11) . A total of 64 sites were approved by local ethics committee (12 Canadian and 52 US sites).

J o u r n a l P r e -p r o o f NACMI included 3 groups of STEMI patients (COVID positive (+) group, contemporary COVID negative (-) group, and a historical control group). The present analysis on trends focused on the COVID positive and contemporary COVID negative group. The COVID positive group was comprised of adult patients (≥18 years) with 1) ST-segment elevation in at least 2 contiguous leads (or new-onset left bundle branch block), 2) a clinical correlate of myocardial ischemia (e.g., chest pain, dyspnea, cardiac arrest, shock, mechanical ventilation) and 3) confirmed COVID positive by any commercially available test during, or 4 weeks before, the index STEMI hospitalization.

The COVID negative group was comprised of adult patients with STEMI who were suspected positive on presentation but subsequently tested negative for COVID-19 infection (person under investigation or PUI). The definition of PUI was left to the discretion of local hospitals but in general included a combination of possible COVID signs and symptoms (fever or respiratory symptoms such as cough, shortness of breath, sore throat), or exposure to a confirmed case or cluster of suspected COVID-19 cases. With advancements in rapid COVID testing and streamlined STEMI protocols, we anticipated the designation of PUI would be less relevant in Y2021 but presented this information to serve as a reference group to compare trends. NACMI was designed in early 2020 prior to the commercialization of vaccines against COVID-19 (12) (13) . Therefore, vaccine status was not routinely captured in the registry.

However, once vaccines became commercially available in North America in 2021 the original protocol was amended to include immunization status including timing and type. The protocol amendment was approved by 20 enrolling sites at the time of this publication. The primary end-point for this analysis was in-hospital mortality. A composite of inhospital death, stroke, or reinfarction was a secondary end-point. Non-fatal events were defined using National Cardiovascular Data Registry (NCDR Cath PCI Registry v4.4) definitions.

We used standardized data collection forms, modeled after the ACC National Cardiovascular Data Registry definitions, and a secure web-based application (REDCap, Research Electronic Data Capture) for data capture. The data coordinating center at the Minneapolis Heart Institute Foundation (MHIF) had full access to the dataset and performed the statistical analysis. The protocol was approved by each local Institutional Review Board (IRB).

Informed consent was waived.

Discrete variables are summarized by counts (%) and continuous variables are summarized by means ± standard deviations if distributed symmetrically, or as medians (25 th percentile, 75 th percentile) if skewed.

COVID positive patients were divided into two groups according to the year of the STEMI presentation during the pandemic, i.e. Y2020 group from 3/1/2020 -12/31/2020; and Y2021 group from 1/1/2021 -12/31/2021. These periods coincided with the commercial introduction of vaccines against COVID-19 in North America. Demographic, clinical, and outcome variables were compared between the groups using Pearson's chi-squared or Fisher's exact test for categorical data and Student's t-test or Wilcoxon rank-sum test for continuous variables, as appropriate.

Given a relatively short hospital length of stay, in-hospital mortality is modeled as a binary variable and the relative risk of death for Y2021 vs Y2020 group is estimated from a J o u r n a l P r e -p r o o f multivariate robust Poisson regression with a canonical log-link and robust sandwich estimator of variance to allow for overdispersion in the data. Model covariates include age, BMI, gender, race, diabetes, abnormal chest X-ray findings, and shock pre-PCI. More specifically, age originally collected as a five-category variable is dichotomized as < 66 or ≥ 66 years; and BMI categories are defined overweight/obese or not per CDC definition. Furthermore, a proxy comorbidity index is defined to capture the pre-existing cardiovascular diseases/conditions as follows: a sum of indicators of hypertension and history of PCI, MI, CABG, stroke, or CHF for each patient is dichotomized to index those with three or more pre-existing conditions. The choice of the variables and categories in the model is informed by existing literature, exploratory data analysis, sample size, and the number of adverse events considerations (4, 14) .

Model parameters are estimated first from complete data, then using imputed data where Table 1 . Significant changes in patients' characteristics occurred over time. Relative to patients treated in 2020, patients treated in 2021 were more likely to be Caucasian (58% vs. 39%, p<0.001), present with chest pain (59% vs 51%, p=0.04) rather than dyspnea (42% vs 56%, p=0.002), and less likely to have shock pre-PCI (13% vs 18%, p=0.07) or infiltrates on chest Xray (33% vs. 47%, p=0.001).

The use of invasive angiography increased over time from 77% in 2020 to 86% in 2021 (p=0.004). Among patients undergoing invasive angiography revascularization strategies are listed in Table 2 . Percutaneous coronary intervention (both primary and facilitated/rescue PCI) was the predominant revascularization modality employed in > 70% of cases with no significant differences between Y2020 and Y2021. Thrombolytics and coronary artery bypass graft (CABG) surgery were infrequently used (< 5% and 2% respectively). Medical therapy alone was used in 19% of patients in Y2020 and 25% in Y2021 (p=0.7) (primarily for patients with no culprit vessel).

Among patients undergoing PPCI the median (IQR) door-to-balloon (D2B) time was 78 minutes (50-122) in Y2020 and 70 minutes (50-106) in Y2021 (p=0.4). The proportion of patients meeting the metric of D2B time < 90 minutes was 59% in Y2020 and 64% in Y2021 (p=0.5).

A marked reduction in mortality from 33% in Y2020 to 23% in Y2021 (p=0.008) was observed with a trend for reduction in the incidence of stroke (Y2020= 2.6% vs. Y2021= 0.8%, Length of stay decreased from 7 days (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) in Y2020 to 5 days (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) in Y2021 (p=0.01) and intensive care unit stay decreased from 4 days (1-11) in Y2020 to 2 days (1-6) in Y2021 (p<0.001). From multivariate analysis of complete data, the risk of in-hospital mortality for Y2021 patients was 25% lower (95% CI: -47-5, p=0.01) than for Y2020. The risk of mortality was 1.7 (95% CI:1.2, 2.4, p=0.002) times higher if infiltrates were observed and nearly three times higher (95% CI:1.9-3.9, p<0.001) if cardiogenic shock was present (Table 3, Figure   2 ). Similar estimates were derived from imputed data (supplementary appendix). Table 4 . Vaccinated patients were less likely to present with respiratory symptoms or infiltrates on chest X-ray. In Y2021, none of the 22 vaccinated patients expired in hospital, whereas in-hospital death was recorded in 37 (22%) of unvaccinated patients.

Trends in clinical characteristics and outcomes for patients who were suspected of having COVID-19 but subsequently tested negative (PUI) are presented in Table 5 . Unlike COVID J o u r n a l P r e -p r o o f positive patients, we observed no differences in the baseline characteristics or in-hospital outcomes for COVID negative patients (mortality Y2020 11% vs. Y2021 9.5%, p= 0.231).

We conducted an analysis of trends in clinical characteristics, management strategies and outcomes of STEMI patients with COVID-19 infection using the NACMI registry, which represents the largest prospective dataset worldwide. There are several important findings (Central Illustration). First, in-hospital mortality decreased 25% (10 absolute points) in Y2021 compared to Y2020. Second, possible mediators of this reduction in mortality have been identified and include a lower risk profile of patients presenting with more typical ischemic symptoms, less cardiogenic shock and pulmonary involvement. Third, a sub-group analysis of patients treated in Y2021 according to vaccination status revealed that vaccinated patients are significantly less likely to develop respiratory complications and none of them expired in the hospital whereas in-hospital death was recorded in 22% of unvaccinated patients in Y2021.

Finally, despite the logistical challenges imposed by the pandemic, PCI remains the dominant revascularization modality in North America with more than 70% of patients treated and two out three meeting the D2B time ≤ 90-minute metric. In fact, we observed increased utilization of invasive angiography for risk stratification and management in Y2021 compared to Y2020.

Taken together, our observations suggest that the clinical profile, management and outcomes of STEMI patients with COVID-19 infection is evolving towards that of STEMI patients prior to the pandemic although mortality remains high for unvaccinated patients.

infection have very high in-hospital mortality (3) (4) (5) (6) (7) . Independent predictors of mortality in STEMI patients with COVID-19 infection are different than those without COVID-19 (14) . Risk J o u r n a l P r e -p r o o f models have identified respiratory variables such as tachypnea, hypoxemia, use of mechanical ventilation, and infiltrates on chest X-ray as significant predictors of mortality in patients with COVID-19 infection (15) . In fact, respiratory variables accounted for ≥ 50% of the NACMI risk score (15) . The introduction of vaccines has significantly reduced hospitalizations and mortality due to COVID-19 infection (12, 13, (16) (17) (18) . Our sub-group analysis according to vaccination status of STEMI patients treated in Y2021 suggest that prevention of severe respiratory illness is a likely mediator and provides additional support to current CDC recommendations to vaccinate adults (19) . In addition to lung infiltrates, age ≥ 66 years and cardiogenic shock pre-PCI are also associated with in-hospital mortality.

During the first wave of the pandemic, we reported a preponderance of minority ethnicity in patients with STEMI and COVID-19 infection. Crowded living conditions, frontline employment, health disparities and higher prevalence of comorbidities may explain these findings (20) . The present analysis demonstrates that, as the pandemic evolved, Caucasians became the predominant ethnic group in NACMI which is consistent with pre-pandemic STEMI registries from North America (21) (22) (23) .

The NACMI registry was designed as a collaboration of 3 North American societies (SCAI, Canadian Association of Interventional Cardiologists, and the ACC Interventional Council) in response to an unprecedented reduction in cardiac catheterization laboratory activations and calls to deviate from the standard of care during the pandemic (24) (25) (26) . The NACMI registry is the largest, prospective dataset of STEMI patients with COVID-19 treated in 2021 and continues to demonstrate that PCI is feasible during the pandemic with the majority of patients being treated within guideline-recommended times despite expected delays caused by testing and other logistical challenges posed by the pandemic. Educational efforts, such as J o u r n a l P r e -p r o o f SCAI's Seconds Still Count Patient Awareness campaign, are helping reverse these trends (27, 28) .

NACMI is the largest, prospective, and multicentric STEMI COVID registry to date.

However, several limitations should be acknowledged. Common to observational registries NACMI lacked independent event adjudication, core lab analysis and lack of pre-hospital data regarding total ischemic and transfer times for patients presenting to a non-PCI hospital.

Angiographic and electrocardiographic core laboratory analysis are underway. Incomplete vaccination data as well as null number of deaths in vaccinated patients did not allow for estimating the association of vaccination with the risk of mortality while adjusting for underlying risk factors. The low proportion of vaccinated patients in a hospitalized cohort such as NACMI is consistent with the known protective effects against hospitalization, and other serious outcomes, of COVID-19 vaccines. Finally, our study did not capture information regarding COVID-19

variants. Omicron has shown signs of being less virulent than earlier variants but it triggered record number of infections and a surge in deaths (29) . Omicron was first reported in the United States on December 1 st 2021, which is the very end of our study period.

Significant changes have occurred in the clinical characteristics, management strategies and outcomes of STEMI patients with COVID-19 infection during the course of the pandemic.

Notably, mortality is 25 % lower for patients treated in Y2021 relative to Y2020 but remains high for unvaccinated patients. 

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DOI

 Table 5 . Trends in baseline characteristics and outcomes for COVID negative patients (PUI) Categorical data summarized using counts (%), continuous using median (25 th