Abstract
Background
In rural settings, women with ST-elevation myocardial infarction (STEMI) are less likely to receive timely reperfusion than men. We explore factors that may impact time to reperfusion by sex for patients with STEMI.
Methods
We conducted a cohort study of adults with STEMI activations from 2016 to 2020 using regional North Carolina STEMI registry data, which included eight rural emergency medical services (EMS) agencies and three percutaneous coronary intervention (PCI) centres. The primary outcome was EMS first medical contact to PCI in ≤90 min. By sex, we evaluated prehospital time intervals (dispatch, response, time-to-ECG, catheterisation laboratory activation, on-scene, transport and total EMS) and door-to-balloon time with clustered Wilcoxon rank-sum tests. We also evaluated agency and patient factors associated with timely reperfusion using generalised estimating equations.
Results
Of the 365 patients included, 30.1% (110/365) were female with a mean age of 62.5 ± 12.7. Fewer women received PCI within 90 min compared with men (43.6% vs 67.8%, p<0.001). Women also experienced significantly longer total EMS time (42.5 vs 40.0 min, p=0.049) and door-to-balloon time (48.5 vs 40.0 min, p=0.01). Other time intervals were similar. After adjustment, women without exertional symptoms, with diabetes or with hypercholesterolaemia had lower odds of timely reperfusion. Among men, lower odds of timely reperfusion were observed among those without pain, who had catheterisation lab activation between 17:00 and 07:00, who were older or who had farther transport.
Conclusion
In rural settings, women without exertional chest pain and those with comorbid conditions were less likely to have timely reperfusion. Women experienced significantly longer total EMS time and door-to-balloon time than men.
INTRODUCTION
Emergency medical service (EMS) is the initial point of medical contact for most of the 2 50 000 patients with ST-elevation myocardial infarction (STEMI) each year in the USA.1 Prompt reperfusion therapy for these patients is critical to reducing the likelihood of morbidity and mortality.2 The American College of Cardiology (ACC) and American Heart Association recommend a time goal of 90 min or less from first medical contact (FMC) to percutaneous coronary intervention (PCI).3 EMS care significantly affects the likelihood of timely reperfusion and strategies to leverage the EMS system to improve prehospital care for STEMI patients are of ongoing interest.4–6 Unfortunately, Americans living in rural areas are eight times less likely to receive timely PCI than their urban counterparts, which has been associated with higher odds of mortality in this population.5
7–10 Improving health equity for rural Americans is a goal of the Centers for Disease Control and Prevention, Department of Health and Human Services Healthy People 2020, the Center for Medicare and Medicaid Services and EMS Agenda 2050.11
12
Beyond the care difference observed among rural Americans with STEMI, women in this setting with STEMI are significantly less likely than men to receive timely reperfusion.4 Further, women with STEMI in general experience significantly longer time to reperfusion compared with men.13–15 A previous Australian investigation of prehospital time intervals among patients with STEMI found that, compared with men, women experienced longer time from the call for EMS to EMS patient contact, longer time from prehospital ECG to initiating patient transport and longer on-scene time.13 In-hospital delays also impact timely reperfusion for women, with women experiencing significantly longer hospital arrival to PCI (door-to-balloon) time.13–15 However, the factors associated with sex differences in timely care for rural Americans with STEMI are not clear.
To explore this gap, we investigate the association of reperfusion timeliness across sex subgroups among rural patients with STEMI cared for by EMS. Further, we explore differences in prehospital and in-hospital time-intervals by sex and incident, agency and patient-level factors that may impact timely reperfusion among men and women with STEMI in rural settings.
METHODS
Study design and setting
We conducted a retrospective cohort study of rural STEMI patients from 2016 to 2020 using previously published methods (trial protocol available in online supplemental file 1).4 Data were queried from a regional, rural STEMI registry that included three tertiary medical centres in the central region of North Carolina (NC) that each provide 24/7 access to interventional cardiology services. Eight nearby county-based EMS agencies were identified as being rural by the 2014 Census at the county level. The population of these counties in 2018 ranged from 22 691 to 1 43 176. The median STEMI transport distance ranged from 24.0 to 51.6 miles. County population, annual patient transports, number of paramedics, number of staffed ambulances, number of included STEMI cases and median STEMI transport distance for the eight rural EMS agencies data are described in online supplemental table 1. A map of NC indicating the included counties, tertiary medical centres and helicopter EMS bases is illustrated in figure 1. As this study was observational, patients were not involved in the research process. This study was approved by the Wake Forest University Institutional Review Board and granted a waiver of informed consent. This study was registered at ClinicalTrials.gov (NCT04381260).
Figure 1.
Map of North Carolina indicated included counties, tertiary medical centres and helicopter EMS bases. EMS, emergency medical services.
Study population and patient involvement
Adult patients who were transported by a rural EMS agency to one of the three PCI-capable hospitals included in the registry and received primary PCI for STEMI were included. Patients were excluded if they had a pre-hospital cardiac arrest or if they did not receive PCI. Patients that were initially evaluated by EMS in a clinic, urgent care, or non-PCI hospital were also excluded. Patients and members of the public were not involved in the design, management, conduct or dissemination of this study.
Measures and outcomes
Patient demographic, clinical and time data from the EMS electronic health record (EHR) were entered into a Research Electronic Data Capture database and linked to data from the ACC’s National Cardiovascular Data Registry (NCDR). Demographic variables were self-reported in the EHR, including age, sex, race and ethnicity at the time of the clinical encounter. Within this study, the sex of transgender patients would be recorded as the sex that they self-reported at the hospital and not necessarily their legal or birth sex. Clinical factors included medical history (diabetes, hypercholesterolaemia, hypertension, prior MI or revascularisation (PCI or coronary artery bypass grafting), cancer, tobacco use), presentation (pain characteristics, provoked symptom onset with activity) and initial prehospital vital signs (eg, systolic blood pressure, heart rate and oxygen saturation). Loaded mileage was defined as the distance from the incident scene to the destination hospital. Agency level factors included annual patient transports per capita, number of full-time employed paramedics per 100 citizens and number of staffed ambulances per 100 citizens.
The primary outcome was the ability to achieve the 90-minute EMS FMC-to-PCI time goal. FMC was defined as patient contact time (recorded by EMS personnel after arrival on scene) and PCI time was the first device activation time (recorded in the NCDR). Secondary outcome measures commonly used in similar studies were FMC-to-PCI time as a continuous variable and previously defined individual time components of the patient encounter, including EMS dispatch time, response time, time to first ECG, PCI centre activation time, scene time, transport time, total EMS time and door to PCI time.4 Individual time components were evaluated to identify which phase of care contributed the most to delayed reperfusion. Further, we examined the time of day relative to hours that the cardiac catheterisation is normally staffed and open (approximated as 07:00–17:00 and described as ‘business hours’) versus times when the team is on-call (17:01–6:59).
Statistical analysis
Counts, percentages, means and SD were used to describe the study population. The proportion of patients with FMC-to-PCI in ≤90 min was compared between sexes using a logistic generalised estimating equation (GEE) to account for clustering within EMS agencies. Time intervals were also described continuously using median and IQR. Continuous FMC-to-PCI time and the individual time components were compared between sexes using clustered Wilcoxon rank-sum tests.
Stratified by sex, patient and agency factors were compared between patients who achieved the FMC-to-PCI time goal and those who did not using logistic GEEs. To allow inclusion of all patients in the multivariable model, multiple imputation was used. Multiple imputation was performed by SAS Proc MI using the Markov Chain Monte Carlo method with 20 iterations. Imputation values were restricted to a minimum and maximum range dictated by each patient factor. Analyses were completed on the imputation data sets and the results analysed by the SAS Proc MI analyse procedure. Unadjusted ORs are reported along with 95% CIs for each patient, incident and agency level factor described in the measures section. Next, multivariable models were created using stepwise selection (0.20 inclusion/0.10 exclusion), forward selection (0.10 inclusion) and backward selection (0.10 inclusion). All three models were reviewed, and a consensus of the results (agreement of at least two of the three models) was selected as the final multivariable model. Subsequently, adjusted OR (aOR) with 95% CIs are reported for factors that remained in the model. A complete case analysis was done as a sensitivity analysis. As this study was a secondary analysis, an a priori sample size calculation was not conducted.
RESULTS
Among eight rural EMS agencies, 365 patients were included with a mean age of 62.5 ± 12.7 years. Of these, 30.1% (110/365) were women and 6.8% (25/365) were non-white patients. See table 1 for a description of demographics, initial vital signs, symptoms, incident and transport characteristics.
Table 1.
Demographics of included patients stratified by sex
Demographics
Combined
n=365
Men
n=255
Women
n=110
Age – years, mean±SD
62.5±12.7
61.3±12.3
65.2±13.2
BMI – kg/m2, mean±SD
29.5±5.9
29.2±5.0
30.0±7.7
Race/ethnicity
Non-white
25 (6.8)
19 (7.5)
6 (5.5)
White
340 (93.2)
236 (92.5)
104 (94.5)
First SBP category
<90 mm Hg
26 (7.4)
17 (6.9)
9 (8.7)
≥90 mm Hg
325 (92.6)
231 (93.1)
94 (91.3)
First pulse rate, beats per minute
<60
55 (15.2)
36 (14.2)
19 (17.4)
60–100
250 (68.9)
178 (70.1)
72 (66.1)
>100
58 (16)
40 (15.7)
18 (16.5)
First SpO2 <90%
<90%
9 (2.7)
6 (2.6)
3 (3.0)
≥90%
319 (97.3)
223 (97.4)
96 (97.0)
Smoking
168 (52.0)
117 (51.5)
51 (53.1)
Hypertension
250 (68.7)
168 (66.1)
82 (74.5)
Hypercholesterolaemia
223 (61.1)
155 (60.8)
68 (61.8)
Diabetes
106 (29.0)
73 (28.6)
33 (30.0)
Prior CAD
106 (29.1)
75 (29.5)
31 (28.2)
Cancer
41 (11.3)
26 (10.2)
15 (13.6)
Pain characteristics (pain/no pain)
317 (95.2)
226 (95.8)
91 (93.8)
Provoked onset – activity
77 (21.1)
56 (22.0)
21 (19.1)
07:00–17:00 or 17:01–06:59 by ECG time (initial time point of activation time)
07:00–17:00
197 (54.4)
145 (57.1)
52 (48.1)
17:01–06:59
165 (45.6)
109 (42.9)
56 (51.9)
Loaded mileage, mean ± SD
26.6±11.0
26.6±11.0
26.5±11.1
Fewer women received PCI within the goal of 90 min compared with men [43.6% (48/110) vs 67.8% (173/255), p<0.001]. Further, women had a significantly longer median FMC-to-PCI time (93 min, IQR 79.0–111.0) compared with men (81 min, IQR 70.0–96.0), p=0.02. Individual prehospital time intervals did not significantly differ between men and women; however, the total EMS time was longer for women (women 42.5 min (IQR 37.3–51.0) vs men 40.0 min (IQR 34.0–47.0), p=0.049). Women also experienced significantly longer door-to-balloon time at 48.5 min (IQR 37.0–65.0) compared with 40.0 min (IQR 32.0–54.0) for men, p value <0.01. Table 2 describes, and figure 2 illustrates prehospital and hospital time intervals stratified by sex.
Table 2.
FMC-to-PCI, prehospital and hospital time intervals stratified by sex
Male
(n=255)
Female
(n=110)
P value
FMC-to-PCI ≤ 90 (n=365)
<0.001*
≤90 min, n (%)
173 (67.8)
48 (43.6)
>90 min, n (%)
82 (32.2)
62 (56.4)
FMC-to-PCI, minutes (n=365)
Median (IQR)
81 (70–96)
93 (79–111)
0.02†
Dispatch time, minutes (n=365) (dispatch – call received)
Median (IQR)
1 (0–2)
1 (0–2)
0.51†
Response time, minutes (n=365) (on scene – dispatch)
Median (IQR)
9 (6–12)
9 (6–12)
0.38†
Time to first ECG, minutes (n=361) (12-lead ECG – at patient)
Median (IQR)
4 (2–6)
4 (3–8)
0.40†
Activation time, minutes (n=327) (cath lab activation – 12-lead ECG)
Median (IQR)
14 (8–23)
16 (8–26)
0.25†
Scene time, minutes (n=365) (depart scene – on scene)
Median (IQR)
13 (11–17)
15.5 (12–20)
0.17 †
Transport time, minutes (n=365) (at destination – depart scene)
Median (IQR)
26 (21–33)
27 (23–34)
0.15†
Total EMS time, minutes (n=365) (at destination – on scene)
Median (IQR)
40 (34–47)
42.5 (37.3–51)
0.049†
Door to balloon time, minutes (n=365) (PCI time – at destination)
Median (IQR)
40 (32–54)
48.5 (37–65)
0.01†
Figure 2.
Prehospital and in-hospital time intervals stratified by sex. FMC, first medical contact; PCI, percutaneous coronary intervention; EMS, emergency medical services.
Factors associated with achieving FMC-to-PCI within 90 min for men and women included care by agencies with higher transports per capita. Among women, exertional symptoms were associated with higher odds of timely reperfusion (aOR 2.84; 95% CI 1.05 to 7.68), while a history of hypercholesterolaemia (aOR 0.47; 95% CI 0.25 to 0.89) and diabetes (aOR 0.39; 95% CI 0.20 to 0.76) was associated with lower odds of timely reperfusion. Among men, the presence of pain was associated with higher odds of meeting time goal (aOR 3.84; 95% CI 1.52 to 9.72) while care outside of normal business hours (aOR 0.37; 95% CI 0.25 to 0.55), increasing age and longer transport distance were associated with lower odds of timely reperfusion. The association of patient and agency factors with unadjusted and adjusted odds of FMC-to-PCI ≤ 90 min using an imputed model, stratified by sex, is available in tables 3 and 4, respectively.
Table 3.
Univariable odds of meeting FMC-to-PCI in 90 min or less by sex in imputed model
PCI goal (binary)
Men
OR (95% CI)
Women
OR (95% CI)
Medics (per 100 citizens)
*
0.98 (0.97 to 1.00)
0.97 (0.96 to 0.98)
Transports (per capita)
*
0.99 (0.97 to 1.00)
0.96 (0.95 to 0.97)
Ambulances (per 100 citizens)
*
0.83 (0.73 to 0.96)
0.69 (0.54 to 0.88)
Age, 10-year increase
0.75 (0.55 to 1.00)
0.93 (0.80 to 1.08)
BMI
0.97 (0.93 to 1.01)
0.99 (0.97 to 1.02)
Loaded mileage, 10-mile increase
0.69 (0.61 to 0.78)
0.57 (0.44 to 0.73)
Race/ethnicity
Non-white
1.36 (0.73 to 2.52)
0.24 (0.16 to 0.38)
White
reference
reference
First SBP category
<90 mm Hg
1.15 (0.52 to 2.59)
0.99 (0.14 to 6.82)
90+ mm Hg
reference
reference
First pulse rate, beats per minute
<60
0.84 (0.49 to 1.42)
1.17 (0.53 to 2.61)
60–100
reference
reference
>100
0.51 (0.21 to 1.26)
1.06 (0.57 to 1.97)
First SpO2
<90%
0.46 (0.30 to 0.73)
2.65 (0.26 to 27.18)
≥90%
reference
reference
Smoking
Yes
1.14 (0.65 to 1.97)
1.07 (0.61 to 1.86)
No
reference
reference
Hypertension
Yes
0.53 (0.30 to 0.95)
0.48 (0.18 to 1.31)
No
reference
reference
Hypercholesterolaemia
Yes
0.67 (0.30 to 1.49)
0.56 (0.33 to 0.97)
No
reference
reference
Diabetes
Yes
0.62 (0.36 to 1.08)
0.54 (0.33 to 0.89)
No
reference
reference
Prior CAD
Yes
0.64 (0.40 to 1.02)
0.51 (0.35 to 0.76)
No
reference
reference
Cancer
Yes
0.50 (0.23 to 1.12)
0.42 (0.20 to 0.90)
No
reference
reference
Pain characteristics (pain/no pain)
Yes
3.46 (1.49 to 8.08)
4.22 (0.26 to 68.72)
No
reference
reference
Provoked onset – activity
Yes
1.99 (1.00 to 3.97)
3.24 (1.08 to 9.68)
No
reference
reference
07:00–17:00 or 17:01–06:59 by ECG time (initial time point of activation time)
07:00–17:00
reference
reference
17:01–6:59
0.38 (0.26 to 0.54)
0.55 (0.35 to 0.88)
Table 4.
Adjusted odds of meeting FMC-to-PCI in 90 min or less by sex in imputed model after variable selection
PCI goal (binary)
Men aOR (95% CI)
Women aOR (95% CI)
Transports (per capita)
0.99 (0.98 to 1.00)
0.96 (0.95 to 0.97)
Age, 10-year increase
0.71 (0.52 to 0.98)
Loaded Mileage, 10-mile increase
0.76 (0.63 to 0.92)
Hypercholesterolaemia
Yes
0.47 (0.25 to 0.89)
No
reference
Diabetes
Yes
0.39 (0.20 to 0.76)
No
reference
Pain characteristics (pain/no pain)
Yes
3.84 (1.52 to 9.72)
No
reference
Provoked onset – activity
Yes
1.98 (0.86 to 4.57)
2.84 (1.05 to 7.68)
No
reference
reference
07:00–17:00 or 17:01–06:59 by ECG time (initial time point of activation time)
07:00–17:00
reference
17:01–6:59
0.37 (0.25 to 0.55)
A sensitivity analysis of only complete cases did not reveal a change in significant factors associated with meeting time goal in the univariable or adjusted models, except among men, among whom age was not significant in the completed case adjusted model. See online supplemental table 2 and 3 for unadjusted and adjusted complete case models, respectively.
DISCUSSION
Among EMS patients in rural settings with STEMI, women were significantly less likely to achieve goal FMC-to-PCI time than men, exposing them to increased risk of morbidity and mortality. Further, women experience significantly longer prehospital total EMS time and door-to-balloon time compared with men. Among women, care by EMS agencies with more annual transports, a history of hyperlipidaemia or diabetes and a lack of exertional symptoms were associated with lower odds of achieving goal FMC-to-PCI time. For men, the factors associated with lower odds of achieving goal FMC-to-PCI time included care by agencies with more annual transports, care outside of standard business hours, older age, longer transport distance and lack of chest pain. These findings provide some insight into the differences observed in achieving timely reperfusion between men versus women in rural settings.
The symptom profile of patients with Acute Coronary Syndrome (ACS) is variable and current guidelines discourage using symptom typicality to identify patients with ACS.16–23 Further, men and women have considerable overlap in their symptom profiles. Nevertheless, women with ACS are less likely than men to report chest pain or diaphoresis, and they are more likely to report symptoms such as back pain, nausea, vomiting or shortness of breath.20 Our finding that women with exertional symptoms were more likely to have timely reperfusion suggests that exertional symptoms, previously considered a typical ACS symptom, may drive clinicians to perform an ECG earlier in the evaluation or to be more convinced of an ECG finding of STEMI. This suggests that the idea of symptom typicality may persist in the prehospital evaluation of patients for STEMI.
Non-white patients with STEMI are less likely to receive guideline-recommended care than white patients.24
25 Although non-white race was a strong predictor of delayed reperfusion among women in our univariable model, it was not significant in the multivariable model. Surprisingly, women who had commonly recognised cardiac risk factors of hypercholesterolaemia and diabetes were significantly less likely to receive timely reperfusion, suggesting that these chronic conditions may complicate decision making among EMS and in-hospital personnel.
Men with catheterisation lab activation outside of normal business hours were significantly less likely to have timely reperfusion. Existing evidence has demonstrated that patients are more likely to receive timely reperfusion when presenting Monday through Friday during times when catheterization labs have staff readily available, rather than on-call.26 These data suggest that particular attention to early cardiac catheterization lab activation may be needed during on-call hours. Additionally, increasing age decreased the odds of timely reperfusion for men, which is likely multifactorial.27 Older adults with ACS are less likely to experience chest pain.28–30 Further, older adults are more prone to poor outcomes and higher complication rates due to comorbidities and medications which may give pause to proceduralists. Unfortunately, older adults are at high risk of STEMI and tend to have higher ischaemic burden, making age an important factor when considering PCI centre activation.27
Several additional systems factors also impacted timely reperfusion. Notably, EMS agencies with more annual transports were less likely to have timely reperfusion. While the association of hospital and procedural patient volume with improved outcomes has been described more generally,31
32 discordant evidence exists on whether increased EMS volume of specific call types impact outcomes.33
34 The specific association of EMS STEMI volume and outcomes has not been previously described. This finding could simply be a marker of system strain, with busier systems being less able to provide timely care to patients with STEMI. Finally, our finding of a large time-interval discrepancy in door-to-balloon time for women is consistent with prior studies yet still requires further investigation into effective interventions.14
35
To reduce reperfusion delays among women in rural settings, a multifaceted strategy that addresses the sex-specific contributors to delayed care is needed. These factors include under-recognition of the spectrum of symptoms experienced by patients with ACS, delayed ECG acquisition and implicit bias. Some tools to reduce the effect of implicit bias include awareness of bias, cross-checking with other clinicians and using clinical decision tools or protocols.36 In this context, solutions could include revising patient care protocols to emphasise early ECG acquisition for patients with symptoms that may be due to STEMI, highlighting differences in care received by women and men in initial and recurring education and ensuring high-quality feedback and continuous quality improvement with attention to sex differences. Future research is needed to identify gaps in decision making and subsequently, implementation and effectiveness of future solutions. Finally, given that this manuscript yet again highlights significant differences in-hospital performance (door-to-balloon time) seen in prior literature, an ongoing focus on improving the in-hospital sex-based differences is also needed.
LIMITATIONS
These data are retrospective and observational, which limits inferences of causality. This study analysed a database of patients from eight EMS agencies and three PCI centres in the Piedmont Triad of NC, limiting generalisability. Further, one PCI centre in our region elected not to participate in the data sharing for the rural STEMI registry, potentially introducing selection bias. Results may not be generalisable to all rural communities. Few patients were non-white, which limits generalisability to rural areas with greater racial diversity. Finally, this study was not powered to investigate delays in timely reperfusion stratified by sex.
CONCLUSION
In rural settings, women with STEMI cared for by EMS are less likely to have timely reperfusion than men. Women with exertional pain had improved FMC-to-PCI time, while those with hypercholesterolaemia or diabetes were less likely to receive timely reperfusion. Men who had STEMI outside of normal business hours, those who required longer distance transports and those without pain were less likely to receive timely reperfusion. Future work should focus on improving protocolised early ECG acquisition and catheterisation lab activation, investigating sex-related decision-making flaws that lead to the observed delays, incorporating bias mitigation strategies such as education and cross-checking and identifying systems-based opportunities to improve time to reperfusion, especially among women.
Supplementary Material
SUPPLEMENTAL
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/10.1136/emermed-2025-215309).
WHAT IS ALREADY KNOWN ON THIS TOPIC
⇒ Women and those living in rural settings more often experience delayed time to reperfusion compared with men and those living in urban settings.
WHAT THIS STUDY ADDS
⇒ In a rural setting, we confirmed that women with ST-elevation myocardial infarction experienced longer prehospital and door-to-balloon times than men. Lack of exertional chest pain and a history of diabetes or hypercholesterolaemia were associated with higher odds of delayed treatment in women.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
⇒ Emergency medical services (EMS) agencies should incorporate structured protocols for early ECG acquisition and catheterisation lab activation, bias mitigation tools such as education and cross-checking and routinely audit reperfusion times by sex and provide direct feedback to EMS clinicians.
Funding
Research reported in this publication was supported by the National Centre for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2TR001421. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Footnotes
Competing interests Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2TR001421. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. MWS receives funding from the National Foundation of Emergency Medicine, SIREN network, AHRQ (R01HS029017 and R21HS029234). NPA receives funding from NHLBI (K23HL169929), AHRQ (R01HS029017) and the Emergency Medicine Foundation. ACS receives funding from Abbott Laboratories, AHRQ (R01HS029017 and R21HS029234), HRSA (1H2ARH399760100), NHLBI (K23HL169929) and the Emergency Medicine Foundation. CDM receives research funding from Siemens, Abbott Point of Care, Creavo Medical Technologies, Grifols and NHLBI (5U01HL123027). He has a US patent on cardiac biomarkers for coronary artery disease related to cholesterol esters. JPS receives research funding from HRSA (H2ARH39976-01-00), Roche Diagnostics, Abbott Laboratories, Pathfast, Genetesis, Cytovale, Forest Devices, Vifor Pharma and Chiesi Farmaceutici. SAM has received funding/support from Roche Diagnostics, Abbott Laboratories, QuidelOrtho Clinical Diagnostics, Siemens, Grifols, Pathfast, Genetesis, Cytovale, Beckman Coulter, Brainbox, Bluejay Diagnostics, AHRQ (R01HS029017 and R21HS029234), The Duke Endowment, National Foundation of Emergency Medicine and HRSA (1H2ARH399760100); is a consultant for Roche, Abbott, Siemens, QuidelOrtho, Genetesis, Inflammatix and Radiometer and is the Chief Medical Officer for Impathiq. The other authors have no conflicts.
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Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Patient consent for publication Not applicable.
Ethics approval This study was approved by the Wake Forest University Institutional Review Board and granted a waiver of informed consent. This study was registered at ClinicalTrials.gov (NCT04381260).
Provenance and peer review Part of a topic collection; not commissioned; externally peer reviewed.
Data availability statement
No data are available.
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