Introduction
A longer total ischemic time, measured from symptom onset to reperfusion, in patients with ST-segment elevation myocardial infarction (STEMI) results in more severe myocardial infarction size and a poorer clinical prognosis. Every 30 minutes of treatment delay increases the death risk by 7.5%. Reference Kim1 Reducing the total tissue ischemic time remains an important focus of health care systems world-wide to reduce morbidity and mortality. Reference Bessonov, Kuznetsov and Gorbatenko2 The American College of Cardiology (ACC; Washington, DC USA) and American Heart Association (AHA; Dallas, Texas USA) guidelines suggest a total ischemic time of 120 minutes or less, consisting of symptom-to-door (S2D) time and door-to-balloon (D2B) time. Reference O’Gara, Kushner and Ascheim3 Many effective strategies have been developed to reduce the D2B time; more efforts should be made to reduce the S2D delay. Reference Kim1,Reference Fazel, Joseph and Sankardas4
Several studies have explored factors related to S2D delay, but the results from these studies are inconclusive. Some studies have identified female sex, Reference Sari, Acar and Ozer5–Reference Poorhosseini, Saadat and Salarifar9 diabetes, Reference Sari, Acar and Ozer5,Reference Peng, Feng and Guo7,Reference Wah, Pek and Ho8,Reference Park, Kang and Song10 and weekday Reference Momeni, Salari and Shafighnia6 as potential risk factors for a prolonged delay in STEMI patients. In contrast, other studies did not indicate that female sex, Reference Park, Kang and Song10,Reference Hafiz, Naidu and DeLeon11 diabetes, Reference Hafiz, Naidu and DeLeon11,Reference Kim, Lee and Eun12 or weekday Reference Sari, Acar and Ozer5,Reference Park, Kang and Song10,Reference Kim, Lee and Eun12 were associated with S2D delay. The identification of factors related to S2D delay is important. To the authors’ knowledge, no attempts have been made to systematically review these factors.
The aim of this review was to identify prehospital factors associated with S2D delay in patients with STEMI.
Methods
Prespecified Systematic Review
A systematic review protocol was completed in PROSPERO (CRD42020159207) before beginning the review process. The review process was organized in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Reference Grammatopoulos, Hunter and Munn13
Search Method and Selection Criteria
The CINAHL (EBSCO Information Services; Ipswich, Massachusetts USA), PubMed (National Center for Biotechnology Information, National Institutes of Health; Bethesda, Maryland USA), and Embase (Elsevier; Amsterdam, Netherlands) databases were systematically searched to identify studies examining the relationship between prehospital factors and S2D time in patients with acute ST-segment myocardial infarction. The inclusion criteria were as follows, using the PICO (population-intervention-comparison group-outcome) strategy:
The following search strategy was constructed with the assistance of qualified librarians: search (((((((prehospital[Title/Abstract]) OR pre hospital[Title/Abstract]) OR time to treatment[Title/Abstract]) OR delayed treatment[Title/Abstract]) OR treatment delay[Title/Abstract]) OR therapy delay[Title/Abstract])) AND ((((ST segment elevation[Title/Abstract]) OR ST elevation[Title/Abstract])) AND Myocardial Infarction [Mesh]).
The search was limited to studies in the English language. No date restrictions were imposed, and the search was completed on May 4, 2022. In addition, references from the selected reports and reference papers were manually searched to identify additional eligible studies.
Duplicate studies were removed. Then, the titles of the retrieved studies were screened to identify potentially relevant studies; if there were any doubts, the abstract was also screened against the inclusion criteria. Studies that appeared to meet the inclusion criteria were then subjected to full-text screening, and their reference lists were checked for additional studies. The reference lists of relevant reviews identified through the search were also searched for additional studies.
Study Quality Assessment
All remaining studies fulfilling the inclusion criteria were evaluated by the Joanna Briggs Institute (JBI; University of Adelaide; Adelaide, South Australia) checklists for cohort studies to assess the risk of bias. Reference Grammatopoulos, Hunter and Munn13
Data Extraction
Two reviewers independently extracted and collected data from the included studies using a standardized data extraction protocol. Data were extracted regarding the type of association that was identified for each examined factor. An association was deemed to exist when the threshold for significance given in each study had been reached. In cases where no threshold for significance was given, P <.05 was specified. Semiquantitative synthesis of the data obtained was conducted based on the procedure described by Wibring, et al. Reference Wibring, Herlitz and Christensson14 Three criteria were used to determine the level of evidence for each reported factor: (1) number of studies evaluating the factor, (2) scored quality of each study evaluating the factor, and (3) the consistency between studies regarding reported association between factor and outcome. If a factor fulfilled the criteria for multiple levels of evidence, the highest level was chosen. The definition of each level of evidence is shown in Table 1. The recommendations of the Cochrane and PRISMA guidelines were followed.
Table 1. Criteria for Each Level of Evidence
Results
Study Identification
The search of the databases yielded 1,831 unique references; 1,770 studies were excluded after title and abstract screening. Two studies were added by cross-reference checking, and thus, 63 studies remained for full-text screening. After full-text screening, 12 studies were found to meet all the inclusion criteria. In those cases, the articles judged to be the most relevant to the objective of this review were included (Figure 1).
Figure 1. PRISMA Flow Diagram. Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Study Characteristics
In total, 12 studies were included; 61 factors were examined within those articles, (Table 2 Reference Sari, Acar and Ozer5–Reference Kim, Lee and Eun12,Reference Austin, Yan and Spratt15–Reference Weininger, Cordova and Wilson18 ), and 28 of those factors were assessed in two or more studies (Table 3).
Table 2. Study Characteristics and Main Results of the Included Studies
Abbreviation: S2D, symptom-to-door.
Table 3. Level of Evidence for Each Factor
Level of Evidence
The results of the semiquantitative synthesis are presented in Table 3. There was strong evidence for the presence of S2D delay in patients with STEMI who were also diabetes patients or of female sex. The level of evidence in regard to factors including older age, smoking, history of hypertension, self-transport, or referral was moderate. The evidence was inconclusive regarding the distance from the emergency room, body mass index, living alone, alcohol use, lack of medical insurance, education time < nine years, symptom onset weekday, typical chest pain, symptom onset time, awareness of acute myocardial infarction, previous coronary artery bypass grafting, myocardial infarction, percutaneous coronary intervention, stroke, dyslipidemia, and family history of coronary artery disease. There was no evidence to support the effects of income, history of chronic kidney disease, symptom-onset-situation, symptom-onset-location, localization of myocardial infarction, or responses to symptoms of myocardial infarction on S2D delay.
Some factors showed an association with S2D delay but were only evaluated in one study; those factors were beyond the scope of this research. Those factors included the following: absence of previous coronary artery disease, number of children < three, history of aspirin use, beta-blocker use, Reference Sari, Acar and Ozer5 anxiety concerning symptoms, type of symptom onset, interpretation of symptoms, Reference Momeni, Salari and Shafighnia6 breathlessness, vomiting, ventricular arrhythmias, Reference Peng, Feng and Guo7 presenting shoulder/jaw pain symptoms, diaphoresis, Reference Wah, Pek and Ho8 longest linger, pain duration, opium abuse, infarct-related artery, Reference Poorhosseini, Saadat and Salarifar9 peripheral vascular disease, heart failure, pulmonary embolism, deep venous thrombosis, valvular surgery, chronic obstructive pulmonary disease, Reference Hafiz, Naidu and DeLeon11 and subjective opinion that the event was not an acute myocardial infarction. Reference Weininger, Cordova and Wilson18 Moreover, ethnicity was examined in four studies, Reference Wah, Pek and Ho8,Reference Poorhosseini, Saadat and Salarifar9,Reference Brown, Shantsila and Varma16,Reference Weininger, Cordova and Wilson18 as there were different races in each study. That factor was also excluded from this study.
Discussion
The major finding from this systematic review was that factors associated with S2D time in STEMI patients were complex and could be divided into sociodemographic, clinical history, and onset characteristics.
According to the included studies, females more often have longer S2D times, which could be explained by women tending to report chest pain less often than men and women having presentation of symptoms that are usually atypical, such as nausea, back pain, and shortness of breath, which they attribute to common health disorders instead of myocardial infarction. Reference Margolis, Letourneau-Shesaf and Khoury17,Reference Weininger, Cordova and Wilson18 Prolonged delay in seeking hospital treatment among elderly individuals likely occurs because they misdiagnosed the symptoms of STEMI as symptoms of aging. Reference Wah, Pek and Ho8 Furthermore, the relatively diminished sensation, high frequency of cognitive impairment, difficulty moving, and dependence on relatives for transportation further challenge elderly patients’ ability to seek care earlier. Reference Peng, Feng and Guo7
Diabetes, hypertension, and dyslipidemia are the main risk factors for STEMI, and patients with those diseases had longer S2D times, which could be explained by the association with silent/painless myocardial infarction. Reference Wah, Pek and Ho8 Additionally, some studies have proposed that diabetes may delay S2D time because of poorer sensory feelings caused by diabetic neuropathy. Reference Peng, Feng and Guo7 Other medical history variables, such as myocardial infarction history, previous percutaneous coronary intervention, previous coronary artery bypass grafting, previous stroke, and family history of coronary artery disease, were found to be related to shorter prehospital delay. Because these patients may be well-aware of the significance of a short delay, they are more easily alarmed, more skilled at recognizing symptoms, and more likely to get to the emergency center quickly. Reference Peng, Feng and Guo7,Reference Margolis, Letourneau-Shesaf and Khoury17 However, several other studies reported an inverse relationship between previous angina and S2D delay. Reference Margolis, Letourneau-Shesaf and Khoury17 This finding can be explained by the fact that patients with previous angina may have a higher threshold of pain because of their chronic condition and assume that the pain will resolve itself as it has in the past. In addition, patients may first attempt to self-treat their symptoms with drugs, particularly nitrates, causing further delay before seeking care.
Onset characteristics were also important factors related to S2D delay. Patients who were not transported by ambulance and first contacted a private physician instead of directly presenting to the emergency department tended to have delayed arrival at the emergency department. Reference Momeni, Salari and Shafighnia6–Reference Wah, Pek and Ho8,Reference Hafiz, Naidu and DeLeon11 These patients were more likely to present during on-hours and have less awareness of STEMI, and they did not believe they were suffering from myocardial infarction. Additionally, onset during the night had longer S2D times, which could be explained by patients being prone to going to the hospital the next day because it is troublesome to travel there at night. Patients with onset at home had a longer prehospital delay as a result of bystander intervention. Reference Peng, Feng and Guo7
Limitations
Initial statistical pooling and meta-analyses were considered for potential factors associated with S2D time in patients with STEMI. However, during the process of screening and quality assessment of potentially relevant studies, there were some difficulties due to methodological heterogeneity regarding statistics and outcome measurement indexes. A semiquantitative synthesis of data was used, obtained based on the procedure described by Wibring, et al. Reference Wibring, Herlitz and Christensson14
There may be a risk of bias for systematic reviews due to the inclusion of English-only articles; potential benefits and problems related to language restriction have been reported in other studies. Reference Moher, Pham and Lawson19,Reference Peterson, Syndergaard and Bowler20 In addition, to reduce the heterogeneity of the studies, studies that collected data during the coronavirus disease 2019/COVID-19 peak pandemic were not included. Reference Sofi, Dinu and Reboldi21 Due to the limited database access, small number of included studies, and limited sample size, the conclusions of this study need to be further studied. Additionally, unpublished results were not reported in this review, since there may be some quality issues in unpublished studies that would be addressed during editorial or peer review. Reference Egger, Dickerson and Smith22
Conclusions
Female sex, older age, previous diabetes, previous hypertension, smoking, and self-transport are all strong or moderate risk factors for S2D delay in patients with STEMI. Greater efforts are needed to educate high-risk populations regarding the symptoms of STEMI and the importance of seeking medical help as soon as possible to reduce the delay of treatment and reduce morbidity and mortality.
Conflicts of interest
There are no conflicts of interest to disclose.
Supplementary Materials
To view supplementary material for this article, please visit https://doi.org/10.1017/S1049023X23006039
