Impact Prognostic of Delayed Reperfusion Time in Patients With Stemi of ≤ 24 Hours Treated in the Emergency Department of a General Hospital

Background. The patients who attend a hospital without a hemodynamic laboratory may have differences in health outcomes, treatment, reperfusion times, the rate of cardiovascular complications, hospital stay, mortality or costs may be affected. The study aimed to analyze the prognostic of patients with STEMI treated in the Emergency Department (ED) and the impact prognostic of the delayed reperfusion time in a Hospital General without hemodynamic laboratory. Methods. After ethics review board approval, this retrospective observational cohort study of patients included acute coronary syndrome with ST elevation of ≤ 24 h in the Illes Balears infarction code registry (CI-IB) between May 2008 and December 2018. The information recorded were age, sex, cardiovascular risk factors, site of AMI, time delays, reperfusion therapy with brinolysis and primary angioplasty (PA). Cardiovascular Event (CE) was dened the combined variable: Killip class progression, malignant arrhythmias, Re-infarction, cerebrovascular disease and mortality. Results.605 patients were analyzed. The reperfusion treatment was 83,1% (80,8% with PA). 19% presented some CE. Hospital and monthly mortality was 6.8% and 7.8% respectively. The main differences between patients with and without CE were: age (66 vs 59 years); Chronic obstructive pulmonary disease (COPD); previous infarction; anterior location; Door-To-Needle Time and FPC-PA time. The risk factors of CE were: age, COPD, anterior location, brinolysis and patients without reperfusion treatment. In the group with PA, the risk of mortality was higher in COPD (p=0.012), Symptom start –FPC time with (p = 0,084) and FPC-PA time > 90 minutes (p= 0.107). FCM-AP> 90 minutes had a higher mortality (10 vs 4.4%;HR 1,79; IC 95% 1,15-2,78; log-rank:p=0,013) Conclussions. In our cohort, most patients received reperfusion were performed within the recommended time. ED, the pacients


Background
In March 2008, the Balearic Islands Infarct Code (CI-IB) 1

assistance program was began in the Balearic
Islands. The data were published in 2016 2 . The Hospital Universitary Son Llàtzer (HUSLL) is a secondlevel university hospital, it does not have a hemodynamic laboratory and patients with ST-segment elevation acute myocardial infarction (STEMI) are referred to other hospital with laboratory (Hospital University Son Espases) to practice primary angioplasty (PA). The patients who attend a hospital without a hemodynamic laboratory may have differences in health outcomes, treatment, reperfusion times, the rate of cardiovascular complications, hospital stay, mortality or costs may be affected 3 .
The objective of our work is to analyze the prognostic of patients with STEMI treated in the Emergency Department (ED) and the impact prognostic of the delayed reperfusion time.

Study design and setting
This is a retrospective cohort study from March 8, 2008 to December 31, 2018, which included 605 patients, included in the CI-IB, treated alive with a diagnosis of STEMI less than 24 hours from the start of the symptoms until rst medical contact (FCM). The study was conducted at Emergency Department of Hospital Universitario Son Llàtzer of Palma Mallorca, Baleares Island, Spain.

Data Collection
The main variables were analyzed were demographic (age, sex, cardiovascular risk factors), clinical (location, Killip grade at admission and worse Killip during admission) and reperfusion treatment ( brinolysis and primary angioplasty). The main time intervals analyzed were: Time from the onset of symptoms-FCM, time from the FCM to brinolysis (door-to-needle time) and time from FCM-to the start of primary angioplasty (door-to-balloon time). The latter was also represented as a binary variable (≤90 minutes) given that they are the recommendations of the STEMI guidelines in patients with primary interventionism 4 . Two population groups were strati ed according to whether or not had a cardiovascular event (CE). The combined variable was de ned as CE: reinfarction during the stay, stroke, malignant arrhythmia (ventricular brillation and sustained ventricular tachycardia, and worse Killip during admission).

Satatistical analysis
A descriptive analysis of the variables was performed, calculating the median with its interquartile range (IQR) for the quantitative variables and frequencies and percentages for the qualitative ones. For hypothesis testing, the Student's t test, the Mann-Whitney U test and the chi-square test / Fisher's exact test were used, respectively. A multivariate analysis was performed using a Cox proportional hazards model to study the relationship of demographic and clinical variables, time intervals, and all potential confounders with cardiovascular events during hospital stay and 30-day mortality. Differences were considered statistically signi cant if the p value was less than 0.05. IBM® SPSS® Statistics v. 22.0. Results 605 patients with STEMI were included. Table 1 shows the main results. Reperfusion was 85.9%, (77.2% PA). 19% had some CE. Hospital and month mortality was 6.8% and 7.8%, respectively. The independent risk factors for CE were: age, COPD, anterior location, brinolysis, and patients without revascularization (See Table II). In patients where an invasive strategy was decided, the independent risk factors for mortality at 30 days were COPD (HR: 2.934; p = 0.012), time onset of symptoms-PCM (HR: 1.001; p = 0.003) and time PCM-AP> 90 minutes (HR: 1.835; p = 0.084) (see table III). Thus, the 30-day mortality in patients with PCM-ICP ARI time> 90 min was 10% compared to 4.4% for those treated before 90 min (HR 1.79; 95% CI 1.15 -2.78; log-rank: p = 0.013) (Figure 1).

Discussion
The results of this cohort study show the favorable evolution of the implementation of the AMI code in patients in our district. Although in our island the distances are not very long, a large part of the population was diagnosed in the Emergency Department (ED) at the beginning of the implantation. Once the initial phase of implementation was over, the referral of patients to reference hospital was modi ed with the intention of guarantee a homogeneous care of the population with greater e ciency of out-ofhospital activation of PA. In our cohort, previous infarction and COPD are more prevalent in the group of patients with CE. A relevant aspect in our study is that COPD is an independent risk factor for mortality. Both COPD and its exacerbation are associated with acute myocardial infarction. These patients frequently present atypical symptoms, delay in the diagnosis of AMI, undertreatment and higher mortality 5,6 .
A large percentage of patients treated at our center are treated within adequate time intervals. Some studies suggest that the cut-off point at which PA is not higher than brinolysis is approximately 2 hours, depending on the duration of ischemia, the size of the myocardium at risk, and the risk of bleeding. Our results demonstrate a brinolytic treatment according to the standards with a gate-to-needle time <30 The incidence of PA is usually lower in hospitals without hemodynamics 3 . In our study, patients who underwent an invasive strategy from the ED presented less CE. We observed that although there was an increase in PA from the beginning of the infarction code, we present a slightly higher percentage of patients without reperfusion in other studies 8 .
The time delay between the appearance of heart attack symptoms and the performance of angioplasty is a very important factor in prognosis. The greater this delay, the greater the injury that occurs. The data published from population registries show that easy access to a hospital with hemodynamics is associated with an increase of the its use, a decrease in the delay in care and lower mortality 9,10,11 . It is clear that the distance to the center with hemodynamic availability is important to achieve optimal times 12 Long transport distances and the lack of initial access to hospitals without hemodynamic availability have been related to prognosis 13,14 . In our registry, the symptoms onset-FCM time and the FCM-AP time were longer in patients with COPD. Furthermore, these delays were associated with inhospital and 1-month mortality. In our city, the distances between the two hospitals are not long, so we must evaluate other circumstances such as the patient going directly to the ED, the delay in diagnosis, and the waiting time for medicalized transport for the transfer. This requires continuous evaluation and critical analysis of the results to optimize existing care networks.

Study Limitations
The main limitation of our study is the limited number of patients and that it is from a single center. Other limitations were the absence of information in some more speci c times in relation to the logistics of transfers and hours of activation of the out-of-hospital Medical Services.

Conclusions
As conclusions, we highlight that despite the fact that distances are short in our community, delay times are an important factor in the prognosis of patients, both onset of symptoms-FCM and in the delay in access to the hemodynamic room. The analysis suggests that patients diagnosed with COPD could increase mortality.

Funding
The authors declare the non-existence of external funding for this article.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate
The Research Ethics Committee obviated the need for informed consent when dealing with anonymous records. A data dissociation procedure has been carried out with the aim of transforming them into anonymous and irreversibly dissociated, destroying any link or nexus that could identify the patient. At all times, the con dentiality of the information was maintained in accordance with the provisions of Organic   Figure 1 Kaplan-Meier survival analysis at 30 days