Presentation, management, and outcomes of STEMI in Egypt: results from the European Society of Cardiology Registry on ST elevation myocardial infarction

Background Apart from few small single-center studies, there are limited data about STEMI patients in Egypt. Nineteen Egyptian centers (with and without PCI facilities) participated in this registry with 1356 patients who were compared to 7420 patients from other ESC countries. The aims of this study were to describe the characteristics of patients with STEMI, to assess STEMI management patterns particularly the current use of reperfusion therapies, to evaluate the organization of STEMI networks across Egypt, to evaluate in-hospital patient outcome, and to compare Egyptian patients with other ESC countries. Results Compared to other ESC countries, Egyptian patients were younger (mean age 55.4 ± 11.3 vs. 62.9 ± 12.4; p < 0.001 and 4.36% vs. 19.41%% were ≥ 75 years old; p < 0.001) with fewer females (18.44% vs. 25.63%; p < 0.001). Egypt had longer median time between symptoms onset and first medical contact: 120.0 (60.0; 240.0) vs.100.0 (50.0; 240.0) p < 0.001. Self-presentation rather than EMS presentation was the mode of admission in 86.06% in Egypt vs. 25.83% in EU countries (p < 0.001). On qualifying ECG, anterior STEMI was in 57.08% in Egypt vs. 45.98% in other countries (p < 0.001). Initial reperfusion therapy was 49.12%, 43.07%, and 7.26% for primary PCI, thrombolytic therapy and no reperfusion in Egypt vs. 85.42%, 7.26%, and 7.82% for EU countries, respectively. In-hospital mortality was 4.65% in Egypt vs. 3.50% in other countries p 0.040 and was 18.87% in no reperfusion vs. 2.10% in primary PCI vs. 4.97% in thrombolysis (p < 0.001) among Egyptians. Patients were discharged on aspirin in 98.61%, clopidogrel in 91.07%, ticagrelor in 7.31%, DAPT in 97.69%, beta blockers in 82.83%, ACE inhibitors in 84.76%, MRAs in 10.01%, and statins in 99.77%. Conclusion Compared to other ESC countries, Egyptian STEMI patients were younger, more frequently current smokers and diabetics, and had longer time between symptoms onset and first medical contact with more self-presentation rather than EMS presentation. Thrombolytic therapy is still a common reperfusion therapy in Egypt while primary PCI was offered to half of the patients. In-hospital mortality was significantly higher in Egypt and was highest among no reperfusion patients and lowest among PPCI patients.


Background
Mortality due to CVD in Egypt is one of the highest compared to other countries in the region and worldwide [1].
Apart from a small number of single center studies there are limited descriptive data about STEMI patients in Egypt [2][3][4]. The lack of data on the clinical characteristics of patients, hospital practice, and treatment patterns as well as the impact of management on outcomes for STEMI in Egypt underscore the need for a national registry database.

Methods
The European Society of Cardiology ACCA-EAPCI Registry on ST elevation myocardial infarction is a Joint initiative of the Acute Cardiovascular Care Association (ACCA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology. It is a registry to evaluate the treatment of STEMI across Europe and the Mediterranean countries. It is a general, prospective, multicenter, and observational registry. The ESC-STEMI registry study design has been described in detail in a recent publication [5].
The EURObservational Research Programme (EORP) department at the European Heart House coordinated the project operationally, provided support to the participating centers, and guided the methodological aspects of the survey. The database was stored and analyzed at the European Heart House.
The Egyptian society of cardiology, being a member of the ESC, participated in this registry with data from 19 Egyptian centers. Site selection aimed at centers of different levels of complexity and in different geographic regions in order to obtain a sample representative of Egyptian population. Onsite PCI capability was present in 15/17 centers (88.24%), onsite cardiac surgery in 11/ 17 centers (64.71%), and 8/16 (50.00%) reported that primary PCI was their usual treatment for STEMI patients. The median number (Q1; Q3) of beds in these centers was 91.5 (35.0; 325.0), MI volume/year was 500.0 (250.0; 720.0), total PCI/year was 800.0 (400.0; 2000.0), and total primary PCI was 220.0 (90.0; 350.0). Local audits were performed in randomly selected centers to check compliance with the protocol and review consecutiveness and quality of data.
The target population was patients with chest pain or equivalent symptoms of more than 20 min duration within the last 24 h prior to admission to hospital and ST segment elevations or LBBB in the diagnostic ECG. Each center was asked to enroll up to 60 consecutive patients. Egypt participated with 1356 (15.45%) patients who will be compared with 7420 patients from other EU or Mediterranean countries. Patient recruitment started from March 2016 to February 2018.
The aims of this study were to describe the demographic, clinical, and biological characteristics of patients with STEMI admitted to a representative setting of cardiology centers in EGYPT, to assess the organization of STEMI management across Egypt, to evaluate how STEMI ESC guidelines were adopted, to evaluate inhospital patient outcome, and to compare Egyptian patients with those from other participating countries.
Continuous variables were reported in means (standard deviation) or as median and interquartile range (IQR) when skewed. Categorical variables were reported as percentages and compared using the χ2 test. Continuous variables were compared by the Mann-Whitney U test. Kruskal-Wallis test was used when more than two groups were compared. A p value of < 0.05 was considered statistically significant. All tests were two-sided.

Results
Patients' characteristics: Table 1 Compared to other countries, Egyptian patients were younger (mean age 55. 4   In Egypt, compared to other countries, ER staff was the first medical contact (81.42% vs. 24.62%; p value < 0.001), self-presentation was the mode of admission (86.06% vs. 25.83%; p value < 0.001) and a non PCI capable center was the first hospital receiving STEMI patients (42.04% vs. 26.99%; p value < 0.001) Patient presentation and initial assessment ( Table 2) Patients admitted after an out of hospital cardiac arrest in Egypt was 2.51% vs. 5.49% in EU countries p value < 0.001. On qualifying ECG, anterior STEMI was in 57.08% in Egypt vs. 45.98% in other countries (p value < 0.001), atrial fibrillation was in 3.47% vs. 6.20% (p value < 0.001), and heart rate (mean ± SD) was 84.8 ± 19.4 vs. 78.4 ± 19.6 (p value < 0.001). Killip class IV was in 2.88% in Egypt vs. 4.27% in other countries (p value < 0.001), mechanical ventilation was used in 4.06% in Egypt vs. 5.67% in other countries (p value 0.016), therapeutic hypothermia was used in 1.40% in Egypt vs. 2.14% in other countries (p value 0.078), and therapeutic hypothermia when used was external cooling pads/blankets/wraps in 100.00% in Egypt vs. 11.41% in other countries (p value < 0.001).
Complications during hospitalization (Table 3) Compared to thrombolytic therapy, patients who were treated with primary PCI had less incidence of

Patients' characteristics
Egyptian STEMI patients were younger than their counterparts in other countries. This observation has been reported repeatedly in many previous Egyptian studies [4]. This might be due to younger age of the whole Egyptian population, the higher prevalence and poor control of  [6,7]. The higher prevalence of traditional risk factors among Egyptian patients highlights the importance of focusing on primary prevention which is as important as treating patients with acute cardiovascular events. Egypt needs a national primary prevention strategic plan to early detect and properly control these risk factors.

Hospital admission process
EMS service is very much under used among Egyptian patients with STEMI. This very low rate of EMS usage among STEMI patients is similar to the lowest rate among European countries which, in one report, ranged from 18 to 85% [8].
In this registry, all indicators of out of hospital delay, like the median time between symptoms onset and call for medical help and the median time between symptoms onset and first medical contact, were significantly longer among Egyptian patients. Self-presentation rather than EMS-presentation, having hospital ER rather than the ambulance as the first medical contact, and presenting to a non-PCI capable hospital were potential causes for pre-hospital delay in Egypt [9].
In this registry, the median time in minutes between symptoms onset and call for medical help in Egypt was 85.0 vs. 74.5 in EU countries, while the median time between symptoms onset and first medical contact was 120 vs.100 min. Among patients treated with primary PCI, the median time from symptom onset to first medical contact ranged from 60 to 210 min, the time between FMC to balloon ranged from 60 to 177 min while the total ischemic time ranged from 180 to 325 min.
In an older European report, among patients treated with thrombolytic therapy, the median time from symptom onset to first medical contact ranged from 68 to 210 min, the time between FMC to thrombolytic therapy ranged from 30 to 110 min while the total ischemic time ranged from 113 to 320 min.
In an Egyptian registry, among 137 STEMI patients treated with primary PCI in a single tertiary center, the mean time of pain to FMC was 378 min while the door to balloon time was 41 min [10].
Many reports from both developed and developing countries have shown marked improvement (reduction) of total ischemic time and prehospital time delay after adopting national plans to increase patient awareness and to connect cardiac centers and EMS via regional networks [11][12][13][14].

Patient presentation and initial assessment
The lower incidence of out of hospital cardiac arrest in Egypt might be due to either under reporting because of culture issues in Egypt to avoid post mortem investigation and the very low rate of EMS use or a true lower incidence due to younger age and lower risk profile of the Egyptian patients. In Egypt, therapeutic hypothermia is not a wellestablished used technique among post-cardiac arrest patients and hypothermia when used was only external cooling pads, blankets, or wraps.
Atrial fibrillation and heart failure were lower among Egyptian patients probably due to the younger age or to under-diagnosis

STEMI reperfusion pattern
The practice of primary PCI in Egypt has improved along the past decade despite a lot of obstacles mainly limited public medical insurance coverage and limited number of 24/7 cath labs with well trained staff especially in remote Egyptian areas. In a registry of the largest two cardiology centers in Egypt, from 2007 to 2011, only 7.2% of PCI procedures were for non-elective patients with STEMI and NSTEM [15].
In the Egyptian National heart Institute Registry, among patients with ST-elevation, 65.5% received streptokinase while only 12.4% were referred for primary PCI [16]. In a more recent registry, the rate of primary PCI among STEMI patients was 37% and thrombolysis in 54.7% [4]. The AC-CESS registry, a prospective observational multinational registry, 134 sites in 19 countries in Latin America, middle east, north, and south Africa, 9732 ACS patients with 1 year follow-up, 45% STEMI and 52% NSTEMI, STEMI had fibrinolysis in 30%, and primary PCI in 26% [17].
The ACCESS registry, a prospective observational multinational registry, 134 sites in 19 countries in Latin America, middle east, north, and south Africa, 9732 ACS patients with 1 year follow-up, 45% STEMI and 52% NSTEMI, STEMI had fibrinolysis in 30% and primary PCI in 26% [17].
Among 20 European countries, there was large difference in the rate and pattern of STEMI reperfusion: primary PCI ranged from 5 to 92%, thrombolysis ranged from 1 to 55%, and no-reperfusion ranged from 7 to 52% in some countries. Egypt was not included in that report.
In a more recent report, the rate of primary PCI per 1 million inhabitants ranged from 25 to 884. The recommended figure is > 600 PPCI per 1 million inhabitants; for Egypt it was 29 per 1 million inhabitants. Egypt short-term target should be 400 PPCI per million, i.e., total of 40000 PPCI/year, i.e., 40% of the estimated total number of 100,000 STEMI/year [18,19].
According to a recent report, Egypt has < 10 interventional cardiologist/million inhabitants compared to Germany which has ≥ 25, < 2 cath labs/million vs. ≥ 5 in Germany, and < 1 PPCI cath lab/million vs. ≥ 4 in Germany. The number of PPCI procedures was < 200 per million compared to ≥ 600 in Germany [20].
Non-reperfused patients are mainly those with late presentation beyond the window of reperfusion. Their number was probably under estimated because we included 19 very active centers that apply guidelines recommendations in the diagnosis and management of STEMI patients.
Thrombolysis is still a very common reperfusion method among STEMI patients in Egypt and is mostly given in the ICU/CCU of the hospitals and almost never in the EMS (out of hospital) nor in the ER. The thrombolytic agent given is mostly streptokinase and not TNK or rTPA due to limited resources. Routinely sending patients post thrombolysis to primary PCI within 2-24 h is generally underused strategy. Egypt should improve all aspects of this mode of reperfusion when applied.

Complications during hospitalization
The highest incidence of complications was among the non-perfused patients, who had the highest incidence of in-hospital mortality compared to re-perfused patients.
Primary PCI patients had fewer incidences of cerebrovascular accidents heart failure and atrial fibrillation probably due to higher incidence of successful reperfusion while they had higher incidence of serious bleeding (probably related to vascular access site bleeding) and stent thrombosis obviously as stenting is their default treatment.
The higher incidence of cerebrovascular accidents among Egyptian Compared to EU patients is probably due to higher use of thrombolytic therapy among the former. The lower incidence of re-infarction, stent thrombosis, AF, and Heart failure among Egyptian patients might be underestimated or due to younger and less risk profile of these patients

In-hospital mortality and status at discharge
The statistically significant higher in-hospital mortality among Egyptian patients despite their younger age and lower risk profile (4.65% vs. 3.50%) is probably due to the lower rate of primary PCI for reperfusion, the longer delay before first medical contact and the less application of advanced techniques like LV assisting devices and hypothermia.
In an older report, the in-hospital mortality in STEMI patients in different European countries ranged from 3 to 13%. In an American report, the in-hospital mortality for STEMI patients treated with PPCI varied between 3.1 and 6.1%. Egypt is to be compared to the lower range of these old reports, but mortality rate has already improved in these countries.
The mortality rate among Egyptian primary PCI patients reported in this registry (2.10%) indicates improvement compared to an older study (Yehia et al. 2010) in which the in-hospital mortality rate among 137 patients treated with primary PCI in one Egyptian tertiary center was 6.57%.
The highest rate of in-hospital mortality among the group of no-reperfusion (18.87%) indicates that we should encourage their earlier presentation because late presentation was the main cause of not offering them any kind of reperfusion.

Medications
Clopidogrel is the most commonly used ADP receptor blocker even among STEMI patients (91.07%) while ticagrelor or prasugrel were only used in 7.31% of Egyptian patients. This might be due either to financial reasons where clopidogrel is available in generic forms, the higher rate of thrombolytic therapy usage where clopidogrel is the default drug, concerns about risk of bleeding or just practice inertia. More potent antiplatelets should be the default drugs used in STEMI patients according to the guidelines [21].
Statins are prescribed for most STEMI patients at discharge (99.77%), but we do not know which doses are prescribed for such high risk patients. We lack longterm follow-up studies to document the rate of patients' compliance and adherence.
Gaps in guideline implementation in Egypt and implications for quality improvement (Table 4) Total ischemic time is much increased due to both patients and system delays. There is an urgent need for public awareness and patient education campaigns to instruct patients with chest pain to seek medical advice as early as possible together with improving the EMS performance in Egypt. The vast majority of patients with STEMI in Egypt have been self-presented to hospitals rather than via EMS system. We need to improve the performance of EMS in Egypt to become a dependable and efficient mode of STEMI patients transfer.
The number of primary PCI/ per million populations is small due to the limited number of primary PCI centers which, when present, is not connected to a regional network of referring hospitals. There is an obvious unmet need to develop such hub and spoke system in Egypt especially in remote and rural areas. The government should extend the umbrella of medical insurance and its reimbursement to health care centers providing emergency STEMI reperfusion [22][23][24].
One of the main obstacles that prevent big hospitals at some times to admit patients with STEMI is the lack of empty beds in the CCU. A solution to this problem is patient repatriation after the primary PCI procedure to the local referring hospital. In our study, there was a lower incidence of patients discharged to another hospital, compared to European countries, which is due to absence of repatriation policy.
Pharmaco invasive approach might be a practical way of treating STEMI patients in remote and rural areas, in major cities with heavy traffic and in areas with inefficient EMS system. Thrombolytic agent should be the TNK and not the streptokinase and better given before reaching hospital. Routine coronary angiography with possible PCI to the infarct related artery within 2-24 h after thrombolytic therapy is a guidelines class IA recommendation but in Egypt it is often either neglected or performed after the recommended time window. Such procedure is not reimbursed by the government assuming that the patient has been already reperfused by the thrombolytic therapy [25][26][27][28][29].

Limitations of this study
Despite every effort to include many centers with diverse activities and geographic locations these centers, and these patients might not represent the actual Egyptian practice especially in some remote and rural areas in Egypt.

Conclusion
Compared to EU countries, Egyptian STEMI patients were younger, more frequently current smokers and diabetics, and had longer time between symptoms onset and first medical contact with more self-presentation rather than EMS presentation. Thrombolytic therapy is still a common reperfusion therapy in Egypt while primary PCI was offered to half of the patients. In-hospital mortality was significantly higher in Egypt and was highest among no reperfusion patients and lowest among PPCI patients. DAPT and statins at discharge were adequately following guideline recommendations.