The national moroccan registry of ST-elevation myocardial infarction (MR-MI)

Background MR-MI is the first national Moroccan ST-elevation myocardial infarction (STEMI) registry. Its objectives are to assess patient management modalities and highlight the clinical and therapeutic characteristics of this pathology in all cardiology centres on a national scale. Methods Adult patients presenting with STEMI within 5 days of symptoms onset were enrolled over a period of 18 weeks from April to August 2018. 57 cardiology centres distributed in 22 cities in Morocco participated in the study, including 5 university hospitals, representing 70% of Moroccan centres managing STEMI patients. A case report form was sent to the investigators in both electronic and paper forms. Sociodemographic, clinical, management, revascularization, and follow-up data were collected. Results A total of 809 patients were recruited. The population was mostly male (74.8%) with an average age of 62.6 ± 11.6 years. The most common risk factors were smoking (38.3%) arterial hypertension (30.7%), and diabetes (28%). 30% of patients were admitted within the first 6 h of symptoms onset and early revascularization was performed on 49.6%. Mortality rate was 5.2% in-hospital and 3.2% at the one-month follow-up. Conclusion MR-MI is the first Moroccan STEMI registry on a national scale. Relevant management delays are much longer than other countries, and less than 50% of the patients that present on time benefit from early revascularization. Efforts remain to be done on the optimal diagnosis and treatment of STEMI.


Background
Despite global improvements in management, cardiovascular disease, and more specifically ischemic heart disease (IHD) still represents a substantial health burden, with major social and economic consequences [1][2][3][4].
In Morocco, IHD has become the number one cause of mortality, with a 31% rate according to the 2019 Global Burden of Diseases Study [1].Among cardiovascular risk factors, a recent meta-analysis remarked that tobacco smoking (20 to 45%) and hypertension (25 to 30%) are the most prevalent in the Moroccan population [5].Management of ST-elevation myocardial infarction (STEMI) remains far from optimal; in a study published in 2012 regrouping patients from Morocco, Tunisia, and Algeria, Moustaghfir et al. reported that almost half of the patients do not receive any reperfusion therapy, explaining the higher rate of 30-day mortality compared to other countries (4.1%) [6].
The 2018 MR-MI (Moroccan Registry of Myocardial Infarction) is a project of the Moroccan Society of Cardiology in partnership with the National College of Myocardial Infarction.Our goals were: • to extensively characterize the clinical profile of STEMI patients throughout Morocco's regions, and set up a reference database for future studies; • to quantitatively and qualitatively assess the current state of STEMI management in Morocco, and consequences on short-and long-term patient outcomes; • to study the implementation of relevant practice guidelines in a real-world setting.Large-scale descriptive studies are far and few in Morocco.The largest myocardial infarction registry is a city-wide effort from Fez, published in 2015 by Akoudad et al. and compiling 1835 patients [7].To our knowledge, this is the first national scale STEMI registry in Morocco.

Study design
This was a national prospective multicentre study, including 70% of Moroccan centres managing STEMI patients.

Study population
Data was collected over a period of 18 weeks, from April to August 2018.
Inclusion criteria were: patients aged > 18 years; admitted for recent (less than 5 days) STEMI, defined as ischaemic symptoms such as chest pain alongside an acute rise of troponin or another cardiac enzyme above the 99th percentile upper reference limit, and at least one of the following: ST-segment elevation in two or more contiguous leads, new abnormal Q waves or new-onset bundle branch block on admission electrocardiogram (ECG).
Exclusion criteria were: STEMI with symptom onset > 5 days; patients admitted for NSTE-ACS (non ST-elevation acute coronary syndrome), defined as chest pain and/or rise of troponin values without ST-segment elevation; patients admitted in cardiac arrest, who died in transport or very early after admission.
All patients gave informed consent to participate in the study.

Participating centres
57 centres across 22 cities accepted to participate in the study, including university and provincial hospitals, military hospitals, and private clinics, and covering a large majority of the Moroccan territory (Fig. 1). 5 university hospitals were represented (Rabat, Casablanca, Fez, Oujda, Marrakech).

Data collection
A standardized case report form was sent to all the participating centres and was filled by the onsite investigator or the attending physician.Sociodemographic data such as mode of living and health coverage was collected.Clinical data included medical history and cardiovascular risk factors, STEMI symptoms and timing, vital constants and Killip class at admission, findings on the first ECGand transthoracic echocardiogram (TTE) such as wall motion abnormalities and LVEF (left ventricular ejection fraction).TTE was performed by the attending physician using onsite available ultrasound machines.LVEF was calculated on the 2-chamber and 4-chamber apical views using Simpson's biplane method.Wall motion abnormalities were defined as the presence of hypokinesia, akinesia or dyskinesia on one or more myocardial wall segments.The speed and quality of management was thoroughly documented; revascularization modalities, angiographic findings, and relevant time delays (symptoms-to-first medical contact and symptoms-to-management) were precisely recorded.For the purpose of symptoms-to-management time measurements, management was defined as either fibrinolysis injection or stent deployment in the context of percutaneous coronary intervention (PCI).Coronary angiography acquisition views and image interpretation were at the discretion of the attending interventional cardiologist.The culprit artery was determined by the presence of arterial occlusion or severe stenosis (> 70%) on a major epicardial artery, assuming it corresponded with the patient's electrocardiographic and echocardiographic data.Follow-up data included in-hospital complication and mortality rates, and outcomes at one month.

Data quality
Data quality measures, such as manual and automated checks by the investigators, were undertaken throughout the study.All the data entered were verified and corrected by external assistants, and carefully stored in a protected electronic database.The amount of missing data was judged acceptable (less than 5% for all variables).

Statistical analysis
Qualitative variables are reported as means ± standard deviations (SD), and median values were calculated when appropriate.Discrete variables are reported as percentages.

Baseline characteristics
A total of 809 STEMI patients was included, originating from 76 cities and 68 rural villages.The majority were admitted in university hospitals (52.9%), followed by regional hospitals (20.7%) and private centres (14.3%).15% didn't have any health coverage (Table 1).
The mean age was 62.6 ± 11.6 years, and 42% of patients were younger than 60.The majority were men (74.8%).The most common modifiable cardiovascular risk factors were smoking (38.3%) and arterial hypertension (30.7%).65% of patients had 3 or more risk factors.63% had no cardiovascular medical history (Table 2).

Management and reperfusion
The median symptoms-to-first medical contact delay was 690 min and 50% of patients presented after the 12-hour mark (Fig. 2).The median symptoms-to-management delay was 815 min (Fig. 3).Regarding medical therapy, most patients received aspirin, clopidogrel and low molecular weight heparin.Fibrinolysis was performed  in 23.4% of patients, with a median time delay of 6 h, with the majority being carried out in university hospitals.98% of the 809 patients underwent coronary angiography, regardless of delay.26.2% of patients underwent PCI, mostly in private centres and university hospitals, with a median delay of 3 h.The most common culprit artery, in 81.2% of cases, was the left anterior descending (Table 3).

Outcomes
In-hospital evolution was marked by a 17.4% rate of complications, the most prevalent being arrhythmias and recurrent ischemia.Mortality rate was 5.2%, with a mean age of 61 ± 11 years (Table 4).Follow-up data was available for 42.4% of the cohort.At the 1-month check, 94.1% of available patients were asymptomatic; the re-hospitalization (either for reinfarction or acute heart failure) and mortality rates were 2.1% and 3.8%, respectively (Table 5).

Discussion
MR-MI aimed to answer two important questions.First, what are the main differences between the Moroccan STEMI patients and those from other countries?Second, does the management in Morocco adhere to current practice guidelines?The size of our cohort (809 patients) was judged sufficient to answer these questions and is in line with other major registries such as Tunisia (459) [8] and France (1872 patients) [9] when adjusted to the population numbers.
To answer the first question, our results should be compared to other Mediterranean countries, such as Tunisia [8] and France [9].Sociodemographic data is similar  in all three countries, with a mean age of 60 to 63 years, and a clear male predominance (74.8% in Morocco and France, 81.5% in Tunisia).Smoking and arterial hypertension are the most common risk factors although hypercholesterolemia is more prevalent in France (36 vs. 13.6%) and smoking is much more frequent in Tunisia (63.6 vs. 38.3%).Smoking is a major health issue in Morocco; with a prevalence of 30 to 50% [5,10].That rate is probably higher due to the social stigma associated with smoking in Morocco, and the increase among young men of other forms of tobacco usage such as water pipe-smoking, which are not reported in many studies [5].The prevalence of arterial hypertension in the Moroccan population ranges from 26 to 29% in most major reports [11][12][13].Arterial hypertension is also severely underdiagnosed and undertreated in Morocco; in the ETHNA study, 29% of patients were newly diagnosed, and in treated hypertensive patients, control rates range from 25 to 35% [13,14].Hypercholesterolemia was probably underreported in our study as 29% of Moroccan patients suffer from this condition [13].This discrepancy is probably explained by the fact that practicians are less likely to perform lipid panels in the emergency setting.In our study, 63% of patients had no cardiovascular medical history, which is lower than in France (84%).Typical chest pain was the most common presentation in all three countries, but heart failure was more frequent in Maghreb countries (13.4 and 11.4%) compared to France (3%), underlining the late presentation of patients in those countries.The prevalence of AF in our study was similar to the French one (3.1 vs. 4%).Anterior and inferior STEMI comprised about 90% of all localizations in the three countries.The mean LVEF was slightly increased in France compared to Morocco (50.2 vs. 45%).Overall, the clinical profile of STEMI patients remains similar between the three countries.
To answer the second question, it is essential to review revascularization modalities used and the various management delays.The 2017 European guidelines on STEMI recommend that a patient undergoes primary PCI within 48 h (but preferably 12 h) after symptom onset.Fibrinolysis should be administered within 12 h after symptom onset if PCI is not available within 2 h [15].Early presentation of the patient is therefore crucial for optimal diagnosis and management.In Morocco, the symptomto-first medical contact delay is much longer than in France (690 vs. 141 min).Half of the patients consult after the key 12-hour mark, which explains why two thirds of the patients do not receive thrombolytic agents even when they're available.Fibrinolysis was used in 23.4% of cases; that rate is higher in Tunisia (31.8%) but much lower in France (6%), underlining the poor availability of cath labs especially in rural areas and provincial hospitals.Only 14.3% benefit from primary PCI, compared to 30% in the Tunisian cohort and 91% in the French registry.These longer delays explain in part the higher rate of complications in Moroccan patients compared to French patients, especially recurrent myocardial infarction (1.7 vs. 0.3%) and in-hospitality death (5.2% vs. 2.8%).The mortality rate reported in our study is slightly inferior to the Tunisian one (5.2 vs. 5.5%).At the one-month followup, it remains stable at 3.8%.What are concrete solutions to improve the situation in Morocco?We need to take a look at the 1995 to 2010 period in France, when 30-day mortality fell from 13.7 to 4.4% [16].In addition to the STEMI demographic shift (patients were younger by 3 years on average), this decrease was mostly explained by shorter management delays (120 to 74 min), a greater involvement of emergency medical services (EMS), whose rate of use grew from 23 to 49% and a higher rate of primary angioplasty (49 to 75%) [17].EMS involvement rate was only 3.2% in our study.By increasing the awareness of the general public about STEMI and the need to call EMS as soon as symptoms begin, management delays would be tremendously reduced, allowing for more efficient revascularization and better outcomes.The availability of cath labs is also an issue, especially in provincial hospitals where the only recourse is fibrinolysis, which is known to be inferior to PCI [7,18].These are the main areas that Morocco is developing in the present and the near future.Since 2018, the Moroccan government has made great strides in the construction of new PCI centres, both private and public, and the development of chest pain awareness programs.

Conclusions
MR-MI is the first national STEMI registry in Morocco with a total of 809 patients and draws some important conclusions.The clinical profile of our patients is similar to that of other Mediterranean countries, but management suffers from many inadequacies, especially long time delays and inefficient revascularization options.
Concrete, proven solutions exist, such as the involvement of EMS and the democratization of urgent angiography and PCI.Since 2018, Moroccan practicians and health officials have been involved in the development of these areas and much progress has been made in the right direction.

Fig. 3
Fig. 3 Symptoms to management delay

Fig. 2
Fig. 2 Symptoms to first medical contact delay

Table 4
In-hospital evolution and outcomes Data are expressed as percentage (%).

Table 5
Follow-up results at one month